Targeting dendritic cells in pancreatic ductal adenocarcinoma

Dendritic cells (DC) are an integral part of the tumor microenvironment. Pancreatic cancer is characterized by reduced number and function of DCs, which impacts antigen presentation and contributes to immune tolerance. Recent data suggest that exosomes can mediate communication between pancreatic cancer cells and DCs. Furthermore, levels of DCs may serve as prognostic factors. There is also growing evidence for the effectiveness of vaccination with DCs pulsed with tumor antigens to initiate adaptive cytolytic immune responses via T cells. Most experience with DC-based vaccination has been gathered for MUC1 and WT1 antigens, where clinical studies in advanced pancreatic cancer have provided encouraging results. In this review, we highlight the role of DC in the course, prognosis and treatment of pancreatic cancer

Goodwill och nedskrivningar - En jämförande studie mellan landet lagom och landet mycket

Syfte: Syftet med denna studie är att undersöka skillnaden i hantering av goodwill mellan Sverige och USA under perioden år 2006 till 2012, med hjälp av varje enskilts land gällande regelverk. Vidare kommer en undersökning av tidigare studier i ämnet göras för att försöka förklara övriga möjliga faktorer som påverkar goodwill. Metod: Metoden som användes i studien är kvantitativ med en deduktiv ansats. Ett urval av sekundär data gjordes för de båda länderna. En spegelbild med 132 företag skapades därefter på den amerikanska marknaden av de 132 valda svenska företagen, för att undersöka skillnaden mellan länderna. Slutligen analyserades insamlad data genom linjediagram, t-test och multipel regression. Teoretiskt ramverk: Teorin i studien består av de två regelverken IFRS och US-GAAP, samt tidigare studier. Fokus för tidigare studier har legat på goodwill och nedskrivningar, men även på andra variabler som kan ha en påverkan på ett företags nedskrivningar. Empiri: Empirin som används i studien är sekundär data samlad i en spegelbild, där data från 132 företag från varje enskilt land används. Balansomslutning, goodwill, EBITDA och land testas som oberoende i den multipla regressionen för nedskrivningar. Slutsats: Studiens slutsats kom fram till att det föreligger en skillnad i hanteringen av goodwill mellan Sverige och USA. Vidare kan denna skillnad förklaras till följd av olika regelverk, handlingsutrymmen och övervakning av implementering av regelverken

A Wireless Future: performance art, interaction and the brain-computer interfaces

Although the use of Brain-Computer Interfaces (BCIs) in the arts originates in the 1960s, there is a limited number of known applications in the context of real-time audio-visual and mixed-media performances and accordingly the knowledge base of this area has not been developed sufficiently. Among the reasons are the difficulties and the unknown parameters involved in the design and implementation of the BCIs. However today, with the dissemination of the new wireless devices, the field is rapidly growing and changing. In this frame, we examine a selection of representative works and artists, in comparison to the current scientific evidence. We identify important performative and neuroscientific aspects, issues and challenges. A model of possible interactions between the performers and the audience is discussed and future trends regarding liveness and interconnectivity are suggested

Impact of Age and HIV Status on Immune Activation, Senescence and Apoptosis

Introduction: Residual immune dysfunctions, resembling those that occur during normal aging, may persist even in well-treated people with HIV (PWH), and accelerated aging has been proposed. We aimed to determine if HIV infection is an independent risk factor for T-cell immune dysfunctions including increased immune activation, senescence and apoptosis. Moreover, in PWH we aimed to identify the associations between age and immune activation, senescence and apoptosis. Materials and Methods: We included 780 PWH with suppressed viral replication (<50 copies/mL) and absence of hepatitis B and hepatitis C co-infection and 65 uninfected controls from the Copenhagen Co-morbidity in HIV Infection (COCOMO) Study. Flow cytometry was used to determine T-cell activation (CD38+HLA-DR+), senescence (CD28-CD57+), and apoptosis (CD28-CD95+). T-cell subsets are reported as proportions of CD4+ and CD8+ T-cells. We defined an elevated proportion of a given T-cell subset as above the 75th percentile. Regression models were used to determine the association between HIV status and T-cell subset and in PWH to determine the association between age or HIV-specific risk factors and T-cell subsets. Furthermore, an interaction between HIV status and age on T-cell subsets was investigated with an interaction term in models including both PWH and controls. Models were adjusted for age, sex, BMI, and smoking status. Results: In adjusted models a positive HIV status was associated with elevated proportions of CD8+ activated (p = 0.009), CD4+ senescent (p = 0.004), CD4+ apoptotic (p = 0.002), and CD8+ apoptotic (p = 0.003) T-cells. In PWH a 10-year increase in age was associated with higher proportions of CD4+ and CD8+ senescent (p = 0.001 and p < 0.001) and CD4+ and CD8+ apoptotic T-cells (p < 0.001 and p < 0.001). However, no interaction between HIV status and age was found. Furthermore, in PWH a CD4+/CD8+ ratio < 1 was associated with elevated proportions of T-cell activation, senescence, and apoptosis. Discussion: We found evidence of residual T-cell immune dysfunction in well-treated PWH without HBV or HCV co-infection, and age was associated with T-cell senescence and apoptosis. Our data supports that HIV infection has similar effects as aging on T-cell subsets. However, since no interaction between HIV status and age was found on these parameters, we found no evidence to support accelerated immunological aging in PWH

Ideal Outcome After Pancreatoduodenectomy:A Transatlantic Evaluation of a Harmonized Composite Outcome Measure

OBJECTIVE: The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden. BACKGROUND: Assessing outcomes after pancreatoduodenectomy among centers and countries requires a broad evaluation that cannot be captured by a single parameter. Previously, 2 composite outcome measures (textbook outcome and optimal pancreatic surgery) for pancreatoduodenectomy have been described from Europe and the United States. These composites were harmonized into ideal outcome (IO). METHODS: This analysis is a transatlantic retrospective study (2018-2020) of patients after pancreatoduodenectomy within the registries from North America, Germany, The Netherlands, and Sweden. After 3 consensus meetings, IO for pancreatoduodenectomy was defined as the absence of all 6 parameters: (1) in-hospital mortality, (2) severe complications-Clavien-Dindo ≥3, (3) postoperative pancreatic fistula-International Study Group of Pancreatic Surgery (ISGPS) grade B/C, (4) reoperation, (5) hospital stay &gt;75th percentile, and (6) readmission. Outcomes were evaluated using relative largest difference (RLD) and absolute largest difference (ALD), and multivariate regression models. RESULTS: Overall, 21,036 patients after pancreatoduodenectomy were included, of whom 11,194 (54%) reached IO. The rate of IO varied between 55% in North America, 53% in Germany, 52% in The Netherlands, and 54% in Sweden (RLD: 1.1, ALD: 3%, P &lt;0.001). Individual components varied with an ALD of 2% length of stay, 4% for in-hospital mortality, 12% severe complications, 10% postoperative pancreatic fistula, 11% reoperation, and 9% readmission. Age, sex, absence of chronic obstructive pulmonary disease, body mass index, performance status, American Society of Anesthesiologists (ASA) score, biliary drainage, absence of vascular resection, and histologic diagnosis were associated with IO. In the subgroup of patients with pancreatic adenocarcinoma, country, and neoadjuvant chemotherapy also was associated with improved IO. CONCLUSIONS: The newly developed composite outcome measure "Ideal Outcome" can be used for auditing and comparing outcomes after pancreatoduodenectomy. The observed differences can be used to guide collaborative initiatives to further improve the outcomes of pancreatic surgery.</p

Transatlantic registries of pancreatic surgery in the United States of America, Germany, the Netherlands, and Sweden: Comparing design, variables, patients, treatment strategies, and outcomes

Background: Registries of pancreatic surgery have become increasingly popular as they facilitate both quality improvement and clinical research. We aimed to compare registries for design, variables collected, patient characteristics, treatment strategies, clinical outcomes, and pathology. Methods: Registered variables and outcomes of pancreatoduodenectomy (2014–2017) in 4 nationwide or multicenter pancreatic surgery registries from the United States of America (American College of Surgeons National Surgical Quality Improvement Program), Germany (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie - Studien-, Dokumentations- und Qualitätszentrum), the Netherlands (Dutch Pancreatic Cancer Audit), and Sweden (Swedish National Pancreatic and Periampullary Cancer Registry) were compared. A core registry set of 55 parameters was identified and evaluated using relative and absolute largest differences between extremes (smallest versus largest). Results: Overall, 22,983 pancreatoduodenectomies were included (15,224, 3,558, 2,795, and 1,406 in the United States of America, Germany, the Netherlands, and Sweden). Design of the registries varied because 20 out of 55 (36.4%) core parameters were not available in 1 or more registries. Preoperative chemotherapy in patients with pancreatic ductal adenocarcinoma was administered in 27.6%, 4.9%, 7.0%, and 3.4% (relative largest difference 8.1, absolute largest difference 24.2%, P < .001). Minimally invasive surgery was performed in 7.8%, 4.5%, 13.5%, and unknown (relative largest difference 3.0, absolute largest difference 9.0%, P < .001). Median length of stay was 8.0, 16.0, 12.0, and 11.0 days (relative largest difference 2.0, absolute largest difference 8.0, P < .001). Reoperation was performed in 5.7%, 17.1%, 8.7%, and 11.2% (relative largest difference 3.0, absolute largest difference 11.4%, P < .001). In-hospital mortality was 1.3%, 4.7%, 3.6%, and 2.7% (relative largest difference 3.6, absolute largest difference 3.4%, P < .001). Conclusion: Considerable differences exist in the design, variables, patients, treatment strategies, and outcomes in 4 Western registries of pancreatic surgery. The absolute largest differences of 24.3% for the use of preoperative chemotherapy, 9.0% for minimally invasive surgery, 11.4% for reoperation rate, and 3.4% for in-hospital mortality require further study and improvement. This analysis provides 55 core parameters for pancreatic surgery registries

Short- and Long-Term Results of Open Versus Laparoscopic Appendectomy

Clinical advantages of laparoscopic appendectomy have been shown in numerous trials and reviews. Most of these advantages are small and of limited clinical relevance, while laparoscopic operation costs are reported to be higher. The present study compares short- and long-term results of conventional appendectomy with or without diagnostic laparoscopy (OA), and laparoscopic appendectomy (LA). All adult patients who underwent appendectomy in our institution from 1995 to 2005 were included retrospectively. Patient data were retrieved from medical records, questionnaires sent by mail, and records of general practitioners. Primary outcome parameters were long-term complications, readmissions, and reinterventions (> 30 days postoperatively). Secondary outcome parameters were short-term complications, readmissions, and reinterventions (a parts per thousand currency sign30 days postoperatively). A total of 755 patients were included, 545 of whom underwent OA, with the remaining 210 undergoing LA. In the long term there were few complications noted, and there were no significant differences in complications between the two groups. Within 30 days postoperatively, LA was associated with a significantly higher incidence of abdominal abscesses with consequent diagnostic investigations, interventions, and readmissions. Although laparoscopic appendectomy is known to deliver clinical advantages, it is associated with a higher incidence of abdominal abscesses. Because the procedure is about to become the standard of care, future research must be directed at solving this issue. The expected lower incidence of incisional hernia and small bowel obstruction after laparoscopic appendectomy was not shown in the present stud

The inpatient burden of abdominal and gynecological adhesiolysis in the US

<p>Abstract</p> <p>Background</p> <p>Adhesions are fibrous bands of scar tissue, often a result of surgery, that form between internal organs and tissues, joining them together abnormally. Postoperative adhesions frequently occur following abdominal surgery, and are associated with a large economic burden. This study examines the inpatient burden of adhesiolysis in the United States (i.e., number and rate of events, cost, length of stay [LOS]).</p> <p>Methods</p> <p>Hospital discharge data for patients with primary and secondary adhesiolysis were analyzed using the 2005 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. Procedures were aggregated by body system.</p> <p>Results</p> <p>We identified 351,777 adhesiolysis-related hospitalizations: 23.2% for primary and 76.8% for secondary adhesiolysis. The average LOS was 7.8 days for primary adhesiolysis. We found that 967,332 days of care were attributed to adhesiolysis-related procedures, with inpatient expenditures totaling $2.3 billion ($1.4 billion for primary adhesiolysis; $926 million for secondary adhesiolysis). Hospitalizations for adhesiolysis increased steadily by age and were higher for women. Of secondary adhesiolysis procedures, 46.3$220 million in attributable costs.</p> <p>Conclusions</p> <p>Adhesiolysis remain an important surgical problem in the United States. Hospitalization for this condition leads to high direct surgical costs, which should be of interest to providers and payers.</p