Radiofrequency-assisted transection of the pancreas vs stapler in distal pancreatectomy: a propensity score matched cohort analysis

[EN] To demonstrate the efficacy of radiofrequency for pancreatic stump closure in reducing the incidence of postoperative pancreatic fistula (POPF) in distal pancreatectomy (DP) compared with mechanical transection methods. Despite all the different techniques of pancreatic stump closure proposed for DP, best practice for avoiding POPF remains an unresolved issue, with an incidence of up to 30% regardless of center volume or surgical expertise. DP was performed in a cohort of patients by applying radiofrequency to stump closure (RF Group) and compared with mechanical closure (Control Group). A propensity score (PS) matched cohort study was carried out to minimize bias from nonrandomized treatment assignment. Cohorts were matched by PS accounting for factors significantly associated with either undergoing RF transection or mechanical closure through logistic regression analysis. The primary end-point was the incidence of clinically relevant POPF (CR-POPF). Of 89 patients included in the whole cohort, 13 case patients from the RF-Group were 1:1 matched to 13 control patients. In both the first independent analysis of unmatched data and subsequent adjustment to the overall propensity score-matched cohort, a higher rate of CR-POPF in the Control Group compared with the RF-Group was detected (25.4% vs 5.3%, p = 0.049 and 53.8% vs 0%; p = 0.016 respectively). The RF Group showed better outcomes in terms of readmission rate (46.2% vs 0%, p = 0.031). No significant differences were observed in terms of mortality, major complications (30.8% vs 0%, p = 0.063) or length of hospital stay (5.7 vs 5.2 days, p = 0.89). Findings suggest that the RF-assisted technique is more efficacious in reducing CR-POPF than mechanical pancreatic stump closure.This work was supported completely by a grant for medical research from the Catalan Surgery Society. Project PI20/00008, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European UnionPueyo-Périz, E.; Téllez-Marquès, C.; Radosevic, A.; Morató, O.; Visa, L.; Ilzarbe, L.; Berjano, E.... (2022). Radiofrequency-assisted transection of the pancreas vs stapler in distal pancreatectomy: a propensity score matched cohort analysis. Scientific Reports. 12(1):1-8. https://doi.org/10.1038/s41598-022-11583-01812

Mean muscle attenuation correlates with severe acute pancreatitis unlike visceral adipose tissue and subcutaneous adipose tissue

Background: Acute pancreatitis (AP) is a frequent disorder with considerable morbidity and mortality. Obesity has previously been reported to influence disease severity. Objective The aim of this study was to investigate the association of adipose and muscle parameters with the severity grade of AP. Methods: In total 454 patients were recruited. The first contrast-enhanced computed tomography of each patient was reviewed for adipose and muscle tissue parameters at L3 level. Associations with disease severity were analysed through logistic regression analysis. The predictive capacity of the parameters was investigated using receiver operating characteristic (ROC) curves. Results: No distinct variation was found between the AP severity groups in either adipose tissue parameters (visceral adipose tissue and subcutaneous adipose tissue) or visceral muscle ratio. However, muscle mass and mean muscle attenuation differed significantly with p-values of 0.037 and 0.003 respectively. In multivariate analysis, low muscle attenuation was associated with severe AP with an odds ratio of 4.09 (95% confidence intervals: 1.61-10.36, p-value 0.003). No body parameter presented sufficient predictive capability in ROC-curve analysis. Conclusions: Our results demonstrate that a low muscle attenuation level is associated with an increased risk of severe AP. Future prospective studies will help identify the underlying mechanisms and characterise the influence of body composition parameters on AP.Peer reviewe

Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses.

OBJECTIVES: To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI). DESIGN: Information about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data. Multivariate logistic regression models were applied to derive ORs and 95% CIs. T2DM and PC-related single nucleotide polymorphism (SNP) were used as instrumental variables (IVs) in bidirectional MR analysis to test for two-way causal associations between PC, NODM and LSDM. Indirect and direct effects of the BMI-T2DM-PC association were further explored using mediation analysis. RESULTS: T2DM was associated with an increased PC risk when compared with non-T2DM (OR=2.50; 95% CI: 2.05 to 3.05), the risk being greater for NODM (OR=6.39; 95% CI: 4.18 to 9.78) and insulin users (OR=3.69; 95% CI: 2.80 to 4.86). The causal association between T2DM (57-SNP IV) and PC was not statistically significant (ORLSDM=1.08, 95% CI: 0.86 to 1.29, ORNODM=1.06, 95% CI: 0.95 to 1.17). In contrast, there was a causal association between PC (40-SNP IV) and NODM (OR=2.85; 95% CI: 2.04 to 3.98), although genetic pleiotropy was present (MR-Egger: p value=0.03). Potential mediating effects of BMI (125-SNPs as IV), particularly in terms of weight loss, were evidenced on the NODM-PC association (indirect effect for BMI in previous years=0.55). CONCLUSION: Findings of this study do not support a causal effect of LSDM on PC, but suggest that PC causes NODM. The interplay between obesity, PC and T2DM is complex

Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age

MAPC transplantation confers a more durable benefit than AC133+ cell transplantation

There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133+ cells and Multipotent Adult Progenitor Cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133+ cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days post-transplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133+-injected animals. While transplantation of hAC133+ cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis and improved muscle regeneration. Incorporation of differentiated hAC133+ or hMAPC progeny into new vessels was limited, however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-, but not hAC133+-conditioned media, stimulated vascular cell proliferation and prevented myoblast, endothelial and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133+ cell and hMAPC transplantation bothcontribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer-term functional improvement

Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches

This is the peer reviewed version of the following article: Gomez‐Rubio, P. , Piñero, J. , Molina‐Montes, E. , Gutiérrez‐Sacristán, A. , Marquez, M. , Rava, M. , Michalski, C. W., Farré, A. , Molero, X. , Löhr, M. , Perea, J. , Greenhalf, W. , O'Rorke, M. , Tardón, A. , Gress, T. , Barberá, V. M., Crnogorac‐Jurcevic, T. , Muñoz‐Bellvís, L. , Domínguez‐Muñoz, E. , Balsells, J. , Costello, E. , Yu, J. , Iglesias, M. , Ilzarbe, L. , Kleeff, J. , Kong, B. , Mora, J. , Murray, L. , O'Driscoll, D. , Poves, I. , Lawlor, R. T., Ye, W. , Hidalgo, M. , Scarpa, A. , Sharp, L. , Carrato, A. , Real, F. X., Furlong, L. I., Malats, N. and , (2019), Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case–control approaches. Int. J. Cancer. doi:10.1002/ijc.31866, which has been published in final form at https://doi.org/10.1002/ijc.31866. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Acción Especial de Genómica, Spain. Grant Number: #GEN2001‐4748‐c05‐03 Swedish ALF. Grant Number: #SLL20130022 Cancer Focus Northern Ireland and Department for Employment and Learning EU H2020 Programme 2014‐2020. Grant Number: 634143 MedBioinformatics676559 Elixir‐Excelerate EU‐6FP Integrated Project. Grant Number: #018771‐MOLDIAG‐PACA EU‐FP7‐HEALTH. Grant Number: #256974‐EPC‐TM‐Net#259737‐CANCERALIA#602783‐ Cam‐Pac Italian Foundation for Cancer Research (FIRC) Italian Ministry of Health. Grant Number: FIMPCUP_J33G13000210001 Red Temática de Investigación Cooperativa en Cáncer, Spain. Grant Number: #RD12/0036/0050#RD12/0036/ 0073(#RD12/0036/0034 The work was partially supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III‐FEDER, Spain. Grant Number: #PI0902102#PI11/01542#PI12/ 00815#PI12/01635#PI13/ 00082CP10/00524PI15/01573 World Cancer Research Fund. Grant Number: WCR #15‐039

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk

Background Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. Methods Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. Results Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01–12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11–2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36–0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9–16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29–2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. Conclusions Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives

Background Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies

Profilaxis del tromboembolismo venoso en embarazo y puerperio: actualización en tiempos de infección por COVID-19

Coronavirus (COVID-19) disease is a highly contagious pandemic disease caused by a novel coronavirus (SARS-CoV-2). It appeared in Wuhan, Hubei, province of China, in November 2019. It may predispose patients to thrombotic disease due to excessive inflammation (cytokine storm), platelet activation, endothelial dysfunction, and stasis. Increased odds of in hospital deaths were associated with remarkably high D-dimer values. Actually, called COVID-19 associated coagulopathy, in particular in pregnancy it is an exceptional challenge for the health systems.There are limited case series reporting the impact on women affected by COVID-19. The first case in our country appeared in March 2020. Pregnancy fulfils the three criteria of Virchow’s triad. The optimalthromboprophylaxis in COVID-19 pregnant women is not known. We work with the combination of the available information at time of this publication, together with our experience and adapted to our hospital requirements. Low molecular weight heparin (LMWH) enoxaparin 40 mg/d was prescribed to pregnant women COVID-19. Outpatient prolongation of thromboprophylaxis depends on risk stratification. In this  article we review the information from other countries, and we describe our venous thromboprophylaxis recommendations.La enfermedad por coronavirus 2019 (COVID-19), considerada desde marzo por la OMS una pandemia, es una infección altamente contagiosa causada por un nuevo coronavirus responsable del síndrome respiratorio agudo relacionado al coronavirus 2 (SARS-CoV-2). Apareció en Wuhan, Hubei, provincia de China, en noviembre de 2019. Puede predisponer a los pacientes a enfermedad trombótica debido a la excesiva inflamación (tormenta de citoquinas), activación plaquetaria, disfunción endotelial y estasis. El incremento del riesgo de muerte se asocia con un marcado incremento de los valores de dímero-D.Actualmente es considerada como una coagulopatía asociada a COVID-19 (CAC). En particular, en embarazo, la infección por COVID-19 es un desafío excepcional para el sistema de salud. El primer caso en Argentina apareció en marzo 2020. En el embarazo se presentan los tres elementos de la clásica tríada de Virchow. El régimen óptimo de tromboprofilaxis en embarazadas con COVID-19 no está establecido. Nosotros trabajamos en base a lo reportado en publicaciones, en conjunto con nuestra experiencia y adaptado a los requerimientos hospitalarios. En embarazadas COVID-19 positivas que se hospitalizan se recomienda la administración de heparina de bajo peso molecular 40 mg/día enoxaparina o heparina no fraccionada en caso de cercanía de parto.La prolongación de la tromboprofilaxis en pacientes externados, ya sea que continúen su embarazo o luego del parto, requiere de una estratificación en base a sus factores de riesgo y evolución del cuadroinfeccioso. En este trabajo revisamos la experiencia de otros países y describimos nuestras recomendaciones