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In ARTEMIS, 58% of AR101-treated subjects vs. 2% of placebo-treated subjects tolerated 1000 mg peanut protein as a single dose at exit double-blind, placebo-controlled food challenge (DBPCFC; P < 0.0001) following treatment with AR101, an investigational oral biologic drug product for peanut oral immunotherapy. Immune responses to AR101 were assessed at 3 timepoints and compared with the placebo treatment group. All enrolled subjects had a clinical history of peanut allergy, demonstrated sensitization to peanut (skin prick test [SPT] mean wheal diameter ≥ 3 mm and/or peanut-specific immunoglobulin E [psIgE] ≥ 0.35 kUA/L), and reacted to ≤ 300 mg peanut protein at screening DBPCFC. SPT wheal diameter (mm), psIgE (kUA/L) and psIgG4 (mgA/L) assessments were performed at screening, end of dose escalation and study completion (following 3 months at 300 mg/day). Differences between treatment groups from screening to exit were analyzed using an ANCOVA model with terms fitted for group, country and screening value. A total of 175 ARTEMIS subjects (AR101 n = 132, placebo n = 43) were treated. SPT wheal diameter, psIgE levels, psIgG4 levels and psIgE/IgG4 ratio are summarized in Table 1. From baseline to exit (AR101 vs. placebo), psIgG4 levels increased (P < 0.0001); SPT wheal diameter (P < 0.0001) and psIgE/psIgG4 (P < 0.0001) decreased. In AR101-treated subjects, psIgE levels 2 increased at the end of dose escalation and decreased back to baseline levels, with no change between treatment groups (P = 0.6089) from baseline to exit. Exposure to AR101 was associated with immunologic changes consistent with immunomodulation: increased psIgG4, decreased peanut SPT wheal size and transient changes in psIgE levels, as reported in previous peanut oral immunotherapy trials. [ABSTRACT FROM AUTHOR]

AR101, an investigational oral biologic drug for peanut oral immunotherapy, was studied in PALISADE and ARTEMIS phase 3 trials. Efficacy and safety are compared. Subjects demonstrated clinical history of peanut allergy; peanut-specific immunoglobulin E ≥ 0.35 kUA/L and/or skin-prick test ≥ 3 mm; reacted to ≤ 100 mg (PALISADE)/≤ 300 mg peanut protein (ARTEMIS) at screening double-blind, placebo-controlled food challenge (DBPCFC). After dose escalation to 300 mg/day (6 months), 300 mg/day dosing continued (PALISADE, 6 months; ARTEMIS, 3 months). Results are reported in subjects 4-17-years-old (intention-to-treat/safety populations). A total of 496 PALISADE (AR101 n = 372, placebo n = 124) and 175 ARTEMIS (n = 132, n = 43) subjects were treated. Ability to tolerate 300 mg, 600 mg or 1000 mg peanut protein at exit DBPCFC was similar (PALISADE vs ARTEMIS; AR101 : 76.6% vs 73.5%, 67.2% vs 68.2%, 50.3% vs 58.3%; placebo : 8.1% vs 16.3%, 4.0% vs 9.3%, 2.4% vs 2.3%). Most treatment-emergent adverse events (TEAEs) were mild/moderate (AR101, placebo : PALISADE 94.4%, 94.4%; ARTEMIS 97.7%, 97.7%); frequency decreased from dose-escalation to 300 mg/day dosing (X). For dose-escalation in-clinic TEAEs, range of median times to symptom onset following ingestion and times from first symptom onset to last symptom resolution were similar (AR101, placebo: PALISADE onset 4.0–5.5 min, 8.0–38.5 min; resolution 16.0–32.5 min, 15.0–38.0 min; ARTEMIS onset 2.0–10.0 min, 1.5–15.0 min; resolution 14.0–47.8 min, 7.0–85.0 min) (Fig. 1). AR101 efficacy and safety results are consistent across trials despite different entry criteria. Most TEAEs were mild/moderate and transient. AR101 has a readily manageable safety profile with high desensitization rates possible as early as 3 months after 300 mg/day dosing. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Following unilateral chronic constriction injury (CCI) of the sciatic nerve, histochemical and gene expression changes were examined in the rat nucleus accumbens (NAcc), a region critical to affective-motivational regulation. Rats were categorised as having Pain alone (45%) or Pain and Disability (30%), on the basis of either unaltered or decreased dominance behaviour in the resident-intruder paradigm, respectively. Tyrosine hydroxylase (TH) expression was significantly increased bilaterally, throughout the rostrocaudal extent of the NAcc in Pain alone animals. Increased TH likely reflects increased dopamine levels in the Pain alone group, which may modulate dopamine receptor subtype 2 (D2) receptor expression. Stereological analyses of D2 receptor immunoreactive (D2-IR) cells revealed lateralised changes which correlated significantly with dominance behaviour. In the contralateral NAcc, D2-IR negatively correlated with post-CCI dominance behaviour (i.e. Pain alone animals have decreased D2-IR), whereas ipsilaterally there was a positive correlation between D2-IR and post-CCI dominance behaviour (i.e. Pain and Disability animals have decreased D2-IR). Western blots for D2 protein expression confirmed these correlations. Additionally, D2 mRNA expression within the NAcc showed lateralised and group specific changes. In the ipsilateral NAcc D2 mRNA was increased in Pain alone animals. It is hypothesised that increased D2 mRNA in the ipsilateral NAcc of Pain alone animals may be a protective mechanism, maintaining D2-IR despite increased dopamine, which may otherwise induce receptor desensitisation. D2 mRNA is not altered in the ipsilateral NAcc of Pain and Disability animals, therefore loss of D2-IR is likely, albeit by an alternate mechanism. In summary, unilateral CCI in rats induces specific and lateralised adaptations in the dopaminergic circuitry of the NAcc. These distinct neural adaptations correlate with changes in social behaviour, and likely underlie some of the affective-motivational state changes associated with neuropathic pain in a subset of rats (i.e. Pain and Disability group). [Copyright &y& Elsevier]

Abstract: In this paper, a numerical model for the pushover analysis of in-plane loaded unreinforced masonry walls is presented. For the analysis of the walls, which consist of vertical piers connected by horizontal masonry spandrels, an equivalent frame model is adopted. The analysis approach consists of two steps: In Step I, ultimate bending moment-shear force strength domains of the masonry spandrels are derived by means of a heterogeneous upper bound FE limit analysis and the results are stored in a database. Assessing the capacity of the spandrels correctly is crucial for the ultimate resistance of masonry walls that are loaded in-plane. Heterogeneous limit analysis is particularly suitable for computing the failure load of unreinforced masonry members since it permits a distinct modelling of bricks and mortar joints. Appropriate static and kinematic boundary conditions are imposed to account for the complex interaction of internal forces and deformed shapes of the spandrel beams at failure. In Step II, a frame model of the masonry wall is assembled. In this frame model the spandrels are modelled as elastic Timoshenko beams. At each analysis step it is checked that the internal forces of these coupling beams are smaller than the failure loads stored in the database created in Step I. If the capacity is exceeded, flexural hinges are introduced at both ends of the coupling beam. The resistance of the element is set to zero when a limit chord rotation is exceeded. The piers are modelled in a similar manner. The shear force and bending moment capacity of the piers are, however, simply estimated according to the Italian Design Code. Pushover analysis results compare favourably with computationally expensive 2D nonlinear heterogeneous FE analyses, but also confirm that the ultimate lateral resistance of masonry walls is very sensitive to the assumed spandrel strength if an equivalent frame model is used. [Copyright &y& Elsevier]

Plasma amino acids were measured in 17 postoperative subjects randomly assigned to receive for >/= 5 d tube feeding or total parenteral nutrition (TPN) that had identical energy, nitrogen, and glutamine contents. Subjects required gastric or pancreatic surgery for malignancy and were well-matched for age and body mass index. Tube feeding or TPN began on postoperative day 1 and advanced in daily 25% increments to meet goals of 105 kJ x kg body wt-1 x d-1, 1.5 g protein x kg body wt-1 x d-1, and 0.3 g glutamine x kg body wt-1 x d-1. Delivered energy, nitrogen, and glutamine were closely matched on day 4. Nitrogen balance and plasma proteins did not differ significantly between feeding groups. Total indispensable amino acids, branched-chain amino acids, and glutamine declined 25% on postoperative day 1 compared with preoperative day 0. Indispensable and branched-chain amino acid concentrations were restored with 5 d of either tube feeding or TPN. Glutamine concentrations did not differ significantly by feeding group, though a trend suggested that glutamine recovered more slowly in the tube-fed than in the TPN-fed subjects. Plasma amino acids otherwise reflected formula composition with ratios of valine to leucine of 1.24 and 3.69 micromol/L in subjects receiving 5 d of tube feeding or TPN, respectively. These findings suggest that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses. (C) 1997 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Purpose: Creation of an optimal bowel anastomosis with low postoperative leakage rate is an immanent part of colorectal surgery contributing to recovery, length of hospital stay and overall hospital costs. We aimed to investigate costs of small and large bowel resection, length of hospital stay, anastomotic leakage rate and its risk factors depending on the anastomotic technique.Methods: Retrospective analysis of 198 patients (67 stapled and 131 hand-sewn anastomoses) undergoing elective bowel resection with a single anastomosis without protective ileostomy either stapled or in double-rowed running suture technique between 1st October 2012 and 30th September 2018 at Charité University Hospital Berlin, Campus Benjamin Franklin. We analyzed costs of treatment, total length of hospital stay, rate of anastomotic leakage and possible risk factors for anastomotic leak.Results: No significant difference between both anastomotic techniques could be detected for hospital stay (p = 0.754), 30-day-readmission rate (p = 0.827), or anastomotic leakage (p = 606). Neither comorbidities (p = 0.449), underlying disease (p = 0.132), experience of the surgical team (p = 0.828) nor scheduling of the operation (p = 0.531) were associated with anastomotic leakage. Stapled anastomoses took 22 min less operation time than sutured anastomoses (130 vs. 152 min. Median) (p = 0.001). Operations with stapled anastomoses saved 183 € in operation costs and 496 € in overall hospital costs.Conclusion: Stapled and hand-sewn bowel anastomoses can be performed equally safe without differences in postoperative outcome. No patient, procedure or surgeon related risk factors for anastomotic leakage could be detected. Bowel resections with stapled anastomoses take less time and save operation and overall hospital costs. [ABSTRACT FROM AUTHOR]

Perceptions of cancer care are impacted by many factors and differ among individuals. Patients generally want consistent support, effective communication, accessible treatments, and information to manage physical, emotional, and psychosocial needs. Black/African American cancer survivors have expressed concerns about providers ignoring the social and financial implications of cancer care and neglecting to address the generations of mistrust between minority communities and the healthcare system. There is limited information about these perceptions as they relate specifically to radiation therapy which we aim to address with this study. Female breast cancer survivors identifying as Black/African American within the metropolitan Milwaukee area were eligible to participate in a semi-structured interview guided by a demographic questionnaire, a life narrative account, and a residential history. Participants were purposively sampled by neighborhood racial and ethnic composition (majority Black, minority Black, and racially diverse communities) to ensure a diversity of experiences. Interviews were transcribed and analyzed using a codebook developed and refined based on a conceptual model. Individuals worked in assigned pairs to open code each transcript. Data coded as "clinical presentation" or "treatment/healthcare" were pulled and reviewed for discussion of radiation therapy. Within these codes, further thematic analysis was performed to breakdown perceptions of this treatment modality. Fifty Black women were interviewed, 25 from majority, 7 from diverse, and 18 from minority communities. In discussing radiation therapy, six key themes emerged: emotional reactions, logistics of daily treatment, social barriers, side effects, general positive experiences, and general negative experiences. Emotional reactions included feelings of fear, anger, and being overwhelmed. Social barriers related to family obligations, transportation, distance from a treatment center, and racism. Commonly discussed side effects included fatigue, dermatitis, impacts on reconstruction, and long-term cardiotoxicity. Women living in majority Black communities were more likely to discuss side effects and general positive experiences while other themes were more equally explored by majority, minority, and diverse community members alike. Black women have diverse and varied perspectives of radiation therapy during breast cancer treatment. Anticipated themes surrounding logistics, side effects, and overall emotions of treatment were observed. Unique to their experiences, Black women have faced racism and an increased burden of social barriers during their treatment. Further studies exploring the perspectives of Black female cancer survivors are needed to optimize quality of care and outcomes. [ABSTRACT FROM AUTHOR]