Impact of SARS-CoV-2-Pandemic on diagnosis of prostate cancer.

Introduction The aim of this study was to prove if the SARS-CoV-2-pandemic resulted in a delay in diagnosis and treatment of prostate cancer (PC). Methods A monocentric, retrospective analysis was conducted at a university cancer center. Included were all patients with untreated PC diagnosed between January 2019 and December 2021. The observation covered 22 months of the SARS-CoV-2-pandemic and 14 months preceding it. Results 969 men prior (T0) and 1343 during pandemic (T1) where included. Mean age was 68.0 (SD 8.2). Median initial PSA was 8.1 ng/ml (T0) and 7.9 ng/ml (T1, p= 0.288). Time from biopsy to tumor board (T0: 1.3 months vs. T1: 0.9 months, p=0.001), to staging (T0: 1,1 months vs. T1: 0.75 months, p=0.707) and to therapy (T0: 3.0 months vs. T1: 2.0 months, p<0.001) were shortened during pandemic. Classified by d'Amico, a significant shift towards higher risk groups was seen (p=0.024). Local staging showed an insignificant increase in locally advanced PCs. Metastatic diseases decreased from 10.3 % to 8.9% (p=0.433). Pathological staging showed pT3+ in 44.4% vs. 44.7% (p=0.565) and pN+ in 9.9 % vs 9.6% (p=0.899). Conclusion Regarding the diagnosis and treatment of PC, we could not demonstrate any delays due to the SARS-CoV-2-pandemic.

Validation of the Spanish version of the Health Literacy Survey (HLS19-Q12) in secondary care specialty consultations.

OBJECTIVES: This study sought to validate the HLS19-Q12 in Spain and in the Spanish language, as well as describe the sociodemographic profile and the general health literacy of the study population. STUDY DESIGN: Descriptive cross-sectional. METHODS: Factor analysis and Cronbach's alpha were used to validate the Spanish version of the HLS19-Q12. Health literacy scores and associated categories were calculated using the scale factsheet, and the patient population sociodemographic profile was determined using frequency analysis. RESULTS: The HLS19-Q12 used in Spain in the Spanish language was found to be both valid and reliable (Cronbach's alpha = 0.87). The sociodemographic profile was primarily male and aged, and the majority of patients were of Spanish origin and had diabetes. General patient health literacy was limited, with 60% of participants having general health literacy categorized as inadequate or problematic, and 40 % sufficient or excellent. CONCLUSIONS: This study validated the HLS19-Q12 in Spain, created a sociodemographic profile of the sample population, and calculated their health literacy scores. This contribution provides another valuable validated tool and associated data to the increasingly important field of health literacy.

Small cyst size and lack of growth as negative predictors of malignant transformation in low-risk intraductal papillary mucinous neoplasms of the pancreas: A systematic review and meta-analysis.

BACKGROUND AND AIM: For branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WFs) or high-risk stigmata (HRS), current guidelines recommend surveillance. However, these intraductal papillary mucinous neoplasm (IPMNs), especially the small and stable-sized ones, carry a low risk of malignant transformation. Our aim was to assess whether small cyst size and absence of rapid growth provide reassurance against the development of WFs/HRS and malignancy (high-grade dysplasia (HGD) or pancreatic cancer (PC)). METHODS: PubMed/Medline, Embase, the Cochrane Library and the Web of Science Core Collection were systematically searched from inception to May 2023 to identify studies investigating surveillance outcomes of low-risk BD-IPMNs. Studies assessing baseline cyst size and/or growth in relation to WFs/HRS and/or HGD/PC were included. The Newcastle-Ottawa scale tool was used to assess study quality. RESULTS: Of the 1937 identified manuscripts, 21 studies were eligible for inclusion. The quality of these studies was considered reasonable. A negative association between cyst size and WFs/HRS development was found in 11 out of 13 relevant studies, but only one out of nine studies reported a negative association between size and malignancy. Regarding cyst growth, four out of six studies described a negative association with the development of WFs/HRS, and all six reported a negative association with malignancy. The pooled relative risk (RR) of developing WFs/HRS or malignancy for cysts ≤15 mm was 0.37 (95% CI 0.25-0.57) and the RR of developing malignancy for cyst growth <2-2.5 mm/year was 0.04 (95% CI 0.02-0.09)). CONCLUSION: This systematic review and meta-analysis shows that small and stable-sized low-risk BD-IPMNs are associated with a markedly low progression rate, with stable cyst size being the most reassuring feature. Because of substantial heterogeneity in definitions and reported outcome measures, prospective studies are needed to confirm that surveillance of small and stable sized cyst can be de-intensified or even discontinued.

The Paradox of Modern Technology in Standardizing Thermal Liver Ablation: Fostering Uniformity or Diversity?

PURPOSE: Currently, significant medical practice variation exists in thermal ablation (TA) of malignant liver tumors with associated differences in outcomes. The IMaging and Advanced Guidance for workflow optimization in Interventional Oncology (IMAGIO) consortium aims to integrate interventional oncology into the standard clinical pathway for cancer treatment in Europe by 2030, by development of a standardized low-complex-high-precision workflow for TA of malignant liver tumors. This study was conducted at the start of the IMAGIO project with the aim to explore the current state and future role of modern technology in TA of malignant liver tumors. MATERIALS AND METHODS: A cross-sectional questionnaire was conducted followed by an expert focus group discussion with core members and collaborating partners of the consortium. RESULTS: Of the 13 participants, 10 respondents filled in the questionnaire. During the focus group discussion, there was consensus on the need for international standardization in TA and several aspects of the procedure, such as planning based on cross-sectional images, the adoption of different techniques for needle placement and the importance of needle position- and post-ablative margin confirmation scans. Yet, also considerable heterogeneity was reported in the adoption of modern technology, particularly in navigational systems and computer-assisted margin assessment. CONCLUSION: This study mirrored the current diversity in workflow of thermal liver ablation. To obtain comparable outcomes worldwide, standardization is needed. While advancements in tools and software hold the potential to homogenize outcome measurement and minimize operator-dependent variability, the rapid increase in availability also contributes to enhanced workflow variation.

Thumb Carpometacarpal Joint Denervation for Early Osteoarthritis: An Overview of the Literature and a Pilot Study on Pain Reduction and Patient Satisfaction.

Background The treatment of patients with osteoarthritis of the first carpometacarpal joint (CMC-I) aims at pain reduction to improve hand function and quality of life. The CMC-I denervation procedure is relatively new and seems appealing, as it is minimally invasive and has few or no disadvantages. To date, however, little research has been done on the results of a CMC-I denervation. The aim of this study was to investigate whether denervation provides pain reduction in patients with early CMC-I osteoarthritis. Methods A literature search was done using PubMed. Studies were excluded if access to full text was not available, if the articles were written in other languages than Dutch or English, and if preoperative testing, follow-up testing, or reporting were incomplete. Studies were included if patients were older than 18 years, had primary CMC-I osteoarthritis with no other wrist pathology, and had received conservative treatment without sustained benefit. The Critical Appraisal Tools of the Joanna Briggs Institute were used for critical appraisal. Clinical data was gathered retrospectively from the medical records to identify patients who underwent CMC-I denervation in The Hand Clinic, Amsterdam. The data of 20 patients were analyzed. Pre- and postoperative visual analog scale (VAS) scores on pain, patient satisfaction, and complications were evaluated. Patients older than 18 years with primary CMC-I osteoarthritis stage I and II and no other wrist pathology, in whom conservative treatment failed were included in the study. Patients with CMC-I osteoarthritis stage III and IV were excluded. Results All 17 search results were screened for full text access, after which 6 case series, 4 systematic reviews, 1 cohort study, 1 comment, and 1 scoping review was included. All but one study showed pain reduction after surgery. In half of the studies, this difference was statistically significant. The average patient satisfaction in these studies was 84.1% and the complication rate was 13.4%. A total of 20 patients were included between 2019 and 2022, with a mean preoperative VAS for pain at rest of 48.2 ± 29.9. After surgery, this decreased to 35.8 ± 34.1. This difference was not statistically significant. The mean VAS for pain during use before denervation was 79 ± 18.4 and this decreased to 49.8 ± 34.2 postoperatively. This difference did appear to be statistically significant. The average patient satisfaction was 60%, and the complication rate was 10%. Conclusion This study provides a literature overview and a pilot study on pain reduction, patient satisfaction, and complications after denervation of the CMC-I joint in patients with early osteoarthritis. Our retrospective case series roughly mirrored the average results found in the literature. There was a statistically significant decrease in pain during use postoperatively. There was no statistically significant difference in pain at rest before and after surgery. The complications were mild and the complication rate was low; however, the average patient satisfaction rate was lower as compared to that reported in the literature.

The changing treatment paradigm in prolactinoma - a prospective series of 100 consecutive neurosurgical cases.

PURPOSE: To evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL). METHODS: Cohort of consecutive patients with prolactinoma undergoing surgery between January 2021 and August 2023. Clinical data were collected during multidisciplinary team (MDT) meetings/from medical records at distinct timepoints: (1) pre-surgery, (2) two weeks post-surgery, (3) six months post-surgery, and (4) follow-up (median 15.0 (10.0-24.8 months). HR-QoL was measured using the Leiden Bothers and Needs Pituitary (LBNQ-P) questionnaire. Data were described for all patients, and patients undergoing elective total resection, with additional subgroups of (a) patients undergoing a high-probability-first-total-resection, and (b) reoperations aiming for total resection. RESULTS: One hundred surgically treated patients with prolactinoma were included (72 female). Dopamine agonist intolerance was the most frequent indication (n=68). The surgical goal (debulking/total resection) was achieved in 90% of patients. Long-term complications occurred in 4% of patients. Seventy-eight patients underwent an elective total resection, achieving remission in 91%. The subsets of preoperatively estimated high-probability-first-total-resections (n=52), and reoperations (n=9), achieved remission in 92% and 89%, respectively. LBNQ-P Total Bothers and Total Needs scores improved significantly after surgery (p<0.001, Δ-3.4 (IQR -14.4- -0.9) and p=0.006, Δ-1.8 (IQR -11.9-1.3), respectively. CONCLUSION: High remission rates were achieved, improving HR-QoL, evidencing (repeat) prolactinoma surgery is effective in an experienced pituitary center, as highlighted in the most recent guideline (2023).

PML is a constitutive component of chromatin domains enriched in repetitive elements and duplicated gene clusters in cancer cells.

Heterochromatin is a pivotal element in the functional organization of genomes. In our study, we delve into the heterochromatin pattern of association by the PML (promyelocytic leukemia) protein. By using PML chromatin immunoprecipitation and sequencing data and comparing computational methodologies to depict PML chromatin association, we describe PML-associated domains or PADs as large heterochromatic regions that exhibit similar genomic features across cancer cell lines. We show that PADs are specifically enriched in non-coding genes, duplicated gene clusters, and repetitive DNA elements. Moreover, we find enriched binding motifs of KZFPs, which are involved in orchestrating epigenetic repression at repetitive DNA elements. Hence, our findings suggest that PML conservatively associates to heterochromatic domains enriched in repetitive DNA elements and duplicated gene clusters in cancer. These findings contribute to a broader understanding of the complex regulatory framework of genome organization by heterochromatin in cancer.

Optimizing ventricular tachycardia ablation through imaging-based assessment of arrhythmic substrate: A comprehensive review and roadmap for the future.

Ventricular tachycardia (VT) is a life-threatening heart rhythm and has long posed a complex challenge in the field of cardiology. Recent developments in advanced imaging modalities have aimed to improve comprehension of underlying arrhythmic substrate for VT. To this extent, high-resolution cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) have emerged as tools for accurately visualizing and characterizing scar tissue, fibrosis, and other critical structural abnormalities within the heart, providing novel insights into VT triggers and substrate. However, clinical implementation of knowledge derived from these advanced imaging techniques in improving VT treatment and guiding invasive therapeutic strategies continues to pose significant challenges. A pivotal concern lies in the absence of standardized imaging protocols and analysis methodologies, resulting in a large variance in data quality and consistency. Furthermore, the clinical significance and outcomes associated with VT substrate characterization through CMR and CCT remain dynamic and subject to ongoing evolution. This highlights the need for refinement of these techniques before their reliable integration into routine patient care can be realized. The primary objectives of this study are twofold: firstly, to provide a comprehensive overview of the studies conducted over the last 15 years, summarizing the current available literature on imaging-based assessment of VT substrate. Secondly, to critically analyze and evaluate the selected studies, with the aim of providing valuable insights that can inform current clinical practice and future research.

How does increasing temperature affect the toxicity of bisphenol A on Cryptomonas ovata and its consumer Daphnia magna?

The global rise in plastic production has led to significant plastic deposition in aquatic ecosystems, releasing chemical compounds as plastics degrade. Among these, bisphenol A (BPA) is a major global concern due to its endocrine-disrupting effects and widespread presence in aquatic environments. Furthermore, the toxicity of BPA on aquatic organisms can be modulated by global change stressors such as temperature, which plays an essential role in the metabolism of organisms, including the degradation and accumulation of toxic compounds. In this study, we aimed to understand how temperature can modulate the toxic effect of BPA on a phytoplankton species (Cryptomonas ovata) and how this effect can be transferred to its herbivorous consumer (Daphnia magna). To do this, we first determined the sensitivity of C. ovata over a BPA gradient (0-10 mg L-1). Subsequently, we experimentally determined how the increase in temperature (+5ºC) could modify the toxic effect of BPA on the physiology, metabolism and growth of the phytoplankton. Finally, we investigated how this effect transferred to the growth rate of D. magna through food. Our results show a negative effect of BPA on C. ovata from 5 mg BPA L-1, affecting its photosynthetic yield of photosystem II, net primary production, respiration, and growth. This effect was accelerated when the temperature was higher. Additionally, the growth rate of D. magna also decreased when fed on C. ovata grown in the presence of BPA and high temperature. Our results indicate that high temperature can accelerate the toxic effects of BPA on organisms located at the base of the food web and this effect could be transferred to higher levels through food.

Intravenous Lidocaine for Refractory Pain in Patients With Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Multicenter Prospective Nonrandomized Pilot Study.

INTRODUCTION: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively. METHODS: Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥1.3 points was considered clinically relevant. RESULTS: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD ± 1.3) points for patients with PDAC and 0.5 (SD ± 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life. DISCUSSION: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

Recurrent Cystitis in Women-A Real-World Analysis of Bacteria Spectrum and Resistance Situation for Calculated Therapy.

Recurrent cystitis in women represents an everyday challenge; however, little to no data regarding this population are available. This study aimed to evaluate this collective with respect to a rational calculated antibiotic therapy. Urine cultures and antibiograms from a urological office were retrospectively evaluated from patient data collected between January 2017 and June 2019. The evaluation was conducted using SPSS ©. In total, 84 female patients, who were aged between 18 and 87 years old (median 60 years), suffered from recurrent cystitis. Escherichia coli was found in 53.9% of cases, Staphylococcus aureus and enterococci were each found in 6.7%, and Proteus spp. and Streptococcus agalactiae were each found in 5.6%. The resistance levels to ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (TRS), nitrofurantoin (NIT), and nitroxoline (NOX) were 18.2%, 30.7%, 16.1%, and 12.5% in the tested cases, respectively. Regarding E. coli, resistance to CIP, TRS, and NIT was found in 17.8%, 25%, and 4.2% of the tested cases, and no resistance to NOX was found. The resistance level to CIP was in a tolerable range of <20% in the overall cohort and the E. coli subgroup. More than a quarter of the bacteria were resistant to TRS. The low resistance rates for NIT and NOX are remarkable, promoting the use of these substances if they are not yet used.

Community engagement and local governance for health equity through trust: lessons from developing the CONNECT Initiative in the Lao People's Democratic Republic.

Community engagement and local governance are important components of health interventions aiming to empower local populations. Yet, there is limited evidence on how to effectively engage with communities and codevelop interventions, especially in Southeast Asian contexts. Despite rapid progress, the Lao People's Democratic Republic (Lao PDR) still has high maternal and child mortality, with essential service coverage showing significant disparities across socioeconomic strata. Long-standing challenges in community health were exacerbated by the COVID-19 pandemic and reinforced by poor trust between users and health providers. However, the pandemic also provided an opportunity to develop approaches for enhanced community engagement and local governance capacity to tackle health inequities. The Community Network Engagement for Essential Healthcare and COVID-19 Responses through Trust (CONNECT) Initiative, developed by the Lao PDR government, WHO and partners, has resulted in initial positive outcomes in community health such as increased vaccination uptake, facility births and trust in health providers. This case study describes the iterative, adaptive process by which the CONNECT Initiative was developed, and how the core components, key stakeholders, theory of change and evaluation framework evolved from grounded observations and hypotheses. Lessons learnt include (1) awareness of entry points and existing structures to strengthen local governance for health through mutually beneficial intersectoral collaboration; (2) building relationships and trust with an adaptive, grounds-up approach for sustainability and scalability. As a model which can be adapted to other settings, this case study provides evidence on how to engage with communities, strengthen local governance and codevelop interventions towards greater health equity.

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah-/- mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.

The role of myocardial blood volume in the pathophysiology of angina with non-obstructed coronary arteries: The MICORDIS study.

BACKGROUND: Angina with Non-Obstructed Coronary Arteries (ANOCA) involves abnormal vasomotor responses. While reduced coronary flow is an established contributor to myocardial hypoxia, myocardial blood volume (MBV) independently regulates myocardial oxygen uptake but its role in ANOCA remains unclear. OBJECTIVES: We hypothesized that reduced MBV contributes to ANOCA, and associates with insulin resistance in ANOCA. METHODS: MBV in ANOCA patients was compared to age- and sex-matched healthy controls. ANOCA patients underwent coronary angiography with invasive coronary function testing (CFT) to identify vasospasm and coronary microvascular dysfunction. In all subjects MBV was quantified at baseline, during hyperinsulinemia and during dobutamine-induced stress using myocardial contrast echocardiography (MCE). The hyperinsulinemic-euglycemic clamp was used to assess insulin resistance. RESULTS: Twenty-eight ANOCA patients (21% men, 56.8 ± 8.6 years) and 28 healthy controls (21% men, 56.5 ± 7.0 years) were included. During CFT 11% of patients showed epicardial vasospasm, 39% microvascular vasospasm, 25% coronary microvascular dysfunction, and 11% of patients had a negative CFT. ANOCA patients had significant lower insulin-sensitivity (p < 0.01). During MCE, ANOCA patients showed a significantly lower MBV at baseline (0.388 vs 0.438 mL/mL, p = 0.04), during hyperinsulinemia (0.395 vs 0.447 mL/mL, p = 0.02), and during dobutamine-induced stress (0.401 vs 0.476 mL/mL, p = 0.030). CONCLUSIONS: In ANOCA patients MBV is diminished at baseline, during hyperinsulinemia and dobutamine-induced stress in the absence of differences in microvascular recruitment. These findings support the presence of capillary rarefaction in ANOCA patients. ANOCA patients showed metabolic insulin resistance, but insulin did not acutely alter myocardial perfusion.

A Structural Comparison of Oral SARS-CoV-2 Drug Candidate Ibuzatrelvir Complexed with the Main Protease (Mpro) of SARS-CoV-2 and MERS-CoV.

Ibuzatrelvir (1) was recently disclosed and patented by Pfizer for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has received fast-track status from the USA Food and Drug Administration (FDA) and has entered phase III clinical trials as a possible replacement for Paxlovid. Like nirmatrelvir (2) in Paxlovid, this orally active drug candidate is designed to target viral main proteases (Mpro) through reversible covalent interaction of its nitrile warhead with the active site thiol of the chymotrypsin-like cysteine protease (3CL protease). Inhibition of Mpro hinders the processing of the proteins essential for viral replication in vivo. However, ibuzatrelvir apparently does not require ritonavir (3), which is coadministered in Paxlovid to block human oxidative metabolism of nirmatrelvir. Here, we report the crystal structure of the complex of ibuzatrelvir with the active site of SARS-CoV-2 Mpro at 2.0 Šresolution. In addition, we show that ibuzatrelvir also potently inhibits the Mpro of Middle East respiratory syndrome-related coronavirus (MERS-CoV), which is fortunately not widespread but can be dangerously lethal (∼36% mortality). Co-crystal structures show that the binding mode of the drug to both active sites is similar and that the trifluoromethyl group of the inhibitor fits precisely into a critical S2 substrate binding pocket of the main proteases. However, our results also provide a rationale for the differences in potency of ibuzatrelvir for these two proteases due to minor differences in the substrate preferences leading to a weaker H-bond network in MERS-CoV Mpro. In addition, we examined the reversibility of compound binding to both proteases, which is an important parameter in reducing off-target effects as well as the potential immunogenicity. The crystal structures of the ibuzatrelvir complexes with Mpro of SARS-CoV-2 and of MERS-CoV will further assist drug design for coronaviral infections in humans and animals.

Endoscopic ultrasound with tissue acquisition of lymph nodes in patients with potentially resectable intrahepatic cholangiocarcinoma.

Background and study aims Lymph node (LN) involvement is a poor prognostic factor for patients with intrahepatic cholangiocarcinoma (iCCA). The aim of this study was to evaluate the yield and impact on clinical decision making of endoscopic ultrasound with tissue acquisition (EUS-TA) of LNs in patients with potentially resectable iCCA. Patients and methods In this multicenter cohort study, patients with potentially resectable iCCA and preoperative EUS between 2010 and 2020 were retrospectively included. The impact of EUS-TA was defined as the percentage of patients who did not undergo surgical exploration due to pathologically confirmed positive LNs found with EUS-TA. Results A total of 56 patients underwent EUS, with 91% of patients to target suspicious LNs on imaging. EUS-TA of LNs confirmed malignancy in 21 LNs among 19 patients (34%). In 17 patients (30%), surgical exploration was withheld due to nodal involvement. Finally, 24 patients (43%) underwent surgical exploration among whom positive regional LNs were identified in six patients (25%). Conclusions In patients with potentially resectable iCCA and suspicious LNs on cross-sectional imaging, EUS-TA confirmed LN involvement in 30% of patients. Surgical exploration was withheld mostly because of extraregional LN involvement and regional LN involvement in patients with high surgical risk.

Shedding Light on the Origin of

Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance. Besides the impact of uncertainties from stellar models and galactic chemical evolution simulations, this discrepancy was further obscured by rather divergent theoretical estimates for the neutron capture cross section of its radioactive precursor in the neutron-capture flow, ^{204}Tl (t_{1/2}=3.78 yr), and by the lack of experimental data on this reaction. We present the first ever neutron capture measurement on ^{204}Tl, conducted at the CERN neutron time-of-flight facility n_TOF, employing a sample of only 9 mg of ^{204}Tl produced at the Institute Laue Langevin high flux reactor. By complementing our new results with semiempirical calculations we obtained, at the s-process temperatures of kT≈8 keV and kT≈30 keV, Maxwellian-averaged cross sections (MACS) of 580(168) mb and 260(90) mb, respectively. These figures are about 3% lower and 20% higher than the corresponding values widely used in astrophysical calculations, which were based only on theoretical calculations. By using the new ^{204}Tl MACS, the uncertainty arising from the ^{204}Tl(n,γ) cross section on the s-process abundance of ^{204}Pb has been reduced from ∼30% down to +8%/-6%, and the s-process calculations are in agreement with the latest solar system abundance of ^{204}Pb reported by K. Lodders in 2021.