Laparoscopic surgery for benign lesions of the pancreas

Background: Minimally invasive pancreatic surgery, although known to be feasible and safe, is still not considered a standard procedure. We report our experience with laparoscopic pancreatic surgery in a retrospective case series. Materials and Methods: Fifteen consecutive patients (3 male, 12 female) underwent primarily laparoscopic pancreatic surgery from February 2000 to June 2005. Histologically confirmed diagnoses were: neuroendocrine pancreatic tumors (n = 11), adult nesidioblastosis (n = 1), serous cystadenoma (n = 1), and pseudocysts due to chronic pancreatitis (n = 2). Results: Enucleation (n = 3) or left pancreatic resection with spleen preservation (n = 6) was performed laparoscopically in 9 patients. The mean (+/-standard deviation) operative time was 173 +/- 48 minutes (range, 120-250 minutes) and the mean postoperative hospital stay was 5.5 +/- 1.2 days (range, 5-8 days) for the laparoscopic cases. Conversion to open surgery was necessary in 6 patients because of: closeness of the lesion to the portal/mesenteric vein (n = 3), inadequate intraoperative tumor localization (n = 2), or stapler device dysfunction (n = 1). In these patients, open enucleation (n = 1), middle segment pancreatectomy (n = 2), left pancreatic resection (n = 2), and pylorus-preserving Whipple resection (n = 1) were performed. The mean operative time was 268 +/- 74 minutes (range, 150-360 minutes) with a mean postoperative hospital stay of 8 +/- 2 days (range, 6-10 days). Both operative time and hospital stay were significantly longer in patients with secondary open surgery compared to patients with successful laparoscopic operations. Conclusion: Laparoscopic enucleation or distal pancreatectomy with spleen preservation for benign lesions located in the body or tail of the pancreas can be performed safely, with all the potential benefits of minimally invasive surgery. Preoperative tumor localization is of utmost importance to limit pancreatic mobilization and to avoid blind pancreatic resection and conversion to open surgery.     

Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer

BACKGROUND: The aim of the study was to evaluate the efficacy of adjuvant chemotherapy on survival after resection for gastric cancer. METHODS: Patients were enrolled if they underwent resection of gastric cancer but had lymph node or serosal involvement or both. Surgical resection was either total or partial gastrectomy according to the site of the tumor, and surgeons were allowed to perform either D1 or D2 gastrectomy. The subjects were random assigned in two treatment groups as follows: surgery alone as the control group, or surgery and adjuvant chemotherapy. Nine cycles of 5 days protocol every 4 weeks was proposed to the patients of the chemotherapy group. The protocol included a daily administration of 200 mg/m(2) of folinic acid, 5-fluorouracil (375 mg/m(2) during the first session increasing 25 mg by session until reaching 500 mg/m(2)) and CDDP 15 mg/m(2). Two hundred patients were required. Kaplan-Meier survival curves were compared according to the log-rank and the Mantel-Haenszel methods. RESULTS: In all, 205 patients were enrolled in the study; 104 had surgery alone and 101 had surgery and adjuvant chemotherapy. The patients' characteristics were similar except for the mean age, which was 4 years less in the control group. Because of toxicity, 54% of the patients stopped the protocol before the end of the nine courses, and 46% of the patients received the nine courses including 32% with a decreased dose and 14% with a full dose. The 5-year survival rate was 39% in the control group and 39% in the chemotherapy group. CONCLUSIONS: This protocol of adjuvant chemotherapy failed to improve the 5-year survival after resection for gastric cancer.     

Modeling Relationships Involving Perceived Recovery Orientation of Mental Health Teams Among Quebec Mental Health Professionals

The Journal of Behavioral Health Services & Research - While mental health (MH) services are expected to support client recovery, very little is known about services provided by MH teams in...     

Characterization of T cell receptors reactive to HCRTNH2, pHA273-287, and NP17-31 in control and narcolepsy patients

Narcolepsy type 1 (NT1), a disorder caused by hypocretin/orexin (HCRT) cell loss, is associated with human leukocyte antigen (HLA)-DQ0602 (98%) and T cell receptor (TCR) polymorphisms. Increased CD4⁺ T cell reactivity to HCRT, especially DQ0602-presented amidated C-terminal HCRT (HCRT_NH2), has been reported, and homology with pHA_273–287 flu antigens from pandemic 2009 H1N1, an established trigger of the disease, suggests molecular mimicry. In this work, we extended DQ0602 tetramer and dextramer data to 77 cases and 44 controls, replicating our prior finding and testing 709 TCRs in Jurkat 76 T cells for functional activation. We found that fewer TCRs isolated with HCRT_NH2 (∼11%) versus pHA_273–287 or NP_17–31 antigens (∼50%) were activated by their ligand. Single-cell characterization did not reveal phenotype differences in influenza versus HCRT_NH2-reactive T cells, and analysis of TCR CDR3αβ sequences showed TCR clustering by responses to antigens but no cross-peptide class reactivity. Our results do not support the existence of molecular mimicry between HCRT and pHA_273–287 or NP_17–31.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin (HCRT) neurons in the mediolateral hypothalamus (1–3), with recent data suggesting reversion of the human and animal phenotype with orexin agonists. The disease is strongly associated with human leukocyte antigen (HLA) DQB1*06:02/DQA1*01:02 (98% vs. 25%) (DQ0602) and displays weaker genetic associations with other immune loci, thus suggesting autoimmunity (4–9), although not meeting all criteria for being classified as an autoimmune disease (10). Like other autoimmune diseases, NT1 presents with increased comorbidity with other autoimmune conditions and asthma (11–13).Onset of NT1 is often abrupt and seasonal, and association with both Streptococcus pyogenes (14, 15) and influenza A infections (16) suggests that it may be triggered by winter infections. Most strikingly, prevalence of NT1 increased several folds in mainland China and Taiwan following the 2009 to 2010 “swine flu” H1N1 influenza pandemic (pH1N1) (4, 17, 18), although association with the pandemic is less clear in other countries (19). Vaccination with the pH1N1 vaccine Pandemrix has also been associated with an elevated relative risk for developing narcolepsy of 5- to 14-fold in children and adolescents and 2- to 7-fold in adults (18, 20–22). As Pandemrix is an AS03-adjuvanted vaccine containing the artificially produced reassortant strain X-179A, a mix of A/Puerto Rico/8/1934 (PR8), an old H1N1 strain derived from pre-2009 seasonal H1N1, and the key H1N1 2009 surface proteins hemagglutinin (HA) and neuraminidase (NA) (23), flu proteins are likely critically involved in triggering NT1. Evidence showing that HLA and T cell receptor (TCR) genetic associations are universal (9, 24–27) is also consistent with a flu trigger, as influenza A infections occur on a global basis (28). Importantly, however, even with Pandemrix vaccination in Europe, only ∼1 in 16,000 vaccinated children developed NT1, thus demanding the consideration of additional factors to fully explain the initiation of NT1 (29).Unlike in other autoimmune diseases, autoantibodies against HCRT cell proteins, HCRT itself (30–32), or other targets such as TRIB2 (33, 34) or HCRT receptor 2 (35–38) have not been consistently found. This has led to the suggestion that HCRT cell loss may be primarily T cell mediated, with limited or no involvement of autoantibodies. Consistent with this hypothesis, mounting evidence suggests involvement of CD4⁺ T cell reactivity to HCRT in NT1 (39–41), notably toward amidated fragments of the secreted, mature peptide (HCRT_54–66-NH2 and HCRT_86–97-NH2, homologous peptides collectively denoted as HCRT_NH2) (42), as critical factors in the development of the disease. Furthermore, CD8⁺ mediation of HCRT cell death has also been shown to cause NT1 in an animal model (43) and Pedersen and colleagues (44) recently highlighted the presence of CD8⁺ T cell responses against intracellular proteins contained in HCRT neurons in narcolepsy patients. Of additional interest is the observation that the TCR polymorphisms associated with NT1 are quantitative trait loci for TRAJ24 (decreasing), TRAJ28, and TRBV4-2 (increasing) usage in peripheral T cells in both controls and patients (29). A significant L to F coding polymorphism located within the antigen-binding complementarity-determining region (CDR) 3 loop of TRAJ24 expressing TCRs is also associated with NT1. Altogether, this suggests that T cell responses involving TRAJ24- or TRAJ28- and TRBV4-2–bearing TCRs may be bottleneck responses in a causative autoimmune T cell response, leading to HCRT cell death (4, 14, 17–19, 45).Based on the evidence provided above, our group hypothesized that a CD4⁺ T cell–mediated response directed against specific flu epitopes could lead to molecular mimicry with HCRT itself, potentially HCRT_NH2, subsequently recruiting CD8⁺ cytotoxic T cells and leading to HCRT cell death. To test this hypothesis, we screened 135 DQ0602 tetramers binding peptides originating from Pandemrix, wild-type 2009 H1N1, and two autoantigens (HCRT and RFX4) for the presence of antigen-restricted CD4⁺ T cells (42). After this systematic survey, it was established that CD4⁺ T cell populations recognizing influenza pHA_273–287 (pH1N1 specific) and PR8 (H1N1 pre-2009 and H2N2)-restricted NP_17–31 epitopes were increased in NT1 versus DQ0602 controls. Supporting this finding, this difference was also present in post-Pandemrix cases versus controls and was stronger in recent onset cases (42). Additionally, studies of single cells recognizing these peptides revealed that TCR clones carrying TRBV4-2 and TRAJ24 were retrieved from both HCRT_NH2 and pHA_273–287 tetramers (42), suggesting involvement of these clones in molecular mimicry and disease pathophysiology. Similarly, Jiang et al. (39) isolated TRAJ24-positive cells recognizing DQ0602 bound to HCRT_87–100 tetramer, many of which expressed perforin and granzyme-B, suggesting a terminally differentiated effector T cell (T_EMRA) phenotype. In one case, a TRAJ24 clone isolated from a narcoleptic patient showed elevated TCR reactivity toward HCRT_87–97-NH2 when transfected in Jurkat 76 (J76) cells, thus implying a role for TRAJ24 reactivity toward DQ0602-HCRT in narcolepsy autoimmunity (39).Here, we extend prior work from our group by doubling the number of patients and controls and increasing the representation of TRAJ24F narcolepsy susceptibility–associated alleles in these subjects. Results validated an increased frequency of pHA_273–287 and HCRT_54–66-NH2 tetramer-positive CD4⁺ T cells in NT1, while also testing isolated T cell clones for potential activation by their cognate ligands when expressed in J76 cells. Importantly, we also analyzed TCR CDR3αβ sequences in this larger dataset and conducted expression profiling of the corresponding T cells, providing insights into T cell characteristics in narcolepsy.     

Modification of outer membrane protein profile and evidence suggesting an active drug pump in Enterobacter aerogenes clinical strains

Two clinical strains of Enterobacter aerogenes that exhibited phenotypes of multiresistance to beta-lactam antibiotics, fluoroquinolones, chloramphenicol, tetracycline, and kanamycin were investigated. Both strains showed a porin pattern different from that of a susceptible strain, with a drastic reduction in the amount of the major porin but with an apparently conserved normal structure (size and immunogenicity), together with overproduction of two known outer membrane proteins, OmpX and LamB. In addition, the full-length O-polysaccharide phenotype was replaced by a semirough Ra phenotype. Moreover, in one isolate the intracellular accumulation of chloramphenicol was increased in the presence of the energy uncoupler carbonyl cyanide m-chlorophenylhydrazone, suggesting an energy-dependent efflux of chloramphenicol in this strain. The resistance strategies used by these isolates appear to be similar to that induced by stress in Escherichia coli cells.     

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background

Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods

Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results

3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions

The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.