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Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague-Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon., (© 2024. The Author(s).)

Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined., Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction., Design, Setting, and Participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023., Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event., Main Outcomes and Measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence., Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02)., Conclusions and Relevance: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction., Trial Registration: ClinicalTrials.gov Identifier: NCT03422003.

Duration of response is an important endpoint used in drug development. Prolonged duration for response is often viewed as an early indication of treatment efficacy. However, there are numerous difficulties in studying the distribution of duration of response based on observed data subject to right censoring in practice. The most important obstacle is that the distribution of the duration of response is in general not identifiable in the presence of censoring due to the simple fact that there is no information on the joint distribution of time to response and time to progression beyond the largest follow-up time. In this article, we introduce the restricted duration of response as a replacement of the conventional duration of response. The distribution of restricted duration of response is estimable and we have proposed several nonparametric estimators in this article. The corresponding inference procedure and additional downstream analysis have been developed. Extensive numerical simulations have been conducted to examine the finite sample performance of the proposed estimators. It appears that a new regression-based two-step estimator for the survival function of the restricted duration of response tends to have a robust and superior performance, and we recommend its use in practice. A real data example from oncology has been used to illustrate the analysis for restricted duration of response., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Biomarker-driven trials are key for precision oncology but challenge design and analysis.

Background: Clinical trial participation at Comprehensive Cancer Centers (CCC) is inequitable for minoritized racial and ethnic groups with acute leukemia. CCCs care for a high proportion of adults with acute leukemia. It is unclear if participation inequities are due to CCC access, post-access enrollment, or both., Methods: We conducted a retrospective cohort study of adults with acute leukemia (2010-2019) residing within Massachusetts, the designated catchment area of the Dana-Farber/Harvard Cancer Center (DF/HCC). Individuals were categorized as non-Hispanic Asian (NHA), Black (NHB), White (NHW), Hispanic White (HW), or Other. Decomposition analyses assessed covariate contributions to disparities in (1) access to DF/HCC care and (2) post-access enrollment., Results: Of 3698 individuals with acute leukemia, 85.9% were NHW, 4.5% HW, 4.3% NHB, 3.7% NHA, and 1.3% Other. Access was lower for HW (age- and sex-adjusted OR = 0.64, 95% CI = 0.45 to 0.90) and reduced post-access enrollment for HW (aOR = 0.54, 95% CI =0.34 to 0.86) and NHB (aOR = 0.60, 95% CI = 0.39 to 0.92) compared to NHW. Payor and socioeconomic status (SES) accounted for 25.2% and 21.2% of the +1.1% absolute difference in HW access. Marital status and SES accounted for 8.0% and 7.0% of the -8.8% absolute disparity in HW enrollment; 76.4% of the disparity was unexplained. SES and marital status accounted for 8.2% and 7.1% of the -9.1% absolute disparity in NHB enrollment; 73.0% of the disparity was unexplained., Conclusions: A substantial proportion of racial and ethnic inequities in acute leukemia trial enrollment at CCCs are from post-access enrollment, the majority of which was not explained by sociodemographic factors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Optimal methods for deploying electronic patient-reported outcomes to manage symptoms in routine oncologic practice remain uncertain. The electronic symptom management (eSyM) program asks chemotherapy and surgery patients to self-report 12 common symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours., Methods: Using questionnaires submitted during the 16 weeks surrounding the recall period change, we assessed the likelihood of reporting severe or moderate and severe symptoms across 12 common symptoms and separately for the 5 most prevalent symptoms. Interrupted time-series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method., Results: In total, 1692 patients from 6 institutions submitted 7823 eSyM assessments during the 16 weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (odds ratio = 0.65, 95% confidence interval = 0.46 to 0.93; P = .02) and lower odds of moderate and severe symptom reporting in the chemotherapy cohort (odds ratio = 0.83, 95% confidence interval = 0.71 to 0.97; P = .02). Among the most prevalent symptoms, 24-hour recall was associated with a lower rate of reporting postoperative constipation but no differences in reporting rates for other symptoms., Conclusion: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether electronic patient-reported outcomes are collected for active symptom management, as a clinical trial endpoint, or another purpose. ClinicalTrials.gov ID NCT03850912., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Adolescents and young adults frequently receive chemotherapy near death. We know less about the use of targeted agents and immunotherapy or trends over time., Methods: We conducted a retrospective cohort study of 1836 adolescents and young adults with cancer who died between 2009 and 2019 after receiving care at 1 of 3 sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs., Results: Over the study period, 35% of adolescents and young adults received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Additionally, 56% received at least 1 form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of adolescents and young adults receiving targeted therapy (odds ratio [OR] = 1.05 per year of death, 95% confidence interval [CI] = 1.02 to 1.10; P = .006), immunotherapy (OR = 1.27, 95% CI = 1.18 to 1.38; P < .0001), and any cancer-directed therapy (OR = 1.04, 95% CI = 1.01 to 1.08; P = .01) in the last 90 days of life increased over time., Conclusions: More than half of adolescents and young adults receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy is increasing over time. Although some adolescents and young adults may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of adolescents and young adults approaching death., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Bone fractures represent a common health problem, particularly in an increasingly aging population. Bioresorbable magnesium (Mg) alloy-based implants offer promising alternatives to traditional metallic implants for the treatment of bone fractures because they eliminate the need for implant removal after healing. The Mg-Y-rare-earth (RE)-Zr alloy WE43, designed for orthopedic implants, has received European Conformity mark approval. However, currently, WE43 is not clinically used in certain countries possibly because of concerns related to RE metals. In this study, we investigated the use of a RE-free alloy, namely, Mg-Zn-Zr alloy (ZK30), as an implant for bone fractures. Hydrofluoric acid (HF) treatment was performed to improve the corrosion resistance of ZK30. HF-treated ZK30 (HF-ZK30) exhibited lower corrosion rate and higher biocompatibility than those of WE43 in in vitro experiments. After implanting a rod of HF-ZK30 into the fractured femoral bones of mice, HF-ZK30 held the bones and healed the fracture without deformation. Treatment results of HF-ZK30 were comparable to those of WE43, indicating the potential of HF-ZK30 as a bioresorbable and safe implant for bone repair., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Importance: Greenhouse gas (GHG) emissions from health care are substantial and disproportionately harm persons with cancer. Emissions from a central component of oncology care, outpatient clinician visits, are not well described, nor are the reductions in emissions and human harms that could be obtained through decentralizing this aspect of cancer care (ie, telemedicine and local clinician care when possible)., Objective: To assess potential reductions in GHG emissions and downstream health harms associated with telemedicine and fully decentralized cancer care., Design, Setting, and Participants: This population-based cohort study and counterfactual analyses using life cycle assessment methods analyzed persons receiving cancer care at Dana-Farber Cancer Institute between May 2015 and December 2020 as well as persons diagnosed with cancer over the same period from the Cancer in North America (CiNA) public dataset. Data were analyzed from October 2023 to April 2024., Main Outcomes and Measures: The adjusted per-visit day difference in GHG emissions in kilograms of carbon dioxide (CO2) equivalents between 2 periods: an in-person care model period (May 2015 to February 2020; preperiod) and a telemedicine period (March to December 2020; postperiod), and the annual decrease in disability-adjusted life-years in a counterfactual model where care during the preperiod was maximally decentralized nationwide., Results: Of 123 890 included patients, 73 988 (59.7%) were female, and the median (IQR) age at first diagnosis was 59 (48-68) years. Patients were seen over 1.6 million visit days. In mixed-effects log-linear regression, the mean absolute reduction in per-visit day CO2 equivalent emissions between the preperiod and postperiod was 36.4 kg (95% CI, 36.2-36.6), a reduction of 81.3% (95% CI, 80.8-81.7) compared with the baseline model. In a counterfactual decentralized care model of the preperiod, there was a relative emissions reduction of 33.1% (95% CI, 32.9-33.3). When demographically matched to 10.3 million persons in the CiNA dataset, decentralized care would have reduced national emissions by 75.3 million kg of CO2 equivalents annually; this corresponded to an estimated annual reduction of 15.0 to 47.7 disability-adjusted life-years., Conclusions and Relevance: This cohort study found that using decentralization through telemedicine and local care may substantially reduce cancer care's GHG emissions; this corresponds to small reductions in human mortality.

Background & Aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes., Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention., Results: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores., Conclusions: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Limitations of using the traditional Cox's hazard ratio for summarizing the magnitude of the treatment effect on time-to-event outcomes have been widely discussed, and alternative measures that do not have such limitations are gaining attention. One of the alternative methods recently proposed, in a simple 2-sample comparison setting, uses the average hazard with survival weight (AH), which can be interpreted as the general censoring-free person-time incidence rate on a given time window. In this paper, we propose a new regression analysis approach for the AH with a truncation time τ. We investigate 3 versions of AH regression analysis, assuming (1) independent censoring, (2) group-specific censoring, and (3) covariate-dependent censoring. The proposed AH regression methods are closely related to robust Poisson regression. While the new approach needs to require a truncation time τ explicitly, it can be more robust than Poisson regression in the presence of censoring. With the AH regression approach, one can summarize the between-group treatment difference in both absolute difference and relative terms, adjusting for covariates that are associated with the outcome. This property will increase the likelihood that the treatment effect magnitude is correctly interpreted. The AH regression approach can be a useful alternative to the traditional Cox's hazard ratio approach for estimating and reporting the magnitude of the treatment effect on time-to-event outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)

Adolescents, young adults with cancer receive limited psychosocial and spiritual support near death.

The cell cycle dependence of radiosensitivity has yet to be fully determined, as it is technically difficult to achieve a high degree of cell cycle synchronization in cultured cell systems and accurately detect the cell cycle phase of individual cells simultaneously. We used human cervical carcinoma HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators (FUCCI), and employed the mitotic harvesting method that is one of the cell cycle synchronization methods. The imaging analysis confirmed that the cell cycle is highly synchronized after mitotic cell harvesting until 18-20 h of the doubling time has elapsed. Also, flow cytometry analysis revealed that the S and G2 phases peak at approximately 12 and 14-16 h, respectively, after mitotic harvesting. In addition, the clonogenic assay showed the changes in surviving fractions following exposure to X-rays according to the progress through the cell cycle. These results indicate that HeLa-FUCCI cells become radioresistant in the G1 phase, become radiosensitive in the early S phase, rapidly become radioresistant in the late S phase, and become radiosensitive again in the G2 phase. Our findings may contribute to the further development of combinations of radiation and cell cycle-specific anticancer agents.

Purpose: The authors sought to understand bereaved family preferences for end-of-life (EOL) care, particularly among Black families and those in the South., Methods: Semi-structured interviews were conducted with parents of children who died of cancer ≥6 months before at Children's of Alabama. Themes were identified via content analysis. Quotes related to medical intensity, chemotherapy, and location of death (LOD) were scored on 5-point Likert scales, ranging from 1 (comfort care, chemotherapy, or home death) to 5 (medically intense care, avoidance of chemotherapy, or hospital death)., Results: Twenty-seven bereaved parents (12 Black) were interviewed. Children died at a mean of 13.1 years (SD = 6.1 years) and a median of 3 years before the interview (range = 1-12 years). Ten children (42%) had central nervous system tumors and the majority (63%) died in the hospital. Family decision-making involved maintaining hope, not causing harm, doing what was best for their child and themselves, and religious beliefs. There was no clear preference for home versus hospital death (3.0 [1.8-4.0]). Instead, parents considered their child's desires and/or medical needs, siblings, and prior experiences with death. To have a comfortable death, parents highlighted the need for comprehensive education about their child's EOL, a caring and comfortable environment, and 24/7 access to their care team. Families expressed a dual preference for comfort care (1.8 [1.3-2.8]) and chemotherapy (3.5 [2.7-4.1]) at EOL., Conclusions: Families did not see chemotherapy and comfort care as conflicting goals. They sought quality care emphasizing flexibility, quality time with their child, and open access to their care team, regardless of LOD., (© 2024 American Cancer Society.)

Objective: Differentiating hepatic epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), the two most common vascular tumors in the liver, is important due to disparities in their prognosis and treatment. We aimed to compare clinical and MRI features of the two tumors., Methods: This retrospective study included patients with pathologically-confirmed AS or EHE who underwent MRI using gadoxetate disodium between 2008 and 2023. Two radiologists independently reviewed MR images. Wilcoxon rank sum and Fisher's exact tests were used to compare clinical and imaging features. Overall survival was compared using restricted mean survival time at 3 years., Results: 32 patients with AS (18 women [56.3%]; median age, 68 years) and 38 with EHE (24 women [63.2%]; 51 years) were included. Patients with AS were generally older (81.3% ≥ 60 years; P < 0.001), had more frequent laboratory abnormalities (P ≤ 0.018), and poorer overall survival (11.2 vs. 31.8 months; P < 0.001) than those with EHE. On MRI, a large dominant mass accompanied by smaller nodules (14/32, 43.8%), often with ill-defined margins (15/32, 46.9%) was prevalent in AS; compared with nodules of similar sizes (24/38, 63.2%; P = 0.015) with well-defined margin (30/38, 78.9%; P = 0.002) in EHE. Cirrhotic appearance of the liver was more frequent in AS (62.5%, P < 0.001), along with decreased parenchymal enhancement on hepatobiliary phase (31.3%, P < 0.001) and ascites (37.5%, P = 0.010). AS frequently presented with avid enhancement of bizarrely-shaped foci, with a centrifugal enhancement pattern. In comparison, targetoid appearance was characteristic of EHE (78.9% on T2-weighted, 54.1% on diffusion-weighted, 65.8% on multiphase images) (P ≤ 0.002), with enhancement degree typically lower than that of the aorta. On hepatobiliary phase, all the AS exhibited hypointensity, while 39.5% of EHE showed targetoid appearance (P < 0.001)., Conclusion: Patients aged ≥ 60 years presenting with laboratory abnormalities, typically with a large dominant mass accompanied by smaller nodules, exhibiting avid, bizarre, and centrifugal enhancement-particularly in the cirrhotic-appearing liver-suggests the likelihood of AS over EHE., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A person's phenotypic sex (i.e., endogenous expression of primary, secondary, and endocrinological sex characteristics) can impact crucial aspects of genetic assessment and resulting clinical care recommendations. In studies with genetics components, it is critical to collect phenotypic sex, information about current organ/tissue inventory and hormonal milieu, and gender identity. If researchers do not carefully construct data models, transgender, gender diverse, and sex diverse (TGSD) individuals may be given inappropriate care recommendations and/or be subjected to misgendering, inflicting medical and psychosocial harms. The recognized need for an inclusive care experience should not be limited to clinical practice but should extend to the research setting, where researchers must build an inclusive experience for TGSD participants. Here, we review three TGSD participants in the Family History and Cancer Risk Study (FOREST) to critically evaluate sex- and gender-related survey measures and associated data models in a study seeking to identify patients at risk for hereditary cancer syndromes. Furthermore, we leverage these participants' responses to sex- and gender identity-related questions in FOREST to inform needed changes to the FOREST data model and to make recommendations for TGSD-inclusive genetics research design, data models, and processes., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

There is emerging evidence that the live herpes zoster (shingles) vaccine might protect against dementia. However, the existing data are limited and refer only to the live vaccine, which is now discontinued in the United States and many other countries in favor of a recombinant vaccine. Whether the recombinant shingles vaccine protects against dementia remains unknown. Here we used a natural experiment opportunity created by the rapid transition from the use of live to the use of recombinant vaccines to compare the risk of dementia between vaccine types. We show that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected. The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus-diphtheria-pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomized control trial to confirm the possible additional benefit of the recombinant shingles vaccine., (© 2024. The Author(s).)

Background: The treatment and prognosis of de novo metastatic hormone-sensitive prostate cancer (mHSPC) vary. We established and validated a novel prognostic model for predicting cancer-specific survival (CSS) in patients with mHSPC using retrospective data from a contemporary cohort., Methods: 1092 Japanese patients diagnosed with de novo mHSPC between 2014 and 2020 were registered. The patients treated with androgen deprivation therapy and first-generation anti-androgens (ADT/CAB) were assigned to the Discovery (N = 467) or Validation (N = 328) cohorts. Those treated with ADT and androgen-receptor signaling inhibitors (ARSIs) were assigned to the ARSI cohort (N = 81)., Results: Using the Discovery cohort, independent prognostic factors of CSS, the extent of disease score ≥ 2 or the presence of liver metastasis; lactate dehydrogenase levels > 250U/L; a primary Gleason pattern of 5, and serum albumin levels ≤ 3.7 g/dl, were identified. The prognostic model incorporating these factors showed high predictability and reproducibility in the Validation cohort. The 5-year CSS of the low-risk group was 86% and that of the high-risk group was 22%. Approximately 26.4%, 62.7%, and 10.9% of the patients in the Validation cohort defined as high-risk by the LATITUDE criteria were further grouped into high-, intermediate-, and low-risk groups by the new model with significant differences in CSS. In the ARSIs cohort, high-risk group had a significantly shorter time to castration resistance than the intermediate-risk group., Conclusions: The novel model based on prognostic factors can predict patient outcomes with high accuracy and reproducibility. The model may be used to optimize the treatment intensity of de novo mHSPC., (© 2024. The Author(s).)

Background: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies., Methods: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS)., Results: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone., Conclusions: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose of Review: Adolescents with haematological malignancies within adult services, in the UK from 16 years old, have unique needs and require developmentally targeted services and approaches to care delivery. High-risk intensive treatments are common for this cohort and a better understanding of what individualised supportive and palliative care means in this context is required., Recent Findings: Being known and understood as an emerging adult, with particular recognition of developmental stage, is an essential component of quality measures and underpins the adolescent, and caregiver, experience when faced with an uncertain or poor cancer prognosis (UPCP). Healthcare professionals (HCPs) can experience increased emotional labour and feelings of professional inadequacy when caring for adolescents with UPCP. Therapeutic alliance improves HCPs understanding of optimum individualised care by improving communication and supported decision making. Access to training and support for HCPs is required to address the emotional impact of therapeutic alliance with teenage/adolescent and young adults (T/AYAs) with advanced cancer., Summary: Investment in therapeutic alliance, alongside robust support mechanisms and targeted training, can improve the skills, confidence and wellbeing for HCPs, and can also ensure optimum individualised care for T/AYAs with UPCP. Evidence for optimum care for adolescents with advanced cancer is relatively scarce, especially for younger T/AYAs (16-24) in the UK who sit within adult services. Further evaluation of the impact of current UK expertise, services and programs are needed to inform future development., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Traditionally, meta-analysis of time-to-event outcomes reports a single pooled hazard ratio assuming proportional hazards (PH). For health technology assessment evaluations, hazard ratios are frequently extrapolated across a lifetime horizon. However, when treatment effects vary over time, an assumption of PH is not always valid. The Royston-Parmar (RP), piecewise exponential (PE), and fractional polynomial (FP) models can accommodate non-PH and provide plausible extrapolations of survival curves beyond observed data., Methods: Simulation study to assess and compare the performance of RP, PE, and FP models in a Bayesian framework estimating restricted mean survival time difference (RMSTD) at 50 years from a pairwise meta-analysis with evidence of non-PH. Individual patient data were generated from a mixture Weibull distribution. Twelve scenarios were considered varying the amount of follow-up data, number of trials in a meta-analysis, non-PH interaction coefficient, and prior distributions. Performance was assessed through bias and mean squared error. Models were applied to a metastatic breast cancer example., Results: FP models performed best when the non-PH interaction coefficient was 0.2. RP models performed best in scenarios with complete follow-up data. PE models performed well on average across all scenarios. In the metastatic breast cancer example, RMSTD at 50-years ranged from -14.6 to 8.48 months., Conclusions: Synthesis of time-to-event outcomes and estimation of RMSTD in the presence of non-PH can be challenging and computationally intensive. Different approaches make different assumptions regarding extrapolation and sensitivity analyses varying key assumptions are essential to check the robustness of conclusions to different assumptions for the underlying survival function., (© 2024 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

Several methods in survival analysis are based on the proportional hazards assumption. However, this assumption is very restrictive and often not justifiable in practice. Therefore, effect estimands that do not rely on the proportional hazards assumption are highly desirable in practical applications. One popular example for this is the restricted mean survival time (RMST). It is defined as the area under the survival curve up to a prespecified time point and, thus, summarizes the survival curve into a meaningful estimand. For two-sample comparisons based on the RMST, previous research found the inflation of the type I error of the asymptotic test for small samples and, therefore, a two-sample permutation test has already been developed. The first goal of the present paper is to further extend the permutation test for general factorial designs and general contrast hypotheses by considering a Wald-type test statistic and its asymptotic behavior. Additionally, a groupwise bootstrap approach is considered. Moreover, when a global test detects a significant difference by comparing the RMSTs of more than two groups, it is of interest which specific RMST differences cause the result. However, global tests do not provide this information. Therefore, multiple tests for the RMST are developed in a second step to infer several null hypotheses simultaneously. Hereby, the asymptotically exact dependence structure between the local test statistics is incorporated to gain more power. Finally, the small sample performance of the proposed global and multiple testing procedures is analyzed in simulations and illustrated in a real data example., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Aims: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out., Methods and Results: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively., Conclusions: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has been the subject of much recent debate. The standard approach is a log-rank test and/or a Cox proportional hazards model. Alternative methods have been explored in the statistical literature, such as weighted log-rank tests and tests based on the Restricted Mean Survival Time (RMST). While weighted log-rank tests can achieve high power compared to the standard log-rank test, some choices of weights may lead to type-I error inflation under particular conditions. In addition, they are not linked to a mathematically unambiguous summary measure. Test statistics based on the RMST, on the other hand, allow one to investigate the average difference between two survival curves up to a pre-specified time point τ $$ \tau $$ -a mathematically unambiguous summary measure. However, by emphasizing differences prior to τ $$ \tau $$ , such test statistics may not fully capture the benefit of a new treatment in terms of long-term survival. In this article, we introduce a graphical approach for direct comparison of weighted log-rank tests and tests based on the RMST. This new perspective allows a more informed choice of the analysis method, going beyond power and type I error comparison., (© 2024 John Wiley & Sons Ltd.)

Aims: To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007-2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system., Results: After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72-0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55-0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA., Conclusions: Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting., (© 2024 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Clinical trials involving novel immuno-oncology therapies frequently exhibit survival profiles which violate the proportional hazards assumption due to a delay in treatment effect, and, in such settings, the survival curves in the two treatment arms may have a crossing before the two curves eventually separate. To flexibly model such scenarios, we describe a nonparametric approach for estimating the treatment arm-specific survival functions which constrains these two survival functions to cross at most once without making any additional assumptions about how the survival curves are related. A main advantage of our approach is that it provides an estimate of a crossing time if such a crossing exists, and, moreover, our method generates interpretable measures of treatment benefit including crossing-conditional survival probabilities and crossing-conditional estimates of restricted residual mean life. Our estimates of these measures may be used together with efficacy measures from a primary analysis to provide further insight into differences in survival across treatment arms. We demonstrate the use and effectiveness of our approach with a large simulation study and an analysis of reconstructed outcomes from a recent combination therapy trial., (© 2024 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

G0 arrest (G0A) is widely recognized as a crucial factor contributing to tumor relapse. The role of genes related to G0A in lung adenocarcinoma (LUAD) was unclear. This study aimed to develop a gene signature based on for LUAD patients and investigate its relationship with prognosis, tumor immune microenvironment, and therapeutic response in LUAD. We use the TCGA-LUAD database as the discovery cohort, focusing specifically on genes associated with the G0A pathway. We used various statistical methods, including Cox and lasso regression, to develop the model. We validated the model using bulk transcriptome and single-cell transcriptome datasets (GSE50081, GSE72094, GSE127465, GSE131907 and EMTAB6149). We used GSEA enrichment and the CIBERSORT algorithm to gain insight into the annotation of the signaling pathway and the characterization of the tumor microenvironment. We evaluated the response to immunotherapy, chemotherapy, and targeted therapy in these patients. The expression of six genes was validated in cell lines by quantitative real-time PCR (qRT-PCR). Our study successfully established a six-gene signature (CHCHD4, DUT, LARP1, PTTG1IP, RBM14, and WBP11) that demonstrated significant predictive power for overall survival in patients with LUAD. It demonstrated independent prognostic value in LUAD. To enhance clinical applicability, we developed a nomogram based on this gene signature, which showed high reliability in predicting patient outcomes. Furthermore, we observed a significant association between G0A-related risk and tumor microenvironment as well as drug susceptibility, highlighting the potential of the gene signature to guide personalized treatment strategies. The expression of six genes were significantly upregulated in the LUAD cell lines. This signature holds the potential to contribute to improved prognostic prediction and new personalized therapies specifically for LUAD patients. [ABSTRACT FROM AUTHOR]

Objective: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated. Methods: In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features. Results: An RNA processing-related prognostic risk model based on 10 genes including FXR1, MFAP1, RBM17, SAGE1, SNRPA1, SRRM4, ADAD1, DDX52, ERI1, and EXOSC7 was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8+ T cells and poorer clinical prognosis than the low-risk group. Conclusion: This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers. [ABSTRACT FROM AUTHOR]

Background and aim: Health anxiety is a mental disorder that characterized by an excessive fear about health and physical symptoms. High anxiety in pregnancy is associated with adverse outcomes. The aim of this study was to investigate the effect of prenatal education on health anxiety of primigravid women. Methods: The present study was quasi-experimental study. 122 primiparous pregnant women referred to comprehensive health services Shahrekord (A city in the southwest of Iran) clinics in 2019, after receiving consent to participate in the study, randomly divided into two intervention and control groups. The intervention group participated in 8 sessions (1.5-h), once every 2 weeks, from 20 to 37th weeks of gestation. The health anxiety questionnaire was completed on 20th (before the beginning of the courses), 28th and 37th weeks by two groups. Consequences of pregnancy included weight, Apgar score, delivery type, labor time and first breastfeeding time. SPSS version 16 software was used for data analysis. Results: No significant difference was found type of delivery, gestational age, height, weight, head length, Apgar score, duration of hospitalization and first breastfeeding time. The duration of the active and latent phase of labor was significantly lower and the weight of newborn was significantly higher in the intervention group than the control group (P < 0.05). At 37th week, the scores of illness concern, negative consequence and total health anxiety in the intervention group decreased by 3.42, 0.93 and 4.36 respectively and in control group increased by 2.82, 0.03 and 2.86. Conclusion: Pregnancy educational courses has positive effects on health anxiety, decrease duration of labor time and increased newborn weight. In order to improve the outcome of pregnancy, educational classes during pregnancy should be considered. [ABSTRACT FROM AUTHOR]

Background: Bone metastases can compromise the integrity of the spinal canal and cause epidural spinal cord compression (ESCC). The Spinal Instability Neoplastic Score (SINS) was developed in order to evaluate spinal instability due to a neoplastic process. The SINS has reached wide acceptance among clinicans but its prognostic value is still controversial. The aim was to investigate the correlation between the SINS and ESCC and the association between SINS and ambulation before and survival after surgery. Methods: Correlations were assessed between SINS and grades of ESCC in patients who underwent spine surgery for spinal metastases. CT and MRI were used to calculate SINS and the grades of ESCC respectively. Correlations were analyzed with the Spearman's correlation test. Postoperative survival was estimated with Kaplan-Meier analysis and survival curves were compared with the log-rank test. The Cox proportional hazard model was used to assess the effect of prognostic variables including age, ambulation before surgery, SINS, and the Karnofsky Performance Status (KPS) as covariates. Results: The study included 256 patients (196 men and 60 women) with a median age of 70 (24–88) years. The mean SINS was 10. One hundred fifty-two patients (59%) had lost ambulation before surgery. One hundred and one patients had grades 0–2 and 155 patients had grade 3 according to the ESCC-scale. SINS correlated with the grades of ESCC (p = 0.001). The SINS score was not associated with ambulation before surgery (p = 0.63). The median postoperative survival was 10 months, and there was no difference in postoperative survival between the SINS categories (p = 0.25). The ability to walk before surgery and a high KPS were associated with longer postoperative survival. Conclusion: SINS correlated with grades of ESCC, which implies that higher SINS may be considered as an indicator of risk for developing ESCC. The SINS was not associated with ambulation before or survival after surgery. [ABSTRACT FROM AUTHOR]

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The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold tumor categorization based on the abundance of intra-tumoral immune cells. By incorporating the spatial immune contexture, the tumor immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, the mechanisms underlying these different immune phenotypes are yet to be comprehensively elucidated. In this review, we discuss how tumor cells and the tumor microenvironment interact collectively to shape the immune landscape from the perspectives of tumor cells, immune cells, the extracellular matrix, and cancer metabolism, and we summarize potential therapeutic options according to distinct immunophenotypes for personalized precision medicine. [ABSTRACT FROM AUTHOR]

Background: HIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear. Methods: The expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients' prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy. Results: HIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p<0.01). GSEA analysis demonstrated that the HIGD1B is closely related to cancer formation and advanced pathways. Moreover, patients with high HIGD1B expression exhibited a higher level of Tumor-infiltration immune cells (TIICs) and were more likely to experience immune escape and drug resistance after chemotherapy and immunotherapy. Conclusion: This study explored the potential mechanisms and diagnostic and prognostic utility of HIGD1B in GC, as well as identified HIGD1B as a valuable biomarker and possible therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Introduction: At‐home colorectal cancer (CRC) screening is an effective way to reduce CRC mortality, but screening rates in medically underserved groups are low. To plan the implementation of a pragmatic randomized trial comparing two population‐based outreach approaches, we conducted qualitative research on current processes and barriers to at‐home CRC screening in 10 community health centers (CHCs) that serve medically underserved groups, four each in Massachusetts and California, and two tribal facilities in South Dakota. Methods: We conducted 53 semi‐structured interviews with clinical and administrative staff at the participating CHCs. Participants were asked about CRC screening processes, categorized into eight domains: patient identification, outreach, risk assessment, fecal immunochemical test (FIT) workflows, FIT‐DNA (i.e., Cologuard) workflows, referral for a follow‐up colonoscopy, patient navigation, and educational materials. Transcripts were analyzed using a Rapid Qualitative Analysis approach. A matrix was used to organize and summarize the data into four sub‐themes: current process, barriers, facilitators, and solutions to adapt materials for the intervention. Results: Each site's process for stool‐based CRC screening varied slightly. Interviewees identified the importance of offering educational materials in English and Spanish, using text messages to remind patients to return kits, adapting materials to address health literacy needs so patients can access instructions in writing, pictures, or video, creating mailed workflows integrated with a tracking system, and offering patient navigation to colonoscopy for patients with an abnormal result. Conclusion: Proposed solutions across the three regions will inform a multilevel intervention in a pragmatic trial to increase CRC screening uptake in CHCs. [ABSTRACT FROM AUTHOR]

The synthesis and application of organoselenium compounds have developed rapidly, and chiral organoselenium compounds have become an important intermediate in the field of medicine, materials, organic synthesis. The strategy of developing a green economy is still a challenge in the synthesis of chiral organoselenium compounds with enantioselective properties. This review covers in detail the synthesis of chiral organoselenium compounds from 1979 to 2024 and their application in the fields of asymmetric synthesis and catalysis. [ABSTRACT FROM AUTHOR]

Background: Anticoagulant drugs are a valuable tool for minimizing thrombotic risks in at-risk patients. The purpose of this study is to conduct a literature review highlighting the management of these drugs during daily clinical dental practice. Materials and Methods: We limited our search to English-language papers published between 1 January 1989, and 7 March 2024, in PubMed, Scopus and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "anticoagulant AND dentistry" were used. Results: Twenty-five clinical trials were included for final review from 623 articles obtained from the databases Web of Science (83), PubMed (382), and Scopus (158), eliminating duplicates and 79 off-topic items, resulting in 419 articles after removing 315 entries and confirming eligibility. Overall, these studies support the use of local hemostatic measures to manage the risk of bleeding in patients on anticoagulant therapy undergoing dental procedures and highlight the importance of greater education and collaboration among healthcare professionals. Conclusions: Research and clinical investigation have improved understanding and management of dental procedures in patients undergoing anticoagulant or antiplatelet therapy. Hemostatic agents, clinical protocols, risk factors, and continuous education are essential for navigating the complexities of anticoagulant therapy, ensuring optimal outcomes and enhancing patient well-being. [ABSTRACT FROM AUTHOR]

Mismatch repair proficient (MMRp) tumors of colorectal origin are one of the prevalent yet unpredictable clinical challenges. Despite earnest efforts, optimal treatment modalities have yet to emerge for this class. The poor prognosis and limited actionability of MMRp are ascribed to a low neoantigen burden and a desert-like microenvironment. This review focuses on the critical roadblocks orchestrated by an immune evasive mechanistic milieu in the context of MMRp. The low density of effector immune cells, their weak spatiotemporal underpinnings, and the high-handedness of the IL-17-TGF-b signaling are intertwined and present formidable challenges for the existing therapies. Microbiome niche decorated by Fusobacterium nucleatum alters the metabolic program to maintain an immunosuppressive state. We also highlight the evolving strategies to repolarize and reinvigorate this microenvironment. Reconstruction of anti-tumor chemokine signaling, rational drug combinations eliciting T cell activation, and reprograming the maladapted microbiome are exciting developments in this direction. Alternative vulnerability of other DNA damage repair pathways is gaining momentum. Integration of liquid biopsy and ex vivo functional platforms provide precision oncology insights. We illustrated the perspectives and changing landscape of MMRp-CRC. The emerging opportunities discussed in this review can turn the tide in favor of fighting the treatment dilemma for this elusive cancer. [ABSTRACT FROM AUTHOR]

The role of network metrics in exploring brain networks of mental illness is crucial. This study focuses on quantifying a node controllability index (CA-scores) and developing a novel framework for studying the dysfunction of attention deficit hyperactivity disorder (ADHD) brains. By analyzing fMRI data from 143 healthy controls and 102 ADHD patients, the controllability metric reveals distinct differences in nodes (brain regions) and subsystems (functional modules). There are significantly atypical CA-scores in the Rolandic operculum, superior medial orbitofrontal cortex, insula, posterior cingulate gyrus, supramarginal gyrus, angular gyrus, precuneus, heschl gyrus, and superior temporal gyrus of ADHD patients. A comparison with measures of connection strength, eigenvector centrality, and topology entropy suggests that the controllability index may be more effective in identifying abnormal regions in ADHD brains. Furthermore, our controllability index could be extended to investigate functional networks associated with other psychiatric disorders. [ABSTRACT FROM AUTHOR]

Activating antibody-dependent cellular cytotoxicity (ADCC) by targeting claudin-18 isoform 2 (CLDN18.2) using zolbetuximab, a monoclonal antibody against CLDN18.2, has been considered a promising novel therapeutic strategy for gastric cancer (GC). However, the impact of CLDN18.2 expression on natural killer (NK) cells and monocytes/macrophages—crucial effector cells of ADCC—in GC has not been fully investigated. In the present study, we assessed the impact of CLDN18.2 expression on clinical outcomes, molecular features, and the frequencies of tumor-infiltrating NK cells and macrophages, as well as peripheral blood NK cells and monocytes, in GC by analyzing our own GC cohorts. The expression of CLDN18.2 did not significantly impact clinical outcomes of GC patients, while it was significantly and positively associated with Epstein–Barr virus (EBV) status and PD-L1 expression. The frequencies of tumor-infiltrating NK cells and macrophages, as well as peripheral blood NK cells and monocytes, were comparable between CLDN18.2-positive and CLDN18.2-negative GCs. Importantly, both CLDN18.2 expression and the number of tumor-infiltrating NK cells were significantly higher in EBV-associated GC compared to other molecular subtypes. Our findings support the effectiveness of zolbetuximab in CLDN18.2-positive GC, and offer a novel insight into the treatment of this cancer type, highlighting its potential effectiveness for CLDN18.2-positive/EBV-associated GC. [ABSTRACT FROM AUTHOR]

Background: Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance. Methods: Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses. Results: A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value. Conclusions: Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis. [ABSTRACT FROM AUTHOR]