Search

Three-dimensional printing has introduced new manufacturing methods. However, information on the influence of the specific printing technology, material, sterilization, and the comparison between printing and milling on the accuracy of surgical guides is lacking.The purpose of this in vitro study was to evaluate the influence of the manufacturing method (printing and milling), printing technology stereolithography (SLA) and digital light processing (DLP), material, and sterilization on the accuracy of digitally designed surgical implant guides.Resin patient replicas with a single edentulous space were used to place 132 implants with digitally designed surgical guides. The accuracy of postoperative implant position was analyzed for the manufacturing method (printing and milling), resin materials, and preoperative autoclaving. To determine 3D accuracy, angular displacement, mean horizontal crestal, apical displacement, and the linear vertical displacement at the apex were calculated separately for each group (n=12). In addition, the surgical guides were qualitatively analyzed by using field emission scanning electron micrograph.The postoperative angular deviation ranged from 0.76 ±0.52 degrees (Rapidshape D20II with NextDent SG) to 2.43 ±0.64 degrees (Form2 with NextDent SG) (P.001). Linear horizontal displacement at the crest was smallest for Rapidshape D20II with 3Delta Guide (0.27 ±0.08 mm) and highest for Form2 with NextDent SG (0.54 ±0.10 mm) (P.001). Linear horizontal displacement at the apex ranged from 0.36 ±0.10 mm (SolFlex 350 with V-Print SG) to 0.89 ±0.32 mm (Form2 with NextDent SG) (P.001). Considering the vertical position displacement was no more than 0.43 ±0.07 mm (Form2 with NextDent SG) short of the apex, none of the implant tips were displaced apically. Preoperative autoclaving differentially impaired the accuracy of surgical guides.The specific manufacturing technique, the 3D printing device, the resin material, and the application of preoperative sterilization all affected the accuracy of the postoperative implant position. Irrespective of the manufacturing method, all implants were placed within the commonly accepted safety distance.

Mutations in the genes that encode the human γ-secretase subunits Presenilin-1, Presenilin Enhancer Protein 2, and Nicastrin (NCSTN) are associated with familial hidradenitis suppurativa (HS); and, regarding Presenilin Enhancer Protein 2, also with comorbidity for the hereditary pigmentation disorder Dowling-Degos disease.Here, the consequences of targeted inactivation of ncstn, the zebrafish homologue of human NCSTN, were studied.After morpholino (MO)-mediated ncstn-knockdown, the possibilities of phenotype rescue through co-injection of ncstn-MO with wildtype zebrafish ncstn or human NCSTN mRNA were investigated. Further, the effects of the co-injection of a human missense, nonsense, splice-site, and frameshift mutation were studied.MO-mediated ncstn-knockdown resulted in a significant reduction in melanophore morphology, size and number; and alterations in their patterns of migration and distribution. This phenotype was rescued by co-injection of zebrafish ncstn RNA, human NCSTN RNA, or a construct encoding the human NCSTN missense mutation p.P211R.Human NCSTN mutations encoding null alleles confer loss-of-function regarding pigmentation homeostasis in zebrafisch. In contrast, the human missense mutation p.P211R was less harmful, asserting sufficient residual ncstn activity to maintain pigmentation in zebrafish. Since fish lack the anatomical structures affected by HS, our data suggest that the zebrafish ncstn gene and the human NCSTN gene have probably acquired different functions during evolution. In fish, one major role of ncstn is the maintenance of pigmentation homeostasis. In contrast, one of the roles of NCSTN in humans is the prevention of inflammatory processes in the adnexal structures of the skin, as seen in familial HS.

Background: In 2006, the Surgical Infection Society (SIS) used a modified Delphi process to enlist SIS member-experts to identify 15 research priorities in the field of surgical infectious diseases; it was intended to serve as a research road map for the next one to two decades. We sought to evaluate the progress made in each of these priority areas. Hypothesis: We examined the progress achieved with respect to the 15 research areas identified by the Delphi process at that time, hypothesizing that advances in knowledge would be achieved in most domains, if not all. Methods: Surgical Infection Society members were surveyed to determine whether each priority area question had been satisfactorily answered in the last 14 years; to assess the quality of evidence answering each question (1-3 scale); and to delineate whether there is a current unmet need for continued research in each area. Randomized controlled trials (RCTs) regarding these initiatives were also identified via literature search and their citations in the literature were tabulated. Results: Sixty-six members of the SIS responded to the survey. Thirteen of 15 research priority areas saw an increase in data perceived to be available as adjudged by experts, as well an increase in the number of RCTs addressing that topic. However, there were only six questions that were deemed by experts to be answered sufficiently, primarily regarding antibiotic duration for certain conditions and the impact of glycemic control on infection. The questions that remained unanswered related to nosocomial infections, sepsis/septic shock, prevention of SSI, and antimicrobial pharmacokinetics. For a majority of the questions that experts believed were not answered sufficiently (8/9), respondents opined that continued research into these areas was warranted. Conclusion: Whereas 40% (6/15) of the research questions prioritized by the SIS in 2006 were answered to the satisfaction of member-experts, there are many questions that remain unanswered despite an increase of available data. Revisiting these research priorities highlights advancements made in the field of surgical infections, but also helps identify the areas that would benefit from continued study. That a majority of questions remain unanswered underscores an opportunity for member-experts to collaborate on SIS-managed or -endorsed RCTs.

OBJECTIVES Colloid carcinoma (CC) of the pancreas is associated with an improved prognosis compared with pancreatic ductal adenocarcinoma (PDAC), yet studies on the optimal management of these rare lesions are lacking. METHODS Patients with CC or PDAC treated from 2004 to 2014 were identified in the National Cancer Database. Clinicopathologic characteristics were compared between groups and stratified by disease stage. Survival analysis evaluating the role of perioperative chemotherapy was performed. RESULTS A total of 1295 CC patients (11%) and 10,855 PDAC patients (89%) were identified. Pancreatic ductal adenocarcinoma was associated with a higher likelihood of mortality compared with CC (hazard ratio, 1.35; 95% confidence interval, 1.25-1.45; P < 0.001). When stratifying by stage, perioperative chemoradiation improved overall survival in early stage (I/IIA) PDAC but had no effect in CC patients. However, for node-positive disease (stage IIB), median overall survival was improved with adjuvant chemoradiation for both CC patients (22 vs 13 months; P < 0.001) and PDAC patients (20 vs 11 months; P < 0.001) compared with surgery alone. CONCLUSIONS Surgery alone may be sufficient for the management of node-negative (I/IIA) CC lesions in contrast to conventional PDAC, whereas CC patients with stage IIB disease have a survival benefit from perioperative chemoradiation.

Aims/hypothesis: We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes. Methods: Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10–14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05. Results: In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2–10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling. Conclusions/interpretation: In children at genetic risk of type 1 diabetes, being overweight at 2–10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes. Trial registration: ClinicalTrials.gov NCT00179777 Graphical abstract: [Figure not available: see fulltext.]

Background Sugaya classification is a widely accepted classification system that is used to analyze postoperative rotator cuff tendon integrity. However, there are inconsistencies in the literature as to whether type 3 Sugaya should be considered as a retear or healed tendon. Purpose We aimed to show that type 3 Sugaya is not a retear by comparing the long-term supraspinatus and infraspinatus muscle degeneration and the functional outcomes of type 3 with those of type 4 and 5 Sugaya. We hypothesized that the clinical course of type 3 Sugaya would be different from type 4 or 5 Sugaya. Method The study was a retrospective multicenter review of all the rotator cuff repair done in 2003-2004. We included all the patients who had undergone supraspinatus repair with 10-year follow-up (magnetic resonance imaging done with full functional assessment). Data collection included pre- and postoperative supraspinatus and infraspinatus fatty infiltration, supraspinatus muscle atrophy, and Constant score with a separate analysis of its Strength subsection. Supraspinatus tendon integrity at 10-year follow-up was determined according to Sugaya classification. The patients were divided into 2 groups: type 3 Sugaya and type 4 and 5 Sugaya. Statistical comparison was done between the groups. Results There was no significant difference in the preoperative fatty infiltration of the supraspinatus and infraspinatus, supraspinatus muscle atrophy, and Constant score between the 2 groups. However, type 3 Sugaya patients had significantly better scores in the preoperative Strength subsection. Postoperatively, type 3 Sugaya patients showed significantly lesser fatty infiltration of the supraspinatus and infraspinatus, lesser supraspinatus muscle atrophy, and higher Constant score compared with type 4 and 5 Sugaya (P Conclusion Patients with type 3 Sugaya supraspinatus tendon exhibited lesser muscle degeneration in the supraspinatus and infraspinatus and performed better in functional assessment compared with type 4 and 5 Sugaya patients. We inferred that type 3 Sugaya should not be considered as a retear.

In this observational case-control study, circulating levels of complement factors C3a and C5a and leukotriene B4 (LTB4) were analysed in abdominal aortic aneurysm (AAA) patients regarding their association with diagnosis and prognosis. Serum C5a was significantly raised in AAA patients compared to healthy controls—median 84.5 ng/ml (IQR = 37.5 ng/ml) vs. 67.7 ng/ml (IQR = 26.2 ng/ml), p = 0.007—but was not elevated in patients with athero-occlusive disease. Serum C5a levels correlated significantly with the increase in maximum AAA diameter over the following 6 months (r = 0.319, p = 0.021). The median growth in the lowest quartile of C5a ( 101 ng/ml): 1.0 mm/6 months (IQR = 0.8 mm) vs. 2.0 mm/6 months (IQR = 1.5 mm), p = 0.014. A log-linear mixed model predicted AAA expansion based on current diameter and C5a level. To our knowledge, this is the first study linking complement activation, in particular C5a serum level, with AAA progression. Graphical Abstract

BackgroundGiven the growing number of people worldwide living with human immunodeficiency virus (HIV), a larger subset of these patients are now susceptible to sustaining a traumatic injury. However, the impact of HIV on outcomes in trauma with modern antiretroviral treatment remains unclear.We hypothesized mortality and rates of infectious and inflammatorycomplicationswould be higher in HIV positive (HIV+) trauma patients.MethodsThe Trauma Quality Improvement Programwas queriedtoidentify trauma patients ≥ 18years of age with HIV.Due to the imbalance between HIV+ and HIV negative(HIV-)trauma patients, a 1:2 propensity-matched model was utilized. Matched variables included age, injury severity score, mechanism of injury, systolic blood pressure, pulse rate, Glasgow Coma Scale score, and patient comorbidities.Results84 HIV+ patients were matched to 168 HIV- patients.Compared toHIV-patients, HIV+ patientshad no significant differences in mortality rate (9.5% vs.4.8%, p = 0.144) or infectious complications, including pneumonia (6.0% vs.4.2%, p = 0.530), urinary tract infection (1.2% vs. 1.2%, p = 1.000), or severe sepsis (1.2% vs.0.0%, p = 0.156). However, higher rates of acute respiratory distress syndrome (ARDS) (9.5% vs.0.6%, p

Lack of durable response to cytotoxic chemotherapy is a major contributor to the dismal outcomes seen in pancreatic ductal adenocarcinoma (PDAC). Extensive tumor desmoplasia and poor vascular supply are two predominant characteristics which hinder the delivery of chemotherapeutic drugs into PDAC tumors and mediate resistance to therapy. Previously, we have shown that STAT3 is a key biomarker of therapeutic resistance to gemcitabine treatment in PDAC, which can be overcome by combined inhibition of the Src and EGFR pathways. Although it is well-established that concurrent EGFR and Src inhibition exert these antineoplastic properties through direct inhibition of mitogenic pathways in tumor cells, the influence of this combined therapy on stromal constituents in PDAC tumors remains unknown. In this study, we demonstrate in both orthotopic tumor xenograft and Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mouse models that concurrent EGFR and Src inhibition abrogates STAT3 activation, increases microvessel density, and prevents tissue fibrosis in vivo. Furthermore, the stromal changes induced by parallel EGFR and Src pathway inhibition resulted in improved overall survival in PKT mice when combined with gemcitabine. As a phase I clinical trial utilizing concurrent EGFR and Src inhibition with gemcitabine has recently concluded, these data provide timely translational insight into the novel mechanism of action of this regimen and expand our understanding into the phenomenon of stromal-mediated therapeutic resistance. Implications: These findings demonstrate that Src/EGFR inhibition targets STAT3, remodels the tumor stroma, and results in enhanced delivery of gemcitabine to improve overall survival in a mouse model of PDAC.

To determine the response of hepatic tissue to percutaneous microwave ablation (MWA) of liver tumors via MR elastography in a clinical setting using MRI and MR elastography.51 Patients (28 m, 23f) underwent MWA of liver tumors (HCC: 20, metastasis: 31) and received MRI and MR elastography immediately before and 24 h after MWA. Retrospective analysis included pre- and post-ablative tumor extent, T1/T2 mapping and stiffness values as well as the duration and energy dose of the MWA session.Total liver stiffness increased by 4.3% from 3.31 kPa to 3.45 kPa (p = 0.036). Total liver stiffness post-MWA significantly correlated with the duration of the MWA session (r = 0.369, p = 0.008). The higher the baseline tumor stiffness was, the more energy had to be applied in MWA (r = 0.391, p 0.001) and the longer the duration of the session (r = 0.391, p = 0.007). Healthy parenchyma stiffness increased by 3.5% from 3.55 kPa to 3.68 kPa (p = 0.142) and was strongly influenced by the cumulative energy (r = 0.436, p 0.001), the duration (r = 0.458, p 0.001) and the energy intensity (r = 0.458, p 0.001) of MWA. 43 patients had a technically successful ablation result (margin ≥ 5 mm). Those with successful ablation had increased ablation margin stiffness (5.3 kPa vs. 4.6 kPa, p = 0.26) and had received higher ablation intensity than those with unsuccessful ablation (5.73 kJ/min vs. 5.03 kJ/min, p = 0.002).Additional MRE may be used before and after MWA to assess treatment response and collateral tissue damage after MWA. Baseline tumor stiffness helps finding the appropriate MWA parameters.

A healthy microbiome plays an important role in the prevention of illness and maintenance of overall health, including reproductive health. Although the therapeutic advantages of probiotics have been shown to run across multiple organ systems, their role in pregnancy is not well explored. The aim of this review is to highlight the potential advantages and adverse effects of probiotics in pregnancy. Data were collected from the literature over the past decade using PubMed, Medline, Google Scholar, Ovid, Scopus, and Science Direct. A total of 40 articles were utilized in this review. Collected data indicated that prenatal and post-natal supplementation with lactobacilli alone or lactobacilli with Bifidobacterium spp. seems to be protective. Probiotics may improve insulin resistance and consequently reduce the risk of gestational diabetes. Probiotics may also reduce anxiety and depression by influencing brain activity. Additionally, they interfere with vaginal flora to make it friendlier to beneficial bacteria, and enhance anti-inflammatory or reduce pro-inflammatory cytokines. They may also decrease eczema in breastfed infants and prevent allergic reactions by downregulating Th2 responses to specific allergens from mid to late gestation. Leveraging the cervicovaginal microbiota could promote a number of positive pregnancy-related health outcomes. Caution should be exercised in the selection, dosing, and monitoring of probiotics administration. More comprehensive randomized clinical trials are needed to reach a more meaningful evidence-based clinical knowledge.

Co-occurrent KRAS and TP53 mutations define a majority of patients with pancreatic ductal adenocarcinoma (PDAC) and define its pro-metastatic proclivity. Here, we demonstrate that KRAS-TP53 co-alteration is associated with worse survival compared with either KRAS-alone or TP53-alone altered PDAC in 245 patients with metastatic disease treated at a tertiary referral cancer center, and validate this observation in two independent molecularly annotated datasets. Compared with non-TP53 mutated KRAS-altered tumors, KRAS-TP53 co-alteration engenders disproportionately innate immune-enriched and CD8+ T-cell-excluded immune signatures. Leveraging in silico, in vitro, and in vivo models of human and murine PDAC, we discover a novel intersection between KRAS-TP53 co-altered transcriptomes, TP63-defined squamous trans-differentiation, and myeloid-cell migration into the tumor microenvironment. Comparison of single-cell transcriptomes between KRAS-TP53 co-altered and KRAS-altered/TP53WT tumors revealed cancer cell-autonomous transcriptional programs that orchestrate innate immune trafficking and function. Moreover, we uncover granulocyte-derived inflammasome activation and TNF signaling as putative paracrine mediators of innate immunoregulatory transcriptional programs in KRAS-TP53 co-altered PDAC. Immune subtyping of KRAS-TP53 co-altered PDAC reveals conflation of intratumor heterogeneity with progenitor-like stemness properties. Coalescing these distinct molecular characteristics into a KRAS-TP53 co-altered “immunoregulatory program” predicts chemoresistance in metastatic PDAC patients enrolled in the COMPASS trial, as well as worse overall survival.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality following distal pancreatectomy (DP). However, the influence of operative technique on VTE risk after DP is unknown. The purpose of this study was to examine the association between the MIS technique versus the open technique and the development of postoperative VTE after DP. Patients who underwent DP from 2014 to 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program pancreas-specific database. Multivariable logistic regression was then used to identify independent associations with the development of postoperative VTE after DP. A total of 3558 patients underwent DP during this time period. Of these cases, 47.8% (n = 1702) were performed via the MIS approach. After adjusting for significant covariates, the MIS approach was independently associated with the development of any VTE (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.06–2.40; p = 0.025), as well as increasing the risk of developing a postdischarge VTE (OR 1.80, 95% CI 1.05–3.08; p = 0.033) when compared with the open approach. There was an association between VTE and the development of numerous postoperative complications, including pneumonia, unplanned intubation, need for prolonged mechanical ventilation, and cardiac arrest. Compared with the open approach, the MIS approach is associated with higher rates of postoperative VTE in patients undergoing DP. The majority of these events are diagnosed after hospital discharge.

Perioperative blood transfusion is common after pancreaticoduodenectomy (PD) and may predispose patients to infectious complications. The purpose of this study is to examine the association between perioperative blood transfusion and the development of post-surgical infection after PD.Patients who underwent PD from 2014 to 2015 were identified in the NSQIP pancreas-specific database. Logistic regression analysis was used to compute adjusted odds ratios (aOR) to identify an independent association between perioperative red blood cell transfusion (within 72 h of surgery) and the development of post-operative infection after 72 h.A total of 6869 patients underwent PD during this time period. Of these, 1372 (20.0%) patients received a perioperative blood transfusion. Patients receiving transfusion had a higher rate of post-operative infection (34.7% vs 26.5%, p 0.001). After adjusting for significant covariates, perioperative transfusion was independently associated the subsequent development of any post-operative infection (aOR 1.41 [1.23-1.62], p 0.001), including pneumonia (aOR 2.01 [1.48-2.74], p 0.001), sepsis (aOR 1.62 [1.29-2.04], p 0.001), and septic shock (aOR 1.92 [1.38-2.68], p 0.001).There is a strong independent association between perioperative blood transfusion and the development of subsequent post-operative infection following PD.

ObjectivesThe Centers for Disease Control disclosed over 600,000 cases of child abuse or neglect in 2016. Single-institution studies have shown that nonaccidental trauma (NAT) has higher complication rates than accidental trauma (AT). Nonaccidental trauma is disproportionately represented in infants. We hypothesized that NAT would increase the risk of mortality in infants. This study aims to provide a contemporary descriptive analysis for infant trauma patients and determine the association between NAT and mortality.MethodsInfants (

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense, desmoplastic stroma and the consequent altered interactions between cancer cells and their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, and chemoresistance. We have previously shown that IL6 secreted from pancreatic stellate cells (PSC) stimulates the activation of STAT3 signaling in tumor cells, an established mechanism of therapeutic resistance in PDAC. We have now identified the tumor cell–derived cytokine IL1α as an upstream mediator of IL6 release from PSCs that is involved in STAT3 activation within the TME. Herein, we show that IL1α is overexpressed in both murine and human PDAC tumors and engages with its cognate receptor IL1R1, which is strongly expressed on stromal cells. Further, we show that IL1R1 inhibition using anakinra (recombinant IL1 receptor antagonist) significantly reduces stromal-derived IL6, thereby suppressing IL6-dependent STAT3 activation in human PDAC cell lines. Anakinra treatment results in significant reduction in IL6 and activated STAT3 levels in pancreatic tumors from Ptf1aCre/+;LSL-KrasG12D/+; Tgfbr2flox/flox (PKT) mice. Additionally, the combination of anakinra with cytotoxic chemotherapy significantly extends overall survival compared with vehicle treatment or anakinra monotherapy in this aggressive genetic mouse model of PDAC. These data highlight the importance of IL1 in mediating tumor–stromal IL6/STAT3 cross-talk in the TME and provide a preclinical rationale for targeting IL1 signaling as a therapeutic strategy in PDAC.

2021 is shaping up to be the year of artificial intelligence (AI) for the dental industry. Not only are providers adopting AI at a rapid pace, payers are tapping this technology to automate their claims review operations and reduce friction in provider interactions. In part three of this six-part dental AI series, the authors offer their view from the frontlines of dental claims processing and the promising future impact of AI. Representing clinical and business viewpoints, the authors draw on experience working at and with some of the largest dental payers in the country. This article presents a forward-looking perspective on the potential of dental AI to improve payer-provider relations, streamline claims review, and ultimately provide an improved patient experience.

The aim of this study was to detect a response difference in primary (PLC) and secondary liver tumors (SLC) with magnetic resonance elastography (MRE) after TACE therapy. Thirty-one patients (25/31 male; mean age 69.6 years [range: 39-85 years]) with repeated TACE therapy of HCC were compared with twenty-seven patients (27/27 female; mean age 61.2 years [range 39-81 years]) with repeated TACE therapy of metastatic liver disease due to breast cancer. Both groups underwent either one (n = 31) or two (n = 27) repetitive magnetic resonance imaging (MRI) and MRE exams in 4- to 6-week intervals using a 1.5-T-scanner. MRE-based liver stiffness and size measurements were evaluated in tumorous lesions and in healthy liver lobe controls. PLC showed a significantly larger tumor size compared to SLC (26.4 cm

Personalization is at the center of medical practice. With the sequencing of the genome, the rise in technologies and big data processing capacities, it was then envisioned in an even more precise way, for more targeted treatments on patients' distinctive features. In the last few years, prospects for this personalization went in the direction of public health. Beyond patients, the aim is thus to pursue the entire population, to identify and adjust action on the social, environmental, and biomedical factors that make individuals vulnerable in a health perspective. This is referred as personalized health. Its objective is to better understand the interactions between these factors for a more efficient approach of healthcare and interventions on the social conditions for maintaining the good health of all.La personnalisation des soins est au centre de la pratique médicale. Avec le séquençage du génome, l’essor des technologies et du traitement de données massives, elle est maintenant envisagée de manière encore plus précise pour des soins toujours plus ciblés sur les caractéristiques des patients. Depuis quelques années, ces techniques déploient aussi leur potentiel en matière de santé publique. Au-delà des patients, il s’agit ici de viser toute la population, pour identifier et ajuster l’action sur les facteurs sociaux, environnementaux et biomédicaux qui rendent les individus vulnérables du point de vue de la santé. On parle de santé personnalisée. Son objectif est de mieux comprendre les interactions entre ces facteurs pour une approche plus efficace des soins et des interventions sur les conditions sociales du maintien de la bonne santé pour tous.

Trauma pancreaticoduodenectomy (TP) remains a challenging operation with morbidity and mortality rates as high as 80% and 50%. Many trauma surgeons consider it surgical dogma to avoid performing a TP during the index operation for patients with severe pancreatic or duodenal injuries. However, there is no modern analysis evaluating this belief. Therefore, we hypothesized no difference in risk of mortality between patients with severe pancreatic or duodenal injury undergoing a TP for penetrating trauma to propensity-matched controls undergoing laparotomy without TP. The Trauma Quality Improvement Program (2010-2016) was queried for adults with severe penetrating pancreatic or duodenal injuries undergoing laparotomy. A 1:2 propensity-matching including demographics/comorbidities, injury severity score, vitals on admission, Glasgow Coma Scale and concomitant injuries for laparotomy with or without TP was performed. Risk of mortality was reported using a univariable logistic regression model. Of 2182 patients with severe pancreatic or duodenal injuries undergoing laparotomy, 54 (2.5%) underwent TP and 2128 (97.5%) underwent laparotomy without TP. There were no differences in propensity-matching characteristics. Patients undergoing TP had a similar mortality rate (20.0% vs. 28.7%, p = 0.302) but a longer length of stay (LOS) (27.5 vs. 16.5days, p = 0.017). The TP group had a similar associated risk of mortality (OR = 0.62, p = 0.302) but higher risk of major complications (OR 3.44, CI 1.35-17.47, p = 0.015). In appropriately selected penetrating trauma patients with severe pancreatic/duodenal injuries, TP is associated with a similar risk of mortality compared to laparotomy without TP. However, TP patients did have an increased associated risk of major complications and longer LOS.

Purpose In patients with pyogenic spondylodiscitis, surgery is considered the treatment of choice to conduct proper debridement, stabilise the spine and avoid extended bed rest, which in turn is a risk factor for complications such as deep vein thrombosis and pulmonary embolism. Methods We conducted a retrospective clinical study with analysis of a group of 99 patients who had undergone treatment for pyogenic discitis at our institution between June 2012 and August 2017. Included parameters were age, sex, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, preexisting comorbidities, tobacco abuse, body mass index, microbiological germ detection and laboratory results. Results Among the analysed cohort, 12% of the treated patients for pyogenic spondylodiscitis suffered from a radiologically confirmed pulmonary embolism. Coronary heart disease (p p p p p p p > 0.05). Conclusion Surgery for pyogenic spondylodiscitis was not associated with an elevated risk of pulmonary embolism in our analysis. However, we describe several risk factors for pulmonary embolism in this vulnerable cohort. Prospective studies are necessary to improve prevention and postoperative management in patients with pyogenic spondylodiscitis.

Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date, only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label. A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT scan confirmed PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data. Out of 584 GBM patients, 8% suffered from postoperative PE. Out of these, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis, or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6 and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS. In our analysis, DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis, and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.

Abdominal surgeries are lifesaving procedures but can be complicated by the formation of peritoneal adhesions, intra-abdominal scars that cause intestinal obstruction, pain, infertility, and significant health costs. Despite this burden, the mechanisms underlying adhesion formation remain unclear and no cure exists. Here, we show that contamination of gut microbes increases post-surgical adhesion formation. Using genetic lineage tracing we show that adhesion myofibroblasts arise from the mesothelium. This transformation is driven by epidermal growth factor receptor (EGFR) signaling. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor, are sufficient to induce these changes. Correspondingly, EGFR inhibition leads to a significant reduction of adhesion formation in mice. Adhesions isolated from human patients are enriched in EGFR positive cells of mesothelial origin and human mesothelium shows an increase of mesothelial EGFR expression during bacterial peritonitis. In conclusion, bacterial contamination drives adhesion formation through mesothelial EGFR signaling. This mechanism may represent a therapeutic target for the prevention of adhesions after intra-abdominal surgery., Abdominal surgery can often lead to complications including the formation of peritoneal adhesions and the molecular mechanisms underlying this process are still unknown. Here, the authors suggest that bacterial contamination drives adhesion formation through mesothelial EGFR signalling.

PURPOSE The purpose of the present study was to establish a semi-automated threshold-based image segmentation algorithm to detect and objectively quantify corneal cystine crystal deposition in ocular cystinosis with anterior segment optical coherence tomography (AS-OCT). METHODS This prospective, observational, comparative study included 88 eyes of 45 patients from the German Cystinosis Registry Study as well as 68 eyes of 35 healthy control subjects. All eyes were imaged with AS-OCT (Cirrus HD-OCT 5000, Carl Zeiss Meditec AG, Jena, Germany). As an initial step, B-scan images were subjectively analysed for typical changes in morphology in comparison to healthy controls. Based on the experience gained, an objective semi-automated B-scan image segmentation algorithm was developed using a grey scale value-based threshold method to automatically quantify corneal crystals. RESULTS On AS-OCT B-scans, corneal crystals appeared as hyperreflective deposits within the corneal stroma. The crystals were distributed either in all stromal layers (43 eyes, 49%) or confined to the anterior (23 eyes, 26%) or posterior stroma (22 eyes, 25%), respectively. The novel automatic B-scan image segmentation algorithm was most efficient in delineating corneal crystals at higher grey scale thresholds (e.g. 226 of a maximum of 255). Significant differences in suprathreshold grey scale pixels were observable between cystinosis patients and healthy controls (p

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy and is highly resistant to standard treatment regimens. Targeted therapies against KRAS, a mutation present in an overwhelming majority of PDAC cases, have been largely ineffective. However, inhibition of downstream components in the KRAS signaling cascade provides promising therapeutic targets in the management of PDAC and warrants further exploration. Here, we investigated Urolithin A (Uro A), a novel natural compound derived from pomegranates, which targets numerous kinases downstream of KRAS, in particular the PI3K/AKT/mTOR signaling pathways. We showed that treatment of PDAC cells with Uro A blocked the phosphorylation of AKT and p70S6K in vitro, successfully inhibited the growth of tumor xenografts, and increased overall survival of Ptf1aCre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mice compared with vehicle or gemcitabine therapy alone. Histologic evaluation of these Uro A–treated tumor samples confirmed mechanistic actions of Uro A via decreased phosphorylation of AKT and p70S6K, reduced proliferation, and increased cellular apoptosis in both xenograft and PKT mouse models. In addition, Uro A treatment reprogrammed the tumor microenvironment, as evidenced by reduced levels of infiltrating immunosuppressive cell populations such as myeloid-derived suppressor cells, tumor-associated macrophages, and regulatory T cells. Overall, this work provides convincing preclinical evidence for the utility of Uro A as a therapeutic agent in PDAC through suppression of the PI3K/AKT/mTOR pathway.

Studies comparing laparoscopic versus open resection of gastrointestinal stromal tumors (GIST) typically involve small comparative groups and often do not control for tumor size or stage of disease. The objective of this study was to compare adjusted survival outcomes for laparoscopic versus open GIST. The National Cancer Database (NCDB) from 2010 to 2014 was evaluated for gastric and small intestinal GIST resections. After stratification by disease stage and adjustment for patient demographics, comorbidity score, tumor size, and tumor location, 90-day mortality rates were compared based on laparoscopic versus open resection. Kaplan–Meier estimates of long-term survival were also compared. A Cox proportional hazards model was used to determine hazard ratios (HR) for survival. There were 5096 cases analyzed, including 2910 (57%) stage I, 954 (19%) stage II, and 1232 (24%) stage III cases. The distribution of laparoscopic versus open cases was 1291 (44%) versus 1619 (56%) for stage I, 318 (33%) versus 636 (67%) for stage II, and 286 (23%) versus 946 (77%) for stage III. There was no significant difference in adjusted 90-day mortality between laparoscopic and open resection. Kaplan–Meier estimates of long-term survival demonstrated improved overall survival curves for laparoscopic resection for stage I and stage II disease, but no significant difference for stage III disease. Factors associated with statistically significant higher adjusted overall mortality included older age (HR 1.06; p

Cancer stem cells resemble normal tissue-specific stem cells in many aspects, such as self-renewal and plasticity. Like their non-malignant counterparts, cancer stem cells are suggested to exhibit a relative quiescence. The established cancer cell lines reportedly harbor slow-proliferating cells that are positive for some cancer stem cells markers. However, the fate of these cells and their progeny remains unknown. We used time-lapse microscopy and the contrast-based segmentation algorithm to identify and monitor actively dividing and non-dividing cells in human osteosarcoma MG-63 cell line. Within the monitored field of view the non-dividing cells were represented by three cells that never divided, and one cell that attempted to divide, but failed cytokinesis, and later, after significantly prolonged division, produced the progeny with enlarged segmented nuclei, thus pointing to a possible mitotic catastrophe. Together, these cells initially constituted about 6.2% of the total number of seeded cells, yet only 0.02% of all cells at the end of the observation period when cells became confluent. Non-dividing cells were characterized by rounded shape, dark nuclei, random cytoplasmic streaming and subtle oscillatory movement, however, they did not migrate and rarely formed cell-cell contacts as compared to actively dividing cells. Our data indicate that the observed non-dividing MG-63 cells do not have a growth advantage over other cells and, therefore, they do not contribute to the cancer stem cells pool.

Background The long-term outcomes of rotator cuff repair are unclear. Recurrent tears are common, although their reported frequency varies depending on the type and interpretation challenges of the imaging method used. The primary objective of this study was to assess the intra- and inter-observer reproducibility of the MRI assessment of rotator cuff repair using the Sugaya classification 10 years after surgery. The secondary objective was to determine whether poor reproducibility, if found, could be improved by using a simplified yet clinically relevant classification. Hypothesis Our hypothesis was that reproducibility was limited but could be improved by simplifying the classification. Material and method In a retrospective study, we assessed intra- and inter-observer agreement in interpreting 49 magnetic resonance imaging (MRI) scans performed 10 years after rotator cuff repair. These 49 scans were taken at random among 609 cases that underwent re-evaluation, with imaging, for the 2015 SoFCOT symposium on 10-year and 20-year clinical and anatomical outcomes of rotator cuff repair for full-thickness tears. Each of three observers read each of the 49 scans on two separate occasions. At each reading, they assessed the supra-spinatus tendon according to the Sugaya classification in five types. Results Intra-observer agreement for the Sugaya type was substantial (κ = 0.64) but inter-observer agreement was only fair (κ = 0.39). Agreement improved when the five Sugaya types were collapsed into two categories (1–2–3 and 4–5) (intra-observer κ = 0.74 and inter-observer κ = 0.68). Conclusion Using the Sugaya classification to assess post-operative rotator cuff healing was associated with substantial intra-observer and fair inter-observer agreement. A simpler classification into two categories improved agreement while remaining clinically relevant. Level of evidence II, prospective randomised low-power study.

Human infantile-onset RNASET2-deficient cystic leukoencephalopathy is a Mendelian mimic of in utero cytomegalovirus brain infection with prenatally developing inflammatory brain lesions. We used an RNASET2-deficient zebrafish model to elucidate the underlying disease mechanisms. Mutant and wild-type zebrafish larvae brain development between 2 and 5 days post fertilization (dpf) was examined by confocal live imaging in fluorescent reporter lines of the major types of brain cells. In contrast to wild-type brains, RNASET2-deficient larvae displayed increased numbers of microglia with altered morphology, often containing inclusions of neurons. Furthermore, lysosomes within distinct populations of the myeloid cell lineage including microglia showed increased lysosomal staining. Neurons and oligodendrocyte precursor cells remained unaffected. This study provides a first look into the prenatal onset pathomechanisms of human RNASET2-deficient leukoencephalopathy, linking this inborn lysosomal disease to the innate immune system and other immune-related childhood encephalopathies like Aicardi-Goutières syndrome (AGS)., Summary: A zebrafish disease model of human RNASET2-deficient cystic leukoencephalopathy displays altered morphology, signs of lysosomal storage disorder, and persistent engulfment of apoptotic neurons in microglia as early disease pathology.

Activating KRAS mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation of cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16INK4a (p16), encoded by the gene CDKN2A, is a potent inhibitor of CDK4/6 and serves as a critical checkpoint of cell proliferation. Mutations in and subsequent loss of the p16 gene occur in PDAC at a rate higher than that reported in any other tumor type and results in Rb inactivation and unrestricted cellular growth. Therefore, strategies targeting downstream RAS pathway effectors combined with CDK4/6 inhibition (CDK4/6i) may have the potential to improve outcomes in this disease. Herein, we show that expression of p16 is markedly reduced in PDAC tumors compared with normal pancreatic or pre-neoplastic tissues. Combined MEK inhibition (MEKi) and CDK4/6i results in sustained downregulation of both ERK and Rb phosphorylation and a significant reduction in cell proliferation compared with monotherapy in human PDAC cells. MEKi with CDK4/6i reduces tumor cell proliferation by promoting senescence-mediated growth arrest, independent of apoptosis in vitro. We show that combined MEKi and CDK4/6i treatment attenuates tumor growth in xenograft models of PDAC and improves overall survival over 200% compared with treatment with vehicle or individual agents alone in Ptf1acre/+;LSL-KRASG12D/+;Tgfbr2flox/flox (PKT) mice. Histologic analysis of PKT tumor lysates reveal a significant decrease in markers of cell proliferation and an increase in senescence-associated markers without any significant change in apoptosis. These results demonstrate that combined targeting of both MEK and CDK4/6 represents a novel therapeutic strategy to synergistically reduce tumor growth through induction of cellular senescence in PDAC.

Diversification of the health care workforce by race and ethnicity offers a strategy for addressing health care disparities. This study explored the experiences with pathways programming and mentoring of minority undergraduates aspiring to health professions careers.We interviewed 21 minority undergraduates in 4 focus groups. The interviews explored participants' backgrounds; perceptions of racial climate; exposure to health professions careers, mentors, and pathways programs; barriers to success; and desired support.Many participants described diminished confidence and feelings of isolation due to stereotyping and discrimination; some were empowered to pursue health care careers because of adversity. Common themes included desire for mentorship, earlier career exposure, and college readiness support.Minority students desire health career exposure, mentoring, pre-college advising, and a positive racial climate; unfortunately, these desires often go unmet.

Introduction Guidelines surrounding abdominal seat belt sign (SBS) were made prior to the use of modern computed tomography (CT) imaging. We sought to prospectively determine whether a negative CT scan is associated with the absence of hollow viscus injury (HVI), and we hypothesized that trauma patients with an abdominal SBS without CT imaging findings would not have a hollow viscus injury (HVI). Methods A prospective cohort of patients with SBS was compiled over one year. Subjects were divided into those with and without HVI. Covariate distributions were summarized by group. Bivariate tests and logistic regression were used to investigate associations between covariates and HVI. Results Of 220 patients with SBS, the incidence of HVI was 7% (n = 15). Radiographic findings were strongly associated with HVI and no patients with a negative CT scan had HVI. Free fluid was seen in 80% (12) of patients with HVI, whereas it was found in only 11% (23) without injury. A composite variable for negative CT scan was found to be associated with the absence of HVI: (Fisher's exact 1-tailed p, doubled = 0.014). Conclusion In this study, the incidence of HVI with SBS is lower than previously reported, and no patients with negative CT imaging required an operation for HVI—suggesting there is a population of patients with SBS who could be discharged from the emergency room. A prospective multicenter study is needed to confirm these findings.

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF

Background Cancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control. Methods This population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and nonmalignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001-10. Incidence rates per million person-years for the 0-14 years and 0-19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0-4 years, 5-9 years, 10-14 years, and 15-19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0-14 years were compared with comparable data obtained in the 1980s. Findings Of 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001-10. 385 509 incident cases in children aged 0-19 years occurring in 2.64 billion person-years were included. The overall WSR was 140.6 per million person-years in children aged 0-14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46.4), followed by CNS tumours (WSR 28.2), and lymphomas (WSR 15.2). In children aged 15-19 years (based on 100 860 cases), the ASR was 185.3 per million person-years, the most common being lymphomas (ASR 41.8) and the group of epithelial tumours and melanoma (ASR 39.5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0-14 years has increased from 124.0 (95% CI 123.3-124.7) to 140.6 (140.1-141.1) per million person-years. Interpretation This unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research., International Agency for Research on Cancer and the Union for International Cancer Control.

Pelvic ring fractures when caused by trauma, either violent or in demineralized bone, generally consist of injuries in both the anterior (pubic symphysis and rami) and posterior (iliac wing, sacrum, sacroiliac joint) portions. Injury classifications are based on injury mechanism and pelvic stability, and are used to determine treatment. Acetabular fractures, associated or not to pelvic ring disruption, are classified on the basis of fracture line, into elementary fractures of the acetabular walls, columns and roof, and into complex fractures. Fractures of the proximal end of the femur occur often on demineralized bone following low-energy trauma. The fractures are categorized by anatomic location (neck, trochanter and subtrochanteric region) and degree of displacement. These variables determine the risk of osteonecrosis of the femoral head, which is the main complication of such fractures.

To determine the impact of maternal obesity and gestational weight gain across pregnancy on fetal indices of inflammation and iron status.Eighty-five healthy term newborns delivered via elective cesarean were categorized by 2 maternal body mass index (BMI) thresholds; above or below 30 kg/m(2) or above or below 35 kg/m(2). Umbilical cord plasma levels of C-reactive protein, interleukin (IL)-6, tumor necrosis factor (TNF)-α, ferritin, and hepcidin were assayed. Cytokines released by phytohemagglutinin-stimulated umbilical cord mononuclear cells (MNCs) were assayed.Maternal class II obesity, defined as BMI of 35 kg/m(2) and above, predicted higher C-reactive protein and TNF-α in umbilical cord plasma (P .05 for both), and also proinflammatory cytokines (IL-1β, IL-6, and TNF-α) from stimulated MNC (P .05 for all). The rise in plasma TNF-α and MNC TNF-α was not linear but occurred when the threshold of BMI 35 kg/m(2) was reached (P .005, P .06). Poorer umbilical cord iron indices were associated with maternal obesity. When ferritin was low, IL-6 was higher (P .04), but this relationship was present primarily when maternal BMI exceeded 35 kg/m(2) (P .03). Ferritin was correlated with hepcidin (P .0001), but hepcidin was unrelated to either maternal BMI or inflammatory indices.Class II obesity and above during pregnancy is associated with fetal inflammation in a threshold fashion. Although maternal BMI negatively impacted fetal iron status, hepcidin, related to obesity in adults, was related to iron status and not obesity in fetuses. Pediatricians should be aware of these relationships.

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. Descriptive epidemiology of pancreatic cancer in South Dakota has not been studied before. All cases of pancreatic cancer reported to the SD Cancer Registry between January 2005 and December 2014 were included in the study. Variables collected included demographics, geographical location including county of residence and zip codes, date of diagnosis, date of last contact or follow-up, size and location of the tumor, grade of the tumor, diagnostic modality as well as therapeutic interventions. Log rank test was used to compare survival curves. Kaplan-Meier product limit estimates were provided. Data was analyzed using SAS 9.1.4 software. One thousand sixty-four cases of pancreatic cancer were reported. Median age was 73 years. Cumulative age-adjusted incidence rate for pancreatic cancer for 2005–2014 was 11.1. Cumulative age-adjusted mortality rate for pancreatic cancer for 2005–2014 was 10.2. Almost half of these patients had distant metastasis at the time of presentation (n = 536; 50.4%). Overall, median survival was 5 months. Median survival for patients under the age of 60 years was 9.5 months as opposed to median survival for patients 60 years or older which was 3.9 months. Median survival of patients with well-differentiated, moderately differentiated, and poorly differentiated tumors, was 20.8 months, 8.2 months and 6.3 months respectively (p value = 0.0017). Incidence of pancreatic cancer in South Dakota is similar to the national trends in the United States. Age at presentation, location of tumor in pancreas, and biological behavior of tumor were all predictors of survival in patients with pancreatic cancer.

Bile is composed of multiple macromolecules, including bile acids, free cholesterol, phospholipids, bilirubin, and inorganic ions that aid in digestion, nutrient absorption, and disposal of the insoluble products of heme catabolism. The synthesis and release of bile acids is tightly controlled and dependent on feedback mechanisms that regulate enterohepatic circulation. Alterations in bile composition, impaired gallbladder relaxation, and accelerated nucleation are the principal mechanisms leading to biliary stone formation. Various physiologic conditions and disease states alter bile composition and metabolism, thus increasing the risk of developing gallstones.

Bacterial spillage into a sterile environment following intestinal hollow-organ perforation leads to peritonitis and fulminant sepsis. Outcome of sepsis critically depends on macrophage activation by extracellular ATP-release and associated autocrine signalling via purinergic receptors. ATP-release mechanisms, however, are poorly understood. Here, we show that TLR-2 and -4 agonists trigger ATP-release via Connexin-43 hemichannels in macrophages leading to poor sepsis survival. In humans, Connexin-43 was upregulated on macrophages isolated from the peritoneal cavity in patients with peritonitis but not in healthy controls. Using a murine peritonitis/sepsis model, we identified increased Connexin-43 expression in peritoneal and hepatic macrophages. Conditional Lyz2cre/creGja1flox/flox mice were developed to specifically assess Connexin-43 impact in macrophages. Both macrophage-specific Connexin-43 deletion and pharmacological Connexin-43 blockade were associated with reduced cytokine secretion by macrophages in response to LPS and CLP, ultimately resulting in increased survival. In conclusion, inhibition of autocrine Connexin-43-dependent ATP signalling on macrophages improves sepsis outcome.

Background It is of major importance in clinical surgery to identify potential patterns and specific causes of complications. Therefore, morbidity and mortality meetings (M&M) are widely used to discuss and evaluate deviations from expected outcomes in order to improve surgical practice. Moreover, M&M represent an important tool for continuous medical education. In this study, we introduced an electronic voting system to assess whether anonymity during M&M could limit potential biases due to hierarchical structures or opinion leaders. Methods This study was conducted in the surgical department of a European tertiary care center. During the study period, electronic voting was applied in 412 M&M cases and compared with a baseline of 330 conventional M&M entries. In this interrupted time series, the educational quality and participant satisfaction of the M&M were assessed using surveys before and after the introduction of electronic voting. The surveys were refined using principle component analysis. In addition, the classification of the cause of the complication was recorded. Results The introduction of electronic voting led to a significant increase in perceived educational quality from 2.63 to 3.36 (p

OBJECTIVE: To perform a comprehensive assessment of long-term quality of life (QOL) and gastrointestinal (GI) function in patients following pancreaticoduodenectomy (PD). SUMMARY OF BACKGROUND DATA: Survival after PD has greatly improved and thus has resulted in a larger population of survivors, yet long-term QOL and GI function after PD is largely unknown. METHODS: Patients were identified from a global online support group. QOL was measured using the Short Form-36, while GI function was assessed using the Gastrointestinal Symptom Rating Scale. QOL and GI function were analyzed across subgroups based on time after PD. QOL was compared with preoperative measurements and with established values of a general healthy population (GHP). Multivariate linear regression was used to identify predictors of QOL. RESULTS: Of the 7605 members of the online support group, 1102 responded to the questionnaire with 927 responders meeting inclusion criteria. Seven hundred seventeen (77.3%) of these responders underwent PD for malignancy. Mean age was 57 ± 12 years and 327 (35%) were male. At the time of survey, patients were 2.0 (0.7, 4.3) years out from surgery, with a maximum 30.7-year response following PD. Emotional and physical domains of QOL improved with time and surpassed preoperative levels between 6 months and 1 year after PD (both P < 0.001). Each GI symptom worsened over time(all P < 0.001). Independent predictors of general QOL in long-term survivors (> 5 years) included total GSRS score [β= −1.70 (−1.91,−1.50)], female sex [β = 3.58 (0.67, 6.46)], and being a cancer survivor [β = 3.93 (0.60, 7.25)]. CONCLUSIONS: Long-term QOL following PD improves over time, however never approaches that of a GHP. GI dysfunction persists in long-term survivors and is an independent predictor of poor QOL. Long-term physical, psychosocial, and GI functional support after PD is encouraged.

Broad consensus assigns T lymphocytes fundamental roles in inflammatory, infectious, and autoimmune diseases. However, clinical investigations have lacked fully characterized and validated procedures, equivalent to those of widely practiced biochemical tests with established clinical roles, for measuring core T cell functions. The Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR) type 1 diabetes prevention trial used consecutive measurements of T cell proliferative responses in prospectively collected fresh heparinized blood samples shipped by courier within North America. In this article, we report on the quality control implications of this simple and pragmatic shipping practice and the interpretation of positive- and negative-control analytes in our assay. We used polyclonal and postvaccination responses in 4,919 samples to analyze the development of T cell immunocompetence. We have found that the vast majority of the samples were viable up to 3 days from the blood draw, yet meaningful responses were found in a proportion of those with longer travel times. Furthermore, the shipping time of uncooled samples significantly decreased both the viabilities of the samples and the unstimulated cell counts in the viable samples. Also, subject age was significantly associated with the number of unstimulated cells and T cell proliferation to positive activators. Finally, we observed a pattern of statistically significant increases in T cell responses to tetanus toxin around the timing of infant vaccinations. This assay platform and shipping protocol satisfy the criteria for robust and reproducible long-term measurements of human T cell function, comparable to those of established blood biochemical tests. We present a stable technology for prospective disease-relevant T cell analysis in immunological diseases, vaccination medicine, and measurement of herd immunity.

This study explored the link between body image and desire to engage in sexual activity (dyadic and solitary desire) in adult women living in a long-term couple relationship. Moreover, it considered two psychological factors that may underlie such a link: the occurrence of body-related distracting thoughts during sexual activity and encoding style (i.e., the tendency to rely on preexisting internal schemata versus external information at encoding). A total of 53 women (29 to 47 years old) in heterosexual relationships completed questionnaires assessing sexual desire (dyadic, solitary), body image, body-related distracting thoughts during sexual activity, and encoding style. Results showed that poor body image was associated with low dyadic and solitary sexual desire. Body-related distracting thoughts during sexual activity mediated the link between body image and solitary (but not dyadic) sexual desire. Finally, the mediation of body-related distracting thoughts between body image and solitary sexual desire was moderated by encoding style. A negative body image promoted the occurrence of body-related distracting thoughts during sexual activity, especially in internal encoders. Our study highlights the importance of body image, distracting thoughts, and encoding style in women's solitary sexuality and suggests possible factors that may reduce the impact of those body-related factors in dyadic sexual desire.

Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer.

This article examines individual variability in sexual desire and sexual satisfaction by exploring the relation between these sexual aspects and sexual attitudes (implicit and explicit) and by taking gender into account, as this has been shown to be an influential factor. A total of 28 men and 33 women living in heterosexual relationships completed questionnaires assessing sexual desire (dyadic, solitary), sexual satisfaction, and explicit sexual attitudes. An adapted version of the Affect Misattribution Procedure was used to assess implicit sexual attitudes. Results showed higher levels of dyadic and solitary sexual desire in men than in women. No gender differences were found regarding sexual satisfaction or sexual attitudes. High dyadic sexual desire was associated with positive implicit and explicit sexual attitudes, regardless of gender. However, solitary sexual desire was significantly higher in men than women and was associated, in women only, with positive implicit sexual attitudes, suggesting that solitary sexual desire may fulfill different functions in men and women. Finally, sexual satisfaction depended on the combination of explicit and implicit sexual attitudes in both men and women. This study highlights the importance of considering both implicit and explicit sexual attitudes to better understand the mechanisms underlying individual variability in sexual desire and satisfaction.