Preventive efficacy of hydrocortisone enema for radiation proctitis in rectal cancer patients undergoing short-course radiotherapy: a phase II randomized placebo-controlled clinical trial.

Purpose: This study aimed to investigate the efficacy of hydrocortisone enema in preventing radiation proctitis in patients with rectal cancer undergoing short-course radiotherapy (SCRT). Methods: This phase II randomized controlled trial enrolled patients with newly diagnosed locally advanced rectal cancer (clinically staged T3-4 and/or N1-2M0). Participants received a median of 4 cycles of neoadjuvant chemotherapy (capecitabine plus oxaliplatin) followed by 3-dimensional conformal SCRT (25 Gy in 5 fractions). Patients were randomly assigned to receive either a hydrocortisone enema (n=50) or a placebo (n=51) once daily for 5 consecutive days during SCRT. The primary endpoint was the incidence and severity of acute proctitis. Results: Of the 111 eligible patients, 101 were included in the study. Baseline characteristics, including sex, age, performance status, and tumor location, were comparable across the treatment arms. None of the patients experienced grade 4 acute gastrointestinal toxicity or had to discontinue treatment due to treatment-related adverse effects. Patients in the hydrocortisone arm experienced significantly less severe proctitis (P<0.001), diarrhea (P=0.023), and rectal pain (P<0.001) than those in the placebo arm. Additionally, the duration of acute gastrointestinal toxicity following SCRT was significantly shorter in patients receiving hydrocortisone (P<0.001). Conclusion: Hydrocortisone enema was associated with a significant reduction in the severity of proctitis, diarrhea, and rectal pain compared to placebo. Additionally, patients treated with hydrocortisone experienced shorter durations of gastrointestinal toxicity following SCRT. This study highlights the potential benefits of hydrocortisone enema in managing radiation-induced toxicity in rectal cancer patients undergoing radiotherapy.

The Impact of Combined Chemotherapy and Intra-Tumoural Injection of Phosphorus-32 Microparticles on Vascularity in Locally Advanced Pancreatic Carcinoma.

BACKGROUND: Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 (32P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following 32P implantation, using contrast-enhanced EUS (CE-EUS). METHODS: This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and 32P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time-intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain. RESULTS: A total of 20 patients underwent 32P implantation, with 15 completing 12-week follow-up. The technical success of 32P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5-38.75) pre-implantation to 24 mm (IQR 16-26) 12 weeks post-implantation (p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08-54.35). This increased to 46.85 (IQR 35.05-76.6; p = 0.007) and 66.3 (IQR 54.7-76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8-12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation. CONCLUSION: This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed 32P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted.

Immunotherapy and Radiotherapy for Older Patients with Locally Advanced Non-Metastatic Non-Small-Cell Lung Cancer Who Are Not Candidates for or Decline Surgery and Chemotherapy: A Practical Proposal by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced non-small-cell lung cancer (NSCLC) is either surgery combined with chemotherapy pre- or postoperatively or concurrent chemotherapy and radiotherapy. However, older and frail patients may not be candidates for surgery and chemotherapy due to the high mortality risk and are frequently referred to radiotherapy alone, which is better tolerated but carries a high risk of disease recurrence. Recently, immunotherapy with immune checkpoint inhibitors (ICIs) may induce a high response rate among cancer patients with positive programmed death ligand 1 (PD-L1) expression. Immunotherapy is also well tolerated among older patients. Laboratory and clinical studies have reported synergy between radiotherapy and ICI. The combination of ICI and radiotherapy may improve local control and survival for NSCLC patients who are not candidates for surgery and chemotherapy or decline these two modalities. The International Geriatric Radiotherapy Group proposes a protocol combining radiotherapy and immunotherapy based on the presence or absence of PD-L1 to optimize the survival of those patients.

The Cost of Opioid Use in High-Risk Hospitalized Infants.

INTRODUCTION: Hospitalizations of high-risk infants are among the most expensive in the United States, with many requiring surgery and months of intensive care. Healthcare costs and resource use associated with hospitalized infant opioid exposure are less well known. METHODS: A retrospective cohort of high-risk infants aged <1 y admitted from 47 children's hospitals from 2010 to 2020 was identified from Pediatric Healthcare Information System. High-risk infants were identified by International Classification of Diseases 9/10 codes for congenital heart disease procedures, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and gastrointestinal tract malformations. Healthcare resource utilization was estimated using standardized unit costs (SUCs). The impact of opioid use on SUC was examined using general linear models and an instrumental variable. RESULTS: Overall, 126,897 high-risk infants were identified. The cohort was majority White (57.1%), non-Hispanic (72.0%), and male (55.4%). Prematurity occurred in 26.4% and a majority underwent surgery (77.9%). Median SUC was $120,585 (interquartile range: $57,602-$276,562) per infant. On instrumental variable analysis, each day of opioid use was associated with an increase of $4406 in SUC. When adjusting for biologic sex, race, ethnicity, insurance type, diagnosis category, number of comorbidities, mechanical ventilation, and total parental nutrition use, each day of opioid use was associated with an increase of $2177 per infant. CONCLUSIONS: Prolonged opioid use is significantly associated with healthcare utilization and costs for high-risk infants, even when accounting for comorbidities, intensive care, ventilation, and total parental nutrition use. Future studies are needed to estimate the long-term complications and additional costs resulting from prolonged opioid exposures in high-risk infants.

PSA Levels and Mortality in Prostate Cancer Patients.

INTRODUCTION: Prostate cancer (PC) is the second most common cancer among men around the world. Several smaller studies have explored the relationship between elevated PSA and mortality, but results have been conflicting. Additionally, studies have shown that Black men are more likely to be diagnosed with PC at late-stages and may have a twofold increase in mortality risk. This study aims to evaluate the relationship between PSA levels and mortality in patients with PC and differences between Black versus White patients. METHODS: In this retrospective study, the TriNetX database, was used to extract de-identified EMRs of 198,083 patients. Patients were included if they were diagnosed with PC and had obtained a PSA level (measured in ng/mL) within 6 months prior to diagnosis. Cohorts were separated into 7 groups based on intervals of PSA, ranging from < 2 to ≥ 500 and compared to a control cohort with a PSA of 4 to 20 for differing 2-year mortality rates. A subgroup analysis was performed to compare mortality differences between Black and White patients. A posthoc analysis evaluated 5- and 10-year mortality amongst all patients with PC. RESULTS: After propensity matching, mortality risk was significantly lower for patients with PSA < 2 (5.9% vs. 7.5%; RR 0.784; P < .001) when compared to the control cohort. Mortality was significantly higher for all other subsequent PSA intervals > 20, with the lowest risk ratios at PSA 20-100 (24.1% vs. 10.0%; RR 2.419; P < .001) and highest at PSA 200 to 500 (50.4% vs. 10.8%; RR 4.673; P < .001). The sub-group analysis showed that when compared to White patients, Black patients with PSA < 20 had similar mortalities, but had significantly lower 2-year mortality rates at PSA levels ≥ 20. The posthoc analysis of PSA levels and 5- and 10-year mortality of all patients with PC showed similar trends to the 2-year outcomes. CONCLUSION: This study found that prostate cancer patients with significantly elevated PSA levels have a greater mortality, and Black patients have lower 2-year mortality rates than their White counterparts when matched for PSA levels greater than 20.

Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.

In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084 ) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.0001). ADE-RS5 was integrated with a previously defined leukemic-stemness signature (pLSC6) to classify patients into four groups. ADE-RS5, pLSC6 and integrated-score was evaluated for association with outcome in one of the largest assembly of ~3600 AML patients from 10 independent cohorts (1861 pediatric and 1773 adult AML). Patients with high ADE-RS5 had poor outcome in validation cohorts and the previously reported pLSC6 maintained strong significant association in all validation cohorts. For pLSC6/ADE-RS5-integrated-score analysis, using Group-1 (low-scores for ADE-RS5 and pLSC6) as reference, Group-4 (high-scores for ADE-RS5 and pLSC6) showed worst outcome (EFS: p < 0.0001 and OS: p < 0.0001). Groups-2/3 (one high and one low-score) showed intermediate outcome (p < 0.001). Integrated score groups remained an independent predictor of outcome in multivariable-analysis after adjusting for established prognostic factors (EFS: Group 2 vs. 1, HR = 4.68, p < 0.001, Group 3 vs. 1, HR = 3.22, p = 0.01, and Group 4 vs. 1, HR = 7.26, p < 0.001). These results highlight the significant prognostic value of transcriptomics-based scores capturing disease aggressiveness through pLSC6 and drug resistance via ADE-RS5. The pLSC6 stemness score is a significant predictor of outcome and associates with high-risk group features, the ADE-RS5 drug resistance score adds further value, reflecting the clinical utility of simultaneous testing of both for optimizing treatment strategies.

Does a Point-of-Care 3-Dimensional Printer Result in a Decreased Length of Surgery for Orbital Fractures?

BACKGROUND: Utilization of point-of-care 3-dimensional printing (3DP) has decreased length of surgery in facial trauma. Little is known regarding 3DP's impact on length of surgery in orbital fracture. PURPOSE: The purpose of this study was to compare length of surgery between 3DP/preadapted (3DPPA) orbital plates and intraoperative adapted plates (IOAP) for orbital fracture reconstruction. STUDY DESIGN, SETTING, SAMPLE: This was a prospective, non-blinded, randomized clinical study of consecutive subjects with orbital fractures presented to Grady Memorial Hospital in Atlanta, Georgia, between January 2018 and June 2021. Subjects ≥ 18 years, unilateral fracture, no previous orbital surgery, and/or congenital craniofacial anomaly were included. We excluded subjects <18 years and bilateral fractures. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: Primary predictor variable was the treatment approach. Randomization software was used, and subjects were randomized to 3DPPA or IOAP groups. MAIN OUTCOME VARIABLE(S): Primary outcome variable was length of surgery in minutes. Secondary outcomes were the time required for plate insertion and fixation in minutes, operating room (OR) charges, and orbital volume (OV) calculation. COVARIATES: Age, sex, race, etiology, laterality, location, dimension, indication for surgery, postoperative enophthalmos, and diplopia. ANALYSES: Univariate and bivariate analyses were calculated. Statistical significance was P < .05. RESULTS: Twenty-five subjects met the inclusion criteria. Mean ages in 3DPPA and conventional IOAP groups were 41.5 (±9) and 38.2 (±10, P = .31), respectively. The mean length of surgery was 32.6 (±13.7) in 3DPPA and 53.3 (±12.8, P < .001) in conventional IOAP. The mean time required for plate insertion and fixation was 15.8n (±14.4) in 3DPPA and 41.4 (±9.4, P < .001) in conventional IOAP. The mean OR charges were $1,072.5 (±524.6) in 3DPPA and $1,757.3 (±422.6, P ≤ 0.001) in conventional IOAP. The mean calculated OV of uninjured and reconstructed orbit for the 3DPPA was 23.5 (±3.2)cm3 and 23 (±3.5, P = .37)cm3, respectively. The mean calculated OV of uninjured and reconstructed orbit for conventional IOAP was 28.6 (±3.6)cm3 and 22.8 (±2.6, P < .001)cm3, respectively. CONCLUSION AND RELEVANCE: Using 3DP to produce a model that enables preoperative plate bending/adaptation reduces the length of surgery, decreases OR charges, and results in predictable OV.

The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer.

Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.Trial registration number: NCT05163106 (ClinicalTrials.gov).

[Box: see text].

Surface Cleaning of Oil Contaminants Using Bulk Nanobubbles.

The removal of oil from solid surfaces, such as textiles and plates, remains a challenge due to the strong binding affinity of the oil. Conventional methods for surface cleaning often require surfactants and mechanical abrasion to enhance the cleaning process. However, in excess, these can pose adverse effects on the environment and to the material. This study investigated how bulk nanobubble water can clean oil microdroplets deposited on surfaces like glass coverslips and dishes. Microscopy imaging and further image analysis clearly revealed that these microdroplets detached from both hydrophobic and hydrophilic surfaces when washed with bulk nanobubble water within a fluidic microchannel. Oil contaminant cleaning was also conducted in water as mobile phase to mimic the circumstances that occur in a dishwasher and washing machine. Cleaning on a larger scale also proved very successful in the removal of oil from a porcelain bowl. These results indicate that nanobubble water can easily remove oil contaminants from glass and porcelain surfaces without the assistance of surfactants. This is in stark contrast to negligible results obtained with a control solution without nanobubbles. This study indicates that nanobubble technology is an innovative, low-cost, eco-friendly approach for oil removal, demonstrating its potential for broad practical applications.

Bibliometric and scientometric analysis of PSMA-targeted radiotheranostics: knowledge mapping and global standing.

Purpose: Bibliometric and scientometric analyses provide a structured approach to large amounts of data, enabling the prediction of research theme trends over time, the detection of shifts in the boundaries of disciplines, and the identification of the most productive countries, institutions and scholars. In the context of prostate-specific membrane antigen (PSMA)-targeted radiotheranostics, no bibliometric or scientometric analysis has been published thus far. Therefore, this study was conducted to identify key contributors to the literature, assess the global scientific production of related research, and possibly predict future development patterns. Methods: Scientometrics and bibliometrics were utilized to analyze the current body of knowledge while tracking its evolution to support scientific decision-making comprehensively and systematically. Science mapping techniques were employed to visualize research activities. Two different tools, Tableau and VOSviewer, were utilized, with VOSviewer being deemed the most suitable for the research objectives. The Web of Science (WoS) was used as the principal database for the searches. Results: Through the search process over a period of 30 years (January 1993-January 2023), 694 original studies in the English language were subjected to comprehensive analysis. By employing bibliometric and scientometric methods, multiple networks were created that mapped various concepts, such as publication trends, leading countries, cocitations, coauthorship among researchers and scientists, as well as coauthorship among organizations and funding agencies. This study revealed the evolutionary patterns, trends, outliers, and key players in the PSMA field, which enabled a more nuanced understanding of the research landscape. Conclusion: This research contributes to the enrichment of knowledge on PSMA-targeted radiotheranostics through detailed global bibliometric and scientometric analyses. It stresses the necessity for the development of communication platforms, the establishment of supportive infrastructures, and the implementation of proactive solutions to address emerging challenges. This study offers a significant resource for delineating effective strategies and identifying prominent funding bodies essential for continuous advancements in the field of PSMA-based diagnosis and therapy for prostate cancer. It is vital to sustain this momentum to ensure further progress in this pioneering area.

Performance of LFSPRO TP53 germline carrier risk predictions compared to standard genetic counseling practice on prospectively collected probands.

Purpose: Current clinical guidelines for genetic testing for Li-Fraumeni Syndrome (LFS) have many limitations, primarily the criteria don't consider detailed personal and family history information and may miss many individuals with LFS. A personalized risk assessment tool, LFSPRO, was created to estimate a proband's risk for LFS based on personal and family history information. The purpose of this study is to compare LFSPRO to existing clinical criteria to determine if LFSPRO can outperform these tools. Additionally, we gauged genetic counselors' (GCs) experience using LFSPRO for their patients. Methods: Between December 2021 and March 2024, GCs identified patients concerning for LFS based on the patients' personal and family history information. This information was entered into LFSPRO to predict the risk to have a pathogenic/pathogenic (LP/P) germline TP53 variant. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was compared between LFSPRO and Chompret criteria. Select GCs were asked to fill out surveys regarding their experience using LFSPRO following their genetic counseling appointments. Results: LFSPRO's sensitivity and specificity were 0.529 and 0.781 compared to Chompret's respective 0.235 and 0.677. Additionally, LFSPRO had a positive predictive value (PPV) of 0.30 compared to Chompret's 0.114. LFSPRO's risk prediction was concordant with genetic testing results in 75% of probands. Eighty-one percent of GC surveys reported LFSPRO being concordant with the GC's expectations and 75% would feel comfortable sharing the results with patients. Conclusion: LFSPRO showed improved sensitivity and specificity compared to Chompret criteria and GCs report a positive experience with LFSPRO. LFSPRO can be used to increase access to genetic testing for patients at risk for LFS and could help healthcare providers give more direct risk assessments regarding LFS testing and management for patients.

Immunotherapy and radiotherapy for older patients with invasive bladder cancer unfit for surgery or chemotherapy: practical proposal by the international geriatric radiotherapy group.

The standard of care for non-metastatic muscle invasive bladder cancer is either radical cystectomy or bladder preservation therapy, which consists of maximal transurethral bladder resection of the tumor followed by concurrent chemoradiation with a cisplatin-based regimen. However, for older cancer patients who are too frail for surgical resection or have decreased renal function, radiotherapy alone may offer palliation. Recently, immunotherapy with immune checkpoint inhibitors (ICI) has emerged as a promising treatment when combined with radiotherapy due to the synergy of those two modalities. Transitional carcinoma of the bladder is traditionally a model for immunotherapy with an excellent response to Bacille Calmette-Guerin (BCG) in early disease stages, and with avelumab and atezolizumab for metastatic disease. Thus, we propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced muscle-invasive bladder cancer who are not candidates for cisplatin-based chemotherapy and surgery.

PSMA-targeted radiotheranostics in modern nuclear medicine: then, now, and what of the future?

In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the landscape dramatically altered. Currently, men face a one-in-nine lifetime risk of PCa, accentuated by improved diagnostic methods and an ageing population. With more than three million men in the United States alone grappling with this disease, the overall risk of succumbing to stands at one in 39. The intricate clinical and biological diversity of PCa poses serious challenges in terms of imaging, ongoing monitoring, and disease management. In the field of theranostics, diagnostic and therapeutic approaches that harmoniously merge targeted imaging with treatments are integrated. A pivotal player in this arena is radiotheranostics, employing radionuclides for both imaging and therapy, with prostate-specific membrane antigen (PSMA) at the forefront. Clinical milestones have been reached, including FDA- and/or EMA-approved PSMA-targeted radiodiagnostic agents, such as [18F]DCFPyL (PYLARIFY®, Lantheus Holdings), [18F]rhPSMA-7.3 (POSLUMA®, Blue Earth Diagnostics) and [68Ga]Ga-PSMA-11 (Locametz®, Novartis/ ILLUCCIX®, Telix Pharmaceuticals), as well as PSMA-targeted radiotherapeutic agents, such as [177Lu]Lu-PSMA-617 (Pluvicto®, Novartis). Concurrently, ligand-drug and immune therapies designed to target PSMA are being advanced through rigorous preclinical research and clinical trials. This review delves into the annals of PSMA-targeted radiotheranostics, exploring its historical evolution as a signature molecule in PCa management. We scrutinise its clinical ramifications, acknowledge its limitations, and peer into the avenues that need further exploration. In the crucible of scientific inquiry, we aim to illuminate the path toward a future where the enigma of PCa is deciphered and where its menace is met with precise and effective countermeasures. In the following sections, we discuss the intriguing terrain of PCa radiotheranostics through the lens of PSMA, with the fervent hope of advancing our understanding and enhancing clinical practice.

Developing a Coordinated Registry Network for devices used for acute ischemic stroke intervention: basilar artery occlusion quality assessment pilot.

BACKGROUND: Real-world data can be helpful in evaluating endovascular therapy (EVT) in ischemic stroke care. We conducted a pilot study to aggregate data on basilar artery occlusion (BAO) EVT from existing registries in the USA. We evaluated the availability, completeness, quality, and consistency of common data elements (CDEs) across data sources. METHODS: We harmonized patient-level data from five registry data sources and assessed the availability, completeness (defined by the presence in at least four data sources), and consistency of CDEs. We assessed data quality based on seven pre-defined critical domains for BAO EVT investigation: baseline patient and disease characteristics; time metrics; description of intervention; adjunctive devices, revascularization scores, complications; post-intervention National Institutes of Health Stroke Scale scores; discharge disposition; 30-day and 90-day mortality and modified Rankin Scale (mRS) scores. RESULTS: The aggregated dataset of five registries included 493 BAO procedures between January 2013 and January 2020. In total, 88 CDEs were screened and 35 (40%) elements were considered prevalent. Of these 35 CDEs, the majority were collected for >80% of cases when aggregated. All seven pre-defined domains for BAO device investigation could be fulfilled with harmonized data elements. Most data elements were collected with consistent or compatible definitions across registries. The main challenge was the collection of 90-day outcomes. CONCLUSIONS: This pilot shows the feasibility of aggregating and harmonizing critical CDEs across registries to create a Coordinated Registry Network (CRN). The CRN with partnerships between multiple registries and stakeholders could help improve the breadth and/or depth of real-world data to help answer relevant questions and support clinical and regulatory decisions.

A "What Matters Most" approach to investigating intersectional stigma toward HIV and cancer in Hanoi, Vietnam.

BACKGROUND: Vietnam is experiencing a growing burden of cancer, including among people living with HIV. Stigma acts as a sociocultural barrier to the prevention and treatment of both conditions. This study investigates how cultural notions of "respected personhood" (or "what matters most") influence manifestations of HIV-related stigma and cancer stigma in Hanoi, Vietnam. METHODS: Thirty in-depth interviews were conducted with people living with HIV in Hanoi, Vietnam. Transcripts were thematically coded via a directed content analysis using the What Matters Most conceptual framework. Coding was done individually and discussed in pairs, and any discrepancies were reconciled in full-team meetings. RESULTS: Analyses elucidated that having chu tín-a value reflecting social involvement, conscientiousness, and trustworthiness-and being successful (eg, in career, academics, or one's personal life) are characteristics of respected people in this local cultural context. Living with HIV and having cancer were seen as stigmatized and interfering with these values and capabilities. Intersectional stigma toward having both conditions was seen to interplay with these values in some ways that had distinctions compared with stigma toward either condition alone. Participants also articulated how cultural values like chu tín are broadly protective against stigmatization and how getting treatment and maintaining employment can help individuals resist stigmatization's most acute impacts. CONCLUSIONS: HIV-related and cancer stigma each interfere with important cultural values and capabilities in Vietnam. Understanding these cultural manifestations of these stigmas separately and intersectionally can allow for greater ability to measure and respond to these stigmas through culturally tailored intervention.

Immunotherapeutic Strategies Targeting Breast Cancer Stem Cells.

Breast cancer is the most commonly diagnosed cancer in women and is a leading cause of cancer death in women worldwide. Despite the implementation of multiple treatment options, including immunotherapy, breast cancer treatment remains a challenge. In this review, we aim to summarize present challenges in breast cancer immunotherapy and recent advancements in overcoming treatment resistance. We elaborate on the inhibition of signaling cascades, such as the Notch, Hedgehog, Hippo, and WNT signaling pathways, which regulate the self-renewal and differentiation of breast cancer stem cells and, consequently, disease progression and survival. Cancer stem cells represent a rare population of cancer cells, likely originating from non-malignant stem or progenitor cells, with the ability to evade immune surveillance and develop resistance to immunotherapeutic treatments. We also discuss the interactions between breast cancer stem cells and the immune system, including potential agents targeting breast cancer stem cell-associated signaling pathways, and provide an overview of the emerging approaches to breast cancer stem cell-targeted immunotherapy. Finally, we consider the development of breast cancer vaccines and adoptive cellular therapies, which train the immune system to recognize tumor-associated antigens, for eliciting T cell-mediated responses to target breast cancer stem cells.

Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial.

BACKGROUND: Use of frozen embryo transfer (FET) in in-vitro fertilisation (IVF) has increased. However, the best endometrial preparation protocol for FET cycles is unclear. We compared natural and modified natural cycle strategies with an artificial cycle strategy for endometrial preparation before FET. METHODS: In this randomised, open-label study, we recruited ovulatory women aged 18-45 years at a hospital in Ho Chi Minh City, Viet Nam, who were randomly allocated (1:1:1) to natural, modified natural, or artificial cycle endometrial preparation using a computer-generated random list and block randomisation. The trial was not masked due to the nature of the study interventions. In natural cycles, no oestrogen, progesterone, or human chorionic gonadotropin (hCG) was used. In modified natural cycles, hCG was used to trigger ovulation. In artificial cycles, oral oestradiol valerate (8 mg/day from day 2-4 of menstruation) and vaginal progesterone (800 mg/day starting when endometrial thickness was ≥7 mm) were used. Embryos were vitrified, and then one or two day-3 embryos or one day-5 embryo were warmed and transferred under ultrasound guidance. If the first FET cycle was cancelled, subsequent cycles were performed with artificial endometrial preparation. The primary endpoint was livebirth after one FET. This trial is registered at ClinicalTrials.gov, NCT04804020. FINDINGS: Between March 22, 2021, and March 14, 2023, 4779 women were screened and 1428 were randomly assigned (476 to each group). 99 first FET cycles were cancelled in each of the natural and modified cycle groups, versus none in the artificial cycle group. The livebirth rate after one FET was 174 (37%) of 476 in the natural cycle strategy group, 159 (33%) of 476 in the modified natural cycle strategy group, and 162 (34%) of 476 in the artificial cycle strategy group (relative risk 1·07 [95% CI 0·87-1·33] for natural vs artificial cycle strategy, and 0·98 [0·79-1·22] for modified natural vs artificial cycle strategy). Maternal and neonatal outcomes did not differ significantly between groups, as the power to detect small differences was low. INTERPRETATION: Although the livebirth rate was similar after natural, modified natural, and artificial cycle endometrial preparation strategies in ovulatory women undergoing FET IVF, no definitive conclusions can be made regarding the comparative safety of the three approaches. FUNDING: None.

Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.

Organ at risk dose-volume metrics in a series of hypofractionated breast radiotherapy with integrated boost.

Dose and volume metrics to organs at risk are used for evaluation and optimization in radiotherapy planning. However, the numerous choices of metrics can be confusing. In a series of patients treated with hypofractionation and an integrated boost for breast cancer, we aim to determine if a parsimonious selection of representative metrics can be identified. The dosimetries of 42 patients receiving 42 Gy to the breast, with or without nodal irradiation, and 51 Gy integrated boost to tumor bed in 15 fractions were reviewed. For each organ-heart, lungs, and contralateral breast-cumulative dose-volume histograms were used to extract values for 3 basic metric classes: Two additional classes were considered: Pearson correlation coefficient R was calculated between pairs of values within each basic class and with the 2 additional classes for each organ. The interquartile ranges of correlations for D.yy, Vrel.xx, and Vabs.xx were as follows: The mean dose correlated with all basic classes for the heart and lungs, and with dose D.yy and volumes at Vrel.10-Vabs.10 for the contralateral breast. The standard deviation correlated with Vrel.xx and Vabs.xx for the heart and lungs (R ≥ 0.70). Among the D.yy, D.50 (median dose) correlated with the mean and standard deviation for all organs (R = 0.65-0.96). The mean, standard deviation, and median doses were the preeminent correlators. These statistics appear to be parsimonious representatives of doses to organs. Further studies with other radiotherapy series will be necessary to validate these observations.