Prognostic value of ABO blood groups in upfront operated pancreatic ductal adenocarcinomas.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has been shown to have a lower incidence in patients with blood group O. It is currently uncertain if patients with group O have a better prognosis after pancreatectomy. This study assessed the overall survival (OS) and disease-free survival (DFS) of PDAC patients who underwent upfront pancreatoduodenectomy based on ABO blood groups. METHODS: A cross-sectional study was performed including patients from two university centers. All consecutive head PDAC patients who underwent upfront pancreatoduodenectomy from 2000 to 2016 were included. OS and DFS were compared between blood groups A, B, AB, and O using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 438 patients were included (215 women, median age 67). Pre- and intraoperative details were comparable between all subgroups. Median OS did not differ between the four blood groups (A: 23 months, 95% CI 18-28; B: 32, 95% CI 20-44; AB: 37, 95% CI 18-56 and O: 26, 95% CI 20-32, p = 0.192). Median DFS were also similar (A: 19 months, 95% CI 15-23; B: 26, 95% CI 19-33; AB: 35, 95% CI 15-55 and O: 22, 95% CI 15-29, p = 0.441). There was no OS difference between O and non-O groups (median: 26 months, 95% CI 20-33 vs. 25 months, 95% CI 20-30, p = 0.773). On multivariable analysis blood groups were not prognostic of OS. Only lymph node involvement, tumor differentiation, and adjuvant chemotherapy were independent prognostic factors. CONCLUSION: OS and DFS were similar between all four blood groups after pancreatoduodenectomy. Independent predictors of OS were associated with tumor characteristics and adjuvant treatment.

Convenience behavior in German university students is associated with sociodemographic, study- and health-related factors.

Background: The transition from school to university is often accompanied by a change in students' lifestyles. So far little is known whether convenience behavior is an essential factor affecting students' health and social interaction. In a heterogeneous population regard to sociodemographic and anthropometric characteristics the Convenience Behavior Questionnaire (CBQ) showed a better relationship between convenience-related behavior with overweight and obesity than established questionnaires. Here we assessed convenience behavior in a large well characterized cohort of university students and its association with health-related (mainly sedentary behavior and physical activity), study-related and sociodemographic factors with the Convenience Behavior Questionnaire (CBQ). Methods: A total of 4,351 students participated in an online survey, of which 3,983 (23.6 ± 5.3 years old, 71.3% females) answered the questions concerning convenience behavior. A low value in the CBQ indicates more convenience behavior [Convenience Behavior Index (CBI) range: 3-15]. Differences with regard to sociodemographic (age, gender, body mass index), study-related (semester, degree, field of study) and health-related (physical activity, sedentary behavior) variables were examined with Mann-Whitney-U test or Kruskal-Wallis test and post-hoc tests (Bonferroni). Results: The CBI of men and women differed significantly (z = -6.847, p < 0.001, r = 0.11). First-year students and students beyond their first year showed significant differences (z = -2.355, p ≤ 0.05, r = 0.04). Differences were also found in the field of study (Chi2 (6) = 147.830, p < 0.001) and the targeted degree (Chi2 (7) = 79.985, p < 0.001). Furthermore, differences were found in the body mass index (Chi2 (5) = 70.678, p < 0.001), physical activity (Chi2 (2) = 279.040, p < 0.001) and sedentary behavior (z = -4.660, p < 0.001, r = 0.07). Conclusion: The results showed risk groups of convenience behavior among students [men, first-year, students enrolled in "Science, Technology, Engineering and Mathematics (STEM)," bachelor]. Our results confirm for the first time in a very homogeneous population a gender difference and an association between CBI and health-related factors. Further studies are needed to analyze the health behavior of students in more detail, especially their convenience behavior.

Prognostic value of tumor regression grade (TRG) after oncological gastrectomy for gastric cancer.

PURPOSE: Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS). METHODS: Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted. RESULTS: Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance. CONCLUSIONS: TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS.

[Surgical management of gastrointestinal stromal tumors of gastric origin]. / Prise en charge chirurgicale des tumeurs stromales gastro-intestinales d'origine gastrique.

Gastrointestinal Stromal Tumors (GISTs) account for 1 to 2% of gastrointestinal malignant tumors. They are characterized by overexpression of the tyrosine kinase (KIT). 60% of GISTs originate in the stomach. Managing them remains complex and varies depending on several factors such as location, size, molecular biology, type of clinical presentation, and the risks/benefits of surgical treatment. Surgery remains the only curative treatment, while tyrosine kinase inhibitors have demonstrated their efficacy as systemic treatment in the perioperative context. Risk stratification for recurrence guides the choice of adjuvant treatment, with a recommended duration of 3 years for high-risk patients.

Les tumeurs stromales gastro-intestinales (GIST) constituent entre 1 et 2 % des tumeurs malignes gastro-intestinales. Elles se caractérisent par une surexpression de la tyrosine kinase (KIT). 60 % des GIST sont d'origine gastrique. Leur prise en charge reste complexe et varie selon plusieurs facteurs tels que la localisation, la taille, la biologie moléculaire, le type de manifestation clinique et les risques/bénéfices du traitement chirurgical. La chirurgie demeure le seul traitement curatif, tandis que les inhibiteurs de tyrosine kinase ont démontré leur efficacité comme traitement systémique dans le contexte périopératoire. La stratification du risque de récidive guide le choix du traitement adjuvant, avec une durée recommandée de 3 ans pour les patients à haut risque.

Functional results after hiatal repair and gastropexy without fundoplication in patients with paraoesophageal hernia.

PURPOSE: Paraoesophageal hernias (PEH) are associated with a high complication rate and often occur in elderly and fragile patients. Surgical gastropexy without fundoplication is an accepted alternative procedure; however, outcomes and functional results are rarely described. Our study aims to evaluate short-term outcomes and the long-term quality of life after gastropexy as treatment for PEH. METHODS: Single center cohort analysis of all consecutive patients who underwent gastropexy for PEH without fundoplication. Postoperative outcomes and functional results were retrospectively collected. Reflux symptoms developed postoperatively were reported using the validated quality of life questionnaire: GERD-Health Related Quality of Life Qestionnaire (GERD-HRQL). RESULTS: Thirty patients (median age: 72 years (65-80)) were included, 40% classified as ASA III. Main PEH symptoms were reflux (63%), abdominal/thoracic pain (47%), pyrosis (33%), anorexia (30%), and food blockage (26%). Twenty-six laparoscopies were performed (86%). Major complications (III-IVb) occurred in 9 patients (30%). Seven patients (23%) had PEH recurrence, all re-operated, performing a new gastropexy. Median follow-up was 38 (17-50) months. Twenty-two patients (75%) reported symptoms resolution with median GERD-HRQL scale of 4 (1-6). 72% (n = 21) reported operation satisfaction. GERD-HRQL was comparable between patients who were re-operated for recurrence and others: 5 (2-19) versus 3 (0-6), p = 0.100. CONCLUSION: Gastropexy without fundoplication was performed by laparoscopy in most cases with acceptable complications rates. Two-thirds of patients reported symptoms resolution, and long-term quality-of-live associated to reflux symptoms is good. Although the rate of PEH recurrence requiring a new re-intervention remained increased (23%), it does not seem to affect long-term functional results.

Neoadjuvant Chemotherapy Does Not Improve Survival in cT2N0M0 Gastric Adenocarcinoma Patients: A Multicenter Propensity Score Analysis.

BACKGROUND: According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences. OBJECTIVE: The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients. METHODS: A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups. RESULTS: Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7 ± 12.8 vs. 69.8 ± 12.1 years for S patients; p < 0.001) and had a better health status (World Health Organization performance status = 0 in 60.3% of CS patients vs. 34.5% of S patients; p = 0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW (p = 0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p = 0.42), as was 5-year DFS (70.4% vs. 68.5%; p = 0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW. CONCLUSIONS: Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone.

The association between health behaviours and academic performance moderated by trait mindfulness amongst university students: an observational study.

Objectives: To target health communication at less health-conscious groups, evidence on health behaviours' effects on non-health-related outcomes - such as academic performance - is necessary. Recent research has highlighted the associations of various health behaviours on academic performance of university students. However, there is a lack of research investigating the most predominant health behaviours simultaneously and their association with academic performance, as well as the factors that potentially influence the direction or strength of these associations. Therefore, this study investigated (I) which of the predominant health behaviours (physical activity, healthy diet, sleep, sedentary behaviour, alcohol consumption, smoking, drug use) are most associated with academic performance and (II) whether the personal resource of trait mindfulness moderates these associations. Methods: An online survey was conducted amongst university students during the 2021 summer semester. Group differences in academic performance regarding health behaviours were analysed using ANOVA (N = 1,049). A first linear regression model (N = 571), considering all selected health behaviours simultaneously, assessed their association with academic performance. A second model (N = 540) assessed interaction effects of health behaviours and trait mindfulness. Separate regressions assessed each interaction's association with academic performance. Results: Sleep, fruit and vegetable consumption, and gender were significantly associated with academic performance. The second model showed no significant interaction effects. Conclusion: Targeting sleep and fruit and vegetable consumption might be the most promising strategies for elevating students' academic performance, thereby enabling health communication strategies to reach groups driven by performance improvements rather than health benefits.

Social contact during the COVID-19 pandemic: The role of long-term connectedness and cumulative inequality in later life.

Though the COVID-19 crisis put many older adults at sudden risk of social isolation, the pandemic was far from the "great equalizer" some pundits and politicians initially claimed it would be. Drawing from Cumulative Inequality Theory, I consider how long-run patterns of social dis/connectedness contextualize key disparities in social contact that manifested during the pandemic. I incorporate data from four rounds of the National Social Life, Health, and Aging Project (2005-2021), constructing multiple operationalizations of connectedness accumulation across pre-COVID years and examining several types of social contact during the pandemic, both in-person and remote. Results from ordered logistic regression show that those most durably connected were especially likely to incorporate digital tools for maintaining contact with family and friends. On the other hand, people experiencing more bouts of social disconnection were least likely to see friends during the pandemic, and were yet relatively tolerant of that level of engagement. Even while many older people's level of social dis/connectedness fluctuates over the course of 15 years, it was long-run accumulation patterns-not conditions observed most recently-that best explain their experience of social contact during the pandemic. Findings point to the role of crises in perpetuating and exacerbating key axes of inequality, and suggest points of attention and intervention in COVID's aftermath.

Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis.

BACKGROUND: Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. METHODS: All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. RESULTS: Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. CONCLUSION: This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women.

Age, Political Participation, and Political Context in Africa.

OBJECTIVES: Political participation differs across the age range, but little is known about these patterns outside of developed countries. Political context is a particularly important consideration for all political behavior in Africa, where only a few countries are fully democratic. Drawing from political opportunity structures theory, we investigate how political freedom conditions the age-based pattern of electoral and nonelectoral political engagement, as well as protesting. METHODS: This study merges the fifth, sixth, and seventh rounds of the Afrobarometer data sets, spanning 36 African countries, with country-level data on political freedom from Freedom House. Using multilevel regression models, we examine how political freedom shapes the relationship between age and 3 forms of political participation. RESULTS: Africans aged from 18 to 60 years and living in nonfree countries are most engaged in electoral and nonelectoral political activities, though participation begins to drop markedly past age 60. For protest participation, young Africans living in partially and non-free countries are the most engaged in protests; yet limited political freedom again means a sharp age-based decline. DISCUSSION: The impact of political context on the age-participation association is nuanced in ways not anticipated by mainstream research on the developed West. Repressive regimes, while spurring engagement at younger ages, appear to disproportionately deter older Africans from political engagement, especially its riskiest forms. We conclude by calling for more country-comparative gerontological research with careful attention to contextual heterogeneity, particularly in the understudied Global South.

Conditional reciprocal stressor-strain effects in university students: a cross-lagged panel study in Germany.

University students worldwide are facing increasing mental health challenges. Traditional stress models, like the Job/Study Demand-Resources Model, link stressors directly to strain. Yet, recent studies suggest the influence of strain on stressors may be even stronger. Our research explored these reciprocal dynamics among university students, considering social support and mindfulness as potential moderators. We conducted a two-wave panel study with 264 university students. We ran separate cross-lagged panel structural equation analyses for three key health outcomes-emotional exhaustion, depression, and well-being-each paired with perceived study stressors, specifically workload and work complexity. Findings revealed significant stressor and strain effects, with social support notably moderating the impact of emotional exhaustion on workload. These insights challenge traditional stress theories and underscore the importance of mental health support and effective stress management strategies for students, emphasizing the need for proactive mental health initiatives in academic environments.

On religious ambiguity: Childhood family religiosity and adult flourishing in a twin sample.

Ambiguity is an important notion in sociology, denoting situations where social actors and groups carry on without shared meaning. The current article applies this concept to the context of religiosity during people's upbringing, recognizing that multiple factors make family-level religion a complex experience. Indeed, though recent research portrays household religiosity in childhood as a sociocultural exposure with long-term implications for well-being, existing studies have yet to incorporate multiple inputs to consider the cohesiveness of that exposure. Using twin data from a national sample, we investigate whether consistency in recalled household religiosity is associated with mid-life flourishing. Multi-level linear regression models reveal that similarity in twin reports matter, above and beyond the actual level of religiosity individuals report and net of dis/similarity across other childhood recollections. We conclude that coherence in religious upbringing-whether religion was understood to be important or not-is a key ingredient for thriving later in life and then reflect more broadly on manifestations of sociocultural ambiguity in families and in larger social units.

Low-Dose Radiation Yields Lower Rates of Pathologic Response in Esophageal Cancer Patients.

BACKGROUND: Although neoadjuvant chemoradiation (nCRT) followed by surgery is standard treatment for locally advanced esophageal or gastroesophageal junction (E/GEJ) cancer, the optimal radiation dose is still under debate. OBJECTIVE: The aim of this study was to assess the impact of different preoperative radiation doses (41.4 Gy, 45 Gy or 50.4 Gy) on pathologic response and survival in E/GEJ cancer patients. METHODS: All consecutive patients with E/GEJ tumors, treated with curative intent between January 2009 and December 2016 in two referral centers were divided into three groups (41.4 Gy, 45 Gy and 50.4 Gy) according to the dose of preoperative radiotherapy. Pathologic complete response (pCR) rates, postoperative morbidity, overall survival (OS) and disease-free survival (DFS) were compared among the three groups, with separate analyses for adenocarcinoma (AC) and squamous cell carcinoma (SCC). RESULTS: From the 326 patients analyzed, 48 were included in the 41.4 Gy group (14.7%), 171 in the 45 Gy group (52.5%) and 107 in the 50.4 Gy group (32.8%). Postoperative complication rates were comparable (p = 0.399). A pCR was observed in 15%, 30%, and 34% of patients in the 41.4 Gy, 45 Gy and 50.4 Gy groups, respectively (p = 0.047). A 50.4 Gy dose was independently associated with pCR (odds ratio 2.78, 95% confidence interval 1.10-7.99) in multivariate analysis. Within AC patients, pCR was observed in 6.2% of patients in the 41.4 Gy group, 29.2% of patients in the 45 Gy group, and 22.7% of patients in the 50.4 Gy group (p = 0.035). No OS or DFS differences were observed. CONCLUSIONS: A pCR was less common after a preoperative radiation dose of 41.4 Gy in AC patients. Radiation dose had no impact on postoperative morbidity, long-term survival, and recurrence.

Prospective evaluation of MR-TRG (Tumor Regression Grade) in esophageal cancer after neo-adjuvant therapy: Preliminary results.

PURPOSE: To develop MRI-based criteria to assess tumor response to neoadjuvant therapies (NAT) of esophageal cancers (EC) and to evaluate its diagnostic performance in predicting the pathological Tumor Regression Grade (pTRG). METHOD: From 2018 to 2022, patients with newly diagnosed locally advanced EC underwent MRI examinations for initial staging and restaging after NAT. Magnetic Resonance TRG (MR-TRG), equivalent to the Mandard and Becker classifications, were developed and independently assessed by two radiologists, blinded to pTRG, using T2W and DW-MR Images. All patients underwent surgery and benefited from a blinded pTRG evaluation by two pathologists. The agreement between readers and between MR-TRG and pTRG were assessed with Cohen's Kappa. The correlation of MR-TRG and pTRG was determined using Spearman's correlation. RESULTS: 28 patients were included. Interrater agreement was substantial between radiologists, improved when grouping grade 1 and 2 (κ = 0.78 rose to 0,84 for Mandard and 0.68 to 0,78 for Becker score). Agreement between pTRG and MR-TRG was moderate with a percentaged agreement (p) = 87.5 %, kappa (κ) = 0.54 and p = 83.3 %, κ = 0.49 for Mandard and Becker, respectively. Agreement was improved to substantial when grouping grades 1-2 for Mandard and 1a-1b for Becker with p = 89.3 %, κ = 0.65 and p = 85.2 %, κ = 0.65 respectively. Sensitivity and specificity of MR-TRG in predicting pTRG were 88.2 % and 72.7 % for Mandard system (scores 1-2 versus 3-5), and 83.3 % and 80 % for Becker system (scores 1a-1b versus 2-3). CONCLUSION: A substantial agreement between MR-TRG and pTRG was achieved when grouping grade 1-2. Hence, MR-TRG could be used as a surrogate of complete and near-complete pTRG.

Cigarette Smoking, Risky Alcohol Consumption, and Marijuana Smoking among University Students in Germany: Identification of Potential Sociodemographic and Study-Related Risk Groups and Predictors of Consumption.

(1) Background: Cigarette smoking, risky alcohol consumption, and marijuana smoking are the most common behaviors related to legal and illicit drug use worldwide, including among university students. To plan effective evidence-based programs to prevent the risky consumption of these substances among university students, the present study aimed to identify potential sociodemographic and study-related risk groups and predictors of consumption. (2) Methods: A cross-sectional online health survey with approximately 270 health-related items was conducted among students at the University of Mainz, Germany. Cigarette smoking, risky alcohol consumption (AUDIT-C score: female ≥ 4, male ≥ 5), and marijuana smoking were chosen as dependent variables. Of the 270 health-related items, 56 were chosen as independent variables and collated into five groups (sociodemographic, psychological, study-related psychosocial, general psychosocial and health behavior). The prevalence of cigarette smoking, risky alcohol consumption, and marijuana smoking was assessed using established and validated instruments. Pearson's chi-square test was used to analyze the differences in prevalence between the sociodemographic and study-related groups, and binary logistic regression was used for analyses with stepwise inclusion of the five variable groups. (3) Results: Of the 3991 university students who entered the analyses, 14.9% reported smoking cigarettes, 38.6% reported risky alcohol consumption, and 10.9% reported smoking marijuana. The prevalence of these differed between genders, fields of study, and aspired degree level, among other factors. Binary logistic regression analyses revealed nine significant predictors (p ≤ 0.05) of cigarette smoking (Nagelkerke R2 = 0.314), 18 significant predictors of risky alcohol consumption (Nagelkerke R2 = 0.270), and 16 significant predictors of marijuana smoking (Nagelkerke R2 = 0.239). (4) Conclusions: This study showed cigarette smoking, risky alcohol consumption, and marijuana smoking among university students in Germany to be associated with multiple factors, especially health behaviors. Furthermore, each of the substances was highly associated with each of the two other substances we examined. Other variable groups, such as psychological or psychosocial variables, seemed to play a rather minor role. Therefore, our recommendation for future prevention programs is that substance use among university students should be addressed as a whole, not just in terms of specific substances.

Impact of preoperative statin medication on long-term outcomes after pancreatoduodenectomy for ductal adenocarcinoma: an international multicentric cross-sectional study.

PURPOSE: Statin treatment has been shown in certain population studies and meta-analyses to improve survival of patients with pancreatic ductal adenocarcinoma (PDAC). This study assessed if patients with statin treatment had better overall survival (OS) and disease-free survival (DFS) after upfront pancreatoduodenectomy for PDAC. METHODS: Consecutive PDAC patients were retrospectively collected from three centers in Europe and USA (study period: 2000-2017). Adult patients who underwent upfront pancreatoduodenectomy and survived the first 90 postoperative days were included. Patients with metastasis at diagnosis or with macroscopic incomplete resection were excluded. Patients were considered under statin if started at least one month before pancreatoduodenectomy. Survival rates were calculated using Kaplan-Meier method and compared with log-rank test. RESULTS: A total of 496 patients were included. Median age was 67 years (IQR 59-75), 48% (n = 236) were women, and 141 patients (28%) received statin treatment already preoperatively. Patients with and without statin treatment were comparable in terms of demographics and pre-/intraoperative characteristics, except for age and pre-existing diabetes. Median OS and DFS were similar in patients with and without statin treatment (OS: 29, 95% CI 22-36 vs. 27 months, 95% CI 22-32, p = 0.370, DFS: 18, 95% CI 14-22 vs. 16 months, 95% CI 14-18, p = 0.430). On multivariable Cox regression, lymph node involvement (HR 1.9, 95% CI 1.6-2.2, p < 0.001), tumor differentiation (HR 1.3, 95% CI 1.1-1.6, p = 0.003), and postoperative chemotherapy (HR 0.5, 95% CI 0.4-0.7, p < 0.001) were predictors of OS, whereas statin treatment was not a prognostic factor (HR 0.9, 95% CI 0.7-1.2, p = 0.376). CONCLUSION: In this international cohort of PDAC patients, statin treatment did not influence survival after upfront pancreatoduodenectomy. Nodal involvement, tumor differentiation, and postoperative chemotherapy were independent predictors of OS.

Essential role of the Pax5 C-terminal domain in controlling B cell commitment and development.

The B cell regulator Pax5 consists of multiple domains whose function we analyzed in vivo by deletion in Pax5. While B lymphopoiesis was minimally affected in mice with homozygous deletion of the octapeptide or partial homeodomain, both sequences were required for optimal B cell development. Deletion of the C-terminal regulatory domain 1 (CRD1) interfered with B cell development, while elimination of CRD2 modestly affected B-lymphopoiesis. Deletion of CRD1 and CRD2 arrested B cell development at an uncommitted pro-B cell stage. Most Pax5-regulated genes required CRD1 or both CRD1 and CRD2 for their activation or repression as these domains induced or eliminated open chromatin at Pax5-activated or Pax5-repressed genes, respectively. Co-immunoprecipitation experiments demonstrated that the activating function of CRD1 is mediated through interaction with the chromatin-remodeling BAF, H3K4-methylating Set1A-COMPASS, and H4K16-acetylating NSL complexes, while its repressing function depends on recruitment of the Sin3-HDAC and MiDAC complexes. These data provide novel molecular insight into how different Pax5 domains regulate gene expression to promote B cell commitment and development.

Distance in Disconnection: The Varied Impact of Core Network Losses on Loneliness Among Older Europeans.

OBJECTIVES: Research among older adults reveals that the loss of core network members is a risk factor for loneliness. Still, it is not clear whether all such losses induce similar levels of loneliness, particularly as network members are distributed at varied geographic distances. Neither is it clear whether tie addition-the other ubiquitous aspect of network turnover in later life-offsets the loneliness that arises from different network loss scenarios. METHODS: This paper scrutinized core network losses across multiple relationship-distance scenarios. We used the fourth and sixth waves of data from the Survey of Health, Ageing, and Retirement in Europe and estimated fixed-effect models. RESULTS: The loss of a child from a core network increases feelings of loneliness across variant distances, especially when not complemented by additional connections. Losing relatives or nonkin core connections in proximity (within 1 km and 5 km radius, respectively) is also associated with increased loneliness, yet such effects are also largely mitigated by the addition of new core network members. DISCUSSION: The relationship between core network member losses and loneliness can significantly differ based on the nature of the lost connection and its geographic distance. Active rebalancing of one's core network following losses and proactive network expansion can serve as pivotal strategies to prevent loneliness for the aging population.