Serum anti-beta2-glycoprotein-I and anticardiolipin antibodies during thrombosis in systemic lupus erythematosus patients

PURPOSE: Antibodies to beta2-glycoprotein-I are more strongly associated with clinical antiphospholipid syndrome than are anticardiolipin antibodies. We previously found a decrease in anticardiolipin antibodies at the time of thrombosis in 6 patients with systemic lupus erythematosus (SLE). We therefore sought to determine the prevalence and levels of antibodies to beta2-glycoprotein-I and to cardiolipin before, during, and after thrombosis in patients with SLE, and to compare them with patients who did not have thrombosis. METHODS: We studied 24 patients with SLE who had at least one episode of thrombosis and 102 patients with SLE without thrombosis. Serum anticardiolipin antibodies were measured by conventional enzyme-linked immunosorbent assay (ELISA) using newborn calf serum as the blocking agent. Serum anti-beta2-glycoprotein-I antibodies were measured by ELISA on nonirradiated plates, using purified human beta2-glycoprotein-I without phospholipid. RESULTS: All patients with thrombosis had anti-beta2-glycoprotein-I antibodies, compared with only 17% of controls (P <0.0001). We observed a significant decrease in serum anti-beta2-glycoprotein-I levels at the time of thrombosis, as compared with previous and subsequent samples. The prevalence and levels of IgG and IgM anticardiolipin antibodies were similar in patients with and without thrombosis. A decrease in IgG or IgM anticardiolipin titers occurred during thrombosis in 6 patients. Anticoagulant, corticosteroid, and immunosuppressive treatments did not appear to affect anti-beta2-glycoprotein-I levels at the time of thrombosis. CONCLUSION: Anti-beta2-glycoprotein-I antibodies are strongly associated with thrombosis in patients with SLE. The decrease of anti-beta2-glycoprotein-I levels at the time of thrombosis may indicate a pathogenic role. This antibody may also be a marker of predisposition for thrombosis in these patients.     

Treatment with Low Doses of Polyclonal Immunoglobulin Improves B Cell Function During Immune Reconstitution in a Murine Model

Propose

After autologous stem cell transplantation (ASCT) the immunological B cell compartment recovers slowly. Delays on the recovery of B cell function after autologous stem cell transplantation are due to the low lymphocytes count and to their intrinsic dysfunction.

Methods

We studied the in vivo B cell reconstitution after ASCT examining the independent effect of polyclonal IgG (PolyIg), Fab or Fc fragments infusions in a murine animal model during a period of 12 weeks. These molecules were used in low doses, mimicking the recommended use of IVIg in the case of hypogammaglobulinemia in humans. Flow cytometry analysis and ELISA tests were conducted to monitor the reconstitution of B cells and serum immunoglobulin production. Panama blot and PCA factor 1 analysis were used to study the kinetics of immunoglobulin repertoires reconstitution. Mechanistic studies were also performed using in vitro cell culture.

Results

During follow-up after ASCT, peripheral B cells expand independently of treatment, correcting the immediate increase in sBAFF (soluble B cell activating factor) induced by previous intense myeloablation. Treatments with Fab and Fc fragments infusions promote significant IgM and IgG production comparing to control. Although the complete recovery of antibody repertoire is only achieved at the end of follow-up after ASCT, there is an earlier and significantly stronger recovery in the treated mice, which is evident at 9 weeks after ASCT. At 30 weeks after ASCT, normal values of antibody repertoire were detected in all individuals. Mechanistic studies show that Fab and Fc fragments promote IgG1 production by indirect pathways.

Conclusions

The results presented here demonstrate that polyclonal immunoglobulin indirectly improves the function of the reconstituted B cells and their IgG production by means of Fc-mediated effects on bystander cells. These results further stimulate the discussion about the advantages of IVIg therapy during immune reconstitution after human ASCT.     

Prognostic value of the immunohistochemical expression of vascular endothelial growth factors in malignant salivary gland neoplasms: a systematic review and meta-analysis

Background The immunohistochemical expression of vascular endothelial growth factor is a prognostic marker in several cancer types. In salivary gland tumors, the association between vascular endothelial growth factor and prognosis remains unclear. The purpose of this study was to perform a systematic review and meta-analysis to assess whether the immunohistochemical expression of vascular endothelial growth factor in patients with salivary gland neoplasms presents prognostic value. Material and Methods Immunohistochemical studies assessing the predictive value of vascular endothelial growth factor in salivary gland neoplasms were systematically reviewed using PubMed, Scopus, Embase, Cochrane Library, and Web of Science databases. It was assessed any survival rates. The fixed-effect model with an adjusted hazard ratio (HR) and 95% confidence intervals (95% CI) as effect measures were performed in the meta-analysis. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of the included studies, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system. Results The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivary gland neoplasms was associated with shortened survival (HR=5.37, 95% CI: 2.67-10.83, P = 0.00001). In addition, the presence of vascular endothelial growth factor was tightly associated with tumor size, lymph node metastasis, clinical stage, perineural invasion, vascular invasion, poor local control of the disease, and recurrence. Conclusions The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivary gland neoplasms has prognostic value and was associated with decreased survival time. However, more primary well-designed studies are necessary to increase the level of evidence. Key words:Salivary gland neoplasms, salivary glands, head and neck neoplasms, vascular endothelial growth factors, prognosis.     

Reliability and validity of a new classification of MIH based on severity

To describe a new molar-incisor hypomineralization (MIH) severity scoring system (MIH-SSS) that focuses on the defects’ severity and to assess the sy     

From the Cover: Satellites can reveal global extent of forced labor in the world’s fishing fleet

While forced labor in the world’s fishing fleet has been widely documented, its extent remains unknown. No methods previously existed for remotely identifying individual fishing vessels potentially engaged in these abuses on a global scale. By combining expertise from human rights practitioners and satellite vessel monitoring data, we show that vessels reported to use forced labor behave in systematically different ways from other vessels. We exploit this insight by using machine learning to identify high-risk vessels from among 16,000 industrial longliner, squid jigger, and trawler fishing vessels. Our model reveals that between 14% and 26% of vessels were high-risk, and also reveals patterns of where these vessels fished and which ports they visited. Between 57,000 and 100,000 individuals worked on these vessels, many of whom may have been forced labor victims. This information provides unprecedented opportunities for novel interventions to combat this humanitarian tragedy. More broadly, this research demonstrates a proof of concept for using remote sensing to detect forced labor abuses.

Forced labor in fisheries, a type of modern slavery, is increasingly recognized as a human rights crisis. The International Labor Organization (ILO) defines forced labor as “all work or service which is exacted from any person under the menace of any penalty and for which the said person has not offered himself voluntarily” (1). The ILO provides a framework of 11 forced labor risk indicators (2) that have all been documented within the fisheries sector, including indicators representative of debt-bonded labor, as well as indicators representative of servitude or slave labor such as abusive working and living conditions. In 2015, reports emerged on forced labor in Thai fisheries (3) and the role of forced labor in producing seafood imported to the United States (4). More recent reports have described the global nature of the problem (5), and there has been a call to integrate social responsibility into ocean science (6). Despite widespread condemnation and ambitious commitments, forced labor remains poorly understood in the fisheries sector. Here we show that recently available high-frequency vessel monitoring of the global industrial fishing fleet can shed new light on forced labor at a much finer resolution. We combine expertise from on-the-ground human rights practitioners and satellite vessel monitoring data for over 16,000 industrial fishing vessels to estimate 1) the number of high-risk vessels and the number of crew who may be victims working on those vessels, 2) where these vessels fish, and 3) what ports these vessels visit. This information can inform new market, policy, and enforcement interventions to combat forced labor in global fisheries. This research more generally demonstrates how remote sensing can detect forced labor abuses by observing dynamic behavior.Current estimates of forced labor in fisheries are coarse and are based on country-level statistics. Using country-level household surveys, the ILO estimated that 16 million people were victims of forced labor in 2016, with 11% of these in agriculture, forestry, or fisheries (7). The Global Slavery Index reports that the seven countries with highest slavery risk in 2018 generated 39% of global fisheries catch (3, 8), and Tickler et al. found that the United States has slavery risks of 0.2 kg per metric ton for domestic seafood and 3.1 kg per metric ton for imported seafood (9). While these studies are important for broadly understanding which countries have risk, current methods are unable to detect this problem at the level of individual fishing vessels, which will be essential for targeted interventions.We empirically examine whether vessels reported to exhibit any of the ILO indicators of forced labor behave in ways that are systematically different from other vessels, and then exploit this information using machine learning to discriminate between vessels that use forced labor from those that do not. We do so by measuring a suite of features that can be observed using satellite Automatic Identification System (AIS) vessel monitoring data made available by Global Fishing Watch (GFW) (10). There may be many behavioral correlates with forced labor that could help to differentiate between high-risk and low-risk vessels. To determine which model features to include, we first conducted a literature review of investigative journalism reports and looked for instances of forced labor case accounts that detailed specific behaviors that could be observed using vessel monitoring data. We next conducted informal phone interviews with experts from several nongovernmental organizations (NGOs) working in this field, during which we asked interviewees what observable vessel behaviors they would look for if they wanted to identify suspicious activity. The machine-learning approach we use does not assume that vessels behave in any particular way; rather, it merely uses the features identified by literature review and expert insight to exploit any observed empirical differences between vessels that use forced labor and other vessels. NGO experts and investigative journalism suggest that gaps in AIS transmission, port avoidance, transshipment, and extended time at sea may indicate the presence of forced labor (11). Certain features, like information on catch and the species being targeted, could also be helpful in discriminating between high- and low-risk behavior by providing more context on the fishing taking place. However, these data are not currently available at the vessel level on a global scale. Data on recruitment practices and vessel ownership and information on from where the crew originates could also be helpful, but, again, these data are not widely available. We arrived at a list of 27 vessel behavior and characteristic features for which we have globally available data at the vessel level (SI Appendix, Table S1, and SI Appendix).To build a predictive model for identifying high-risk vessels, we developed a training dataset that includes the behavior and characteristics of known forced-labor vessels, as well as the behavior and characteristics of other vessels. We compiled a comprehensive database of vessels that were reported to display one or more of the ILO forced labor indicators (2); these vessels are labeled as “positives.” We do not, however, know which vessels do not use forced labor (“negatives”). Rather, any vessel that we do not label as positive is “unlabeled,” and may in fact be a positive vessel that has not yet been identified or may truly be a negative vessel. This is an example of “positive-unlabeled (PU)” learning, a less straightforward problem than traditional supervised machine learning (12). We use PU learning to predict whether or not 16,261 longliner, trawler, and squid jigger fishing vessels were high-risk during each year they operated between 2012 and 2018 (“vessel-years”). We focus on this subset of vessels because they broadcasted sufficient and reliable AIS positions and because these are the only fishing gear types with documented cases of forced labor aboard vessels that broadcasted sufficient AIS data. These vessels represent 33% of the total time at sea spent by all fishing vessels operating in this time period tracked by GFW. Our PU approach leverages information from all positively labeled vessels (n = 22 unique vessels across 22 vessel-years using our baseline model assumption), but places less emphasis on unlabeled vessels given their uncertain nature (n = 16,257 unique vessels across 66,314 vessel-years using our baseline model assumption).     

Stem cell bioengineering strategies to widen the therapeutic applications of haematopoietic stem/progenitor cells from umbilical cord blood

Umbilical cord blood (UCB) transplantation has observed a significant increase in recent years, due to the unique features of UCB haematopoietic stem/progenitor cells (HSCs) for the treatment of blood‐related disorders. However, the low cell numbers available per UCB unit significantly impairs the widespread use of this source for transplantation of adult patients, resulting in graft failure, delayed engraftment and delayed immune reconstitution. In order to overcome this issue, distinct approaches are now being considered in clinical trials, such as double‐UCB transplantation, intrabone injection or ex vivo expansion. In this article the authors review the current state of the art, future trends and challenges on the ex vivo expansion of UCB HSCs, focusing on culture parameters affecting the yield and quality of the expanded HSC grafts: novel HSC selection schemes prior to cell culture, cytokine/growth factor cocktails, the impact of biochemical factors (e.g. O₂) or the addition of supportive cells, e.g. mesenchymal stem/stromal cell (MSC)‐based feeder layers) were addressed. Importantly, a critical challenge in cellular therapy is still the scalability, reproducibility and control of the expansion process, in order to meet the clinical requirements for therapeutic applications. Efficient design of bioreactor systems and operation modes are now the focus of many bioengineers, integrating the increasing 'know‐how' on HSC biology and physiology, while complying with the GMP standards for the production of cellular products, i.e. through the use of commercially available, highly controlled, disposable technologies. Copyright © 2013 John Wiley & Sons, Ltd.     

Colorectal carcinoma in different age groups

Purpose  

Although colorectal cancer is typical in the older population, tumor onset before age 40 is not infrequent. However, the behavior, characteristics, and prognosis of this disease in young patients are unclear when compared to the older population. It is believed that young patients have a poor prognosis. We hypothesized that young patients have a poor prognosis because they have advanced-stage cancer with more aggressive pathologic features.     

Gallbladder-associated ectopic liver: A rare finding during a laparoscopic cholecystectomy

INTRODUCTIONEctopic hepatic tissue is due to an uncommon failure of embryological liver development that is rarely described in the world medical literature. The incidence of ectopic liver (EL) has been reported to be anywhere from 0.24% to 0.47% as diagnosed at laparotomy or laparoscopy. We describe a case of EL adherent to the gallbladder, removed at laparoscopic cholecystectomy.PRESENTATION OF CASEA 37-year-old female was admitted for elective cholecystectomy having had an episode of acute cholecystitis provoked by gallstones. During the procedure, a 30 mm × 10 mm × 5 mm section of EL tissue attached to the anterior wall of the gallbladder was identified and removed by en-bloc excision during laparoscopic cholecystectomy. Histological examination confirmed the absence of malignant degeneration of the hepatic tissue. The patient recovered well postoperatively and was discharged the day after the operation. She was well when seen six months later.DISCUSSIONEL has been reported in several sites, such as the gallbladder, gastrohepatic ligament, adrenal glands, esophagus, and thoracic cavity. EL is often clinically silent and discovered incidentally during abdominal surgical procedures or autopsies. Because patients with ectopic liver may suffer complications such as torsion, peritoneal bleeding, fatty change, and evolution to cirrhosis or malignant degeneration to hepatocellular carcinoma, any ectopic liver tissue needs to be correctly identified and removed.CONCLUSIONDespite the rare occurrence of EL, it should be recognized and removed by the surgeon to prevent a higher risk of complications and malignant transformation.