bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splenic artery aneurysm rupture in a pregnant woman with hepatosplenic schistosomiasis: case report and literature review
Authors: Razafindrazoto Chantelli Iamblaudiot , Randrianiaina Antsa Fihobiana , Ralaizanaka Behoavy Mahafaly , Rakotoniaina Henintsoa , Randriamifidy Nitah Harivony , Rasolonjatovo Anjaramalala Sitraka , Rakotozafindrabe Andry Lalaina Rinà , Rabenjanahary Tovo Harimanana , Razafimahefa Soloniaina Hélio , Ramanampamonjy Rado Manitrala 
Published: January 2024

Abstract
Background
Pregnancy is not uncommon in patients with non-cirrhotic portal hypertension. Rupture of a splenic artery aneurysm remains a rare complication, associated with a very poor maternal–fetal prognosis. Our aim is to report a case of ruptured splenic aneurysm and to show the maternal–fetal over-risks during the association of pregnancy and portal hypertension, even in non-cirrhotic patients.

Case presentation
We report a case of a 34-year-old woman, pregnant at 24 weeks gestation, with non-cirrhotic portal hypertension due to hepatic schistosomiasis. She was hospitalized for variceal bleeding. Patient had undergone endoscopic variceal band ligation and no bleeding recurrence. An unexplained hypovolemic shock appeared during the hospitalization with the occurrence of an in utero fetal death. The fetus was delivered by vaginal delivery. Abdominal CT scan angiogram showed a splenic artery aneurysm rupture. The patient underwent an emergency laparotomy with ligation of the splenic artery associated with splenectomy. Postoperative course was simple. Management of portal hypertension was continued at discharge (diuretic, beta-blockers, and esophageal varices ligation).

Conclusion
The association of pregnancy and portal hypertension remains a serious situation with a high risk of maternal–fetal complications. Splenic artery aneurysm rupture is one of the rare complications of this association with a very poor maternal–fetal prognosis. Open repair is the surgical treatment of choice with a non-negligible morbi-mortality.
Assessment of potential drug–drug interaction knowledge, attitude, and practice among Egyptian hospital and community pharmacists: a cross-sectional multicenter study
Authors: Wahsh Engy A. , Warda Ahmed E. Abou , Abdallah Mahmoud S. , Elsayed Aya , Daiem Yasser Soliman Abdel , Sadek Eman Mohamed 
Published: January 2024

Abstract
Background
Pharmacists have an important role in preventing prescribing errors and providing appropriate information. They can detect potential drug–drug interactions (DDIs), which are associated with a more extended hospital stay and higher medical costs that lead to substantial financial burdens on healthcare systems. This study aimed to evaluate and assess the knowledge of community and hospital pharmacists toward drug–drug interaction and their attitude and motivation to find DDI information, in addition to identifying the pharmacist factors affecting this knowledge. A cross-sectional multicenter study was conducted using a self-administered questionnaire. Nineteen drug pairs, that are common in clinical practice, were evaluated. This study aimed to evaluate and assess the knowledge of community and hospital pharmacists toward drug–drug interaction and their attitude and motivation to find DDI information, in addition to identifying the pharmacist factors affecting this knowledge.

Results
A total of 4363 pharmacists (2260 community pharmacists and 2103 hospital pharmacists) have completed the survey. The participants' knowledge of DDIs was 58.25%, and there was no significant difference in pharmacist knowledge between community and hospital pharmacists (p = 0.834). The highest correct answer was for sildenafil and isosorbide mononitrate pair 78.8%. The most used source of information was the internet or mobile applications, 47.1%. Participants who always considered PDDIs while prescribing detected more drug interactions than those who did not (p = 0.001).

Conclusion
According to the findings of this study, community and hospital pharmacists had comparable knowledge of DDIs. However, before dispensing uncommon prescriptions, they should consult evidence-based drug information resources and DDI software to identify potential drug interactions.
Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with penile squamous cell carcinoma.
Authors: Patel Mukti , Tan Alan 
Published: January 2024

11 Background: Penile squamous cell carcinoma (SCC) is an extremely rare, aggressive disease, representing 0.4-0.6% of all malignancies in males in the U.S. and Europe. Early diagnosis is imperative, as lymphatic spread is associated with a dismal prognosis. The estimated 5-year survival rate in patients with pelvic lymph node involvement is 0%. Moreover, there are limited treatment options that carry significant toxicity risks. Accurate biomarkers to evaluate treatment response and guide treatment to improve outcomes are needed. Molecular residual disease monitoring with circulating tumor DNA (ctDNA) may be helpful in these scenarios. Methods: This is a retrospective analysis of a cohort of 7 patients with advanced HPV-unassociated penile SCC treated at Rush University Medical Center who monitored closely for molecular residual disease (MRD). Signatera (Natera Inc.), a personalized tumor-informed ctDNA assay, was utilized for detection and quantification of ctDNA in patients’ plasma samples, measured at regular intervals. Progression of disease was based on radiographic imaging. Results: In our cohort, personalized, tumor-informed ctDNA assays were designed for 100% (7/7) of the patients. ctDNA was detectable in at least one time point in all of the patients. One patient underwent partial penectomy and lymph node (LN) dissection with 1/11 LN involved. He is being monitored without adjuvant treatment and has sustained ctDNA clearance. Another patient underwent surgery, and had positive post-operative ctDNA. He was treated with adjuvant TIP (paclitaxel, ifosfamide, and cisplatin) with subsequent ctDNA clearance. In 3 of the patients, ctDNA was checked at regular intervals and rising ctDNA prompted imaging studies that showed progression. These patients proceeded to second line treatment options. The remaining 2 patients are non-surgical candidate with LN positivity, who will begin treatment with TIP and monitoring of ctDNA after each cycle of chemotherapy. Twenty-eight percent (2/7) of patients remain alive with sustained ctDNA clearance. Twenty-eight percent (2/7) of patients remain alive with ctDNA positivity, planned to initiate treatment and monitoring of ctDNA at regular intervals. Forty-three percent (3/7) of patients who had persistent ctDNA positivity are now deceased. Conclusions: Our data suggests that a personalized, tumor-informed ctDNA assay is not only useful for MRD monitoring, but also highly predictive of treatment response and imaging-based progression in patients with penile SCC. In our sample, MRD status correlated with both radiographic progression and clinical outcomes. Prospective studies are needed to better understand how ctDNA can be used to guide neoadjuvant and adjuvant approaches, including treatment intensification or de-escalation, in patients with penile SCC.
Maintenance of patient-reported quality of life (EQ-5D-3L) post neoadjuvant relugolix prior to the initiation of prostate radiation therapy.
Authors: Koh Min Ji , Koh Min Jung , Hsueh Jessica , Gallagher Lindsey , Danner Malika , Zwart Alan , Ayoob Marilyn , Yung Thomas M. , Kumar Deepak , Carrasquilla Michael , Leger Paul Denis , Dawson Nancy Ann , Suy Simeng , Collins Sean P. 
Published: January 2024

117 Background: Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy (RT) for unfavorable intermediate- to high-risk prostate cancer. Relugolix is a new oral GnRH receptor antagonist that achieves high rates of rapid profound castration (total testosterone < 20 ng/dL), which may impact health-related quality of life. This prospective study sought to evaluate the impact of neoadjuvant relugolix on health-related quality of life in prostate cancer patients prior to the start of prostate RT. Methods: Patients treated at Georgetown between May 2021 and August 2023 with neoadjuvant relugolix (at least 2 months prior to RT) per an institutional protocol were included in the study (IRB 12-1775). The 5-item EQ-5D-3L, a validated questionnaire that assesses the patient-reported health status outcome, was collected for each patient at baseline (before relugolix initiation) and one hour prior to RT initiation. EQ VAS Score Overall ranges from 0-100 with a higher score indicating better quality of life. Individual items including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were scored on a three-point scale from 1 (No problems) to 3 (Extreme). To examine changes before and after relugolix treatment, McNemar’s test and paired samples t-test were used. Minimally important difference (MID) calculated by 0.5 of standard deviation at baseline was used to examine clinical significance. Results: Of 79 patients, the median age was 73 years, and 42% were non-white. Patients initiated relugolix at a median of 4 months prior to questionnaire administration (IQR: 3.9-5.4), at which most (95%) patients achieved castration (≤ 50 ng/dL). The VAS Score Overall was significantly higher at baseline (Mean ± SD: 83 ± 10) than the paired score at the start of RT (80 ± 14, p = 0.01). This change was not clinically significant. There were no statistically or clinically significant differences in any of the 5 individual items. Conclusions: Neoadjuvant relugolix prior to prostate radiation therapy did not clinically significantly affect patient-reported quality of life. Also, there was no statistically significant decrease in each of the 5 individualized items evaluating health-related quality of life. Future studies should focus on comparing it to GnRH agonist-induced change in quality of life. [Table: see text]
PETRANHA: Phase 1/2 study of AZD5305 + novel hormonal agents in patients with metastatic prostate cancer–Interim safety and pharmacokinetic results.
Authors: Azad Arun , Voskoboynik Mark , Joshua Anthony M. , Weickhardt Andrew James , Sankey Peter , Pacey Simon , Heath Elisabeth I. , Krieger Laurence , Horvath Lisa , Pilié Patrick Glen , Womersley Lynsey , Linardopoulos Spiros , Moorthy Ganesh , Zhou TJ , Brown Jessica , de Paula Bruno , Lukacs Edit , Hudson Andrew 
Published: January 2024

123 Background: The combination of PARP inhibitors (PARPi) with novel hormonal agents (NHAs) has recently demonstrated significant improvement in progression-free survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) compared with NHAs alone. AZD5305, a PARP1-selective inhibitor, has the potential for an improved safety profile and limited drug-drug interactions (DDIs) compared with first-generation PARPi. PETRANHA, an open-label nonrandomized study, is evaluating the safety and DDIs of AZD5305 with physician’s choice of NHA (enzalutamide [enza], abiraterone acetate [abi] or darolutamide [daro]) in pts with metastatic prostate cancer. Methods: Pts were aged ≥18 years with histologically confirmed mCRPC or metastatic castration-sensitive prostate cancer (mCSPC), suitable for NHA treatment, with or without HRR mutations in tumor tissue. Key exclusion criteria were previous PARPi, platinum chemotherapy, or targeted radioligand therapy for pts with mCRPC or mCSPC; and previous NHA or docetaxel in pts with mCSPC. Pts were assigned to receive AZD5305 60 mg once daily (OD; first dose level tested) and either enza 160 mg OD (Arm 1), abi 1000 mg + 5 mg prednisone OD (Arm 2), or daro 600mg twice daily (Arm 3) until disease progression or any intolerable adverse event (AE) occurred. Primary objectives were safety and tolerability. DDIs were evaluated for each combination. Results: At data cutoff (July 10, 2023), 48 pts were included in the interim safety analysis (Arm 1, n=11; Arm 2, n=19; Arm 3, n=18). In total, 32 (66.7%) pts had mCRPC, 16 (33.3%) pts had mCSPC, and 8 (16.7%) pts were pre-exposed to NHAs. Median duration of AZD5305 exposure was 6.3 months (range, 1.05–12.58) across all arms. Safety data are presented in the Table. The most common AEs were anemia (52.1%; Gr ≥3, 16.7%), fatigue (50.0%; Gr ≥3, 2.1%), and neutropenia (33.3%; Gr ≥3, 6.3%). No dose-limiting toxicities or AE-related deaths occurred in any arm; AEs leading to discontinuations were uncommon. No clinically significant DDIs were measured with any of the combinations. Conclusions: Initial safety, tolerability, and DDI data from the PETRANHA study indicates that AZD5305 can be safely combined with three individual NHAs with low rates of dose interruptions or reductions. The study is ongoing in Australia, Italy, UK, and USA. Clinical trial information: NCT05367440 . [Table: see text]
Association of prior poly(ADP-ribose) polymerase (PARP) inhibitor therapy with response to 177Lu-PSMA-617 (LuPSMA) in men with DNA damage repair (DDR) mutations.
Authors: Raychaudhuri Ruben , Mo George , Moradi Tuchayi Abuzar , Graham Laura , Gulati Roman , Pritchard Colin C. , Haffner Michael C. , Yezefski Todd , Hawley Jessica E. , Montgomery Robert Bruce , Cheng Heather H. , Nelson Peter , Chen Delphine L , Hope Thomas A. , Iravani Amir , Schweizer Michael Thomas 
Published: January 2024

128 Background: LuPSMA, a radioligand therapy targeting the cell surface protein PSMA, is approved for men with PSMA-positive mCRPC previously treated with androgen receptor signaling inhibitor (ARSI) and taxane chemotherapy. Several PARP inhibitors (PARPi) are also currently approved for patients with mCRPC harboring alterations in genes associated with DNA damage repair (DDR). Given that both therapeutics result in DNA damage, we hypothesized that there would be clinical evidence of cross-resistance between the two classes of agents, with decreased efficacy in patients receiving LuPSMA following a PARPi. Methods: We abstracted retrospective data from patients at three centers who received at least one cycle of LuPSMA per the FDA label and had panel-based tumor sequencing performed. Patients with PARPi qualifying mutations were included in the analysis. PSA50 responses (i.e. ≥50% decline in PSA from baseline), PSA progression free survival (PFS) and overall survival (OS) following treatment with LuPSMA were compared between patients who received prior PARPi (PARPi-T cohort) and those who did not (PARPi-NT cohort). Results: Forty-nine patients with a PARPi qualifying alteration who received at least one cycle of LuPSMA were identified. Baseline characteristics (Gleason score, visceral metastases, race, ECOG PS, PSMA SUVmean/max) were similar between cohorts. Prior non-PARPi lines of therapy, including receipt of radium-223 (14% vs 21%), carboplatin (33% vs 36%), ≥ 2 prior ARSI (67% vs 68%), and ≥ 2 prior taxanes (43% vs 47%) were also similar between the PARP-NT and PARP-T cohorts respectively. Median PSA PFS and OS were both significantly increased in the PARPi-NT cohort as compared to the PARPi-T cohort (Table). PSA50 responses were numerically increased in the PARP-NT cohort, although this did not reach statistical significance. The most common PARPi qualifying alteration was BRCA2 (N=15). PARP-NT patients with BRCA2 alterations had significantly increased PSA PFS and OS as well as PSA50 response rates compared to the PARP-T patients. Conclusions: Prior receipt of PARPi therapy appears to negatively associate with the clinical activity of LuPSMA, with the largest difference in outcomes observed in patients with BRCA2 mutations. These data support the hypothesis that PARPi therapy may lead to clinically significant cross-resistance with LuPSMA. Prospective studies to evaluate the optimal sequence of LuPSMA and PARPi therapy are justified. [Table: see text]
Comparison of adverse event rate of prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) with antibody or small molecule ligand targeting vector.
Authors: Ruder Samuel Francis , Sun Michael Philip , Thomas Charlene , Molina Ana M. , Nauseef Jones T. , Osborne Joseph , Sternberg Cora N. , Nanus David M. , Bander Neil Harrison , Tagawa Scott T. 
Published: January 2024

161 Background: PSMA-targeted radionuclide therapy (PSMA-TRT) has been established with use of either monoclonal antibodies (mAb) or small molecule ligands (SML) as the targeting vectors for delivery of 177Lu to PSMA-expressing prostate cancer. mAb and SML differ in their molecular weight, pharmacokinetics, and biodistribution which is predicted to result in different adverse effect profiles. Methods: In this study with written informed consent, we compare the adverse effects from individual patients receiving PSMA-TRT for mCRPC using mAb (J591) vs SML (PSMA-617 or PSMA I&T) for delivering 177Lu in prospective clinical trials or registry. All-grade treatment-emergent adverse events (TEAEs) were extracted from trial databases. Adverse effects were graded 0-5. Pearson’s Chi-squared test was used to assess TEAEs and association with treatment type. Multivariable logistic regression was used to compare TEAEs after adjusting for administered radioactivity dose and CALGB (Halabi) prognostic score. Results: 248 patients with mCRPC were treated from March 2001 to February 2023. 166 (67.7%) received mAb (177Lu-J591), 81 received SML [76 (30.6%) 177Lu-PSMA-617, 5 (2%) 177Lu-PSMA-I&T)]. The median age was 70.9 years (44.5 yrs to 93.8 yrs). At the time of trial enrollment, 137 (55.2% [68% SML and 49% mAb]) patients had exposure to chemotherapy, 112 (45.1%) had exposure to androgen-receptor pathway therapy, 193 (77.8%) had bone metastases, 120 (48.3%) LN mets, 42 (16.9%) lung mets, and 20 (8.0%) liver mets. 142 (57.2%) had Halabi score high disease. All-grade hematologic TEAEs were more common with mAb: neutropenia in 122 (74%) patients vs 16 (20%) (p<0.001), anemia in 122 (73%) vs 26 (33%) (P<0.001), and thrombocytopenia in 145 (87%) vs 25 (32%) (p<0.001). Gr >3 neutropenia occurred in 79 (47%) and Gr >3 thrombocytopenia in 98 (59%) receiving mAb. All-grade non-hematologic TEAEs were generally more common with SML: fatigue in 31 (53%) vs 79 (48%) (p=0.5), pain in 32 (54%) vs 73 (44%) (p=0.2), nausea in 21 (36%) vs 34 (20%) (p=0.02) and xerostomia in 36 (61%) vs 1 (0.6%) (p<0.001). After adjusting for administered dose and Halabi score, treatment with 177Lu via SML vector was associated with less neutropenia (OR 0.04, 95% CI 0.02-0.09, p<0.001), anemia (OR 0.11, 95% CI 0.06-0.22, p<0.001), and thrombocytopenia (OR 0.04, 95% CI 0.02-0.09, p<0.001) but more nausea (OR 3.2, 95% CI 1.54-6.72, p=0.002) and xerostomia (NA due to low event rate in mAb). Conclusions: As predicted, PSMA-TRT with mAb vs SML is associated with different toxicity profiles. PSMA-TRT with the mAb 177Lu-J591 is more commonly associated with hematologic toxicities compared to the SML 177Lu-PSMA-617 and 177Lu-PSMA-I&T, which are more commonly associated with non-hematologic toxicities.
The prognostic value of ductal adenocarcinoma of the prostate in patients with advanced prostate cancer treated with abiraterone acetate.
Authors: Shi Yifu , Wei Xinyuan , Zhao Fengnian , Zhao Jinge , Shen Pengfei , Chen Ni , Zeng Hao 
Published: January 2024

167 Background: Previous studies have indicated that ductal adenocarcinoma of the prostate (DA) is associated with adverse prognosis in patients with localized prostate cancer (PCa). However, the clinical significance of DA in advanced PCa remains largely ambiguous. This study endeavors to investigate the relationship between the existence of DA in prostate biopsy specimens and treatment outcomes among patients with advanced PCa receiving abiraterone acetate (AA) therapy. Methods: We retrospectively analyzed data from 440 patients with advanced PCa who received AA at either the metastatic hormone-sensitive (mHSPC, N=123) or castration-resistant PCa (mCRPC, N=317) stage. The presence of DA and its proportion was evaluated based on prostate biopsy specimens. Kaplan-Meier curves and COX regression were used to evaluate the predictive significance of DA on AA efficacy, including PSA response, PSA progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS). Results: In aggregate, DA was detected in 35/440 (8.0%) patients, with 13/440 (3.0%) and 22/440 (5.0%) men harboring DA<5% and ≥5%, respectively, in the total tumors. The overall PSA response rate in the entire cohort was 302/440 (68.6%), and it was comparable for people with and without DA, with both groups having a response rate of 68.6%. Of note, compared with patients without DA, men with DA have significantly longer median PSA-PFS (mPSA-PFS, 12.1- vs. 25.0-Mo, P=0.005) and median rPFS (mrPFS, 19.8 vs. 38.2-Mo, P=0.034). Subgroup analysis based on DA proportion further revealed that in comparison with PCa without DA, DA≥5% was an indicator of favorable PSA-PFS (HR, 95%CI: 0.28, 0.14-0.56, p<0.001) and rPFS (HR, 95%CI: 0.35, 0.18-0.72, p=0.004), while DA<5% was not. In multivariate COX regression analysis, after adjusting by clinicopathological factors, including mCRPC/mHSPC stage, ISUP grading, metastatic burden, pain score and pretreatment hemoglobin, alkaline phosphatase, and lactate dehydrogenase, DA≥5% was still independently associated with better therapeutic efficacy of AA treatment (PSA-PFS: HR, 95%CI: 0.36, 0.17-0.74, p<0.001; rPFS: HR, 95%CI: 0.47, 0.23-0.96, p=0.040). Conclusions: A DA proportion ≥5% in the tumor is related to improved treatment efficacy for individuals with advanced PCa receiving AA. Thus, in the pathological diagnosis of PCa, it is necessary to routinely report the presence and proportion of DA in order to aid with treatment decision-making.