bluuebunny/crossref_metadata_2025 huggingface dataset:
Using 42 CFR part 2 revisions to integrate substance use disorder treatment information into electronic health records at a safety net health system
Authors: Tillman Alexandra R. , Bacon Emily , Bender Brooke , McEwen Dean , Blum Joshua , Hoag Matthew , Scott Kenneth A. , Everhart Rachel , Hanratty Rebecca , Podewils Laura J. , Close Carolina , Mills John , Davidson Arthur J.
Published: June 2024

Background

Regulations put in place to protect the privacy of individuals receiving substance use disorder (SUD) treatment have resulted in an unintended consequence of siloed SUD treatment and referral information outside of the integrated electronic health record (EHR). Recent revisions to these regulations have opened the door to data integration, which creates opportunities for enhanced patient care and more efficient workflows. We report on the experience of one safety-net hospital system integrating SUD treatment data into the EHR.

Methods

SUD treatment and referral information was integrated from siloed systems into the EHR through the implementation of a referral order, treatment episode definition, and referral and episode-related tools for addiction therapists and other clinicians. Integration was evaluated by monitoring SUD treatment episode characteristics, patient characteristics, referral linkage, and treatment episode retention before and after integration. Satisfaction of end-users with the new tools was evaluated through a survey of addiction therapists.

Results

After integration, three more SUD treatment programs were represented in the EHR. This increased the number of patients that could be tracked as initiating SUD treatment by 250%, from 562 before to 1,411 after integration. After integration, overall referral linkage declined (74% vs. 48%) and treatment episode retention at 90-days was higher (45% vs. 74%). Addiction therapists appreciated the efficiency of having all SUD treatment information in the EHR but did not find that the tools provided a large time savings shortly after integration.

Conclusions

Integration of SUD treatment program data into the EHR facilitated both care coordination in patient treatment and quality improvement initiatives for treatment programs. Referral linkage and retention rates were likely modified by a broader capture of patients and changed outcome definition criteria. Greater preparatory workflow analysis may decrease initial end-user burden. Integration of siloed data, made possible given revised regulations, is essential to an efficient hub-and-spoke model of care, which must standardize and coordinate patient care across multiple clinics and departments.
Opioid-sparing effects of ultrasound-guided erector spinae plane block for video-assisted thoracoscopic surgery: a randomized controlled study
Authors: Xu Huan , Wu Wei , Chen Xue , He Wenxin , Shi Hong
Published: June 2024

Background

The erector spinae plane block (ESPB) is a new analgesic method used in thoracic surgery. However, few studies have characterized their effects on perioperative opioid consumption. We aimed to evaluate the effects of ESPB on perioperative opioid consumption in patients who underwent video-assisted thoracoscopic surgery (VATS).

Methods

This was a randomized, observer-blinded clinical trial at a single-centre academic hospital. Eighty patients were scheduled for thoracoscopic segmentectomy or lobectomy by VATS for lung cancer. Forty participants were randomly assigned to ESPB or control group. All patients received intravenous patient-controlled postoperative analgesia. Perioperative opioid consumption, visual analogue scale (VAS) scores, and adverse events were recorded.

Results

Intraoperative and postoperative opioid consumption and static/dynamic VAS scores were significantly lower in the early hours after VATS in the ESPB group (p < 0.05) than the control group. No significant differences were observed in adverse effects between the two groups.

Conclusions

ESPB reduced intraoperative opioid consumption and early postoperative pain in patients undergoing VATS. Our findings support the view that ESPB is a safe and highly effective option for regional analgesia for VATS.

Trial registration

http://www.chictr.org.cn, ChiCTR1800019335.
C-reactive protein is a predictor for lower-extremity deep venous thrombosis in patients with primary intracerebral hemorrhage
Authors: Wang Gang , Wu Bao-Fang , Zhao Wen-Jun , Hu Wei-Peng , Wang Jia-Yin , Gao Hong-Zhi
Published: June 2024

Objective

Our study aimed to determine whether there exists an association between low-grade systemic inflammation, as measured by serum C-reactive protein (CRP), and the risk of lower-extremity deep venous thrombosis (LEDVT) in patients with primary intracerebral hemorrhage (ICH).

Methods

This observational study was retrospectively conducted on patients with primary ICH who were presented to two tertiary medical centers between January 2021 and August 2022. The primary outcome was detecting LEDVT occurrence within 14 days from the onset of the acute ICH episode. Weighted logistic regression and restricted cubic spline models were employed to estimate the association between CRP and LEDVT following 1:1 propensity score matching (PSM).

Results

Of the 538 patients with primary ICH who met the inclusion criteria, 76 (14.13%) experienced LEDVT. Based on the cut-off levels of CRP measured upon admission from the receiver operating characteristic (ROC) curve, patients with primary ICH were categorized into two groups: (i) CRP < 1.59 mg/L and (ii) CRP ≥ 1.59 mg/L. After 1:1 PSM, the LEDVT events occurred in 24.6% of patients with CRP ≥ 1.59 mg/L and 4.1% of patients with CRP < 1.59 mg/L (P < 0.001). ROC curve revealed the area under the ROC curve of 0.717 [95% confidence interval (CI) 0.669–0.761, P < 0.001] for CRP to predict LEDVT with a sensitivity of 85.71% and specificity of 56.29%. After adjusting for all confounding variables, the occurrence of LEDVT in ICH patients with higher CRP levels (≥ 1.59 mg/L) was 10.8 times higher compared to those with lower CRP levels (95% CI 4.5–25.8, P < 0.001). A nonlinear association was observed between CRP and an increased risk of LEDVT in the fully adjusted model (P for overall < 0.001, P for nonlinear = 0.001). The subgroup results indicated a consistent positive link between CRP and LEDVT events following primary ICH.

Conclusions

Higher initial CRP levels (CRP as a dichotomized variable) in patients with primary ICH are significantly associated with an increased risk of LEDVT and may help identify high-risk patients with LEDVT. Clinicians should be vigilant to enable early and effective intervention in patients at high risk of LEDVT.
Effect of atractylenolide III on zearalenone-induced Snail1-mediated epithelial–mesenchymal transition in porcine intestinal epithelium
Authors: Kim Na Yeon , Kim Myoung Ok , Shin Sangsu , Kwon Woo-Sung , Kim Bomi , Lee Joon Yeop , In Lee Sang
Published: June 2024

Background

The intestinal epithelium performs essential physiological functions, such as nutrient absorption, and acts as a barrier to prevent the entry of harmful substances. Mycotoxins are prevalent contaminants found in animal feed that exert harmful effects on the health of livestock. Zearalenone (ZEA) is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals. Here, we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium.

Results

Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin, which induced Snail1-mediated epithelial-to-mesenchymal transition (EMT). In addition, ZEA induces Snail-mediated EMT through the activation of TGF-β signaling. The treatment of IPEC-J2 cells with atractylenolide III, which were exposed to ZEA, alleviated EMT.

Conclusions

Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epithelial cells and ways to mitigate it.
The relationship between self-regulation, cognitive flexibility, and resilience among students: a structural equation modeling
Authors: Nakhostin-Khayyat Mohammad , Borjali Mahmoud , Zeinali Maryam , Fardi Deniz , Montazeri Ali
Published: June 2024

Background

Cognitive flexibility is an important construct that contributes to one’s own thoughts, behaviors, and feelings to achieve his or her goals. Thus, it could play an essential role in students’ educational achievements. This study aimed to investigate the mediating role of cognitive flexibility in the relationship between self-regulation and resilience among students.

Method

This was a cross-sectional study conducted on a sample of students during the 2022 and 2023 academic years. Students were selected from Tehran and Karaj universities (two metropolitans in central Iran). Data collection instruments included the Bouffard’s Self-Regulation Scale, the Cognitive Flexibility Inventory (CFI), and the Connor-Davidson Resilience Scale (CD-RSC). Subsequently, the data were analyzed using structural equation modeling via SPSS and AMOS software to examine the relationships among variables.

Results

In all 302 students participated in the study. The mean age of students was 25.8 (SD = 4.05) years. The findings indicated that self-regulation had a marked positive direct effect on cognitive flexibility (β = 0.23, p < 0.001), and resilience (β = 0.88, t = 19.50, p < 0.001). Similarly, cognitive flexibility displayed a strong positive influence on resilience (β = 0.1, p < 0.001) it showed an indirect mediating role between self-regulation and resilience (0.02), while resilience demonstrated a negative indirect effect on self-regulation and cognitive flexibility (-0.23). The goodness of fit indices validated the proposed model. Furthermore, the analysis revealed the significance of the final model’s direct path coefficients, underscoring the mediating role of cognitive flexibility between self-regulation and resilience among students.

Conclusion

The findings indicated a pivotal interrelationship among self-regulation, cognitive flexibility, and resilience in students. The significant positive relationship among these constructs underscores the importance of fostering cognitive flexibility practices and self-regulation in educational settings.
A case of successful contribution of therapeutic drug monitoring of valganciclovir as the prophylaxis against cytomegalovirus infection in a lung transplant recipient
Authors: Katada Yoshiki , Umemura Keisuke , Nakagawa Shunsaku , Katsube Yurie , Tsuda Masahiro , Tanaka Satona , Date Hiroshi , Nagao Miki , Terada Tomohiro
Published: June 2024

Background

Ganciclovir and its prodrug, valganciclovir, are first-line agents for cytomegalovirus infection prophylaxis after lung transplantation. Although valganciclovir prophylaxis is known to result in severe leukopenia as an adverse effect, dosage adjustment based on therapeutic drug monitoring (TDM) of ganciclovir concentration is not generally implemented in clinical practice.

Case presentation

In this report, we describe the case of a female in her fifties after lung transplantation who successfully maintained valganciclovir prophylaxis under TDM with a minimal occurrence of severe leukopenia. Valganciclovir administration was initiated at a conventional dose of 450 mg/day on postoperative day 43 but was reduced to 450 mg/2 days on postoperative day 69 because of a decrease in white blood cell count and an increase in trough ganciclovir concentration. Subsequently, the valganciclovir dose adjustment was switched from label-indicated renal function-guided dosing to TDM-based dosing, targeting a trough level of 300–800 ng/mL. This target range was determined through deliberations with infectious disease specialists and pharmacists based on previously reported data. The TDM-based dose adjustment successfully prevented cytomegalovirus reactivation without causing significant adverse effects. Valganciclovir prophylaxis was completed on postoperative day 256, and the patient was transferred to another hospital for rehabilitation.

Conclusions

The findings of the present case suggest that TDM-based dosing could be helpful for clinicians in optimizing the prophylactic administration of valganciclovir in patients undergoing lung transplantation.
The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial
Authors: Huschtscha Zoya , Silver Jessica , Gerhardy Michael , Urwin Charles S. , Kenney Nathan , Le Viet Hung , Fyfe Jackson J. , Feros Simon A. , Betik Andrew C. , Shaw Christopher S. , Main Luana C. , Abbott Gavin , Tan Sze-Yen , May Anthony , Smith Craig M. , Kuriel Vicky , Barnard Jackson , Hamilton D. Lee
Published: June 2024

Background

Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training.

Methods

The primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults. In a randomized, controlled, double-blinded trial, 52 untrained, recreationally active participants aged 18–35 y were allocated to either the PEA or PLA groups. Participants consumed either 2 × 175 mg Levagen + PEA or identically matched maltodextrin capsules during an 8-week period of whole-body resistance training. This trial assessed the pre- to post- changes in total and regional lean body mass, muscular strength (1-RM bench, isometric mid-thigh pull), muscular power [countermovement jump (CMJ), bench throw], pain associated with exercise training, sleep, and wellbeing compared with the PEA or PLA condition.

Results

48 Participants were included in the final intention to treat (ITT) analysis and we also conducted per protocol (PP) analysis (n = 42). There were no significant between-group differences for total or regional lean muscle mass post-intervention. There was a significantly higher jump height (CMJ) at week 10 in the PEA group compared to the PLA (Adjusted mean difference [95% CI] p-value; ITT: − 2.94 cm [− 5.15, − 0.74] p = 0.010; PP: − 2.93 cm [− 5.31, − 0.55] p = 0.017). The PLA group had higher 1-RM bench press post-intervention compared with the PEA group (ITT: 2.24 kg [0.12, 4.37] p = 0.039; PP: 2.73 kg [0.40, 5.06] p = 0.023). No significant treatment effects were noted for any of the other outcomes.

Conclusion

PEA supplementation, when combined with 8 weeks of strength training, did not impair lean mass gains and it resulted in significantly higher dynamic lower-body power when compared with the PLA condition.

Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).
Statin therapy improves outcomes in infective endocarditis: evidence from a meta-analysis
Authors: Yaghoobi Mojtaba Hedayat , Heidari Ehsan , Shafiee Arman , Seighali Niloofar , Maghsoodi Mohammad Reza , Bakhtiyari Mahmood
Published: June 2024

Background

Beyond its ability to decrease cholesterol, statin medication has been proved to have a variety of pleiotropic effects, such as anti-inflammatory and immunomodulatory effects. Statins are an appealing therapeutic option for individuals with infective endocarditis because of these effects, as the condition is linked to a strong inflammatory response.

Methods

A comprehensive search was done in Medline/PubMed, Cochrane database (CENTRAL), and Google Scholar to identify relevant studies reporting outcomes of interest (rate of mortality, intensive care unit admission, and embolic events) comparing those who are on statin therapy to nonusers were included. We performed a random effect meta-analysis to pool each study's individual results.

Results

Three articles were included in the study. The pooled results regarding our primary endpoint showed there was a significant reduction in mortality among statin users in all time points (1-year mortality: OR 0.69, 95% CI 0.61–0.79, I2: 0%; Chi2 = 0.01; p < 0.0001). Meta-analysis for the secondary outcome showed statin users are less frequently admitted to the intensive care unit (OR 0.73, 95% CI 0.59–0.90, I2: 0%; Chi2 = 0.00; p = 0.0004). The rate of mortality was significantly lower for those with a previous history of cerebrovascular disease who were on statin therapy compared to those without cerebrovascular diseases (CVD).

Conclusions

The results of the present study support a significant association with statin therapy as a potential treatment proposed for individuals at risk of infective endocarditis.
When Bad News Comes Through the Portal: Strengthening Trust and Guiding Patients When They Receive Bad Results Before Their Clinicians
Authors: Salmi Liz , Hubbard Joleen , McFarland Daniel C.
Published: June 2024

Communication in oncology was challenging long before the emergence of the US 21st Century Cures Act. Before 2021, a growing body of evidence had demonstrated the benefits of patients' access to and review of the clinical notes in their charts (open notes); however, studies examining the benefits of immediate access to test results were scarce until the implementation of the Cures Act's Information Blocking Rule. Individuals grappling with cancer today now possess immediate access to their laboratory results, imaging scans, diagnostic tests, and progress notes as mandated by law. To many clinicians, the implementation of the Cures Act felt sudden and presented new challenges and concerns for oncologists surrounding patients' potential emotional reactions to medical notes or lack of control over the careful delivery of potentially life-changing information. Despite data that show most patients want immediate access to information in their records before it is communicated directly by a health care professional, surveys of oncologists showed trepidation. In this chapter, perspectives from a patient with cancer, an oncologist, and a cancer psychiatrist (in that order) are shared to illuminate the adjustments made in clinician-patient communication amid the era of nearly instantaneous results within the electronic health record.
Endometrial cancer and obesity trends in the United States in the 21st century.
Authors: Francoeur Alex Andrea , Liao Cheng-I , Chang Jenny , Johnson Caitlin Ruth , Clair Kiran , Tewari Krishnansu Sujata , Kapp Daniel Stuart , Chan John K , Bristow Robert E.
Published: June 2024

5507

Background: Using two comprehensive national databases, we explore trends in obesity and endometrial cancer rates in the United States. Methods: Data on endometrial adenocarcinoma were obtained from the United States Cancer Statistics (USCS) from 2001-2018 and corrected for hysterectomy and pregnancy using Behavioral Risk Factor Surveillance System data. Data on obesity was collected from the National Health and Nutrition Examination Survey (NHANES) database from 1988-2018. Average annual percentage changes (AAPC) were used to describe trends. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used for statistical analysis. Results: Using USCS data, 615,656 cases of endometrial adenocarcinoma were identified from 2001-2018. The annual increase in endometrial cancer is as follows: Hispanic 1.37% (p<0.0001), Black 1.30% (p<0.0001), and White: -0.17 (p=0.656). Women aged 20-29 have a 4.48% annual increase (p<0.0001) and women aged 30-39 have a 3.00% annual increase (p<0.0001). On intersection analysis, Hispanic women have the largest rate of increase in the 30-39 age group at 4.67% (p<0.0001), followed by Black women, 3.85% (p<0.0001), and White women 2.12% (p=0.02). In the 20-29 age group, rates of endometrial adenocarcinoma are increasing in White women at 4.79% (p<0.0001) and in Hispanic women 4.29% annually (p<0.0001) (Table). Using the NHANES data, the prevalence of obesity in 2018 in adult women is as follows: Black 56.8%, Hispanic 44.1%, and White 40.9%. Rates of obesity for all women are rising 4.6% yearly since 1988 (p<0.05). Class III obesity rates are rising at 9.19% annually (p<0.05). When looking at trends by age, the 20–29 year old women have the highest annual rise in obesity compared to other age groups (AAPC 7.36%, p<0.05). Rates of Class III obesity are increasing at the highest rate in this group as well (AAPC 14.22%, p<0.05). In the 30–39 year old age group, Class III obesity has been increasing 9.48% annually, p<0.05. Conclusions: The current data demonstrate a temporal association between the increasing incidence of endometrial cancer and obesity, and this effect disproportionately impacts younger women and women of color. While additional research is required to confirm a causal relationship, these data warrant targeted health services and public health interventions to stabilize and ultimately reverse the concomitantly rising rates of obesity and endometrial cancer. [Table: see text]
Pelvic ultrasound-based deep learning models for accurate diagnosis of ovarian cancer: Retrospective multicenter study.
Authors: Cho Hyun-Woong , Lee Sanghoon , Hong Jin Hwa , Kim Seonkyung , Song Jaeyun , Lee Jae Kwan
Published: June 2024

5543

Background: Although pelvic ultrasound is useful modality to diagnose ovarian cancer, there is few studies to evaluate the performance of deep learning model. Development of deep learning based on aggregating ultrasound images and clinical information such as age and CA-125 data might be beneficial to differentiated malignancy from benign ovarian cyst. The objective of this study is to build a deep learning model with advanced accuracy of differential diagnosis between malignant and benign lesions of ovary. Methods: Pelvic ultrasound images, information of age and ca-125 level at diagnosis from patients diagnosed with ovarian cancer or benign cyst during 2015-2022 were retrieved. The images were segmented into cystic and solid component and processed data for feature extraction. For convolutional neural network model development, patients were assigned to training dataset (565 patients), validation dataset (76 patients), and test dataset (163 patients). After feature extraction using this convolutional neural network, we also used age and tumor marker to classify these images as either malignant or benign. Using these datasets, we assessed the diagnostic value of the deep learning model. A new AI model to utilize image feature and clinical information together was developed. This model separates feature extractor and classifier from the architecture of conventional AI models, and the classifier receives clinical information data in addition to image information. ResNet50 and DenseNet121 were used in the conventional AI model. Results: In total, 804 patients who had ovarian tumors were included; 446 benign and 358 malignant. When pelvic ultrasound image of ovary was only used, ResNet50 showed AUC of 0.84 and DenseNet121 had AUC of 0.82 for this model to detect ovarian cancer. However, when segmented solid portion image and clinical data was combined with the ovary image, ResNet50 showed AUC of 0.95 and DenseNet121 had AUC of 0.96 for this model to detect ovarian cancer. Using the test data set, ResNet50 and DenseNet121 had sensitivities of 90% and 81%, specificity of 93% and 97%, positive predictive value of 92% and 95%, and negative predictive value of 92% and 86% to detect ovarian cancer, respectively. Conclusions: Binary classification model based on deep learning algorithms using pelvic ultrasound images can distinguish between benign and malignant ovarian tumors accurately. Segmentation of solid portion and clinical information of age and CA-125 at diagnosis combined with the pelvic ultrasound images increased the accuracy of the classification model.
Efficacy, safety, and biomarkers of neoadjuvant niraparib monotherapy in homologous recombination deficiency (HRD) advanced ovarian cancer: A prospective, multicenter, phase II, single-arm NANT study.
Authors: Gao Qing-lei , Liu Dan , Li Huayi , Zhang Wei , Wang Ping , Li Jundong , Shan Wanying , Liu Ronghua , Chen Gang , Wu Mingfu , Li Xiao , Liu Cheng , Yin Rutie , Zhou Shengtao , Li MaoMao , He Shanyang , Zhao Guangnian , Song Kun , Hong Li , Ma Ding
Published: June 2024

5549

Background: The efficacy of PARP inhibitors as neoadjuvant therapy and its clear association with tumor microenvironment (TME) status remain enigmatic. Here, for the first time, we reported the efficacy and safety of niraparib monotherapy, an oral low-toxicity PARP inhibitor, as the neoadjuvant therapy in patients (pts) with HRD high-grade serous ovarian cancer (HGSOC), and directly linked pre-treatment TME components with response using cutting-edge technologies. Methods: Treatment-naïve pts with newly diagnosed advanced unresectable HGSOC and those who could not endure primary debulking surgery were enrolled to receive laparoscopic biopsies. TME landscape was profiled by single-cell RNA sequencing and multiplex immunohistochemistry. Pts with HRD ( BRCA1/2 mutations and/or genomic instability score ≥ 42) HGSOC received daily oral niraparib for two 28-day cycles. Pts with complete response, partial response (PR), or stable disease (SD) received interval debulking surgery (IDS). The co-primary endpoints were objective response rate (ORR) and R0 resection rate. Results: Between January 18, 2021 and July 18, 2023, 127 pts from six centers were screened for eligibility. Totally, 67 HRD pts received neoadjuvant niraparib monotherapy, 48 pts completed response evaluations, and 40 pts underwent IDS. Thirty pts achieved PR and 12 pts reached SD, resulting in an ORR of 62.5% and a disease control rate (DCR) of 87.5%. BRCAm pts exhibited improved responses with increased ORR (77.3%) and DCR (100.0%). For surgical outcomes, 80.0% of pts achieved R0 resection and 95.0% of pts accomplished optimal debulking. Treatment-related adverse events (TRAEs) of grade ≥3 were observed in 61.2% of pts and hematological toxicities were the most common. No fatal TRAEs were reported. Co-enrichment of MRC1+ macrophages, effector regulatory T cells, and myofibroblastic cancer-associated fibroblasts were associated with lack of response. Conclusions: Neoadjuvant niraparib monotherapy regimen achieved encouraging ORR and R0 resection rate with tolerable toxicities in pts with HRD unresectable HGSOC, offering an alternative option for those pts unwilling to receive or unable to tolerate neoadjuvant chemotherapy. Pre-treatment TME factors were correlated with clinical response to PARP inhibitors. Clinical trial information: NCT04507841 . [Table: see text]
Outcomes of reduced dosing of lenvatinib with pembrolizumab for advanced endometrial cancer.
Authors: Ta Quang Dang , Do Connie , Sharma Kavita , Sorooshian Hormozan , Cushing Merta , Shah Nina , Bookman Michael A. , Kavecansky Juraj , Niu Fang , Hui Rita L.
Published: June 2024

5588

Background: The advent of immunotherapy combined with multitargeted tyrosine kinase inhibitors has significantly improved the treatment of platinum-resistant endometrial cancer (EC). The phase three 309–KEYNOTE-775 trial demonstrated a survival benefit with lenvatinib/pembrolizumab in patients with mismatch repair-proficient (pMMR) advanced EC. However, lenvatinib was discontinued in 31% of patients and dose reduced in 67% due to adverse events (AE). Retrospective reports suggest that reduced dosing for lenvatinib may result in fewer dose reductions, longer time to treatment-related toxicity, and better tolerability without compromising effectiveness. Methods: This multisite, retrospective, cohort study evaluated various dosing strategies of lenvatinib in Kaiser Permanente (KP) California patients treated with lenvatinib/pembrolizumab for pMMR advanced EC between September 1, 2019 and June 30, 2023, and followed through end of membership, December 31, 2023, or death, whichever occurred first. Patients were grouped based on their initial lenvatinib dose: 20 mg daily (Group 1), <20 mg daily (Group 2), and 20 mg daily 5 of 7 days per week (Group 3). The primary outcome was 6-month progression-free survival (PFS); secondary outcomes included incidence rate of lenvatinib dose discontinuation or dose reduction due to AE. Primary analysis of outcomes was performed between Groups 1 and 2; Group 3 was described but not compared to other groups due to small sample size. Results: A total of 369 patients were included in this study (Group 1, n=204; Group 2, n=154; Group 3, n=11). Baseline characteristics were similar between all three groups with mean age of 66.6 ± 9 years; mean body mass index of 29.6 ± 8 kg/m2; and median number of prior lines of systemic therapy of 1 (IQR 1-2). There was no difference in PFS at 6 months between Groups 1 and 2 (40.2% and 33.8%, respectively; p=0.26). There was no difference between Groups 1 and 2 in the rate of lenvatinib discontinuation due to AE (7.2 and 6.6, respectively, per 100 person-year; p=0.61). However, a significantly higher incidence in dose reduction was found in Group 1 when compared to Group 2 (28.1 vs 14.3 per 100 person-year; p<0.01). Conclusions: A lower lenvatinib starting dose (<20 mg daily) in combination with pembrolizumab was no different to the FDA-approved daily dose of 20 mg for the treatment of advanced EC with respect to 6-month PFS. In addition, those who received a lower starting dose experienced fewer dose reductions but no difference in dose discontinuation due to AE. Prospective studies of dose and schedule are needed to confirm these findings and define an optimal dosing strategy.
Germline genetic profiles of women with uterine cancer: A Myriad Collaborative Research Registry study.
Authors: Johnson Caitlin Ruth , Aryasomayajula Chinmayi , Francoeur Alex Andrea , Stewart Chelsea , Kapp Daniel Stuart , Chan John K
Published: June 2024

5617

Background: To compare uterine cancer patient characteristics and genetic mutational profiles by age and self-identified ancestry. Methods: Data on uterine cancer patients who had germline, MyChoice, and/or Precise testing were collected from the Myriad Collaborative Research Registry. Mutations in genes of interest were obtained from TAPUR studies currently under enrollment. Graph Pad Prism v 10.1.1 was utilized for statistical calculations. Results: Of the 38,133 uterine cancer patients, 42.8% were diagnosed at <50 years (younger) and 57.2% at ≥50 years (older). Approximately, 77.1% identified as Non-Hispanic White (NHW), 7.0% as Non-Hispanic Black (NHB), 2.2% as Hispanic, and 3.7% as Non-Hispanic Asian/Pacific Islander (NHAPI). Approximately 29.1% patients had germline Lynch gene mutations with 16.5%, 28.8%, 36.1%, and 18.4% occurring in MLH1, MSH2, MSH6, and PMS2, respectively (p<0.001). Younger patients were more likely to have Lynch syndrome (9.6% vs 7.5%; p<0.001) and MLH1 (1.2% vs 0.8%; p<0.001) or MSH2 (3.1% vs 1.5%; p<0.0001) mutations compared to older patients. Regarding race, MLH1 mutations were found in 5.2% of NHW and NHAPI, 4.9% of Hispanics, and 2.2% of NHB (p<0.001). MSH2 mutations were most common among NHAPI (9.8%) and NHW (9.7%) followed by Hispanics (5.8%) and NHB (3.2%; p<0.001). MSH6 mutations were most common in NHW (12.8%) vs Hispanics (6.5%), NHAPI (6.3%), or NHB (4.5%; p<0.001). PMS2 mutations were highest among NHW (5.8%) followed by Hispanics (4.7%), NHAPI (4.4%), and NHB (2.9%; p=0.004). There were no differences in TMB (p=0.07), PDL1 (p=0.16), or MSI status (p=0.13) by age; however, younger patients had more HRD positivity (37.8% vs 30.9%; p<0.0001) vs the older group. Regarding race, 50.0% of NHAPI, 36.9% of NHW, 30.8% of Hispanic, and 11.6% of NHB patients had high TMB (p=0.004). There were no significant differences in tumor HRD status (p=0.3), MSI status (p=0.3), or PDL1 positivity (p=0.4) by racial group. Additionally, 6.8%, 6.6%, 6.3%, and 4.4% of Hispanics, NHW, NHAPI, and NHB were BRCA positive. BRCA2 mutations were more present among Hispanics (4.2%) vs NHW (3.7%), NHAPI (3.4%), and NHB (2.3%; p=0.02). There were no differences in BRCA1 (p=0.3) or PTEN (p=0.8) mutations by racial group. Hispanic patients had the most germline p53 mutations (2.0%) followed by NHAPI (1.5%), NHW (1.4%), and NHB patients (0.7%; p=0.01). PDL-1 inhibitors may be useful among NHB based on germline POLE mutations (4.3%) vs NHW (1.2%), Hispanic (1.1%), and NHAPI patients (0.8%; p<0.001). Conclusions: There are significant differences in germline testing results for women with uterine cancer by race/ethnicity and age, especially in Lynch genes which has implications for immunotherapy eligibility in the advanced and recurrent setting. Further work must be done to identify targetable mutations in minority populations.
Safety and efficacy profile of belzutifan, a hypoxia-inducible factor-2α inhibitor, in patients with renal cell carcinoma: Meta-analysis and systematic review.
Authors: Shafique Nouman , Javeed Zainab , Bajwa Shammas , Ghaffar Umar , Muhibullah - , Ahmed Jawad , Zain Sarmad , Kaur Navneet , Ghaffar Ali , Kunwar Digbijay , Farooqui Sabeeh , Iqbal Abdul Ghani , Naqvi Syed Mujtaba Ali , Qadeer Abdul , Ehsan Amna , Shafiq Iqra , Shafique Adeena , Rizwan Umer , Hussain Rida , Lohana Abhi
Published: June 2024

e16531

Background: Hypoxia-inducible Factor-2α (HIF-2α) is a transcription factor that accumulates in clear cell renal cell carcinoma (ccRCC) and is responsible for genes involved in oncogenesis. Belzutifan is a HIF-2α inhibitor that has shown promising anti-tumor effects in patients with ccRCC. Our objective is to summarize the available literature on the safety and efficacy profile of the drug. Methods: An electronic search was conducted on PubMed, Embase, and Cochrane from inception till January 31st, 2024. We identified patients aged ≥ 18 years with ccRCC who received Belzutifan. We extracted data on objective response rate, complete response rate, any grade adverse effect (AE) and grade ≥3 AE. Data was analyzed using R (v.4.3) and reported as proportions with respective 95% confidence intervals (CI) on forest plots. Results: Three studies (n=168 patients) were identified that reported the use of Belzutifan in ccRCC. Our analysis showed that pooled proportion of objective response rate and complete response rate was 35% (95% CI: 24% – 47%) and 1% (95% CI: 0% – 5%) respectively. Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 98% (95% CI: 95% – 99%) and 49% (95% CI: 29% – 69%) respectively. Conclusions: Belzutifan is a novel drug that inhibits HIF-2α which in turn results in anti-tumor effects of the drug against ccRCC. The drug has an acceptable safety and efficacy profile from limited data but more studies are needed to establish a complete picture of drug’s adverse effects and clinical benefits. Pooled proportion of patients developing (A) Objective Response, (B) Complete response (C) Any adverse effect and (D) Grade ≥3 adverse effects. [Table: see text]
Association of body mass index (BMI) with survival outcomes in patients with metastatic renal cell carcinoma (mRCC).
Authors: Goswamy Rohit Vivek , Yildirim Ahmet , Choi Yujin , Wei Mengting , Liu Yuan , Brown Jacqueline T , Nazha Bassel , Martini Dylan J. , Hartman Caitlin , McClintock Greta Russler , Zhuang Tony , Kissick Haydn , Harris Wayne Bernard , Carthon Bradley Curtis , Kucuk Omer , Master Viraj A. , Bilen Mehmet Asim
Published: June 2024

e16535

Background: Recent data have reported on obesity as a probable protective factor in metastatic RCC (mRCC). Current knowledge and expanding data suggests a higher BMI (overweight and obese patients) have better survival outcomes. We hypothesize that mRCC patients studied at our institution, Emory’s Winship Cancer Institute, will display similar clinical outcome trends. Methods: We conducted a retrospective analysis of patients with mRCC treated at Winship Cancer Institute between 1/1/2018 and 8/31/23. Overall survival (OS) and progression-free survival (PFS) were defined as months from treatment initiation to death or clinical/radiographic progression, respectively. The correlation between BMI and OS/PFS was studied in 399 patients diagnosed with metastatic RCC under systemic therapy. The groups were divided into overweight and obesity (BMI > 25 kg/m2) and underweight or normal (BMI < 25 kg/m2). Univariate (UVA) and multivariate (MVA) analyses were carried out for OS and PFS using Cox proportional hazard model. Results: A total of 401 eligible patients were included with a median follow up of 60 months. Median age was 66 years (range = 18-95), 71% were male, 29% were female, and 81% had clear cell histology. 36% received checkpoint inhibitor (CPI) monotherapy, 28% received combination CPI, and 26% received CPI in combination with tyrosine kinase inhibitor (TKI). 4% received other therapies. Lower BMI (<25) at initiation of systemic therapy was significantly associated with worse OS and PFS (table). Conclusions: Lower BMI at baseline and during therapy was associated with worse clinical outcomes. This helps validate the association between obesity and improved survival, a potential "obesity paradox." Results should be validated in a larger, prospective study to further understand the complex relationship between BMI, lipid metabolism, and clinical outcomes in mRCC. [Table: see text]
Incidence and outcomes of thromboembolic events in renal cancer related hospitalization in the United States: A propensity matched national study.
Authors: Sultan Muhammad , Kumar Manoj , Farooq Faryal , Afzal Muhammad Sohaib , Nasir Bilal , Byreddi Laxman Yashwant , Atluri Sundeep , Devarkonda Vishal , Ali Shafaqat
Published: June 2024

e16544

Background: Venous thromboembolic events (VTE) are a significant cause of morbidity and mortality in cancer patients. We aim to investigate the incidence and outcomes of acute DVT and PE in renal cancer compared to all other malignancies. Methods: The National Readmission Database (2016-2020) was queried to identify all-cause admissions for patients with any active malignancy. Cohorts were divided into renal cancer vs other cancers. A Propensity Score Matching (PSM) model matched both cohorts. Multivariate regression & Mahalanobis distance propensity matching were used to compare incidence rates and outcomes. Results: Among 1.2 million all-cause hospitalizations of patients with renal cancers, about 3.8% suffered an acute VTE. The majority had DVT (1.8%), followed by PE (1.4%) & DVT with PE (0.6%). On a propensity-matched & multivariate analysis, patients with renal cancers have a lower incidence of DVT (2.1% vs 2.8%, aOR: 0.76) & DVT with PE (0.7% vs 1%, aOR: 0.73) [p <0.001] as compared to other malignancies. Interestingly, rates of acute PE are similar to other malignancies (p>0.05). Among VTEs, acute PE was associated with the highest mortality (aOR: 3.17), followed by DVT with PE (aOR: 2.52) & DVT (aOR: 2.15) [p <0.001]. Resource utilization is also higher in renal cancers complicated by VTE, with patients suffering a DVT having the highest LOS (8 vs 3 days) & total cost of hospitalization ($24,403 vs $16,628) [p<0.001] followed by DVT with PE and only PE [p<0.05]. Interestingly, readmission rates are similar in patients with different VTEs (DVT, PE, or DVT with PE, p >0.05). Conclusions: Hospitalizations in renal cancers were less frequently complicated by venous thromboembolism as compared to other malignancies. Mortality was highest for PE while resource utilization was highest for the DVT group.
Kidney outcomes in patients with bladder cancer: Insights from real-world data—A National Inpatient Sample (NIS) study, 2020.
Authors: Tanariyakul Manasawee , Saowapa Sakditad , Polpichai Natchaya , Wannaphut Chalothorn , Yingchoncharoen Pitchaporn , Thongpiya Jerapas , Siladech Pharit , Olavarria Bernal Diego Alonso , Chaisrimaneepan Nattanicha , Dejthevaporn Thitiya Sirisinha , Wattanachayakul Phuuwadith
Published: June 2024

e16622

Background: Bladder cancer constitutes a notable etiological factor in kidney disease, precipitating acute kidney injuries (AKI) through mechanisms such as post-renal obstruction, with the potential for progression to chronic kidney disease (CKD) over time. The objective of this study is to systematically evaluate the correlation between bladder cancer and the manifestation of acute or chronic kidney disease across various stages, with a focus on hospitalized patients undergoing treatment for bladder cancer. Methods: The 2020 United States National Inpatient Sample (NIS) database was subjected to analysis in this study. We focused on adult patients (≥18 years) with a primary discharge diagnosis of bladder cancer, specifically those who were hospitalized for cancer and presented with a diagnosis of acute kidney injury or diverse stages of chronic kidney disease, as identified through pertinent ICD-10 CM codes. Utilizing survey multivariable logistic and linear regression analysis, we calculated adjusted odds ratios (ORs) to assess the outcomes of interest. A p-value of <0.05 was deemed statistically significant in this analytical framework. Results: In 2020, 81,995 eligible patients were identified, with 75.62% being male. The ethnic distribution was 81% Caucasian, 8% Black, 5% Mexican American, and 2% Asian. Using a multivariable regression model adjusting for patient and hospital-level factors, bladder cancer showed a significant association with acute kidney injury (OR 1.92, 95% CI: 1.85-2.00, P < 0.001) and all stages of chronic kidney disease (OR 1.66, 95% CI: 1.58-1.74, P < 0.001). Further analysis revealed no significant association with early CKD stages 1 and 2 (P = 0.25 and 0.26), but a notable association with increased risk for CKD stages 3 and 4 (OR 1.45, 95% CI: 1.37-1.52, P < 0.001) and (OR 1.69, 95% CI: 1.56-1.83, P < 0.001), respectively. Intriguingly, bladder cancer displayed a negative association with CKD stage 5 (OR 0.76, 95% CI: 0.63-0.78, P < 0.001). Conclusions: In summary, our study reveals that bladder cancer in hospitalized cancer patients is linked to increased risks of acute kidney injury (AKI), CKD stages 3 and 4, and a decreased risk of CKD stage 5. Vigilant kidney function monitoring is crucial during cancer hospitalization, given the elevated risk of worsening function. Proactive interventions are necessary to address kidney-related complications. Further longitudinal cohort studies are warranted to enhance our understanding and devise strategies to reduce the risk of CKD in individuals with bladder cancer.
Chemotherapy plus PD-1/PD-L1 inhibitor versus chemotherapy alone in first-line treatment for recurrent or advanced endometrial cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: de Liz Caio Dabbous , Maia Melissa , Alves Ana Caroline Fonseca , Silva Isadora Mamede Mendes da , Oliveira João Pedro , Oliveira Audrey Cabral Ferreira de
Published: June 2024

e17597

Background: More recently, the standard of care for primary advanced or recurrent DNA mismatch repair deficient (MMRd)/microsatellite instability-high (MSI-H) endometrial carcinoma has become a combination of chemotherapy (CT) and PD-1/PD-L1 inhibitor. Whether this should also be applied to all-comers and MMRp/MSS population is still an open question. Methods: PubMed, Embase, and Cochrane database were searched for randomized controlled trials (RCTs) comparing first-line CT plus PD-1/PD-L1 inhibitor versus CT, with or without (w/w) placebo, for patients with primary advanced or recurrent endometrial cancer. The primary endpoints of interest were progression free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and adverse events (AE) grade ≥ 3. Heterogeneity was examined with I2 statistics, and a fixed-effects model was employed for analysis. Statistical analysis was performed using Review Manager Web. Results: We included 5 RCTs with 2460 patients, of whom 1143 (46.5%) received CT plus PD-1/PD-L1 inhibitor, and 1672 (68.0%) had MMRp/MSS tumors. Mean follow-up ranged from 7.9 to 28.3 months. The combination of CT plus anti-PD-1/PD-L1 demonstrated superiority in PFS (HR 0.72; 95% CI 0.65-0.80; p < 0.0001) and OS (HR 0.77; 95% CI 0.65-0.91; p=0.002), compared to CT w/w placebo in the all-comer population. In MMRd/MSI-H patients, PFS (HR 0.34; 95% CI 0.27-0.44; p < 0.00001) and OS (HR 0.37; 95% CI 0.24-0.59; p < 0.0001) were statistically significantly better in combination group. For patients with MMRp/MSS disease, PFS was improved (HR 0.76; 95% CI 0.68-0.86; p < 0.0001), but OS was not significantly different between groups (HR 0.92; 95% CI 0.74-1.14; p=0.44). CT plus PD-1/PD-L1 inhibitor also led to a higher ORR (OR 1.50; 95% CI 1.13-2.00; p=0.006) and CRR (OR 1.56; 95% CI 1.12-2.18; p=0.009) in MMRp/MSS patients. AE grade ≥ 3 were more often when immune checkpoint inhibitor was added (HR 1.46; 95% CI 1.23-1.75; p < 0.0001). Conclusions: These findings suggest that combining PD-1/PD-L1 inhibitor to CT improves PFS, but not OS, in first-line treatment for recurrent or advanced MMRp/MSS endometrial cancer, despite grater toxicity. It supports the hypothesis that the benefit seen in survival for all-comer population appears to be driven by MMRd/MSI-H patients. However, given the immaturity of OS data, it is possible that the higher rate of complete responses may translated into more cured patients in long-term follow-up.
Predictive analysis of placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) using machine learning.
Authors: Alenezy Abdalwahab , Alshwayyat Sakhr Abdulsalam , Alshwayyat Mustafa , Alshwayyat Tala Abdulsalam
Published: June 2024

e17608

Background: The characteristics and outcomes of PSTT and ETT have not been well documented. To improve personalized care, machine learning was used to assess treatment effectiveness and develop accurate prognostic models. Gestational choriocarcinoma (GCC) was used as a control to emphasize the clinical features of PSTT and ETT. Methods: The Surveillance, Epidemiology, and End Results database provided the data used for this study’s analysis (2000–2019). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or other concurrent malignancies, or unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: The study population comprised 725 patients. Among them, 139 patients had ETT, 107 had PSTT, and 479 had GCC. The median patient age was 37 years. Most of the patients were of white race (62.3%) and more than half were married (52.7%). The most common stage of primary tumor histology was distant metastasis, which occurred in 330 patients. The average tumor size was 6.13 cm. More than two-thirds of patients underwent chemotherapy (75.9%), 57.9% underwent surgery, and 4.3% underwent radiotherapy. There were no significant differences in survival between the different tumor groups. Multivariate Cox regression analysis revealed that older age, marital status, metastasis, and radiotherapy were poor prognostic factors, while surgery was a good prognostic factor. ML models revealed that the random forest classifier (RFC) accurately predicted the outcomes. The most important characteristics that influenced the model prediction performance were tumor size, years of diagnosis, race, and age. The performance metrics for all ML algorithms are summarized in Table. Conclusions: Our research sheds light on crucial aspects of clinical decision-making, emphasizing the significance of key factors affecting patient outcomes and offering hope for personalized treatment. Further research should explore the molecular markers and validate the generalizability of our findings. [Table: see text]