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

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

Research of working area development parameters in conditions of deep steep deposit finalizing

Отримано формули розрахунку об’єму запасів корисних копалин в приконтурній та глибинній зоні. Встановлено характер впливу параметрів доробки глибоких крутоспадних родовищ відкритим способом на доцільне положення поточних та проектних контурів кар’єру. Встановлено, що найменший середній коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу в проектному положенні. Найменший поточний коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу, а також робочого борту кар'єру в поточному положенні

Adhesion Awareness: A National Survey of Surgeons

Contains fulltext : 87943.pdf (publisher's version ) (Closed access)BACKGROUND: Postoperative adhesions are the most frequent complication of abdominal surgery, leading to high morbidity, mortality, and costs. However, the problem seems to be neglected by surgeons for largely unknown reasons. METHODS: A survey assessing knowledge and personal opinion about the extent and impact of adhesions was sent to all Dutch surgeons and surgical trainees. The informed-consent process and application of antiadhesive agents were questioned in addition. RESULTS: The response rate was 34.4%. Two thirds of all respondents (67.7%) agreed that adhesions exert a clinically relevant, negative effect. A negative perception of adhesions correlated with a positive attitude regarding adhesion prevention (rho = 0.182, p < 0.001). However, underestimation of the extent and impact of adhesions resulted in low knowledge scores (mean test score 37.6%). Lower scores correlated with more uncertainty about indications for antiadhesive agents which, in turn, correlated with never having used any of these agents (rho = 0.140, p = 0.002; rho = 0.095, p = 0.035; respectively). Four in 10 respondents (40.9%) indicated that they never inform patients on adhesions and only 9.8% informed patients routinely. A majority of surgeons (55.9%) used antiadhesive agents in the past, but only a minority (13.4%) did in the previous year. Of trainees, 82.1% foresaw an increase in the use of antiadhesive agents compared to 64.5% of surgeons (p < 0.001). CONCLUSIONS: The magnitude of the problem of postoperative adhesions is underestimated and informed consent is provided inadequately by Dutch surgeons. Exerting adhesion prevention is related to the perception of and knowledge about adhesions.1 december 201

Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis