Racial and socioeconomic disparities in fertility treatment provision for patients with polycystic ovary syndrome.

OBJECTIVE: To assess whether provision of fertility treatment for patients with polycystic ovary syndrome (PCOS) varies by patient and physician level demographics. DESIGN: Retrospective cohort study SUBJECTS: Patients at a university health system seeking care for PCOS and infertility from 2007-2021. EXPOSURE: Patient age, BMI, race, ethnicity, estimated household income, primary insurance payor, provider sex, and provider medical specialty. MAIN OUTCOME MEASURES: Prescriptions for fertility treatment, including clomiphene citrate, letrozole, and injectable gonadotropins. Differences in patient and physician demographics between patients who did and did not receive a prescription were identified with univariable analysis. Multilevel mixed-effects logistic regression was performed to determine associations between patient and physician demographics and prescription receipt. RESULTS: 3,435 patients with PCOS and infertility were identified with a mean age of 31.1 +/- 5.7 years. Of the 68.8% of patients who received a prescription, 47.8% of prescriptions were clomiphene citrate, 38.6% letrozole, and 13.7% injectable gonadotropins. There were lower odds of prescription receipt for Black patients compared to White patients (aOR 0.75, 95% CI 0.61-0.93), those with estimated household income below the federal poverty level (FPL) compared to above the national median (aOR 0.71, 95% CI 0.46-0.97), and those with public compared to commercial insurance (aOR 0.53, 95% CI 0.40-0.71). These disparities persisted in a subanalysis of patients prescribed oral medications only with lower odds of prescription receipt for Black compared to White patients (aOR 0.74, 95% CI 0.57-0.95), those with estimated household income below the FPL compared to above the national median (aOR 0.93, 95% CI 0.87-0.98), and those with public compared to commercial insurance (aOR 0.57, 95% CI 0.42-0.76). Black patients waited on average 153.3 days longer than White patients from initial visit to prescription receipt. Patients had lower odds of receiving any prescription from family medicine physicians (aOR 0.36, 95% CI 0.24-0.52) and general internal medicine physicians (aOR 0.55, 95% CI 0.42-0.73) compared to reproductive endocrinologists. CONCLUSION: Racial and socioeconomic disparities exist in the provision of infertility treatments for patients with PCOS. Fewer primary care physicians engaged in first-line fertility treatment, indicating an opportunity for physician education to improve access to fertility care.

Large language models reshaping molecular biology and drug development.

The utilization of large language models (LLMs) has become a significant advancement in the domains of medicine and clinical informatics, providing a revolutionary potential for scientific breakthroughs and customized therapies. LLM models are trained on large datasets and exhibit the capacity to comprehend and analyze intricate biological data, encompassing genomic sequences, protein structures, and clinical health records. With the utilization of their comprehension of the language of biology, they possess the ability to reveal concealed patterns and insights that may evade human researchers. LLMs have been shown to positively impact various aspects of molecular biology, including the following: genomic analysis, drug development, precision medicine, biomarker development, experimental design, collaborative research, and accessibility to specialized expertise. However, it is imperative to acknowledge and tackle the obstacles and ethical implications involved. The careful consideration of data bias and generalization, data privacy and security, explainability and interpretability, and ethical concerns around responsible application is vital. The successful resolution of these obstacles will enable us to fully utilize the capabilities of LLMs, leading to substantial progress in the fields of molecular biology and pharmaceutical research. This progression also has the ability to bolster influential impacts for both the individual and the broader community.

Zwitterionic Hydrogel Coating with Antisediment Properties for Marine Antifouling Applications.

Biofouling is a serious issue affecting the marine industry because the attached micro- and macrocontaminants can increase fuel consumption and damage ship hulls. A hydrophilic hydrogel-based coating is considered a promising antifouling material because it is environmentally friendly and the dense hydration layer can protect the substrate from microbial attachment. However, sediment adsorption can be an issue for hydrogel-based coatings. Their natural soft and porous structures can trap sediment from the marine environment and weaken the antifouling capability. There is still little research on the antisediment properties of hydrogels, and none of them deal with this problem. Here, we report on optimizing zwitterionic hydrogel-based coatings to improve their antisediment properties and achieve comparable performance to commercial biocidal coatings, which are the gold standard in the antifouling coating area. After 1 week of sediment contamination and 2 weeks of diatom coculturing, this optimized zwitterionic hydrogel coating maintained its antifouling properties with a few diatoms on the surface. Its large-scale samples also achieved antifouling performance similar to that of biocidal coatings in the Atlantic Ocean for 1.5 months. More importantly, our research provides a universal strategy to improve the antisediment properties of soft hydrogel-based coatings. For the first time, we report that the introduction of interfacial electrostatic interactions enhanced the antisediment properties of hydrogels.

Operative Time and Accrual of Postoperative Complications in Minimally Invasive Versus Open Myomectomy.

STUDY OBJECTIVE: To compare the prevalence and accrual of 30-day postoperative complications by operative time for open myomectomy (OM) and minimally invasive myomectomy (MIM). DESIGN: Retrospective cohort study SETTING: Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2021. PATIENTS: Female patients aged ≥18 years undergoing OM or MIM. INTERVENTIONS: Patients were categorized into OM and MIM cohorts. Covariates associated with operative time and composite complications were identified using general linear model and chi-square or Fisher's exact test as appropriate. Adjusted spline regression was performed as a test of linearity between operative time and composite complications. Adjusted risk ratios of 30-day postoperative individual, minor, major, and composite complications by 60-minute operative time increments were estimated using Poisson regression with robust error variance. MEASUREMENTS AND MAIN RESULTS: Of 27 728 patients, 11 071 underwent MIM and 16 657 underwent OM. Mean operative times (SD) were 164.6 (82.0) for MIM and 129.2 (67.0) for OM. Raw composite complication rates were 5.5% for MIM and 15.8% for OM. Adjusted spline regression demonstrated linearity between operative time and relative risk of composite postoperative complications for both MIM and OM. MIM had higher adjusted relative risk (aRR, 95% CI) compared to OM of blood transfusion (1.55, 1.45-1.64 versus 1.29, 1.25-1.34), overall minor complications (1.13, 1.03-1.23 versus 1.01, 0.92-1.10), and overall major complications (1.43, 1.35-1.51 versus 1.27, 1.12-1.32). Operative time had greater impact on risk of composite complications for MIM than OM, reaching aRR 2.0 at 296 minutes versus 461 minutes for OM. CONCLUSION: OM has a higher overall rate of composite, minor, and major complications compared to MIM. While operative time is independently and linearly associated with postoperative complications with myomectomy regardless of approach, optimizing surgical efficiency for MIM may be more critical than for OM.

Dual Incontinence and Risk of Fall: A Retrospective Cohort Study.

IMPORTANCE: Although there is a known association between urinary incontinence (UI) and fall risk, it is unclear if having both UI and fecal incontinence, or dual incontinence (DI), increases this risk. OBJECTIVE: The objective of our study was to elucidate a relationship between DI and falls. STUDY DESIGN: This was a retrospective cohort study at a tertiary academic health system of female patients 65 years and older presenting for a new patient visit to a urogynecology health care professional for UI from 2019 to 2021. Demographic data and responses to intake questionnaires on fall and markers of frailty were extracted. Multivariable logistic regression was performed to identify factors associated with fall adjusting for covariates identified upon univariate comparison. RESULTS: A total of 2,814 women were included in the analysis; 2,661 patients reported UI alone, and 153 reported DI. A greater proportion of women with DI reported a fall in the past year compared with those with UI alone (22.9% vs 12.2%, P < 0.001). Univariable comparison showed that these 2 groups differed regarding age, body mass index, and estimated median household income. On multivariable logistic regression, DI was significantly associated with falls (adjusted odds ratio 2.56; 95% confidence interval, 1.02-5.46). Other factors independently associated with falls in older women with UI include (adjusted odds ratio, 95% confidence interval): lower income groups (2.35, 1.50-3.67 for $20,000-$40,000, compared with $100,000 and higher-income group), difficulty with activities of daily living (1.60, 1.25-2.13), and unintentional weight loss (1.68, 1.05-2.68). CONCLUSION: Patients with DI have a 2-fold higher risk of fall compared with patients with UI alone.

Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma.

PURPOSE: To investigate if combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization results in superior outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC). METHODS: A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included. Propensity score matching was conducted to account for baseline demographic differences. Kaplan-Meier analysis was used to compare median progression-free survival (PFS) and overall survival (OS), and univariate statistics identified disease response and control rate differences. Duration of imaging response was defined as number of months between the first scan after therapy and the first scan showing progression as defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or immune Response Evaluation Criteria in Solid Tumors (iRECIST). Adverse events were analyzed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Patients in the 90Y+ICI therapy group had better objective response rates (ORRs) (89.5% vs 36.8%; P < .001) and disease control rates (DCRs) (94.7% vs 63.2%; P < .001) by mRECIST and iRECIST (ORR: 78.9% vs 36.8%; P < .001; DCR: 94.7% vs 63.2%; P < .001). Median PFS (8.3 vs 4.1 months; P = .37) and OS (15.8 vs 14.3 months; P = .52) were not statistically different. Twelve patients (63.1%) in the 90Y+TKI group did not complete systemic therapy owing to adverse effects compared with 1 patient (5.3%) in the 90Y+ICI group (P < .001). Grade 3/4 adverse events were not statistically different (90Y+TKI: 21.1%; 90Y+ICI: 5.3%; P = .150). CONCLUSIONS: Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.

Radiation Segmentectomy for Hepatocellular Carcinoma.

The application of trans-arterial radioembolization (TARE) with Yttrium-90, historically a palliative treatment option for patients with advanced hepatocellular carcinoma (HCC), is evolving. Radiation segmentectomy (RADSEG), the segmental delivery of an ablative radiation dose, is a treatment option for patients with earlier-stage HCC. This review presents an in-depth exploration of RADSEG, emphasizing its technical considerations, dosimetry advancements, and patient selection. The integration of RADSEG into the Barcelona Clinic Liver Cancer (BCLC) paradigm will be highlighted. RADSEG outcomes concerning safety and efficacy will be explored and compared with traditional locoregional cancer treatments like trans-arterial chemoembolization (TACE), percutaneous thermal ablation, and surgical resection, with an eye on future directions and considerations.

Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial.

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRASG12C-mutated metastatic colorectal cancer. Here, we report the results in a dose-exploration cohort and a dose-expansion cohort. Patients received sotorasib (960 mg, once daily) plus panitumumab (6 mg kg-1, once every 2 weeks). The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and pharmacokinetics. Exploratory biomarkers at baseline were assessed. Forty-eight patients (dose-exploration cohort, n = 8; dose-expansion cohort, n = 40) were treated. Treatment-related adverse events of any grade and grade ≥3 occurred in 45 (94%) and 13 (27%) patients, respectively. In the dose-expansion cohort, the confirmed objective response rate was 30.0% (95% confidence interval (CI) 16.6%, 46.5%). Median progression-free survival was 5.7 months (95% CI 4.2, 7.7 months). Median overall survival was 15.2 months (95% CI 12.5 months, not estimable). Prevalent genomic coalterations included APC (84%), TP53 (74%), SMAD4 (33%), PIK3CA (28%) and EGFR (26%). Sotorasib-panitumumab demonstrated acceptable safety with promising efficacy in chemotherapy-refractory KRASG12C-mutated metastatic colorectal cancer. ClinicalTrials.gov identifier: NCT04185883 .

Correlation Between Mobile-Application Electronic Bowel Diary and Validated Questionnaires in Women with Fecal Incontinence.

INTRODUCTION AND HYPOTHESIS: Despite growing interest in a mobile-app bowel diary to assess fecal incontinence (FI) symptoms, data are limited regarding the correlation between mobile-app diary and questionnaire-based outcomes. The primary aim is to determine whether percentage reduction in FI episodes (FIEs)/week recorded on a mobile-app diary correlates with changes in scores of validated FI-symptom measures from baseline to 12 weeks in women with FI undergoing percutaneous tibial nerve stimulation (PTNS) versus sham. METHODS: This is a planned secondary analysis of a multicenter randomized trial in which women with FI underwent PTNS or sham. FIEs were collected using a mobile-app diary at baseline and after 12 weekly sessions. FI-symptom-validated measures included St. Mark's, Accidental Bowel Leakage Evaluation, FI Severity Index (FISI), Colorectal Anal Distress Inventory, Colorectal Anal Impact Questionnaire, FI Quality of Life, Patient Global Impression of Improvement (PGI-I), and Patient Global Symptom Control (PGSC) rating. Spearman's correlation coefficient (ρ) was computed between %-reduction in FIEs/week and change in questionnaire scores from baseline to 12 weeks. Significance was set at 0.005 to account for multiple comparisons. RESULTS: Baseline characteristics of 163 women (109 PTNS, 54 sham) include mean age 63.4±11.6, 81% white, body mass index 29.4±6.6 kg/m2, 4% previous FI surgeries, 6.6±5.5 FIEs/week, and St. Mark's score 17.4±2.6. A significant correlation was demonstrated between %-reduction in FIEs/week and all questionnaires (p<0.005). A moderate-strength correlation (|ρ|>0.4) was observed for St. Mark's (ρ=0.48), FISI (ρ=0.46), PGI-I (ρ=0.51), and PGSC (ρ=-0.43). CONCLUSIONS: In women with FI randomized to PTNS versus sham, a moderate correlation was noted between FIEs measured via mobile-app diary and FI-symptom-validated questionnaire scores.

Learning From a National Quality Improvement Collaborative for Brief Resolved Unexplained Events.

OBJECTIVE: In 2016, the American Academy of Pediatrics published the Brief Resolved Unexplained Event (BRUE) Clinical Practice Guideline (CPG). A multicenter quality improvement (QI) collaborative aimed to improve CPG adherence. METHODS: A QI collaborative of 15 hospitals aimed to improve testing adherence, the hospitalization of lower-risk infants, the correct use of diagnostic criteria, and risk classification. Interventions included CPG education, documentation practices, clinical pathways, and electronic medical record integration. By using medical record review, care of emergency department (ED) and inpatient patients meeting BRUE criteria was displayed via control or run charts for 3 time periods: pre-CPG publication (October 2015 to June 2016), post-CPG publication (July 2016 to September 2018), and collaborative (April 2019 to June 2020). Collaborative learning was used to identify and mitigate barriers to iterative improvement. RESULTS: A total of 1756 infants met BRUE criteria. After CPG publication, testing adherence improved from 56% to 64% and hospitalization decreased from 49% to 27% for lower-risk infants, but additional improvements were not demonstrated during the collaborative period. During the collaborative period, correct risk classification for hospitalized infants improved from 26% to 49% (ED) and 15% to 33% (inpatient) and the documentation of BRUE risk factors for hospitalized infants improved from 84% to 91% (ED). CONCLUSIONS: A national BRUE QI collaborative enhanced BRUE-related hospital outcomes and processes. Sites did not improve testing and hospitalization beyond the gains made after CPG publication, but they did shift the BRUE definition and risk classification. The incorporation of caregiver perspectives and the use of shared decision-making tools may further improve care.

Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy.

OBJECTIVES: Radiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC. MATERIALS AND METHODS: Patients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated. RESULTS: Eighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4-2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763-0.825, PPV: 0.966-1), LI-RADS TRA (accuracy: 0.700-0.825, PPV: 0.983-1), and subtraction (accuracy: 0.775-0.825, PPV: 0.967-1), with no difference in accuracy between criteria (p range 0.053 to > 0.9). CONCLUSION: mRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy. CLINICAL RELEVANCE STATEMENT: Response assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96). KEY POINTS: • Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value. • There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.

Extreme coronary radiation doses from intravascular brachytherapy.

PURPOSE: To evaluate coronary artery integrity after very high radiation doses from intravascular brachytherapy (IVBT) in the setting of source asymmetry. METHODS: Ten patients treated for right coronary artery (RCA) in-stent restenosis (ISR) between 2017 and 2021 and for whom follow-up angiograms were available were identified from departmental records. Procedural angiograms, taken to document source position, were used to estimate vascular wall doses. The 2.5 mm proximal source marker was used to estimate the distance from source center to the media and adventitia. Distances were converted to dose (Gy) using the manufacturers' dose fall-off table, measured in water. Follow-up films were scrutinized for any sign of late vascular damage. RESULTS: The average minimal distance from catheter center to the adjacent media and the adventitia was 0.9 mm (±0.2) mm and 1.4 mm (±0.2), respectively. The average maximum media and adventitial doses adjacent to the source were 75 Gy (±26) and 39 Gy (±14), respectively. Follow-up angiograms were available from 0.6 years to 3.9 years following IVBT (median: 1.6 years). No IVBT-treated vascular segment showed signs of degeneration, dissection or aneurysm. CONCLUSION: IVBT vascular wall doses are frequently far higher than prescribed. The lack of complications in this unselected group of patients gives a modicum of reassurance that raising the prescription dose is unlikely to lead to a sudden appearance of complications.

Phase I/II trial of BMS-986,205 and nivolumab as first line therapy in hepatocellular carcinoma.

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) helps orchestrate immune suppression and checkpoint inhibitor resistance in hepatocellular carcinoma (HCC). BMS-986,205 is a novel oral drug that potently and selectively inhibits IDO. This Phase I/II study evaluated the safety and tolerability of BMS-986,205 in combination with nivolumab as first-line therapy in advanced HCC. METHODS: Adults with untreated, unresectable/metastatic HCC received BMS-986,205 at two dose levels (50-100 mg orally daily) in combination with fixed dose nivolumab (240mg/m2 IV on Day 1 of each 14-day cycle). The primary objective was to determine the safety and tolerability of this combination; secondary objectives were to obtain preliminary efficacy. RESULTS: Eight patients received a total of 91 treatment cycles in the dose escalation phase. All patients were Child Pugh A and 6 patients had underlying viral hepatitis. In the 6 evaluable patients, no dose-limiting toxicities (DLTs) were observed. The most common treatment-related adverse events (TRAEs) were aspartate transaminase (AST) and alanine transaminase (ALT) elevation (3 patients) and diarrhea, maculopapular rash and increased alkaline phosphatase (2 patients each). Grade 3 events were diarrhea and AST elevation (1 patient), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 patient). No grade 4-5 events occurred. Partial response was observed in 1 patient (12.5%) and stable disease in 3 patients (37.5%), yielding a disease control rate of 50%. Median PFS was 8.5 weeks; median OS was not reached. CONCLUSION: Combination BMS-986,205 and nivolumab showed a manageable safety profile with durable benefit as first-line therapy in a meaningful subset of advanced HCC patients.

NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma.

BACKGROUND: Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib. PATIENTS AND METHODS: This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR). RESULTS: Fifty-one patients received ramucirumab and olaparib. The RP2D was olaparib 300 mg twice daily with ramucirumab 8 mg/kg. In evaluable patients at the RP2D the ORR was 6/43 (14%) (95% CI 4.7-25.6). The median progression-free survival (PFS) was 2.8 months (95% CI 2.3-4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7-13.0). Non-statistically significant improvements in PFS and OS were observed for patients with tumours with mutations in HRD genes. CONCLUSIONS: Olaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a heavily pre-treated patient population.

Update on Locoregional Therapies for Liver Cancer: Radiation Segmentectomy.

Over 900,000 people worldwide were diagnosed with liver cancer in 2022 alone, with hepatocellular carcinoma (HCC) accounting for 75-85% of cases. Treatment for HCC includes some combination of systemic therapies, surgery, liver transplantation, ablation, and intra-arterial therapies with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE). Currently, the Barcelona Clinic Liver Cancer (BCLC) guidelines have acknowledged liver transplantation, surgical resection, and thermal ablation as curative therapies in very early to early stage HCC (BCLC-0 and BCLC-A). While these modalities are the preferred curative treatments for a very early to early stage disease, there are challenges associated with these options, such as organ availability and patient eligibility. Current data shows the role of radiation segmentectomy as a curative therapeutic option for very early to early stage HCC that is unresectable and not amenable to ablation. As future data continues to elucidate the ability for radiation segmentectomy to achieve complete pathologic necrosis, the goal is for the BCLC staging model to acknowledge its role as a curative treatment in this patient population and incorporate it into the ever-evolving guidelines.

Development of an Automated and Scalable Virtual Assistant to Aid in PPE Adherence: A Study with Implications for Applications within Anesthesiology.

Virtual assistants (VAs) are conversational agents that are able to provide cognitive aid. We developed a VA device for donning and doffing personal protective equipment (PPE) procedures and compared it to live human coaching to explore the feasibility of using VAs in the anesthesiology setting. An automated, scalable, voice-enabled VA was built using the Amazon Alexa device and Alexa Skills application. The device utilized voice-recognition technology to allow a touch-free interactive user experience. Audio and video step-by-step instructions for proper donning and doffing of PPE were programmed and displayed on an Echo Show device. The effectiveness of VA in aiding adherence to PPE protocols was compared to traditional human coaching in a randomized, controlled, single-blinded crossover design. 70 anesthesiologists, anesthesia assistants, respiratory therapists, and operating room nurses performed both donning and doffing procedures, once under step-by-step VA instructional guidance and once with human coaching. Performance was assessed using objective performance evaluation donning and doffing checklists. More participants in the VA group correctly performed the step of "Wash hands for 20 seconds" during both donning and doffing tests. Fewer participants in the VA group correctly performed the steps of "Put cap on and ensure covers hair and ears" and "Tie gown on back and around neck". The mean doffing total score was higher in the VA group; however, the donning score was similar in both groups. Our study demonstrates that it is feasible to use commercially available technology to create a voice-enabled VA that provides effective step-by-step instructions to healthcare professionals.

Survival and Radiation Dose Differences Between Single Versus Multi-Session Gamma Knife Stereotactic Radiosurgery in Patients Treated for Multiple (≥10) Brain Metastases.

OBJECTIVE:  To explore whether treatment with multiple Gamma Knife sessions (mGK) resulted in different survival outcomes or cumulative radiation doses compared to single session Gamma Knife (sGK) in patients who have been treated for ≥10 brain metastases (BMs). METHODS:  Thirty-five patients with ≥10 BMs treated with Gamma Knife stereotactic radiosurgery (GK SRS) were identified and separated into sGK vs. mGK cohorts. Survival outcomes and dosimetry data were compared between the two groups. Recursive partitioning analysis (RPA) classes were used to further stratify patients. RESULTS:  mGK patients survived longer from the first GK treatment (p<0.009). By RPA class, patients with class 1 had a prolonged survival from BM diagnosis than those in classes 2 and 3 (p=0.004). However, survival was not significantly different between the classes from the first GK treatment (p=0.089). Stratified by mGK vs. sGK and RPA classes, sGK patients in RPA class 1 had the longest survival from BM diagnosis but the worst survival from GK treatment. mGK patients in any RPA class had the best survival from the first GK treatment. For patients with RPA class 2+3, mGK was associated with longer survival from both BM diagnosis and first treatment. Statistical but not clinical differences between the mGK vs. sGK groups were observed in the max dose to the targets and cochlea, and the V40Gy whole brain dose. CONCLUSIONS:  mGK may be beneficial if GK is initiated early at first BM diagnosis vs. sGK initiated late. Future research is required to confirm these findings and explore additional areas of interest, such as quality-of-life and economic considerations.

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy in Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial.

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts. Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions. Design, Setting, and Participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis was performed from August 2016 to September 2022. Interventions: Two doses of IT GLA-SE (5 µg and 10 µg for 8 weekly doses) were tested for safety in combination with concurrent radiotherapy of the injected lesion. Main Outcomes and Measures: Primary end points were safety and tolerability. Secondary and exploratory end points included local response rates as well as measurement of antitumor immunity with immunohistochemistry and T-cell receptor (TCR) sequencing of tumor-infiltrating and circulating lymphocytes. Results: Twelve patients (median [range] age, 65 [34-78] years; 8 [67%] female) were treated across the 2 dose cohorts. Intratumoral GLA-SE was well tolerated, with only 1 patient (8%) experiencing a grade 2 adverse event. All patients achieved local control of the injected lesion after 8 doses, with 1 patient having complete regression (mean regression, -25%; range, -100% to 4%). In patients with durable local response, there were detectable increases in tumor-infiltrating lymphocytes. In 1 patient (target lesion -39% at 259 days of follow-up), TCR sequencing revealed expansion of preexisting and de novo clonotypes, with convergence of numerous rearrangements coding for the same binding sequence (suggestive of clonal convergence to antitumor targets). Single-cell sequencing identified these same expanded TCR clones in peripheral blood after treatment; these T cells had markedly enhanced Tbet expression, suggesting TH1 phenotype. Conclusions and Relevance: In this nonrandomized controlled trial, IT GLA-SE with concurrent radiotherapy was well tolerated and provided more durable local control than radiotherapy alone. Patients with durable local response demonstrated enhanced IT T-cell clonal expansion, with matched expansion of these clonotypes in the circulation. Additional studies evaluating synergism of IT GLA-SE and radiotherapy with systemic immune modulation are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02180698.

Increased prescription dose for large vessel intravascular brachytherapy.

BACKGROUND: Most randomized studies testing the effectiveness of IVBT were limited to vessels less than 4 mm diameter. In fact, it is now common to treat vessels larger than 4 mm. Accordingly, the authors instituted a prescription dose increase to 34 Gy at 2 mm from source center for vessels greater than 4.0 mm. The increase in prescription dose to 34 Gy at 2 mm from center is substantial, being 50% higher than the conventional maximum of 23 Gy. AIM: To take a close look at group of patients treated to 34 Gy, and for whom follow-up angiograms are available. METHODS: Ten patients treated for ISR with a prescription dose of 34 Gy and for whom follow-up angiograms were available were studied. Beta-radiation brachytherapy was performed with a Novoste Beta-Cath System using a strontium-90 (beta) source (Best Vascular, Springfield, VA). Source lengths of 40 or 60 mm were used. A dose of 34 Gy was prescribed at 2 mm from the source center. RESULTS: Patients were re-catheterized from 2 to 21 months (median: 16 months) following IVBT, all for symptoms suggested of restenosis. All patients had some degree of ISR of the target vessel, but no IVBT-treated vascular segment showed angiographic signs of degeneration, dissection or aneurysm. CONCLUSION: The authors' clinical impression, along with detailed review of the 10 cases, suggest that using a 34 Gy prescription dose at 2 mm from source center does not result in increased toxicity.