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Background: Presurgical blood orders are important for patient safety during surgery, but excess orders can be costly to patients and the healthcare system. We aimed to assess clinician perceptions on the presurgical blood ordering process and perceived barriers to reliable decision‐making. Methods: This descriptive qualitative study was conducted at a single large academic medical center. Semi‐structured interviews were conducted with surgeons, anesthesiologists, nurse anesthetists, nurse practitioners working in preoperative assessment clinics, and transfusion medicine physicians to assess perceptions of current blood ordering processes. Interview responses were analyzed using an inductive open coding approach followed by thematic analysis. Results: Twenty‐three clinicians were interviewed. Clinicians felt that the current blood ordering process was frequently inconsistent. One contributor was a lack of information on surgical transfusion risk, related to lack of experience in ordering clinicians, insufficient communication between stakeholders, high turnover in academic settings, and lack of awareness of the maximum surgical blood ordering schedule. Other contributors included differing opinions about the benefits and harms of over‐ and under‐preparing blood products, leading to variation in transfusion risk thresholds between clinicians, and disagreement about the safety of emergency‐release blood. Conclusion: Several barriers to reliable decision‐making for presurgical blood orders exist. Future efforts to improve ordering consistency may benefit from improved information sharing between stakeholders and education on safe transfusion practices. [ABSTRACT FROM AUTHOR]

Objectives To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. Methods Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t -test and Wilcoxon signed rank test. Results The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P  = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P  = .006) and DC (87.2 vs 77.4, P  = .006) were significantly lower, and median HD (25.2 vs 31.0, P  = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. Conclusion The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. Advances in Knowledge This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy. [ABSTRACT FROM AUTHOR]

Background: There has been longstanding uncertainty over whether lower healthcare spending in Canada might be associated with inferior outcomes for hospital-based care. We hypothesized that mortality and surgical complication rates would be higher for patients who underwent four common surgical procedures in Canada as compared to the US. Design, Setting, and Participants: We conducted a retrospective cohort study of all adults who underwent hip fracture repair, colectomy, pancreatectomy, or spine surgery in 96 Canadian and 585 US hospitals participating in the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) between January 1, 2015 and December 31, 2019. We compared patients with respect to demographic characteristics and comorbidity. We then compared unadjusted and adjusted outcomes within 30-days of surgery for patients in Canada and the US including: (1) Mortality; (2) A composite constituting 1-or-more of the following complications (cardiac arrest; myocardial infarction; pneumonia; renal failure/; return to operating room; surgical site infection; sepsis; unplanned intubation). Results: Our hip fracture cohort consisted of 21,166 patients in Canada (22.3%) and 73,817 in the US (77.7%), for colectomy 21,279 patients in Canada (8.9%) and 218,307 (91.1%), for pancreatectomy 873 (7.8%) in Canada and 12,078 (92.2%) in the US, and for spine surgery 14,088 (5.3%) and 252,029 (94.7%). Patient sociodemographics and comorbidity were clinically similar between jurisdictions. In adjusted analyses odds of death was significantly higher in Canada for two procedures (colectomy (OR 1.22; 95% CI 1.044–1.424; P =.012) and pancreatectomy (OR 2.11; 95% CI 1.26–3.56; P =.005)) and similar for hip fracture and spine surgery. Odds of the composite outcome were significantly higher in Canada for all 4 procedures, largely driven by higher risk of cardiac events and post-operative infections. Conclusions: We found evidence of higher rates of mortality and surgical complications within 30-days of surgery for patients in Canada as compared to the US. [ABSTRACT FROM AUTHOR]

The quest to understand how allogeneic transplanted tissue is not rejected and how tolerance is induced led to fundamental concepts in immunology. First, we review the research that led to the Clonal Deletion theory in the late 1950s that has since dominated the field of immunology and transplantation. At that time many basic mechanisms of immune response were unknown, including the role of lymphocytes and T cells in rejection. These original observations are reassessed by considering T regulatory cells that are produced by thymus of neonates to prevent autoimmunity. Second, we review "operational tolerance" induced in adult rodents and larger animals such as pigs. This can occur spontaneously especially with liver allografts, but also can develop after short courses of a variety of rejection inhibiting therapies. Over time these animals develop alloantigen specific tolerance to the graft but retain the capacity to reject third-party grafts. These animals have a "split tolerance" as peripheral lymphocytes from these animals respond to donor alloantigen in graft versus host assays and in mixed lymphocyte cultures, indicating there is no clonal deletion. Investigation of this phenomenon excludes many mechanisms, including anti-donor antibody blocking rejection as well as anti-idiotypic responses mediated by antibody or T cells. This split tolerance is transferred to a second immune-depleted host by T cells that retain the capacity to effect rejection of third-party grafts by the same host. Third, we review research on alloantigen specific inhibitory T cells that led to the first identification of the CD4+CD25+T regulatory cell. The key role of T cell derived cytokines, other than IL-2, in promoting survival and expansion of antigen specific T regulatory cells that mediate transplant tolerance is reviewed. The precise methods for inducing and diagnosing operational tolerance remain to be defined, but antigen specific T regulatory cells are key mediators. [ABSTRACT FROM AUTHOR]

CD4+CD25+Foxp3+T cell population is heterogenous and contains three major sub-groups. First, thymus derived T regulatory cells (tTreg) that are naïve/resting. Second, activated/memory Treg that are produced by activation of tTreg by antigen and cytokines. Third, effector lineage CD4+CD25+T cells generated from CD4+CD25- T cells' activation by antigen to transiently express CD25 and Foxp3. We have shown that freshly isolated CD4+CD25+T cells are activated by specific alloantigen and IL-4, not IL-2, to Ts2 cells that express the IL-5 receptor alpha. Ts2 cells are more potent than naïve/resting tTreg in suppressing specific alloimmunity. Here, we showed rIL-5 promoted further activation of Ts2 cells to Th2-like Treg, that expressed foxp3, irf4, gata3 and il5. In vivo , we studied the effects of rIL-5 treatment on Lewis heart allograft survival in F344 rats. Host CD4+CD25+T cells were assessed by FACS, in mixed lymphocyte culture and by RT-PCR to examine mRNA of Ts2 or Th2-like Treg markers. rIL-5 treatment given 7 days after transplantation reduced the severity of rejection and all grafts survived ≥60d whereas sham treated rats fully rejected by day 31 (p<0.01). Treatment with anti-CD25 or anti-IL-4 monoclonal antibody abolished the benefits of treatment with rIL-5 and accelerated rejection. After 10d treatment with rIL-5, hosts' CD4+CD25+ cells expressed more Il5ra and responded to specific donor Lewis but not self. Enriched CD4+CD25+ cells from rIL-5 treated rats with allografts surviving >60 days proliferated to specific donor only when rIL-5 was present and did not proliferate to self or third party. These cells had more mRNA for molecules expressed by Th2-like Treg includin g Irf4, gata3 and Il5. These findings were consistent with IL-5 treatment preventing rejection by activation of Ts2 cells and Th2-like Treg. [ABSTRACT FROM AUTHOR]

The Princess Alexandra Hospital (PAH) Gamma Knife® Centre of Queensland (GKCoQ) began operations in October of 2015 as a sub‐specialty located within a larger radiation oncology service at PAH. It is uniquely positioned as the only Leksell Gamma Knife® (LGK) treatment unit available in the public hospital system in Australia, and the first and only service in Queensland. The GKCoQ treated the 1000th patient on 23 January 2019. LGK is a non‐invasive alternative to neurosurgery which uses radioactive cobalt sources to treat a variety of intracranial conditions ranging from tumours and metastases to functional disorders. It is a platform for stereotactic radiosurgery, a highly precise form of radiotherapy utilising very high doses to the target while maximally sparing surrounding normal brain. LGK enables patient planning and treatment to be done in one day as an outpatient procedure. This paper will outline our LGK service and provide insight into the expanded role that radiation therapists have within the multidisciplinary team required to deliver radiosurgery in a timely manner. The training programme and radiation licensing pathway that have been established for radiation therapists will also be described. [ABSTRACT FROM AUTHOR]

Background and local problem: Patients who take warfarin require frequent testing of their international normalized ratio (INR) level to ensure accurate dosage. Frequent testing can be inconvenient for patients in rural settings, the workforce, the homebound, or those who travel. Patients who have a home INR monitor can test their blood remotely. Methods: To circumvent barriers to INR testing, a quality improvement project was designed to implement home INR testing in an anticoagulation clinic setting. Interventions: Patients who received a home INR monitor were compared against two usual care testing arms (laboratory and clinic testing patients) in the outcomes of time in therapeutic range (TTR), adverse events, and patient satisfaction using the Duke Anticoagulation Satisfaction Scale (DASS). Results: The DASS survey demonstrated the home testing patients had a statistically significant advantage over the clinic testing group in the subdomain of hassles and burdens (p = .048), as well as the lowest overall scores (indicating highest satisfaction) over the clinic testing group (p = .041). No patients in the home testing group had clotting or bleeding issues necessitating hospital admission. There were no significant differences between groups in the TTR analysis (laboratory 70.8%, home 68.9%, and clinic 64.5%) (p = .683). Conclusions: Home INR testing provides convenience for patients and reduces the hassles and burdens of warfarin management, leading to improved satisfaction. This engagement in self-care translates to reduced adverse events. Home INR testing can be used inwarfarin patients who are highlymotivated andwilling to engage in their care. [ABSTRACT FROM AUTHOR]

Resting and activated subpopulations of CD4+CD25+CD127loT regulatory cells (Treg) and CD4+CD25+CD127+ effector T cells in MS patients and in healthy individuals were compared. Peripheral blood mononuclear cells isolated using Ficoll Hypaque were stained with monoclonal antibodies and analysed by flow cytometer. CD45RA and Foxp3 expression within CD4+ cells and in CD4+CD25+CD127loT cells identified Population I; CD45RA+Foxp3+, Population II; CD45RA−Foxp3hi and Population III; CD45RA−Foxp3+ cells. Effector CD4+CD127+ T cells were subdivided into Population IV; memory /effector CD45RA− CD25−Foxp3− and Population V; effector naïve CD45RA+CD25−Foxp3−CCR7+ and terminally differentiated RA+ (TEMRA) effector memory cells. Chemokine receptor staining identified CXCR3+Th1-like Treg, CCR6+Th17-like Treg and CCR7+ resting Treg. Resting Treg (Population I) were reduced in MS patients, both in untreated and treated MS compared to healthy donors. Activated/memory Treg (Population II) were significantly increased in MS patients compared to healthy donors. Activated effector CD4+ (Population IV) were increased and the naïve/ TEMRA CD4+ (Population V) were decreased in MS compared to HD. Expression of CCR7 was mainly in Population I, whereas expression of CCR6 and CXCR3 was greatest in Populations II and intermediate in Population III. In MS, CCR6+Treg were lower in Population III. This study found MS is associated with significant shifts in CD4+T cells subpopulations. MS patients had lower resting CD4+CD25+CD45RA+CCR7+ Treg than healthy donors while activated CD4+CD25hiCD45RA−Foxp3hiTreg were increased in MS patients even before treatment. Some MS patients had reduced CCR6+Th17-like Treg, which may contribute to the activity of MS. [ABSTRACT FROM AUTHOR]

Hypofractionated stereotactic radiotherapy is a treatment option for large vestibular schwannomas supported by an increasing evidence. A single institution retrospective review of large (>3.5cc) vestibular schwannomas treated with hypofractionated stereotactic radiotherapy and singlesession radiosurgery was conducted. Using serial follow up scans, a volumetric analysis of tumor volume change over time was performed. Vestibular schwannomas treated with hypofractionated stereotactic radiotherapy appeared to reduce in volume significantly faster than those treated with single-session radiosurgery. Cystic lesions reduced in volume faster than solid lesions. There was no significant difference in the rates of radiological and symptomatic oedema, nor subsequent dexamethasone requirement between the two treatment modalities. [ABSTRACT FROM AUTHOR]

This article discusses the temporal and geographic expansion of racial frameworks in historical and social scientific scholarship in Africa and the Middle East. After discussing the important distinction made by the sociologist Loïc Wacquant between what he calls "folk" and analytical notions of race, the article then argues that race is an appropriate analytic model for understanding some of the internal dynamics within the societies of these regions. Examples of recent scholarship on the regions which uses an analytic model of race are then critically explored. [ABSTRACT FROM AUTHOR]

Background: Jaundice due to biliary obstruction leads to multiple physiologic derangements and a decline in performance status that may result in unfavorable intra- and postoperative outcomes following a Whipple procedure. While preoperative biliary decompression may improve synthetic function, this strategy has been reported to increase the incidence of infectious complications following surgery. We hypothesized that hyperbilirubinemia at the time of pancreatoduodenectomy (PD) would be a risk factor for increased morbidity and mortality postoperatively.Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Pancreatectomy Demonstration Project and the 2014 Procedure Targeted Pancreatectomy databases were queried for patients with a bilirubin level obtained within 7 days of PD. Results were compared among patients with bilirubin level percentiles <80th (0-2.9 mg/dL), 80-90th (3-7.3 mg/dL), and >90th (>7.3 mg/dL). Data were further evaluated between those with a bilirubin ≥10 mg/dL and those with a normal level and by utilizing bilirubin as a continuous variable. Outcomes included 30-day mortality and overall and serious morbidity as previously defined by ACS-NSQIP. Categorical variables were compared using chi-squared, Fisher's exact, Kruskal-Wallis, or Wilcoxon rank sum tests with a p = 0.05 considered significant.Results: The combined databases yielded 2556 patients who had PD and a preoperative bilirubin level for analysis. When comparing patients with bilirubin levels at the 80th (n = 2055), 80-90th (n = 273), and >90th percentiles (n = 228), no difference was observed among groups with respect to overall and serious morbidity or mortality. Similarly, no difference in postoperative outcomes was observed between the 147 patients who had a bilirubin ≥10 mg/dL and those with normal levels or when bilirubin increased when levels were analyzed as a continuous variable.Conclusion: Modest degrees of hyperbilirubinemia were not shown to affect morbidity and mortality following pancreatoduodenectomy. The indication and need for preoperative biliary decompression should be reserved, and utilized selectively, only for those with symptomatic, elevated bilirubin levels. [ABSTRACT FROM AUTHOR]

Introduction: Post-operative bile leak (BL) and post hepatectomy liver failure (PHLF) are the major potential sources of morbidity among patients undergoing liver resection. We sought to define the incidence of BL and PHLF among a large cohort of patients, as well as examine the prognostic impact of model for end-stage liver disease (MELD) and albumin-bilirubin (ALBI) scores to predict these short-term outcomes.Materials and Methods: Patients who underwent a hepatectomy between January 1, 2014 and December 31, 2014 were identified using the National Surgical Quality Improvement Program (NSQIP) liver-targeted database. Risk factors for BL and PHLF were identified using multivariable logistic regression.Results: Among the 3064 patients identified, median age was 60 years (IQR 50-68). Most patients underwent surgery (78.9 %) for malignant lesions. Post-operatively, 250 (8.5 %) patients experienced a BL while PHLF occurred in 149 cases (4.9 %). Both MELD (MELD <10 4.9 %; MELD ≥10, 10 %; P = 0.001) and ALBI (grade 1, 4.0 %; grade 2, 7.2 %; grade 3, 10.0 %; P = 0.001) were associated with PHLF occurrence, while only ALBI predicted PHLF severity (P = 0.008). Moreover, ALBI was associated with BL (grade 1, 7.1 %; grade 2, 11.5 %; grade 3, 14.0 %; P < 0.001), whereas MELD was not (MELD <10, 8.4 %; MELD ≥10, 11.2 %; P = 0.13). On multivariable analysis, ALBI grade 2/3 was associated with PHLF (OR 1.57, 95 % CI 1.08-2.27; P = 0.02), PHLF severity (OR 3.06, 95 % CI 1.50-6.23; P = 0.003), and the development of a BL (OR 1.35, 95 % CI 1.02-1.80; P = 0.04).Conclusion: The ALBI score was associated with short-term post-operative outcomes following hepatic resection and represents a useful pre-operative risk-assessment tool to identify patients at risk for adverse post-operative outcomes. [ABSTRACT FROM AUTHOR]

Aim: To assess whether extent of surrounding edema correlates with acute adverse clinical outcomes within 3 months after stereotactic radiosurgery (SRS) for melanoma brain metastases (BM). Methods: Patients with melanoma BM treated with SRS were included in a single center retrospective analysis. A contrast-enhanced magnetic resonance image (MRI) brain was acquired on the day of treatment and used to calculate the volume of the largest lesion (the index BM) and total volume of all BM. Their corresponding volume of surrounding edema was defined based on the fluid attenuated inversion recovery (FLAIR) sequence. After SRS, MRI was performed every 3 months for at least 2 years if the patient remained well enough to do so. Adverse neurologic events after SRS were defined using common terminology criteria for adverse events (CTCAE) version 5.0. Multivariate regression analyses assessed for associations between BM size and edema at baseline with increasing edema and neurologic adverse events within 3 months after SRS. Results: Mean volume of the index BM reduced from 2.2 to 0.5 cm3 at 3 months after SRS (p = 0.03). Mean volume of edema surrounding the index BM was 6.4 cm3 at baseline, 10.2 cm3 at 3 months and 5.5 cm3 at 6 months. There were 7/43 (16%) patients that experienced an adverse neurological event within 3 months (attributable to any cause) and 4/43 (9%) were associated with an increase in BM edema. On univariate and multivariate analyses, there were no correlations between any baseline factors and volume of edema at 3 months. However, SRS dose delivered and systemic therapy use within 4 weeks of SRS both correlated with a reduction in edema surrounding the index BM. Conclusion: A transient increase in mean volume of edema was apparent at 3 months after SRS. However, this resolved by 6 months and did not correlate with adverse events or dexamethasone requirement. Thus, the clinical significance is uncertain. [ABSTRACT FROM AUTHOR]

Therapy with alloantigen-specific CD4+CD25+ T regulatory cells (Treg) for induction of transplant tolerance is desirable, as naïve thymic Treg (tTreg) are not alloantigen-specific and are weak suppressor cells. Naïve tTreg from DA rats cultured with fully allogeneic PVG stimulator cells in the presence of rIL-2 express IFN-gamma receptor (IFNGR) and IL-12 receptor beta2 (IL-12Rβ2) and are more potent alloantigen-specific regulators that we call Ts1 cells. This study examined additional markers that could identify the activated alloantigen-specific Treg as a subpopulation within the CD4+CD25+Foxp3+Treg. After culture of naïve DA CD4+CD8−CD25+T cells with rIL-2 and PVG alloantigen, or rIL-2 without alloantigen, CD8α was expressed on 10–20% and CD8β on <5% of these cells. These cells expressed ifngr and Il12rb2. CD8α+ cells had increased Ifngr that characterizes Ts1 cells as well was Irf4 , a transcription factor induced by TCR activation. Proliferation induced by re-culture with rIL-12 and alloantigen was greater with CD4+CD8α+CD25+Treg consistent with the CD8α+ cells expressing IL-12R. In MLC, the CD8α+ fraction suppressed responses against allogeneic stimulators more than the mixed Ts1 population, whereas the CD4+CD8−CD25+T cells were less potent. In an adoptive transfer assay, rIL-2 and alloantigen activated Treg suppress rejection at a ratio of 1:10 with naïve effector cells, whereas alloantigen and rIL-2 activated tTreg depleted of the CD8α+ cells were much less effective. This study demonstrated that expression of CD8α by rIL-2 and alloantigen activation of CD4+CD8−CD25+Foxp3+T cells was a marker of activated and potent Treg that included alloantigen-specific Treg. [ABSTRACT FROM AUTHOR]

Background: Assessments of surgical quality should consider both surgeon and patient perspectives simultaneously. Focusing on patients undergoing major gastrointestinal cancer surgery, we sought to characterize hospitals, and their patients, on both these axes of quality.Methods: Using the American College of Surgeons' National Surgical Quality Improvement Program registry, hospitals were profiled on a risk-adjusted composite measure of death or serious morbidity (DSM) generated from patients who underwent colectomy, esophagectomy, hepatectomy, pancreatectomy, or proctectomy for cancer between January 1, 2015 and December 31, 2016. These hospitals were also profiled using the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. Highest-performing hospitals on both quality axes, and their respective patients, were compared to the lowest-performing hospitals.Results: Overall, 60,526 patients underwent their cancer operation at 530 hospitals. There were 38 highest- and 48 lowest-performing hospitals. The correlation between quality axes was poor (ρ = 0.10). Compared to the lowest-performing hospitals, the highest-performing hospitals were more often NCI-designated cancer centers (29.0% vs. 4.2%, p = 0.002) and cared for a lower proportion of Medicaid patients (0.14 vs. 0.23, p < 0.001). Patients who had their operations at the lowest- versus highest-performing hospitals were more often black (17.2% vs. 8.4%, p < 0.001), Hispanic (8.3% vs. 3.5%, p < 0.001), functionally dependent (3.8% vs. 0.9%, p < 0.001), and not admitted from home (4.4% vs. 2.4%, p < 0.001).Conclusions: Hospital performance varied when assessed by both risk-adjusted surgical outcomes and patient experiences. In this study, poor-performing hospitals appeared to be disproportionately serving disadvantaged and minority cancer patients. [ABSTRACT FROM AUTHOR]

Background: While minimally invasive surgery (MIS) to treat liver tumors has increased, data on perioperative outcomes of MIS relative to open liver resection (O-LR) are lacking. We sought to compare short-term outcomes among patients undergoing MIS vs. O-LR in a nationally representative database.Methods: The National Surgical Quality Improvement Program database was used to identify patients undergoing hepatectomy between January 1 and December 31, 2014. Propensity score matching algorithm was used to balance differences in baseline characteristics among MIS and O-LR groups.Results: A total of 3064 patients were included in the study. After propensity matching, the baseline characteristics for O-LR and MIS groups were comparable (minimum p value = 0.12). Incidence of superficial surgical site infections, intraoperative or postoperative blood transfusions, and pulmonary embolism was lower among patients in MIS group compared to O-LR (p < 0.02). Liver failure and biliary leakage were also less frequent among patients undergoing MIS (p < 0.01). Similarly, MIS was associated with a shorter length of hospital stay (LOS) compared to O-LR (p < 0.001). Of note, 30-day postoperative mortality and readmission were comparable between the two groups.Conclusions: Patients undergoing MIS had a lower postoperative morbidity and shorter LOS compared with patients undergoing O-LR. MIS is safe and may be associated with improved short-term outcomes following hepatic surgery. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine whether (1) the propensity for concurrent fundoplication during gastrostomy varies among hospitals, and (2) postoperative morbidity differs among institutions performing fundoplication more or less frequently.Methods: Children who underwent gastrostomy with or without concurrent fundoplication were identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric (ACS-NSQIP-P). A hierarchical multivariate regression modeled the excess effects that hospitals exerted over propensity for concurrent fundoplication adjusting for preoperative clinical variables. Hospitals were designated as low outliers (significantly lower-adjusted odds of concurrent fundoplication than the average hospital with similar patient mix), average hospitals, and high outliers based on their risk-adjusted concurrent fundoplication practice. The postoperative morbidity rates were compared among low-outlier, average, and high-outlier hospitals.Results: Between 2011 and 2013, 3775 children underwent gastrostomy at one of 54 ACS-NSQIP-P participating hospitals. The mean hospital concurrent fundoplication rate was 11.7% (range 0-64%). There was no significant difference in unadjusted morbidity rate in children with concurrent fundoplication, 11.0% compared to 9.7% in children without concurrent fundoplication. After controlling for clinical variables, 8 hospitals were identified as low outliers (fundoplication rate of 0.4%) and 16 hospitals were identified as high outliers (fundoplication rate of 34.6%). The average unadjusted morbidity rate among hospitals with low, average, and high odds of concurrent fundoplication were 9.6, 10.6, and 8.4%, respectively.Conclusion: Hospitals vary significantly in propensity for concurrent fundoplication during gastrostomy yet postoperative morbidity does not differ significantly among institutions performing fundoplication more or less frequently. [ABSTRACT FROM AUTHOR]

Objective: To examine if the protective effect of parasite infection on experimental autoimmune encephalomyelitis (EAE) was due to interleukin (IL)-5, a cytokine produced by a type-2 response that induces eosinophilia. We hypothesize that, in parasite infections, IL-5 also promotes expansion of antigen-specific T regulatory cells that control autoimmunity. Methods: Nippostrongylus brasiliensis larvae were used to infect Lewis rats prior to induction of EAE by myelin basic protein. Animals were sham treated, or given blocking monoclonal antibodies to interleukin 4 or 5 or to deplete CD25+ T cells. Reactivity of CD4+CD25+ T regulatory cells from these animals was examined. Results: Parasite-infected hosts had reduced severity and length of EAE. The beneficial effect of parasitic infection was abolished with an anti-IL-5 or an anti-CD25 monoclonal antibody (mAb), but not anti-IL-4 mAb. Parasite-infected animals with EAE developed antigen-specific CD4+CD25+ T regulatory cells earlier than EAE controls and these expressed more Il5ra than controls. Treatment with IL-5 also reduced the severity of EAE and induced Il5ra expressing CD4+CD25+ T regulatory cells. Interpretation: The results of this study suggested that IL-5 produced by the type-2 inflammatory response to parasite infection promoted induction of autoantigenspecific CD25+Il5ra+ T regulatory cells that reduced the severity of autoimmunity. Such a mechanism may explain the protective effect of parasite infection in patients with multiple sclerosis where eosinophilia is induced by IL-5, produced by the immune response to parasites. [ABSTRACT FROM AUTHOR]

This article is the product of a collaboration between a scholar of West African cinema (Fofana) and a historian of northern Mali (Hall), who together offer an interpretation of the politics of Abderrahmane Sissako's film Timbuktu (2014). This film is about the Islamist jihadist occupation of the Malian town of Timbuktu in 2012-13, and it succeeds in demonstrating some of the ways that the jihadist project tried to reorganize the lives of people in northern Mali by using violence or its threat to force women and men to dress according to Salafi sartorial codes, preventing men and women from socializing together outside of their immediate families, and banning soccer and music. Sissako's style of filmmaking lingers on a number of scenes in which the jihadists reveal themselves to be alternately confused and hypocritical about the edicts that they enforce, but also deeply intolerant and uninformed about the sophisticated Muslim culture that has thrived in Timbuktu for centuries. Yet the violence depicted in the film is not all at the hands of the jihadists, and in fact the climax of the film is produced by a conflict between a fisherman and a herder. This article is a close reading of Timbuktu in an effort to unpack what appears to be an urgent call to action by one of Africa's finest filmmakers, but also to appreciate Sissako's film aesthetic while problematizing the shortcomings of his representation of an otherwise complicated history. [ABSTRACT FROM AUTHOR]

Transplant tolerance induced in adult animals is mediated by alloantigen-specific CD4+CD25+ T cells, yet in many models, proliferation of CD4+ T cells from hosts tolerant to specific-alloantigen in vitro is not impaired. To identify changes that may diagnose tolerance, changes in the patterns of proliferation of CD4+, CD4+CD25+, and CD4+CD25− T cells from DA rats tolerant to Piebald Virol Glaxo rat strain (PVG) cardiac allografts and from naïve DA rats were examined. Proliferation of CD4+ T cells from both naïve and tolerant hosts was similar to both PVG and Lewis stimulator cells. In mixed lymphocyte culture to PVG, proliferation of naïve CD4+CD25− T cells was greater than naïve CD4+ T cells. In contrast, proliferation of CD4+CD25− T cells from tolerant hosts to specific-donor PVG was not greater than CD4+ T cells, whereas their response to Lewis and self-DA was greater than CD4+ T cells. Paradoxically, CD4+CD25+ T cells from tolerant hosts did not proliferate to PVG, but did to Lewis, whereas naïve CD4+CD25+ T cells proliferate to both PVG and Lewis but not to self-DA. CD4+CD25+ T cells from tolerant, but not naïve hosts, expressed receptors for interferon (IFN)-γ and IL-5 and these cytokines promoted their proliferation to specific-alloantigen PVG but not to Lewis or self-DA. We identified several differences in the patterns of proliferation to specific-donor alloantigen between cells from tolerant and naïve hosts. Most relevant is that CD4+CD25+ T cells from tolerant hosts failed to proliferate or suppress to specific donor in the absence of either IFN-γ or IL-5. The proliferation to third-party and self of each cell population from tolerant and naïve hosts was similar and not affected by IFN-γ or IL-5. Our findings suggest CD4+CD25+ T cells that mediate transplant tolerance depend on IFN−γ or IL-5 from alloactivated Th1 and Th2 cells. [ABSTRACT FROM AUTHOR]