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Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March–September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5–34.4) and 4.2 (1.1–15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.

the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival.All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure.A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively.In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.

Introduction: Detection of specific food allergens brought into circulation following ingestion is complicated by the minute amounts present in serum. We therefore aimed to assess the utility of selective removal of IgE against peanut components using ImmunoCAP combined with the basophil histamine release (HR) assay (BHRA) to identify the absorbed allergen components after ingestion of peanut. Methods: Serum from six healthy individuals was drawn before and 1 h after ingestion of 100 g peanut. Serum from two peanut allergic patients was depleted for IgE against single allergen components by incubation with ImmunoCAPs coupled with either Ara h 1; 2; 3 or 6 before donor basophils were passively sensitized with the serum preparations. The sensitized cells were challenged with serum obtained from the six individuals before and after ingestion of peanut, and HR was measured after serum provocation. Results: Ara h 2 and Ara h 6 were detected in serum 1 h after ingestion in 6/6 individuals by negative selection. Depletion of specific IgE against Ara h 2 or Ara h 6 almost completely abolished the response to serum provocation, indicating a sequence homology between the two allergen components in serum. Ara h 1 was demonstrated in 5/6 sera and Ara h 3 in 1/6 sera. Conclusion: This study is a proof of concept showing that passive sensitization of basophils with sera depleted of component-specific IgE can be used to identify food allergen components present in serum after ingestion.

Background Dog dander consists of several allergenic molecules including Can f 5, which is a protein expressed in the prostate of male dogs. Objective To investigate whether children monosensitized to Can f 5 show different reactions to provocation tests with male versus female dog dander in a double-blind randomized clinical trial. Methods Twenty-two children (15-18 years) with a history of dog sensitization were enrolled from the COpenhagen Prospective Studies on Asthma in Childhood2000 mother-child cohort. Skin prick test, specific IgE levels to dog dander (e5), and dog components Can f 1, 2, 3, and 5 were first assessed. We subsequently performed skin prick test and conjunctival allergen provocation test using dog dander collected separately from male and female dogs. Results Seven of the 22 children were monosensitized to Can f 5. Eight were sensitized to a mix of the dog components, and 7 were no longer sensitized to dog. Of the children monosensitized to Can f 5, all had a positive skin prick test result to male dog extract and 1 of 7 was also positive to female dog extract (P = .01). Furthermore, 5 of 7 had a positive conjunctival allergen provocation test result to male dog extract and 1 of 7 also reacted to the female dog extract (P = .03). There was no difference between reactions to male and female dog extract provocation in children sensitized to a mix of the dog components. Conclusions Children monosensitized to Can f 5 show different reactions to male and female dog extract provocation using both skin prick test and conjunctival allergen provocation test, suggesting tolerance to female dogs.

Reducing intra-abdominal pressure from 12 mmHg to 6-8 mmHg during laparoscopy may reduce pain after minor laparoscopic procedures. We hypothesised that post-operative pain following ambulatory laparoscopic surgery was a limiting factor for day surgery. The primary aim of the study was to analyse risk factors for hospital admittance following laparoscopic ambulatory surgery.In this explorative prospective uncontrolled study, patients were included consecutively from 1 June 2013 to 31 March 2015 in an ambulatory setting using a standardised anaesthetic and post-operative multimodal analgesic regimen. Patients underwent the following three surgical procedures: laparoscoscopic cholecystectomy and laparoscopic inguinal and umbilical hernia repair. In the post-anaesthesia care unit, pain was repeatedly recorded using a visual analogue scale. The need for intravenously administered on-demand sufentanil was registered. The main reason for admittance to hospital was registered in a structured questionnaire.A total of 1,212 consecutive patients were included. Post-operative pain was the main reason for admittance in 14 patients, and 97% of all patients were discharged after a median of 5 h post-operatively (range: 0.4-5.0 h).In patients undergoing ambulatory laparoscopic surgery using a perioperative multimodal analgesic regimen, pain was the limiting factor for discharge in 1% of patients operated in an ambulatory set-up.none.Danish Data Protection Agency: 2012-58-0004, Danish Health Authority: 3-3013-1435/1, Clinicaltrial.gov: NCT02782832.

Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4+CD25+CD127low/- Tregs and ILT2+CD4+CD25+CD127low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3+CD4+CD25+CD127low/- Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2+ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.

This study aims to investigate the effect of topical applications of 10% casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) on white spot lesions (WSL) detected after treatment with fixed orthodontic appliances. Sixty healthy adolescents with ≥1 clinically visible WSL at debonding were recruited and randomly allocated to a randomised controlled trial with two parallel groups. The intervention group was instructed to topically apply a CPP–ACP -containing agent (Tooth Mousse, GC Europe) once daily and the subjects of the control group brushed their teeth with standard fluoride toothpaste. The intervention period was 4 weeks and the endpoints were quantitative light-induced fluorescence (QLF) on buccal surfaces of the upper incisors, cuspids and first premolars and visual scoring from digital photos. The attrition rate was 15%, mostly due to technical errors, and 327 lesions were included in the final evaluation. A statistically significant (p

Information on multimodal analgesic efficacy in patients undergoing a Bascom cleft lift operation is limited. The aim of this prospective consecutive study was to evaluate early post-operative pain in patients receiving a standardised multimodal analgesic regimen.A total of 48 patients undergoing a Bascom cleft lift operation were included over an 8-month period in a day-case set-up. The operation was performed under saddle block. In addition, patients received a standardised multi-modal analgesic regimen consisting of gabapentin, ketorolac, dexamethasone, acetaminophen (paracetamol) and ibuprofen. The intensity of pain was registered preoperatively and at 2, 24, 48 h, and 30 days post-operatively. Nausea, vomiting, dizziness, ability to void, morphine consumption and post-anaesthesia care unit (PACU) time were registered.Thirty patients were available for analysis. Post-operative visual analogue scale pain scores were low (at 2, 24, and 48 h (median values: 0 (range: 0-40), 25 (0-70), and 30 (0-60), respectively), but changed significantly over time (p0.001). The median overall morphine consumption was 0 (range: 0-30). None of the patients experienced vomiting or dizziness. Only two patients reported mild nausea during the stay in the PACU.This study suggests that the Bascom cleft lift operation is feasible with minimal post-operative pain when using a multimodal analgesic regimen together with saddle block.not relevant.ClinicalTrials.gov: NCT02196727. Regional Ethics Committee Reg. no.: H-3-2013-073. Danish Data Protection Agency Reg. no.: HVH-2013-031, with I-Suite no.: 02408.

The use of NSAIDs for postoperative pain management following orthopaedic surgery or during conservative treatment of fractures is controversial. Experimental animal models suggest NSAIDs inhibit bone healing. In a review of the literature, there was no clinical evidence to support categorical discard of NSAID for postoperative pain relief in uncomplicated cases. However, NSAID should be considered a potentiel risk factor of impaired bone healing and avoided in patients with a high risk of pseudoarthrosis. Recommended daily doses should be respected and duration of treatment should be limited.

Peripheral nerve blockade (PNB) is an important part of the anaesthesiologist's armamentarium. It constitutes an alternative to general anaesthesia, thus it is important that all anaesthesiologists have adequate skills in this area. Lack of sufficient experience during training makes many graduates uncomfortable about performing PNB. An answer to this problem is to provide adequate education in PNB in the early stage of postgraduate training. This article presents how we, at our institution, have set up a PNB program that provides value.

Summary Few studies have measured the frequency of atopy with objective measures, and most of these studies have been done in industrialised countries. We analysed serum samples from 859 15–80-year-old Greenlanders who had participated in population-based screening campaigns in 1987 and in 1998. We defined atopy as a positive result in an assay that tests for specific IgE against the eight most common inhalant allergens in one pool (grass, birch, mugwort, dog, cat, horse, Cladosporum herbarum , house dust mite). The frequency of atopy doubled between 1987 (39 [10%] of 392) and 1998 (87 [19%] of 467; risk ratio 1·88 [95% CI 1·31–2·68]). This increase was largest in 15–19-year olds, but also occurred in older people, suggesting that the risk factors responsible for the increase in atopy do not operate only in childhood.

Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease.To determine efficacy of helminth therapy for allergic rhinitis.We conducted a double-blind, placebo-controlled, parallel group trial in which 100 subjects age 18 to 65 years with grass pollen-induced allergic rhinitis were randomly assigned to ingest a total of 8 doses with 2500 live T suis ova or placebo with an interval of 21 days. The primary outcome was a change in mean daily total symptom score for runny, itchy, sneezing nose (maximum change, 9.0) or in percentage of well days during the grass pollen season.Treatment with T suis ova (N = 49) compared with placebo (N = 47) caused transient diarrhea peaking at day 41 in 33% of participants (placebo, 2%), and increased eosinophil counts (P.001) and T suis-specific IgE (P.05), IgG (P.001), IgG(4) (P.003), and IgA (P.001), whereas there was no significant change in symptom scores (0.0; 95% CI, -0.5 to 0.4; P = .87), well days (3%; 95% CI, -9% to 14%; P = .63), total histamine (P = .44), grass-specific IgE (P = .76), or diameter of wheal reaction on skin prick testing with grass (P = .85) or 9 other allergens.Repeated treatment with the helminth T suis induced a substantial clinical and immunologic response as evidence of infection, but had no therapeutic effect on allergic rhinitis.

ContextIt has been suggested that BCG vaccination may protect against development of allergic diseases, particularly when given just after birth. BCG vaccination was given routinely to all infants in Greenland until 1990, when it was withdrawn from the vaccination program. Whether this resulted in an increased prevalence of atopy in children born after the stop of BCG vaccination is unknown.ObjectiveTo determine whether BCG vaccination and age at BCG vaccination are associated with development of atopy.Design, Setting, and ParticipantsCross-sectional study among schoolchildren aged 8 to 16 years in 4 towns on the northwest coast of Greenland. Participants had a blood sample drawn and information on BCG vaccination was obtained during 2 periods, November 1998 and November 2001. A total of 1686 children (79% of available children) participated, 1575 of whom had complete information on vaccination status. Atopy was defined as a positive test result in an assay that tests for IgE specific against the most common inhalant allergens in serum.Main Outcome MeasuresOdds ratio (OR) of atopy in BCG-vaccinated compared with unvaccinated children and OR according to age at vaccination.ResultsThe risk of atopy was the same in BCG-vaccinated compared with unvaccinated children after adjustment for confounders (OR, 1.03; 95% confidence interval, 0.72-1.48). The risk of atopy in BCG-vaccinated children was not associated with age at vaccination (P = .17).ConclusionsBCG vaccination administered to infants is not associated with reduced risk of development of atopy.

Background: Previous studies show that 6-9% of young adults in Reykjavik are sensitised to the house dust mite (HDM) Dermatophagoides pteronyssinus ( D . pteronyssinus ). However, only negligible amounts of HDM and HDM allergens were detected in their homes. The study investigates what characterizes these individuals. Methods: We investigated all participants in the European Community Respiratory Health Surveys I and II (ECRHS I and II) with D . pteronyssinus specific IgE, in the years 1991–92. A grass positive but D . pteronyssinus negative control group was recruited from the same cohort. A detailed questionnaire was administered and the specific IgE (Pharmacia CAP system) against six D . pteronyssinus cross-reactive allergens was measured. Results: Of 601 ECRHS I participants with available IgE results, 88% returned for ECRHS II, 8.4years later. Of 49 individuals with D . pteronyssinus specific IgE in ECRHS I, 24 had become negative in ECRHs II. Compared with controls, HDM sensitive subjects were more often men who had lived on farms or kept aquaria fish in childhood. Of those with specific IgE against D . pteronyssinus in ECRHS I and II, 75% had detectable IgE antibodies (>0.35 kU/l) to cross-reactive allergens compared with none in the control group (p Lepidoglyphus destructor ( L . destructor ) (67%), shrimp (58%), cockroach (33%), mosquito (17%), tropomyosin (17%) and blood worm (4%). Conclusions: Icelanders with specific IgE to D . pteronyssinus are more often men who spent time on farms in childhood and today have high prevalence of IgE antibodies cross-reactive to D . pteronyssinus .

Hip fracture surgery usually carries a high demand for rehabilitation and a significant risk of perioperative morbidity and mortality. Postoperative epidural analgesia may reduce morbidity and has been shown to facilitate rehabilitation in elective orthopedic procedures. No studies exist on the effect of postoperative epidural analgesia on pain and rehabilitation after hip fracture surgery.Sixty elderly patients were included in a randomized, double-blind study comparing 4 days of continuous postoperative epidural infusion of 4 ml/h bupivacaine, 0.125%, and 50 mug/ml morphine versus placebo. Both patient groups received balanced analgesia and intravenous nurse-controlled analgesia with morphine. All patients followed a well-defined multimodal rehabilitation program. Pain, ability to participate in four basic physical functions, and any factors restricting participation were assessed on the first 4 postoperative days during physiotherapy.Epidural analgesia provided superior dynamic analgesia during all basic physical functions, and patients were significantly less restricted by pain, which was the dominating restricting factor in the placebo group. Motor blockade was not a restricting factor during epidural analgesia. Despite improved pain relief, scores for recovery of physical independence were not different between groups.Postoperative epidural analgesia after hip fracture surgery provides superior analgesia attenuating pain as a restricting factor during rehabilitation without motor dysfunction. However, superior analgesia did not translate into enhanced rehabilitation. Future studies with multimodal rehabilitation are required to establish whether superior analgesia can be translated into enhanced rehabilitation and reduced morbidity in hip fracture patients.