Biocompatible Rhamnolipid Self-Assemblies with pH-Responsive Antimicrobial Activity.

There is an urgent need for alternative antimicrobial materials due to the growing challenge of bacteria becoming resistant to conventional antibiotics. This study demonstrates the creation of a biocompatible pH-switchable antimicrobial material by combining bacteria-derived rhamnolipids (RL) and food-grade glycerol monooleate (GMO). The integration of RL into dispersed GMO particles, with an inverse-type liquid crystalline cubic structure in the core, leads to colloidally stable supramolecular materials. The composition and pH-triggered structural transformations are studied with small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. The composition-structure-activity relationship is analyzed and optimized to target bacteria at acidic pH values of acute wounds. The new RL/GMO dispersions reduce Staphylococcus aureus (S. aureus) populations by 7-log after 24 h of treatment with 64 µg mL-1 of RL and prevent biofilm formation at pH = 5.0, but have no activity at pH = 7.0. Additionally, the system is active against methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration of 128 µg mL-1 at pH 5.0. No activity is found against several Gram-negative bacteria at pH 5.0 and 7.0. The results provide a fundamental understanding of lipid self-assembly and the design of lipid-based biomaterials, which can further guide the development of alternative bio-based solutions to combat bacteria.

Solvent Dependent Folding of an Amphiphilic Polyaramid.

A series of synthetic alternating and amphiphilic aromatic amide polymers were synthesized by a step growth polymerization. Alternating meta- and para-linkages were introduced to force the polymer chain into a helical shape in the highly polar solvent water. The polymers were analyzed by 1H NMR spectroscopy and SEC in polar aprotic solvents such as DMSO and DMF. However, the polymers also showed good solubility in water. 1H NMR spectroscopy, small-angle X-ray scattering, and dynamic light scattering provided clear evidence of polymer folding in water but not DMF. We employed parallel tempering metadynamics in the well-tempered ensemble (PTMetaD-WTE) to simulate the free energy surfaces of an analogous model polymer in DMF and water. The simulations gave a molecular model of an unfolded structure in DMF and a helically folded tubular structure in water.

A Potential Pitfall and Clinical Solutions in Surface-Guided Deep Inspiration Breath Hold Radiation Therapy for Left-Sided Breast Cancer.

Purpose: Deep inspiration breath hold (DIBH) is an effective technique to spare the heart in treating left-sided breast cancer. Surface-guided radiation therapy (SGRT) is increasingly applied in DIBH setup and motion monitoring. Patient-specific breathing behavior, either thoracically driven or abdominally driven (A-DIBH), should be unaltered, online identified, and monitored accordingly to ensure reproducible heart-sparing treatment. Methods and Materials: Sixty patients with left-sided breast cancer treated with SGRT were analyzed: 20 A-DIBH patients with vertical chest elevation (VCE ≤ 5 mm) were prospectively identified, and 40 control patients were retrospectively and randomly selected for comparison. At simulation, both free-breathing (FB) and DIBH computed tomography (CT) were acquired, guided by a motion surrogate placed around the xiphoid process. For SGRT treatment setups, the region of interest (ROI) was defined on the CT chest surface, and the surrogate-based setup was a backup. For all 60 patients, the VCE was measured as the average of the FB-to-DIBH elevations at the breast and xiphoid process, together with abdominal elevation. In the 40-patient control group, A-DIBH patients (VCE ≤ 5 mm) were identified. Of the 20 A-DIBH patients, 10 were treated with volumetric modulated arc therapy plans, and 10 patients were treated with tangent plans. Clinical DIBH plans were recalculated on FB CT to compare maximum dose (DMax), 5% of the maximum dose (D5%), mean dose (DMean), and V30Gy, V20Gy, and V5Gy of the heart and lungs and their significance. Results: In the 20 A-DIBH patients, VCE = 3 ± 2 mm, surrogate motion (9 ± 6 mm), and abdomen motion of 14 ± 5 mm are found. Heart dose reduction from FB to DIBH is significant (P < .01): ∆DMax = -8.4 ± 9.8 Gy, ∆D5% = -2.4 ± 4.4 Gy, and ∆DMean = -0.6 ± 0.9 Gy. Six out of 40 control patients (15%) are found to have VCE ≤ 5 mm. Conclusions: A-DIBH (VCE ≤ 5 mm) patient population is significant (15%), and they should be identified in the SGRT workflow and monitored accordingly. A new abdominal ROI or an abdominal surrogate should be used instead of the conventional chest-only ROI. Patient-specific DIBH should be preserved for higher reproducibility to ensure heart sparing.

Racial and Ethnic Disparities in Gynecologic Carcinosarcoma: A Single-Institution Experience.

We aimed to determine the incidence, treatment regimen, and treatment outcomes (including progression-free survival and overall survival) of gynecologic carcinosarcoma, a rare, aggressive, and understudied gynecologic malignancy. This retrospective review included all patients with gynecologic cancers diagnosed and treated at a single tertiary care comprehensive cancer center between January 2012 and May 2021. A total of 2116 patients were eligible for review, of which 84 cases were identified as carcinosarcoma: 66 were uterine (5.2% of uterine cancers), 17 were ovarian (3.6% of ovarian cancers), 1 was cervical (0.28% of cervical cancers), and 1 was untyped. Of the patients, 76.2% presented advanced-stage disease (stage III/IV) at the time of diagnosis. Minority patients were more likely to present with stage III/IV (p < 0.0001). The majority of patients underwent surgical resection followed by systemic chemotherapy with carboplatin and paclitaxel. The median PFS was 7.5 months. Of the patients, 55% were alive 1 year after diagnosis, and 45% were alive at 5 years. In the studied population, minorities were more likely to present with more advanced disease. The rate of gynecologic carcinosarcomas was consistent with historical reports.

Comparison of setup accuracy of optical surface image versus orthogonal x-ray images for VMAT of the left breast using deep-inspiration breath-hold.

To compare the setup accuracy of optical surface image (OSI) versus orthogonal x-ray images (2DkV) using cone beam computed tomography (CBCT) as ground truth for radiotherapy of left breast cancer in deep-inspiration breath-hold (DIBH). Ten left breast DIBH patients treated with volumetric modulated arc therapy (VMAT) were studied retrospectively. OSI, 2DkV, and CBCT were acquired weekly at treatment setup. OSI, 2DkV, and CBCT were registered to planning CT or planning DRR based on a breast surface region of interest (ROI), bony anatomy (chestwall and sternum), and both bony anatomy and breast surface, respectively. These registrations provided couch shifts for each imaging system. The setup errors, or the difference in couch shifts between OSI and CBCT were compared to those between 2DkV and CBCT. A second OSI was acquired during last beam delivery to evaluate intrafraction motion. The median absolute setup errors were (0.21, 0.27, 0.23 cm, 0.6°, 1.3°, 1.0°) for OSI, and (0.26, 0.24, 0.18 cm, 0.9°, 1.0°, 0.6°) for 2DkV in vertical, longitudinal and lateral translations, and in rotation, roll and pitch, respectively. None of the setup errors was significantly different between OSI and 2DkV. For both systems, the systematic and random setup errors were ≤0.6 cm and ≤1.5° in all directions. Nevertheless, larger setup errors were observed in some sessions in both systems. There was no correlation between OSI and CBCT whereas there was modest correlation between 2DkV and CBCT. The intrafraction motion in DIBH detected by OSI was small with median absolute translations <0.2 cm, and rotations ≤0.4°. Though OSI showed comparable and small setup errors as 2DkV, it showed no correlation with CBCT. We concluded that to achieve accurate setup for both bony anatomy and breast surface, daily 2DkV can't be omitted following OSI for left breast patients treated with DIBH VMAT.

Lessons in Cultural Adaptations: Translation of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cervical Cancer Module From English to Chichewa in Malawi.

INTRODUCTION: To complete a culturally appropriate translation of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Cervical Cancer module (QLQ-CX24) from English to Chichewa (one of the official languages of Malawi) in preparation for postsurgical outcomes research in rural Malawian cervical cancer patients. METHODS: Following the EORTC translation procedure manual, two distinct forward translations from English were reconciled into a preliminary Chichewa translation, followed by two distinct back-translations to English. The English back-translation was reconciled and the translation report sent for discussion and proofreading by EORTC; this was followed by pilot testing. All translators were physicians fluent in English and Chichewa. RESULTS: Of 24 questions in QLQ-CX24, three had prior translations available; all three required revision to clarify tense or wording. Three discussion exchanges with EORTC refined the translation and ensured faithfulness to the original English meaning; proofreaders contributed minor changes. Pilot testing was completed on 10 female patients (three with cervical cancer, four suspicious cervical lesions, and three screening only). Three patients were illiterate. During pilot testing, translation of question 46 (Q46) was misunderstood as referring to vaginal discharge instead of feeling "feminine". The remaining questions were understood, with minor feedback for six questions. Final revision of Q46 yielded a phrase describing "feminine" as "appearance or activities as a woman". Concepts comparable to "feminine" were absent in the Chichewa language/regional Malawian culture. The final revision of Q46 was pilot-tested on five patients (three illiterate) and found acceptable. CONCLUSIONS: Translation of the QLQ-CX24 module was completed successfully and revealed absence of the modern concept of femininity in Chichewa language and regional Malawian culture. Care should be taken when creating and translating healthcare-related documents for surgical research to ensure broad applicability across cultures.

Automated VMAT treatment planning using sequential convex programming: algorithm development and clinical implementation.

Objective.To develop and clinically implement a fully automated treatment planning system (TPS) for volumetric modulated arc therapy (VMAT).Approach.We solve two constrained optimization problems sequentially. The tumor coverage is maximized at the first step while respecting all maximum/mean dose clinical criteria. The second step further reduces the dose at the surrounding organs-at-risk as much as possible. Our algorithm optimizes the machine parameters (leaf positions and monitor units) directly and the resulting mathematical non-convexity is handled using thesequential convex programmingby solving a series of convex approximation problems. We directly integrate two novel convex surrogate metrics to improve plan delivery efficiency and reduce plan complexity by promoting aperture shape regularity and neighboring aperture similarity. The entire workflow is automated using the Eclipse TPS application program interface scripting and provided to users as a plug-in, requiring the users to solely provide the contours and their preferred arcs. Our program provides the optimal machine parameters and does not utilize the Eclipse optimization engine, however, it utilizes the Eclipse final dose calculation engine. We have tested our program on 60 patients of different disease sites and prescriptions for stereotactic body radiotherapy (paraspinal (24 Gy × 1, 9 Gy × 3), oligometastis (9 Gy × 3), lung (18 Gy × 3, 12 Gy × 4)) and retrospectively compared the automated plans with the manual plans used for treatment. The program is currently deployed in our clinic and being used in our daily clinical routine to treat patients.Main results.The automated plans found dosimetrically comparable or superior to the manual plans. For paraspinal (24 Gy × 1), the automated plans especially improved tumor coverage (the average PTV (Planning Target Volume) 95% from 96% to 98% and CTV100% from 95% to 97%) and homogeneity (the average PTV maximum dose from 120% to 116%). For other sites/prescriptions, the automated plans especially improved the duty cycle (23%-39.4%).Significance.This work proposes a fully automated approach to the mathematically challenging VMAT problem. It also shows how the capabilities of the existing (Food and Drug Administration)FDA-approved commercial TPS can be enhanced using an in-house developed optimization algorithm that completely replaces the TPS optimization engine. The code and pertained models along with a sample dataset will be released on our ECHO-VMAT GitHub (https://github.com/PortPy-Project/ECHO-VMAT).

Pharmacologic Management of Pain, Agitation, and Delirium in Burn Patients.

The majority of hospitalized burn patients experience pain, agitation, and delirium. The development of each one of these conditions can also lead to, or worsen, the others. Providers, therefore, need to thoroughly assess the underlying issue to determine the most effective treatment. Multimodal pharmacologic regimens are often used in conjunction with non-pharmacologic strategies to manage pain, agitation, and delirium. This review focuses on the pharmacologic management of these complicated patients in a critical-care setting.

Searching for the source: Extraovarian primary peritoneal carcinoma presenting as chest wall masses.

Background: Extraovarian primary peritoneal carcinoma (EOPPC) is a rare form of epithelial adenocarcinoma arising from the peritoneal lining with little to no ovarian involvement. To date, very few cases of EOPPC with primary tumors outside of the peritoneum have been described, the majority of which present with a primary tumor in the retroperitoneum. No cases have been reported with primary presentation as a chest wall mass. Case report: This case describes a 64-year-old woman referred for the evaluation of PAX8 positive chest wall masses. Biopsies of these masses demonstrated tumor architecture that was predominantly micropapillary with rare psammomatous calcifications. Immunohistochemically, the tumor was PAX8, CK7, ER, MOC31, and BerEP4 positive, with a mutational pattern of p53. This was consistent with Mullerian adenocarcinoma markers and suggestive of high-grade serous carcinoma. The patient was diagnosed with a unique presentation of EOPPC and is currently alive at 36 months post initial diagnosis. She has been treated with a combination of diagnostic surgery, chemotherapy and radiation therapy. Conclusion: To the best of our knowledge, this is the first documented case of EOPPC presenting with a primary tumor of the chest wall. This case highlights the importance of pathology, immunohistology, and interdisciplinary collaboration in diagnosing and treating rare malignancies.

Accuracy and Efficiency of Patient Setup Using Surface Imaging versus Skin Tattoos for Accelerated Partial Breast Irradiation.

Purpose: Skin tattoos represent the standard approach for surface alignment and setup of breast cancer radiation therapy, yet permanent skin markings contribute to adverse cosmesis and patient dissatisfaction. With the advent of contemporary surface-imaging technology, we evaluated setup accuracy and timing between "tattoo-less" and traditional tattoo-based setup techniques. Methods and Materials: Patients receiving accelerated partial breast irradiation (APBI) underwent traditional tattoo-based setup (TTB), alternating daily with a tattoo-less setup via surface imaging using AlignRT (ART). Following initial setup, position was verified via daily kV imaging, with matching on surgical clips representing ground truth. Translational shifts (TS) and rotational shifts (RS) were ascertained, as were setup time and total in-room time. Statistical analyses used the Wilcoxon signed rank test and Pitman-Morgan variance test. Results: A total of 43 patients receiving APBI and 356 treatment fractions were analyzed (174 TTB fractions and 182 using ART). For tattoo-less setup via ART, the median absolute TS were 0.31 cm in the vertical (range, 0.08-0.82), 0.23 cm in the lateral (0.05-0.86), and 0.26 cm in the longitudinal (0.02-0.72) axes. For TTB setup, the corresponding median TS were 0.34 cm (0.05-1.98), 0.31 cm (0.09-1.84), and 0.34 cm (0.08-1.25), respectively. The median magnitude shifts were 0.59 (0.30-1.31) for ART and 0.80 (0.27-2.13) for TTB. ART was not statistically distinguishable from TTB in terms of TS, except in the longitudinal direction (P = .154, .059, and .021, respectively), and was superior to TTB for magnitude shift (P < .001). The variance of each TS variable was significantly narrower for ART compared with TTB (P ≤ .001 vertical, P = .001 lateral, P = .005 longitudinal). The median absolute RS for ART was 0.64° rotation (range, 0.00-1.90), 0.65° roll (0.05-2.90), and 0.30° pitch (0.00-1.50). The corresponding median RS for TTB were 0.80° (0.00-2.50), 0.64° (0.00-3.00), and 0.46° (0.00-2.90), respectively. ART setup was not statistically different from TTB in terms of RS (P = .868, .236, and .079, respectively). ART showed lower variance than TTB in terms of pitch (P = .009). The median total in-room time was shorter for ART than TTB (15.42 vs 17.25 minutes; P = .008), as was the median setup time (11.12 vs 13.00 minutes; P = .001). Moreover, ART had a narrower distribution of setup time with fewer lengthy outliers versus TTB. Conclusions: These findings suggest that a tattoo-less setup approach with AlignRT may be sufficiently accurate and expeditious to supplant surface tattoos for patients receiving APBI. Further analyses with larger cohorts will determine whether tattoo-based approaches can be replaced by noninvasive surface imaging.

A case of niraparib PARP-Inhibitor induced Sweet Syndrome in gynecologic cancer.

Sweet Syndrome, or acute febrile neutrophilic dermatosis, is a rare inflammatory dermatologic disorder that can be spontaneous, associated with malignancy, or drug-induced. Reports of Sweet Syndrome in gynecologic oncology patients are sparse, and the majority are thought to be malignancy-associated. The case presented here represents the third case of drug-induced Sweet Syndrome in a gynecologic oncology patient. To the best of our knowledge, this is the first report of Sweet Syndrome after initiation of a poly (ADP-ribose) polymerase inhibitor (PARPi) for maintenance therapy in the treatment of high grade serous ovarian carcinoma (HGSOC). This represents one of the most severe dermatologic adverse effects of treatment with PARPi reported to date, requiring treatment discontinuation.

Regional multidisciplinary team approach to the management of placenta accreta spectrum disorder.

OBJECTIVE: Patients with suspected placenta accreta spectrum (PAS) disorder are often referred to specialized medical centers for antepartum management and definitive treatment via cesarean hysterectomy. In 2019, our institution formed the only multidisciplinary team for the management of PAS within two of the largest counties in California. The purpose of this study was to evaluate the effects of the multidisciplinary team on patient volume and surgical outcomes for patients with PAS. METHODS: This was a single center retrospective cohort study, based in the only tertiary referral center within two of the largest counties in California. Patients who underwent cesarean hysterectomy for suspected PAS from January 2014 to April 2021 were included and divided into two groups, based on management by the multidisciplinary team from January 2019 and onward or routine care prior to that time. The outcomes of interest were quantitative blood loss, total units of packed red blood cell transfusion, referral volume, and diagnostic accuracy as well as ICU admission, bladder injury, and postoperative length of stay. Furthermore, we wanted to determine if patient's distance to the hospital impacted outcomes. Normally distributed variables were compared between groups using the t-test. Categorical variables were compared between the two groups using the chi square test. RESULTS: A total of 114 patients were included in the cohort, 59 patients were from January 2014 to December 2018 and 55 patients were from January 2019 to April 2021. Since the establishment of the multidisciplinary center, there was a 2.5-fold increase in the total patient volume (0.8 case/month to 2 cases/month) and a 2.8-fold increase in the referred patient volume. Patients undergoing cesarean hysterectomy since the establishment of the multidisciplinary team had less quantitative blood loss (1500 mL vs 2000 mL, p = .005) and required less units of packed red blood cell transfusion (2 vs 4 units, p < .001). In addition, blood loss of ≥2000 mL decreased from 57.6% to 38.2% (p = .04) and diagnostic accuracy improved from 35.6% to 83.6% (p < .001). Furthermore, we found that patient distance to the hospital did not significantly impact surgical outcomes. CONCLUSIONS: Since the establishment of the multidisciplinary team, our center experienced an increase in PAS volume and was able to demonstrate a statistically significant improvement in patient outcomes.

Genetic Testing in the Latinx community: Impact of acculturation and provider relationships.

OBJECTIVES: The current study aimed to explore attitudes toward genetic germline testing and intentions to test in Latinas from Southern California. We hypothesized that patients' acculturation and education levels, as well as comfort with health care providers, are positively associated with attitudes and intentions toward genetic testing. METHODS: A survey was offered concurrently to Latinx female patients at a gynecologic oncology practice and to unaffiliated Latinx community members. The survey assessed demographics, structural, psychosocial, and acculturation factors and genetic testing attitudes and intentions via validated scales. RESULTS: Of 148 surveys collected, 66% of responders had low levels of acculturation. 50% of women had government-subsidized insurance; 22% had no schooling in the US. 67% of participants did not carry a diagnosis of cancer. Women with higher acculturation levels were more likely to consider genetic testing (rs = 0.54, p = .001). Higher acculturated women and less acculturated women under 50 were more likely to consider testing if it had been recommended by a female, trusted, or Hispanic/Latinx provider (rs = 0.22, p = .01, rs = 0.27, p = .003 and rs = 0.19, p = .003, respectively) or if there was a recent cancer diagnosis (self or family, rs = 0.19, p = .03). Overall, education correlated with intention to test. The more education outside of the US, the less negative was the attitude toward being tested (rs = -0.41, p = .002). CONCLUSIONS: Direct experiences with cancer, more schooling and higher acculturation coupled with provider characteristics determined if Latinas were more open to testing. Provider characteristics mattered: having a female, Latinx, Spanish speaking provider was important for genetic testing decision-making. These findings are particularly pertinent in areas with high Latinx populations.

Reproducibility of chestwall and heart position using surface-guided versus RPM-guided DIBH radiotherapy for left breast cancer.

This study compared the reproducibility of chestwall and heart position using surface-guided versus RPM (real-time position management)-guided deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer. Forty DIBH patients under either surface-guided radiotherapy (SGRT) or RPM guidance were studied. For patients treated with tangential fields, reproducibility was measured as the displacements in central lung distance (CLD) and heart shadow to field edge distance (HFD) between pretreatment MV (megavoltage) images and planning DRRs (digitally reconstructed radiographs). For patients treated with volumetric modulated arc therapy (VMAT), sternum to isocenter (ISO) distance (StID), spine to rib edge distance (SpRD), and heart shadow to central axis (CAX) distance (HCD) between pretreatment kV images and planning DRRs were measured. These displacements were compared between SGRT and RPM-guided DIBH. In tangential patients, the mean absolute displacements of SGRT versus RPM guidance were 0.19 versus 0.23 cm in CLD, and 0.33 versus 0.62 cm in HFD. With respect to planning DRR, heart appeared closer to the field edge by 0.04 cm with surface imaging versus 0.62 cm with RPM. In VMAT patients, the displacements of surface imaging versus RPM guidance were 0.21 versus 0.15 cm in StID, 0.24 versus 0.19 cm in SpRD, and 0.72 versus 0.41 cm in HCD. Heart appeared 0.41 cm further away from CAX with surface imaging, whereas 0.10 cm closer to field CAX with RPM. None of the differences between surface imaging and RPM guidance was statistically significant. In conclusion, the displacements of chestwall were small and were comparable with SGRT- or RPM-guided DIBH. The position deviations of heart were larger than those of chestwall with SGRT or RPM. Although none of the differences between SGRT and RPM guidance were statistically significant, there was a trend that the position deviations of heart were smaller and more favorable with SGRT than with RPM guidance in tangential patients.

Automated and Clinically Optimal Treatment Planning for Cancer Radiotherapy.

Each year, approximately 18 million new cancer cases are diagnosed worldwide, and about half must be treated with radiotherapy. A successful treatment requires treatment planning with the customization of penetrating radiation beams to sterilize cancerous cells without harming nearby normal organs and tissues. This process currently involves extensive manual tuning of parameters by an expert planner, making it a time-consuming and labor-intensive process, with quality and immediacy of critical care dependent on the planner's expertise. To improve the speed, quality, and availability of this highly specialized care, Memorial Sloan Kettering Cancer Center developed and applied advanced optimization tools to this problem (e.g., using hierarchical constrained optimization, convex approximations, and Lagrangian methods). This resulted in both a greatly improved radiotherapy treatment planning process and the generation of reliable and consistent high-quality plans that reflect clinical priorities. These improved techniques have been the foundation of high-quality treatments and have positively impacted over 4,000 patients to date, including numerous patients in severe pain and in urgent need of treatment who might have otherwise required longer hospital stays or undergone unnecessary surgery to control the progression of their disease. We expect that the wide distribution of the system we developed will ultimately impact patient care more broadly, including in resource-constrained countries.

Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data.

Over a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the TF occupancy landscape, let alone quantify how it changes across conditions. We developed TF occupancy profiler (TOP), a Bayesian hierarchical regression framework, to profile genome-wide quantitative occupancy of numerous TFs using data from a single chromatin accessibility experiment (DNase- or ATAC-seq). TOP is supervised, and its hierarchical structure allows it to predict the occupancy of any sequence-specific TF, even those never assayed with ChIP. We used TOP to profile the quantitative occupancy of hundreds of sequence-specific TFs at sites throughout the genome and examined how their occupancies changed in multiple contexts: in approximately 200 human cell types, through 12 h of exposure to different hormones, and across the genetic backgrounds of 70 individuals. TOP enables cost-effective exploration of quantitative changes in the landscape of TF binding.

Gynecologic Oncology and Inclusion of Women Into the Surgical Workforce: The Canary in This Coal Mine.

Objective: Women make up a majority of the gynecologic oncology workforce. Increasing the numbers of women in leadership has been proposed as a path towards professional gender equity. This study examined whether leadership gender and departmental infrastructure impact the work environment for women gynecologic oncologists. Methods: Members of a 472-member private Facebook group "Women of Gynecologic Oncology" (WGO) who self-identified as women gynecologic oncologists provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions using a REDcap survey platform. Results: Of 250 (53%) respondents to this survey, most were younger than age 50 years (93.6%); White (82.2%) and non-Hispanic (94.3%); married (84.7%); and parenting (75.2%). Practice environments included academic (n=152, 61.0%), hospital employed (n=57, 22.9%), and private practice (n=31, 12.4%), and 89.9% supervised trainees. A significant percent of respondents had experienced bullying (52.8%), gender discrimination (57%) and microaggressions (83%). Age, race, ethnicity, practice setting, or mentorship were not statistically significantly associated with these experiences. Reported perpetrators were varied and included colleagues (84%), patients (44%), staff (41%), administrators (18%), and trainees (16%). Prevalence of bullying (55.0 vs 47.7%, p=0.33), gender discrimination (59.1 vs 52.3%, p=0.33) and microaggressions (83.3 vs 83.0%, p=1.00) were similar irrespective of departmental leadership gender. Conclusions: Women gynecologic oncologists report a high prevalence of workplace bullying, gender discrimination and microaggressions regardless of the gender of their immediate leadership. Proactive and deliberate structural interventions to improve the work environment for surgeons who are women are urgently needed.

A uniform and versatile surface-guided radiotherapy procedure and workflow for high-quality breast deep-inspiration breath-hold treatment in a multi-center institution.

PURPOSE: We share our experiences on uniformly implementing an effective and efficient SGRT procedure with a new clinical workflow for treating breast patients in deep-inspiration breath-hold (DIBH) among 9 clinical centers using 26 optical surface imaging (OSI) systems. METHODS: Our procedures have five major components: (1) acquiring both free-breathing (FB) and DIBH computed tomography (CT) at simulation to quantify the rise of the anterior surface, (2) defining uniformly a large region of interest (ROI) to accommodate large variations in patient anatomy and treatment techniques, (3) performing two-step setup in FB by first aligning the arm and chin to minimize breast deformation and reproduce local lymphnode positions and then aligning the ROI, (4) aligning the vertical shift precisely from FB to DIBH, and (5) capturing a new on-site reference image at DIBH to separate residual setup errors from the DIBH motion monitoring uncertainties. Moreover, a new clinical workflow was developed for patient data preparation using 4 OSI offline workstations without interruption of SGRT treatment at 22 OSI online workstations. This procedure/workflow is suitable for all photon planning techniques, including 2-field, 3-field, 4-field, partial breast irradiation (PBI), and volumetric-modulated arc therapy (VMAT) with or without bolus. RESULTS: Since 2019, we have developed and applied the uniform breast SGRT DIBH procedure with optimized clinical workflow and ensured treatment accuracy among the nine clinics within our institution. About 150 breast DIBH patients are treated daily and two major upgrades are achieved smoothly throughout our institution, owing to the uniform and versatile procedure, adequate staff training, and efficient workflow with effective clinical supports and backup strategies. CONCLUSION: The uniform and versatile breast SGRT DIBH procedure and workflow have been developed to ensure smooth and optimal clinical operations, simplify clinical staff training and clinical troubleshooting, and allow high-quality SGRT delivery in a busy multi-center institution.

Human Antimicrobial Peptide Triggered Colloidal Transformations in Bacteria Membrane Lipopolysaccharides.

Growing concerns of bacterial resistance against conventional antibiotics shifts the research focus toward antimicrobial peptide (AMP)-based materials. Most AMPs kill gram-negative bacteria by destroying their inner membrane, but have to first pass the outer membrane covered with lipopolysaccharides (LPS). Their interplay with the LPS is crucial for bactericidal activity, but is yet to be elucidated in detail. In this study, self-assemblies of Escherichia coli LPS with the human cathelicidin AMP LL-37, free and encapsulated into glyceryl monooleate (GMO) lipid nanoparticles, are analyzed using synchrotron small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. Circular dichroism spectroscopy is used to study modifications in LL-37's secondary structure. LPS is found to form elongated micelles and the addition of LL-37 induces their transformation to multilamellar structures. LPS' addition to GMO cubosomes triggers the swelling of the internal cubic structure, while in multilamellar GMO/LL-37 nanocarriers it causes transitions into unstructured particles. The insights on the interactions among LPS and LL-37, in its free form or encapsulated in GMO dispersions, may guide the design of LPS-responsive antimicrobial nanocarriers. The findings may further assist the formulation of antimicrobial nanomaterials with enhanced penetration of LPS layers for improved destruction of bacterial membranes.

Deep learning auto-segmentation and automated treatment planning for trismus risk reduction in head and neck cancer radiotherapy.

BACKGROUND AND PURPOSE: Reducing trismus in radiotherapy for head and neck cancer (HNC) is important. Automated deep learning (DL) segmentation and automated planning was used to introduce new and rarely segmented masticatory structures to study if trismus risk could be decreased. MATERIALS AND METHODS: Auto-segmentation was based on purpose-built DL, and automated planning used our in-house system, ECHO. Treatment plans for ten HNC patients, treated with 2 Gy × 35 fractions, were optimized (ECHO0). Six manually segmented OARs were replaced with DL auto-segmentations and the plans re-optimized (ECHO1). In a third set of plans, mean doses for auto-segmented ipsilateral masseter and medial pterygoid (MIMean, MPIMean), derived from a trismus risk model, were implemented as dose-volume objectives (ECHO2). Clinical dose-volume criteria were compared between the two scenarios (ECHO0 vs. ECHO1; ECHO1 vs. ECHO2; Wilcoxon signed-rank test; significance: p < 0.01). RESULTS: Small systematic differences were observed between the doses to the six auto-segmented OARs and their manual counterparts (median: ECHO1 = 6.2 (range: 0.4, 21) Gy vs. ECHO0 = 6.6 (range: 0.3, 22) Gy; p = 0.007), and the ECHO1 plans provided improved normal tissue sparing across a larger dose-volume range. Only in the ECHO2 plans, all patients fulfilled both MIMean and MPIMean criteria. The population median MIMean and MPIMean were considerably lower than those suggested by the trismus model (ECHO0: MIMean = 13 Gy vs. ≤42 Gy; MPIMean = 29 Gy vs. ≤68 Gy). CONCLUSIONS: Automated treatment planning can efficiently incorporate new structures from DL auto-segmentation, which results in trismus risk sparing without deteriorating treatment plan quality. Auto-planning and deep learning auto-segmentation together provide a powerful platform to further improve treatment planning.