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The complex technological processes involved in radiation therapy can be intimidating to patients, causing increased treatment-related anxiety and reduced satisfaction. An intervention was implemented to provide direct consultations between patients and medical physicists to reduce patient anxiety and improve patient satisfaction. A randomized clinical trial was conducted to test the intervention's effect on anxiety, distress, treatment adherence, technical understanding, and satisfaction in patients receiving radiation therapy.Eligible patients were recruited into "intervention" and "standard of care" arms within a phase 2 screening randomized trial. Intervention-arm patients met with a medical physicist who provided technical information and addressed patient questions or concerns at the time of treatment simulation and before the first treatment. In addition to baseline information collected before randomization, participants were surveyed (1) before simulation, (2) before the first treatment, and (3) before the completion of treatment to evaluate the study endpoints. Primary endpoints included patient anxiety and distress. Secondary endpoints included patient treatment adherence, overall satisfaction, and technical understanding of treatment. Patients in the intervention arm were surveyed before and after each physicist meeting.Participant anxiety was significantly reduced in the intervention arm (difference, -0.29; 95% confidence interval, -0.57 to -0.02; P = .038). No differences in distress or treatment adherence were observed between groups. Although measures of technical understanding and satisfaction were evaluated as exploratory objectives, participants in the intervention group were more likely to feel that technical aspects of treatment were adequately explained (difference, 0.78; 95% confidence interval, 0.03-1.54), and all measures of technical understanding and satisfaction were considerably higher in the intervention group at the time of the first visit.The establishment of a direct patient-provider relationship with the medical physicist reduced anxiety in patients receiving radiation therapy. In addition, increases in patient understanding of the technical aspects of care and in satisfaction were observed at the initiation of treatment.

The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients.Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed.A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI: 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI: 36.3-89.9) for those with escalation.A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.

Introduction: Breast cancer is the most common type of cancer among women in the United States with more than 281,550 new cases in 2021. Definitive treatment for early/localized disease includes a combination of surgery, radiation and systemic therapy with high cure rates but significant potential morbidity. Lymphedema (LE) is the chronic swelling of tissue due to damage caused by breast cancer surgery and/or radiation therapy, occurring in approximately 25-60% of patients who undergo axillary dissection with or without radiation. LE is a morbid disease that decreases patient quality of life and has limited treatment options. Thus, identifying risk factors to prevent the development of LE is crucial. To our knowledge, uncontrolled hypertension has not been previously studied as a potential risk factor for the development of arm lymphedema after breast cancer treatment. Methods: In this single institution prospective cohort study, women were enrolled before their surgery for stage 0-III breast cancer. Baseline interviews were conducted and data including ethnic background, weight, medical comorbidities, and medications were collected. Breast cancer clinicopathologic features and treatment were also recorded. Bilateral arm measurements and blood pressure (BP) readings were taken at baseline and intervals of 3 months for up to 5 years after surgery. An increase in volume >5% from baseline was classified as lymphedema. The association between baseline BP and development of lymphedema was tested with univariate Cox regression model. Results: 176 women were enrolled between 1999 and 2004, of which 46% were Caucasian, 42% African American, 12% other. The average age at enrollment was 51 years. 68% were overweight or obese. 11% had Stage 0, 33% Stage I, 42% Stage II, and 14% had Stage III breast cancer. The most common type of surgery was mastectomy (52%) with remaining patients undergoing lumpectomy. Most patients underwent nodal evaluation with 55% receiving axillary node dissection, 40% receiving sentinel node biopsy or axillary node sampling, and 6% undergoing no nodal surgery. 57% of patients underwent chemotherapy and 53% received radiation therapy. At baseline, 65% of the patients reported a history of hypertension, of which approximately 50% were taking antihypertensive medications and 57% had uncontrolled blood pressure (defined as office BP ≥ 140/90). Using the 5% cutoff, 27% of patients developed lymphedema within 5 years after surgery, of which 14% occurred within the first year. Women who were obese, had mastectomy or more than 9 LNs removed were at higher risk of developing LE. Age, ethnicity and cancer stage had no association with the development of LE (Table 1). Women with uncontrolled or controlled hypertension did not have a higher risk for LE compared to those that were normotensive with hazard ratios of 0.82 (95%CI: 0.39, 1.76; p value 0.616) and 0.70 (95%CI: 0.31, 1.59; p value 0.396) respectively. Conclusion: Baseline uncontrolled or controlled hypertension does not increase the risk for the development of LE after surgery and radiation for breast cancer. Further analysis of BP control over time as another risk factor for the development of LE in this dataset is also planned. Identifying BP control as a risk factor for LE would aid in prevention efforts to decrease the development of this morbidity in breast cancer survivors. Table 1. Univariate Cox regression hazard ratios (HR) for development of lymphedema with 5% cutoffVariableEvent/nHR (95% CI)P valueAge at enrollment48/1741.00 (0.98-1.02)0.984RaceCaucasian19/81Ref.African American23/741.53 (0.83-2.82)0.171Other6/201.17 (0.47-2.93)0.741StageI13/58Ref.04/190.74 (0.24-2.29)0.605II25/741.39 (0.71-2.71)0.341III6/251.22 (0.46-3.20)0.693BMINormal9/52Ref.Underweight1/32.95 (0.37-23.43)0.306Overweight15/551.73 (0.76-3.95)0.195Obesity23/652.21 (1.02-4.78)0.044Number of Nodes Removed Citation Format: Elizabeth Weisberg, Hadeel Assad, Lydia Choi-Kim, Tammy DeMeere, Hyejeong Jang, Wei Chen, Mary Ann Kosir. Uncontrolled hypertension and the development of lymphedema after breast cancer surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-07.

Introduction. Socioeconomic and racial factors have been reported as influencing breast cancer outcomes. Low income and African American race are associated with worse outcomes after a breast cancer diagnosis. Lymphedema is a common side effect of cancer treatment, occurring in approximately 25-60% of patients who undergo axillary dissection with or without radiation. In our urban, heavily African American population, we examined socioeconomic risk factors for arm lymphedema development. Methods. 176 women were enrolled before surgery for stage 0-III breast cancer. Baseline interviews were conducted, including job descriptions, income, ethnic background, marital status, weight, and medical comorbidities. Pathologic stage as well as treatment regimen including receipt of radiation to the axilla were also recorded. Baseline arm measurements were also taken. Arm measurements were repeated at intervals of 3 months up to 2 years, and any increase >5% was classified as lymphedema. Median follow-up was 2 years. Results. Cox regression was used to identify patient factors associated with lymphedema development. Median age at enrollment was 51 (29-86). 46% of patients enrolled were Caucasian, and 42% were African American. 11% had carcinoma in situ, 33% had stage I, 42% had stage II, and 14% had stage III breast cancer at presentation. 68% of patients were overweight or obese at presentation. Of the patients who had income data available, 30% had income >$50,000 per year, 15% had income $15,000-50,000 per year, and 24% of patients had income Citation Format: Lydia Choi, Hadeel Assad, Wei Chen, Tammy Demeere, Hyejeong Jang, Elizabeth Weisberg, Mary Ann Kosir. Arm lymphedema and socioeconomic factors in an urban cancer center [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-22.

Utilization of novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CI) has increased in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL). We conducted a retrospective study of 209 patients who had ASCT for r/r cHL at our institution and compared outcomes of those who had ASCT from 2010-2018 (cohort 2, n = 110) with those who had ASCT between 2000 and 2009 (cohort 1, n = 99). The median OS was 7.6 years for cohort 1 [HR 2.08; 95% CI 1.14-3.80; p = 0.017] and not reached for cohort 2; with 4-year improved OS difference of 15% (80% vs 65%) in cohort 2 vs cohort 1. The median PFS of cohort 1 was 30 months vs 39 months for cohort 2[HR 1.24; 95% CI 0.82-1.88; p = 0.3]. This study highlights improved OS of r/r cHL patients who have received ASCT in the novel agent era due to the exposure to agents such as BV and CIs.

ImportanceThe current standard of care for the treatment of small cell lung cancer (SCLC) is concurrent chemoradiation for patients with limited-stage SCLC (LS-SCLC) and chemoimmunotherapy for extensive-stage SCLC (ES-SCLC). The backbone of chemotherapy regimens in both is a platinum-etoposide doublet: cisplatin is traditionally the preferred platinum agent in the curative intent setting, whereas carboplatin is preferred in ES-SCLC because of its favorable toxicity profile.ObjectiveTo determine whether cisplatin is associated with better survival outcomes than carboplatin in treating LS-SCLC and ES-SCLC.Design, Setting, and ParticipantsIn this cohort study, data were compiled from the National Veterans Affairs Central Cancer Registry for patients with SCLC who received platinum-based multiagent chemotherapy between 2000 and 2020 for ES-SCLC and 2000 and 2021 for LS-SCLC. Only patients with pathologically confirmed cases of LS-SCLC who received concurrent chemoradiation and ES-SCLC who received chemotherapy were included.Main Outcomes and MeasuresThe primary end point was overall survival (OS). The secondary end points included OS by Eastern Cooperative Oncology Group performance status, age, and laterality. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median OS and hazard ratios (HRs), respectively. Survival curves were compared by a Wald test.ResultsA total of 4408 SCLC cases were studied. Most patients were White (3589 patients [81.4%]), male (4252 [96.5%]), and non-Hispanic (4142 [94.0%]); 2262 patients (51.3%) were 60 to 69 years old, followed by 1476 patients (33.5%) aged 70 years or older, 631 patients (14.3%) aged 50 to 59 years, and 39 patients (0.9%) aged 30 to 49 years. Among 2652 patients with ES-SCLC, 2032 were treated with carboplatin-based therapy and 660 received cisplatin; the median OS was 8.45 months (95% CI, 7.75-9.20 months) for cisplatin and 8.51 months (95% CI, 8.07-8.97 months) for carboplatin (HR, 1.01; 95% CI, 0.91-1.12; P = .90). Subset analysis showed no survival difference between the 2 agents in different age or performance status groups except for patients aged 70 years and older, for whom the median OS was 6.36 months (95% CI, 5.31-7.56 months) for cisplatin and 8.47 months (95% CI, 7.79-9.19 months) for carboplatin (HR, 0.77; 95% CI, 0.61-0.96; P = .02). Multivariable analysis of performance status and age did not show a significant difference in survival between the 2 groups (HR, 0.96; 95% CI, 0.83-1.10; P = .54). Of 1756 patients with LS-SCLC, 801 received carboplatin, and 1018 received cisplatin. The median OS was 26.92 months (95% CI, 25.03-28.81 months) for cisplatin and 25.58 months (95% CI, 23.64-27.72 months) for carboplatin (HR, 1.04; 95% CI, 0.94-1.16; P = .46). The median OS was not significantly different between 2 agents according to cancer stage (I-III), performance status, and age groups. A multivariable analysis of factors associated with OS accounting for stage (I-III), performance status, and age did not demonstrate a significant difference in survival between carboplatin and cisplatin in patients with LS-SCLC (HR, 0.995; 95% CI, 0.86-1.15; P = .95).Conclusions and RelevanceCisplatin is not associated with a survival advantage over carboplatin among patients with either ES-SCLC or LS-SCLC, irrespective of performance status and age. The favorable toxicity profile of carboplatin and comparable OS support its use in both LS-SCLC and ES-SCLC in clinical practice and may allow more room for combination with novel treatment strategies in clinical trials.

Context.— Intraoperative consultation—frozen section diagnosis (FSD)—determines tumor pathology and guides the optimal surgical management of ovarian neoplasms intraoperatively. Objective.— To evaluate the diagnostic accuracy of the FSD and analyze the discrepancy between the FSD and final diagnosis. Design.— This is a retrospective study of 618 ovarian neoplasm FSDs from 2009 to 2018 at a tertiary health care center. The discrepant cases were reviewed and reevaluated by gynecologic and general surgical pathologists. The outcomes of interest were performing unnecessary procedure, returning for a second surgery, and 30-day postoperative mortality. Results.— The sensitivity and the positive predictive value of the FSD were lower in borderline tumors than in benign and malignant epithelial ovarian tumors. Major and minor discrepancies were identified in 5.3% (33 of 618) and 12.3% of (76 of 618) cases, respectively. A root cause analysis of the major discrepant cases showed that sampling error accounted for 43% (14 of 33). The discrepancy distributions of gynecologic and general surgical pathologists were statistically similar in the overall cohort (P = .65). The overall κ for diagnostic agreement among gynecologic pathologists, general surgical pathologists, and final diagnosis was 0.18 (0.10–0.26, P < .001), implying only a slight overall agreement. Of the major discrepant cases, only 3 had a clinical implication. One overdiagnosed patient underwent an unecessary procedure, and 2 underdiagnosed patients were recommended to return for a second surgery. No patient had 30-day postoperative mortality. Conclusions.— Frozen section diagnosis remains a definitive diagnostic tool in ovarian neoplasms and plays a crucial role in guiding intraoperative surgical management.

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women. Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing. Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as “negative for intraepithelial lesion,” the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01–338.62; p

Aims: Polymyxin B (PMB) is known to require reactive oxygen species (ROS) for its bactericidal activity, but the mechanism of PMB resistance in various Pseudomonas aeruginosa strains has been poorl...

Background: Carriers of pathogenic variants in BRCA1 and BRCA2 have an elevated lifetime risk of breast, ovarian and other cancers. Current NCCN guidelines recommend specific screening for early cancer detection and risk reducing surgeries. Previous studies investigating the choices women make following the identification of pathogenic germline BRCA1 or BRCA2 variants reveal racial disparities in uptake of recommendations with black patients having lower rates of risk-reducing surgical procedures. We report on screening and prevention practices among 128 women identified with a pathogenic BRCA1 or BRCA2 variant at a large, urban comprehensive cancer center in Detroit, Michigan to evaluate racial differences in compliance with screening and prevention practices and to identify potential barriers to guideline-recommended care. Methods: The study population included women evaluated for genetic counseling and testing at the Karmanos Cancer Institute (KCI) from January 1, 2000 through December 31, 2017, who tested positive for a pathogenic variant in BRCA1 or BRCA2. A 54-item mail or telephone-based questionnaire was used to measure sociodemographics, medical history, cancer screening and risk reducing surgery, and cancer worries and fears. The primary and secondary outcomes were rate of risk reducing salpingo-oophorectomy (RRSO) and risk reducing mastectomy (RRM). Univariable logistic regression analyses were performed to identify potential predictors of RRSO and RRM, including race, personal cancer history, age at survey, time interval since BRCA1 or BRCA2 diagnosis, education, income, marital status and family history of a pathologic BRCA variant. P values less than 0.05 were considered statistically significant. Results: Of 374 women with pathogenic BRCA1 or BRCA2 variants during the study period, 129 (35%) completed the study survey (75 written, 54 telephone) with one ineligible. Of the 128 BRCA1 or BRCA2 carriers, 94 (73%) and 76 (59%) underwent RRSO and RRM, respectively and 13 (38%) and 10 (19%) planned to complete those procedures in the future. The rate of RRSO was 72% for white and 71% for black carriers. Black women tended to be less likely to have RRM compared to white women, but this difference did not reach statistical significance (OR 0.5 [95% CI 0.17 - 1.43], p = 0.193). Women who had RRM were 3 times more likely to have RRSO (and vice versa) (OR = 3.28, p = 0.004). With each increasing year of age at the time of genetic counseling, the odds of RRSO increased by 6% (OR = 1.06, p = Conclusion: There was no racial difference in the rate of RRSO or RRM between white and black carriers of pathogenic BRCA1 or BRCA2 variants. Further multivariable models will assess predictors of risk reducing surgeries and will include assessment of screening practices as well as cancer worries and fears. Citation Format: Maria Levitin, Hadeel Assad, Hyejeong Jang, Wei Chen, Nancie Petrucelli, Michael Simon. Uptake of screening and risk reducing recommendations among women with hereditary breast and ovarian cancer syndrome evaluated at a large urban comprehensive cancer center [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-70.

Background Peripheral NLR, PLR, and LMR have prognostic value in various malignancies as they are surrogates for inflammation. Recent studies have identified NLR, PLR, and LMR correlate with patient outcomes in cervical cancer patients however there remains uncertainty regarding the optimal time point for assessing these markers. Methods We retrospectively reviewed cervical cancer patients underoing definitive chemoradiation therapy (dCRT). NLR, PLR, and LMR values were identified before, during, and after dCRT and both relative and absolute changes in these values were calculated and compared with patient outcmoes. Results Ninety-nine patients who met the includsion criteria were identified. NLR values before, during, and after dCRT correlated with progression free survival (PFS) and overall survival (OS). In addition, increasing NLR after treatment was associated with worse PFS and OS. LMR before and after treatment had a positive correlation with PFS however increasing LMR during dCRT was found to have a negative correlation with PFS and OS. Conclusions NLR serves as a prognostic indicator irrespective of timing with response to dCRT. While higher LMR before treatment was a positive prognostic indicator, increasing LMR was found to negatively correlate with PFS and OS.

The use of G-CSF post allogeneic transplant has become a common practice to accelerate neutrophil engraftment. There is some controversy in its use. To further evaluate the effectiveness, we compared outcomes in patients who underwent PBSCT, either with or without the planned use of G-CSF post SCT. Among consecutive 162 patients from October 2012 to October 2014, 65 patients received G-CSF post-PBSCT, and 97 did not. More patients in G-CSF group received MAC (78% vs. 55%). Patients who received G-CSF had earlier neutrophil engraftment (median days 11 vs. 14) and shorter post-transplant hospital stay (median days 16 vs. 20

Ubiquitin-specific peptidase 10 (USP10) stabilizes both tumor suppressors and oncogenes in a context-dependent manner. However, the nature of USP10’s role in non-small cell lung cancer (NSCLC) remains unclear. By analyzing The Cancer Genome Atlas (TCGA) database, we have shown that high levels of USP10 are associated with poor overall survival in NSCLC with mutant p53, but not with wild-type p53. Consistently, genetic depletion or pharmacological inhibition of USP10 dramatically reduces the growth of lung cancer xenografts lacking wild-type p53 and sensitizes them to cisplatin. Mechanistically, USP10 interacts with, deubiquitinates, and stabilizes oncogenic protein histone deacetylase 6 (HDAC6). Furthermore, reintroducing either USP10 or HDAC6 into a USP10-knockdown NSCLC H1299 cell line with null-p53 renders cisplatin resistance. This result suggests the existence of a “USP10-HDAC6-cisplatin resistance” axis. Clinically, we have found a positive correlation between USP10 and HDAC6 expression in a cohort of NSCLC patient samples. Moreover, we have shown that high levels of USP10 mRNA correlate with poor overall survival in a cohort of advanced NSCLC patients who received platinum-based chemotherapy. Overall, our studies suggest that USP10 could be a potential biomarker for predicting patient response to platinum, and that targeting USP10 could sensitize lung cancer patients lacking wild-type p53 to platinum-based therapy.

Purpose: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants to evaluate compliance with NCCN recommendations and to identify barriers to guideline-recommended care.Methods: We evaluated women tested positive for pathogenic variant in BRCA1/2 via 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. We reported rates of compliance with risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM) and NCCN guidelines (version 3.2019). A multivariable logistic regression analyses was used to identify predictors of these outcomes. Results: Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) and 77 (60%) underwent RRSO and RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. After multivariable analyses, personal history of breast or ovarian cancer was positively associated with RRM (OR = 2.81; 95% CI 1.10 – 7.44; p = 0.025). Increasing age was associated with an increased likelihood of RRSO (OR=1.05; 95% CI 1.01 – 1.09; p = 0.022) and a decreased likelihood for RRM (OR=0.96; 95%CI 0.92 – 0.99; p value = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 3.28; p = 0.004). Rates of RRSO or RRM were not impacted by participant race, education, annual household income, marital status, or family history. There was near universal (127/129) disclosure of genetic test results to family members resulting in the discovery of 1 relative with a pathogenic variant (range = 0-8) through cascade testing. Conclusion: Long term follow up of a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of compliance with screening and risk reducing recommendations. Further efforts should focus on increasing compliance among unaffected carriers especially for RRSO.

Context.— Metaplastic breast carcinoma is an aggressive form of breast cancer that accounts for 0.5% to 3% of all breast cancers. Objective.— To study the clinicopathologic characteristics and outcomes of this rare disease. Design.— Retrospective study of patients with a diagnosis of metaplastic breast carcinoma between 2000 and 2019. Hematoxylin-eosin–stained slides were reviewed and additional clinical data were obtained from electronic medical records. Univariable and multivariable Cox proportional hazard regression analyses were used to determine associations between overall survival and several clinicopathologic variables. Results.— Of the 125 patients with metaplastic breast carcinoma identified, only patients with high-grade disease (N = 115) were included in the data analysis. A total of 38 participants (33%) were white, 66 (57%) were African American, and 11 (10%) belonged to other ethnicities. The median age at diagnosis was 57 years. The median tumor size was 3 cm. Heterologous histology was seen in 30% of cases. Multivariable analyses showed that patients with a larger tumor size had worse overall survival (hazard ratio [HR], 1.25; 95% CI, 1.10–1.44; P < .001). Distant metastatic disease was also associated with worse overall survival on multivariable analysis (HR, 10.27; 95% CI, 2.03–55.54; P = .005). In addition to treatment with either partial or complete mastectomies, 84 patients (73%) received chemotherapy. Multivariable analyses showed that chemotherapy had no effect on overall survival (HR, 0.53; 95% CI, 0.09–6.05; P = .55). Conclusions.— A larger tumor size and distant metastatic disease are associated with worse overall survival in patients with metaplastic breast carcinoma. Additional studies are needed to further characterize our findings.

Semiconductor nanocrystals with an anisotropic morphology exhibit unique properties, most notably their linear polarization. The colloidal growth of semiconductor nanorods with core dots inside, also referred to as dot-in-rod (DIR) structure, has enabled the synthesis of anisotropic nanocrystals with better stability and controllable fluorescence polarization. In this study, we synthesize CdSe/CdS DIR nanocrystals, in which the position of the CdSe core particle can be controlled by using different ligand compositions during the CdS growth. Varying the core position within the DIR structure, e.g., from the center to the end of the DIR particles, results in a change in the degree of linear polarization. When the core is positioned at the center of the nanorod, the linear polarization turns out to be higher compared with tip-core DIRs. Time-resolved photoluminescence analysis reveals that the center-core DIRs have higher electron–hole interaction than tip-core DIRs because of weak uniaxial strain in center-core DIR that arises from lattice dislocations at the interface to relieve accumulated strain.

Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of disease progression and evaluating the effects of specific phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS/MS). HepG2 (hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in NAFLD/NASH development. Several PLs and their relative ratios were significantly associated with NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis, lipid oxidation, autophagy, apoptosis, inflammation, and fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the disease progression of obesity associated NAFLD, likely through a causal cascade of impacts on the function of different liver cells.

To determine if the origin of article published in Gynecologic Oncology ("Journal") is correlated with quality of the article when measured per US institution and per country, using an index of citation (IOC) metric as a stand-in for article quality.PubMed was used to query the Journal from 2005 to 2020. Articles not deemed original research were excluded. A US-only cohort ("US-Only") was evaluated separately from the entire cohort ("Whole"). The IOC for each article was calculated by dividing the number of citations listed in PubMed by the days from the publication date to 9/1/2021. The IOC per US institution was summarized by the median value. All articles were hand reviewed for correctness. The Whole cohort included all countries with 3 or more publications (including all of the US-Only cohort) and underwent similar analysis. Correlation coefficients were estimated using Pearson's correlation after log-transformation.In the US-only cohort, 2733 articles from 276 institutions within the US contributed original articles to the Journal. The association between the number of publications per institution and the median IOC was not well correlated (Pearson's Correlation coeffeicient r = 0.16, p = 0.009). In the Whole cohort, 5,848 original research articles were published from 40 countries. There was no difference between median IOC for articles from US compared to non-US institutions was (0.0026 vs 0.0027, p = 0.287). The US median IOC was ranked 17/40. The US accounted for just over half (51.2%) of publications, and there was a trend of decreasing Non-US publications over time (p = 0.0004).The Journal was fairly consistent in the quality of articles published over the 15-year study period when using the IOC as a surrogate for quality, regardless of the article's country or US institution of origin.

Drug repositioning, the approach to explore existing drugs for use in new therapeutic indications, has emerged as an alternative drug development strategy. In this study, we found that a mucolytic drug, N-acetylcysteine (NAC) showed antibacterial activity against Vibrio cholerae. NAC can provide acid stress that selectively inhibited the growth of V. cholerae among other bacterial pathogens. To address the antibacterial mechanism of NAC against V. cholerae, six acr (acetylcys-teine-resistant) mutants were isolated from 3,118 random transposon insertion clones. The transposon insertion sites of the six mutants were mapped at the five genes. All these mutants did not display NAC resistance under acidic conditions, despite their resistance to NAC under alkaline conditions, indicating that the NAC resistance directed by the acr mutations was independent of the unusual pH-sensitivity of V. cholerae. Furthermore, all these mutants displayed attenuated virulence and reduced biofilm formation, suggesting that the acr genes are required for pathogenesis of V. cholerae. This study validates the relevance of drug repositioning for antibacterials with new modes of action and will provide an insight into a novel antibacterial therapy for V. cholerae infections to minimize side effects and resistance emergence.

Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non-liver GVHD” group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non-liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.

Introduction. Antipathogenic or antivirulence strategy is to target a virulence pathway that is dispensable for growth, in the hope to mitigate the selection for drug resistance. Hypothesis/Gap Statment. Peroxide stress responses are one of the conserved virulence pathways in bacterial pathogens and thus good targets for antipathogenic strategy. Aim. This study aims to identify a new chemical compound that targets OxyR, the peroxide sensor required for the full virulence of the opportunistic human pathogen, Pseudomonas aeruginosa . Methodology. Computer-based virtual screening under consideration of the ‘eNTRy’ rules and molecular docking were conducted on the reduced form of the OxyR regulatory domain (RD). Selected hits were validated by their ability to phenocopy the oxyR null mutant and modulate the redox cycle of OxyR. Results. We first isolated three robust chemical hits that inhibit OxyR without affecting prototrophic growth or viability. One (compound 1) of those affected the redox cycle of OxyR in response to H2O2 treatment, in a way to impair its function. Compound 1 displayed selective antibacterial efficacy against P. aeruginosa in Drosophila infection model, without antibacterial activity against Staphylococcus aureus . Conclusion. These results suggest that compound 1 could be an antipathogenic hit inhibiting the P. aeruginosa OxyR. More importantly, our study provides an insight into the computer-based discovery of new-paradigm selective antibacterials to treat Gram-negative bacterial infections presumably with few concerns of drug resistance.

Purpose Adjuvant whole breast radiation therapy after breast-conserving surgery is the standard of care in the management of early-stage breast cancer. Two of the most common acute toxicities of breast radiation therapy are radiation esophagitis (RE) and radiation dermatitis (RD). African American individuals are at higher risk for experiencing treatment-related toxic effects and are often underrepresented in clinical trials. Methods and Materials An institutional database was developed to include all African American patients with a history of breast cancer or ductal carcinoma in situ undergoing adjuvant radiation therapy at a single institution from 2013 to 2019. Records were reviewed to identify patient age, body mass index (BMI), radiation dose, prone versus supine position, inclusion of boost, and inclusion of regional nodal irradiation. Radiation treatment plans were reviewed to identify breast size as well as dosimetric parameters to the breast and esophagus. Medical records were reviewed to identify which patients were prescribed Silvadene or Mylanta-lidocaine during or immediately after their course of radiation therapy, which was used as a surrogate for grade 2 (G2) or higher RD or RE, respectively. Results A total of 272 patients were included in the final analysis. On univariable analysis, patients with morbid obesity were more likely to develop G2RD, whereas hypofractionated radiation therapy was associated with lower rates of G2RD. On multivariable analysis, greater breast volume was associated with higher rates of G2RD. In the subset of patients receiving regional node irradiation, 19% of the patients experienced G2RE, and the best predictor on multivariable analysis was the mean radiation dose (Dmean) to the esophagus. Conclusions Radiation dermatitis and esophagitis are common toxic effects in African American patients undergoing adjuvant breast radiation therapy. In this study, greater breast size, irrespective of the patient's BMI, was associated with a higher rate of dermatitis. Prone positioning during treatment and hypofractionated radiation reduced rates of G2RD. The Dmean to the esophagus was the dosimetric parameter most correlated with G2RE. These results may be used to help select patients at higher risk for toxic effects of G2 or greater during radiation therapy.

Polyunsaturated fatty acid (PUFA) plays an important role in cancer biology. Fatty acid desaturase1 (FADS1) is a key rate-limiting enzyme in omega-3 and omega-6 PUFA metabolism. We aim to investigate the association between FADS1 and survival outcomes among cancer patients. Univariable and multivariable Cox regression models were performed for FADS1 mRNA expression levels on disease-free survival (DFS) and overall survival (OS) using The Cancer Genome Atlas (TCGA) public datasets. We also investigated the pathways associated with altered FADS1 expression in the TCGA dataset. A FADS1 inhibitor (D5D-IN-326) was used to study the proliferation in vitro in 6 different cancer cell lines. FADS1-shRNA knockdown system was introduced in the renal cell carcinoma (RCC) 786-O cell line to further study the signaling pathway associated with proliferation. Transcriptomic, metabolomic, and lipidomic profiles of stable cell lines were studied. Our analysis showed that among all cancer patients (N=11,490), those with a higher FADS1 mRNA expression in their tumor have a significantly worse DFS and OS (p.value Citation Format: Gioia Heravi, Hyejeong Jang, Seongho Kim, Wanqing Liu. Fatty acid desaturase 1 (FADS1) is associated with cancer survival via altering cell growth and can be a novel drug target for cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3370.

101 Background: Cancer clinical trial enrollment rates are low, with Black individuals especially underrepresented. We tested Partnering Around Cancer Clinical Trials (PACCT), a multi-level intervention designed to improve patient-physician communication and increase trial invitations among Black and White men with prostate cancer. This study reports only on PACCT Phase 1, the patient-focused intervention, because data collection for PACCT Phase 2, the physician-focused intervention, was halted by the COVID-19 pandemic. Methods: Black and White men with prostate cancer and their physicians were invited to participate. Patients were tracked

Non-mammalian infection models have been developed over the last two decades, which is a historic milestone to understand the molecular basis of bacterial pathogenesis. They also provide small-scale research platforms for identification of virulence factors, screening for antibacterial hits, and evaluation of antibacterial efficacy. The fruit fly, Drosophila melanogaster is one of the model hosts for a variety of bacterial pathogens, in that the innate immunity pathways and tissue physiology are highly similar to those in mammals. We here present a relatively simple protocol to assess the key aspects of the polymicrobial interaction in vivo between the human opportunistic pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, which is based on the systemic infection by needle pricking at the dorsal thorax of the flies. After infection, fly survival and bacteremia over time for both P. aeruginosa and S. aureus within the infected flies can be monitored as a measure of polymicrobial virulence potential. The infection takes ~24 h including bacterial cultivation. Fly survival and bacteremia are assessed using the infected flies that are monitored up to ~60 h post-infection. These methods can be used to identify presumable as well as unexpected phenotypes during polymicrobial interaction between P. aeruginosa and S. aureus mutants, regarding bacterial pathogenesis and host immunity.