Real-world accuracy of computed tomography in patients admitted with small bowel obstruction: a multicentre prospective cohort study.

PURPOSE: Small bowel obstruction (SBO) is a common surgical emergency. Previous studies have shown the value computed tomography (CT) scanning in both confirming this diagnosis and identifying indications for urgent surgical intervention, such as strangulated bowel or closed loop obstructions. However, most of the literature is based on retrospective expert review of previous imaging and little data regarding the real-time accuracy of CT reporting is available. Here, we investigated the real-world accuracy of CT reporting in patients admitted with SBO. METHODS: This was a multicentre prospective study including consecutive patients admitted with SBO. The primary outcomes were the sensitivity and specificity of CT scanning for bowel obstruction with ischaemia and closed loop obstruction. Data were retrieved from the original CT reports written by on-call radiologists and compared with operative findings. RESULTS: One hundred seventy-six patients were included, all of whom underwent CT scanning with intravenous contrast followed by operative management of SBO. Bowel obstruction with ischaemia was noted in 20 patients, with a sensitivity and specificity of CT scanning of 40.0% and 85.5%, respectively. Closed loop obstructions were noted in 26 patients, with a sensitivity and specificity of CT scanning of 23.1% and 98.0%, respectively. CONCLUSIONS: The real-world accuracy of CT scanning appears to be lower than previously reported in the literature. Strategies to address this could include the development of standardised reporting schemas and to increase the surgeon's own familiarity with relevant CT features in patients admitted with SBO.

Management and short-term outcomes of patients with small bowel obstruction in Denmark: a multicentre prospective cohort study.

AIMS: The optimal management of small bowel obstruction (SBO) remains a matter of debate and treatment varies internationally. In Denmark, a more surgically aggressive strategy has traditionally been used, but to what extent patient outcomes differ from international reports is unknown. This study aimed to describe the current management and outcomes of patients admitted with SBO in Denmark. METHODS: This was a prospective cohort study conducted at six acute hospitals in Denmark over a 4-month period. Patients aged ≥ 18 years with a clinical or radiological diagnosis of SBO were eligible. Primary outcomes were 30 day morbidity and mortality rates. RESULTS: 316 patients were included during the study period. The median age was 72 years and 56% were female. Diagnosis was made by computed tomography (CT) in 313 patients (99.1%), with the remaining three diagnosed clinically. Non-operative management was the initial strategy in 152 patients (48.1%) and successful in 119 (78.3%). Urgent surgery was performed in the remaining 164 (51.9%), with a laparoscopic approach used in 84 patients (51.2%). The entire cohort had a 30 day mortality rate of 7.3% and a 30 day morbidity rate of 17.1%. CONCLUSIONS: The management of SBO in Denmark differs markedly to previous international reports, with an almost ubiquitous use of CT for diagnosis and a high proportion of patients undergoing urgent surgery. Despite higher rates of surgery, patient outcomes are broadly similar to reports of more conservative strategies, perhaps due to a reduction in delayed operations. TRIAL REGISTRATION: Trial registration number: NCT04750811. Trial registration date: 11/02/2021.

Umbilical cord mannan-binding lectin and infections in early childhood.

To investigate whether mannan-binding lectin (MBL) in umbilical cord blood (UCB) is associated with the incidence rate of hospitalizations for infections during early childhood. A follow-up study from birth to 31 months of age, with endpoint data from the Danish National Hospital Discharge Registry. The concentration of MBL and immunoglobulin A (IgA) in UCB was measured in a time-resolved immunofluorometric assay. Information on possible confounding factors was obtained from questionnaires completed by mothers during their pregnancy, and characteristics of the child at birth were registered by a midwife on a structured coding sheet. A total of 2104 infants born in the period between 1 February 1990 and 25 May 1991 to mothers living in the municipality of Aarhus. Concentration of MBL and IgA in UCB, gestational age, birth weight, number of siblings less than 3 years old, mother's smoking habits, alcohol and coffee consumption, educational and marital status and previous spontaneous abortions and stillbirths. Of 2104 children, 626 were hospitalized at least once, and 346 of these were hospitalized with infection. The hazard ratio (HR) of hospitalization with infections in children with low levels of MBL (<120 ng/ml) was 1.4 (95% confidence interval (CI), 1.0-1.8), which was similar to our findings on hospitalization because of other diseases. The HR of hospitalization for viral infections was 2.8 (CI, 1.3-5.9). Low levels of MBL in UCB were associated with hospitalization in general and particularly with hospitalization for viral infections.

Asthma and atopy - a total genome scan for susceptibility genes.

BACKGROUND: Allergic asthma is an increasingly common disease of complex inheritance. Several studies have suggested candidate regions, but genetic heterogeneity, ethnic differences and varying study designs may in part explain the lack of identified and confirmed susceptibility genes. Investigation of different populations will further clarify the topic. We therefore evaluated allergic asthma and increased total and specific IgE in 39, 45 and 57 sib-pairs from 100 Danish allergy families. METHODS: Affected sib-pairs meeting a narrow phenotype definition were selected for the three phenotypes atopy, allergic asthma and increased total IgE. We performed a total genome scan using 446 microsatellite markers and obtained nonparametric linkage results from the MAPMAKER/SIBS computer program. RESULTS: Our study revealed four candidate regions (MLS > 2) on chromosome 1p36, 3q21-q22, 5q31 and 6p24-p22, and 15 candidate regions (1 < MLS < 2) that may contain susceptibility genes for asthma and atopy. We did not find linkage to the candidate genes TNF-beta, FcER1beta and Il4R-alpha, except for weak support for linkage of the asthma phenotype to TNF-beta (MLS = 1.18). CONCLUSIONS: We found evidence for two new asthma and atopy loci, 1p36 and 3q21-q22, and supported linkage in the Danish population to seven previously reported candidate regions.

No linkage and association of atopy to chromosome 16 including the interleukin-4 receptor gene.

BACKGROUND: Several susceptibility genes for atopy have been suggested in recent years. Few have been investigated as intensively as the interleukin-4-receptor alpha (IL4Ralpha) gene on chromosome 16. The results remain in dispute. Therefore, in a robust design, we tested for association of type I allergy to the IL4R variations I50V and Q576R, and investigated chromosome 16 for atopy candidate regions in general. METHODS: We identified 100 Danish allergy sib-pair families. Five conservative phenotypes for type I allergy were defined and evaluated. The IL4R variations were genotyped in trios and evaluated by the transmission disequilibrium test (TDT). Multipoint linkage analysis and exclusion mapping were conducted with sib-pairs analyzed for 17 microsatellite markers. RESULTS: No evidence for association or linkage to the IL4R polymorphisms was found (P values: 0.12-0.90). Linkage analysis did not support linkage of any of the phenotypes to chromosome 16. Major parts of chromosome 16 were excluded as candidate regions harboring oligogenes for type I allergy. CONCLUSION: We found chromosome 16 unlikely to harbor strong candidate genes for type I allergy. The role of the IL4Ralpha gene in the inheritance of atopy was insignificant in the Danish population. The use of conservative allergy phenotypes in the search for genes predisposing to atopic disease was discussed.

SNARE proteins are critical for regulated exocytosis of ECP from human eosinophils.

The SNARE hypothesis, describing a protein assembly-disassembly pathway, was recently proposed for the sequential steps of synaptic vesicle docking, activation, and fusion. To determine if SNARE proteins are involved in regulated exocytosis in eosinophils, the presence and functional role of SNAREs was examined in human blood eosinophils. Immunoblotting, subcellular fractionation, and immunocytochemistry documented that vesicle-associated membrane protein-2 (VAMP-2), a vesicle-SNARE, was expressed in human eosinophils. Syntaxin 4 and SNAP-25 were also detected. Sequencing of cloned RT-PCR products amplified from a domain conserved among VAMP isoforms revealed identity only to VAMP-2 but not to VAMP-1 or cellubrevin. Functional experiments revealed that tetanus toxin pretreatment, which cleaved VAMP-2 in eosinophils, significantly inhibited both IgE receptor- and phorbol ester-mediated exocytosis of eosinophil cationic protein (ECP) from streptolysin-O-permeabilized eosinophils. Thus, these results strongly suggest a critical role of SNAREs in regulated exocytosis in eosinophils.

SNARE proteins are critical for regulated exocytosis of ECP from human eosinophils.

The SNARE hypothesis, describing a protein assembly-disassembly pathway, was recently proposed for the sequential steps of synaptic vesicle docking, activation and fusion. To determine if SNARE proteins are involved in regulated exocytosis in eosinophils, the presence and functional role of SNAREs was examined in human blood eosinophils. Immunoblotting, subcellular fractionation, and immunocytochemistry documented that vesicle-associated membrane protein-2 (VAMP-2), a vesicle-SNARE, was expressed in human eosinophils. Syntaxin 4 and SNAP-25 were also detected. Sequencing of cloned RT-PCR products amplified from a domain conserved among VAMP isoforms revealed identity only to VAMP-2 but not to VAMP-1 or cellubrevin. Functional experiments revealed that tetanus toxin pretreatment, which cleaved VAMP-2 in eosinophils, significantly inhibited both IgE receptor- and phorbol ester-mediated exocytosis of eosinophil cationic protein (ECP) from streptolysin-O-permeabilized eosinophils. Thus, these results strongly suggest a critical role of SNAREs in regulated exocytosis in eosinophils.

Allergic rhinitis--a total genome-scan for susceptibility genes suggests a locus on chromosome 4q24-q27.

Allergic rhinitis is a common disease of complex inheritance and is characterised by mucosal inflammation caused by allergen exposure. The genetics of closely related phenotypes such as asthma, atopy and to some extend atopic dermatitis has attracted attention in recent years. Genetic reports of allergic rhinitis on the contrary have as yet been most sparse. To identify candidate regions holding genes for allergic rhinitis we performed a total genome-scan on affected sib-pair families. From 100 Danish sib-pair families selected for allergy, families containing sib-pairs matching a phenotype definition of both clinical allergic rhinitis and confirmed specific allergy were chosen. Thirty-three affected sib-pair families qualified for the scan that was undertaken using 446 microsatellite markers. Non-parametric linkage results were obtained from MAPMAKER/SIBS computer program. The study revealed one major candidate region on chromosome 4q24-q27 (LOD=2.83) and eight minor candidate regions 2q12-q33, 3q13, 4p15-q12, 5q13-q15, 6p24-p23, 12p13, 22q13, and Xp21 (LOD=1.04-1.63) likely to contain susceptibility genes for allergic rhinitis. Our findings did not support a previous report of linkage of allergic rhinitis to chromosome 12q14-q24 but they added positive evidence to the asthma and atopy candidate regions 2q33 and 6p23. Further identification of the specific genes involved in allergic rhinitis will give opportunities for improved diagnosis and treatment.

Recommended care for young people (15-19 years) after suicide attempts in certain European countries.

Data on recommended care for young people aged 15-19 years after attempted suicide from nine European research centres during the period 1989-1992 were analysed in terms of gender, history of previous suicide attempt and methods used. Altogether 438 suicide attempts made by 353 boys and 1,102 suicide attempts made by 941 girls were included. Analyses of the total data from all centres showed that young people with a history of previous suicide attempt and those using violent methods had significantly higher chance of being recommended aftercare than first-time attempters or those choosing self-poisoning. There were no significant differences of being recommended care between genders. Logistic regression analyses of the material were performed and the results were similar. Both having previous attempted suicide (odds ratio 2.0, 95% CI 1.53-2.61) and using "hard" methods (odds ratio 1.71, 95% CI 1.49-1.96) were significantly associated with increased possibility of being recommended aftercare. When individual centres were analysed, large disparities of recommended care after suicide attempts were found and there were no uniform criteria of recommending care for young suicide attempters in Europe.

Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin-induced airway inflammation in mice.

Macrophage migration inhibitory factor (MIF) has recently been forwarded as a critical regulator of inflammatory conditions, and it has been hypothesized that MIF may have a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Hence, we examined effects of MIF immunoneutralization on the development of allergen-induced eosinophilic inflammation as well as on lipopolysaccharide (LPS)-induced neutrophilic inflammation in lungs of mice. Anti-MIF serum validated with respect to MIF neutralizing capacity or normal rabbit serum (NRS) was administered i.p. repeatedly during allergen aerosol exposure of ovalbumin (OVA)-immunized mice in an established model of allergic asthma, or once before instillation of a minimal dose of LPS into the airways of mice, a tentative model of COPD. Anti-MIF treatment did not affect the induced lung tissue eosinophilia or the cellular composition of bronchoalveolar lavage fluid (BALF) in the asthma model. Likewise, anti-MIF treatment did not affect the LPS-induced neutrophilia in lung tissue, BALF, or blood, nor did it reduce BALF levels of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). The present data suggest that MIF is not critically important for allergen-induced eosinophilic, and LPS-induced neutrophilic responses in lungs of mice. These findings do not support a role of MIF inhibition in the treatment of inflammatory respiratory diseases.

Methods used for parasuicide: results of the WHO/EURO Multicentre Study on Parasuicide.

BACKGROUND: National suicide statistics show remarkable differences in the frequencies of various methods used for completed suicide. The WHO/EURO Multicentre Study on Parasuicide makes possible for the first time an international comparison of the frequencies of methods used in attempted suicide, because the data are based on geographical catchment areas of medical institutions. METHOD: Ongoing standardized monitoring of attempted suicide in all medical institutions serving the catchment areas was performed in 14 centres in 12 European countries. The data analysis is based on 20,649 events involving 15,530 persons, recorded between 1989 and 1993. RESULTS: The comparison of rates per 100,000 shows striking differences between the centres. The highest rates for drug overdoses were found for female attempters in Oxford (347/100,000), Helsinki (238/100,000) and Stockholm (221/100,000). Guipuzcoa had the lowest rates (61/100,000). The differences were most prominent in the age group 15-24, with outstanding rates for women in Oxford (653/100,000), which was mainly due to the frequent use of analgesics. Szeged had outstandingly high rates for pesticides and solvents. In some centres the use of multiple methods was frequent. CONCLUSIONS: There is a need, especially for areas with high frequencies for certain methods, to understand the factors involved and to develop new and specific prevention projects and to monitor their effects. The WHO/EURO Multicentre Study on Parasuicide has proved to be a useful and reliable instrument for continuous monitoring of trends in parasuicide.

Locus of control and attitudes toward large carnivores.

It has been hypothesized tha the negative attitudes toward carnivores found among rural groups is only one element embedded in a larger sociopolitical complex of disputes over resource use and rural development. Negative attitudes may reflect a protest against increased control of land use by central political authorities. In a survey among sheep farmers, wildlife managers, and research biologists in Norway we found that the sheep farmers expressed an external locus of control, indicating a belief that external forces control events, relative to the two other groups. Among sheep farmers and research biologists a positive association was found between an external locus of control and negative attitudes toward large carnivores.

Physical illness and parasuicide: evidence from the European Parasuicide Study Interview Schedule (EPSIS/WHO-EURO).

OBJECTIVE: The aim of this research was to identify psychosocial characteristics which might predict future suicidal behavior in parasuicidal subjects in Europe. METHOD: The interview utilized for the survey (European Parasuicide Study Interview Schedule--EPSIS) was administered to 1269 parasuicides aged fifteen years and over, within one week of hospital admission after a suicide attempt, and is part of a longitudinal multicenter study. EPSIS included a brief medical questionnaire, scales rating depression, hopelessness, self-esteem, suicide intention, questions on sociodemographic characteristics, an interview on life events and social support, a description of the parasuicidal act, and an evaluation of factors precipitating the index parasuicide. RESULTS: Physical illness proved to be very frequent among suicide attempters. One in two subjects suffered from an acute, chronic, or chronic disorder in relapse at the time of the parasuicide. Subjects with a physical illness were significantly more depressed, particularly subjects from the intermediate age band and ones affected by a chronic physical disease in relapse. Forty-two percent of patients with physical illness rated their somatic problem as a factor precipitating the attempt and 22 percent judged it to be major one. Furthermore, subjects with physical illnesses considered psychiatric symptoms and disorders to be relevant factors in triggering suicidal behavior, to a greater extent than non-sufferers. The importance of physical illness in contributing to suicidal behavior increased with advancing age. CONCLUSIONS: More careful attention to somatic conditions and their subjective implications would probably augment chances of effectively preventing suicide.

Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses.

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

Regulation of FcepsilonARI synthesis in human eosinophils.

FcepsilonRI, the high-affinity receptor for IgE, and eosinophils are thought to be key components of the allergic reaction underlying asthma and rhinitis. We provide evidence at the protein level that FcepsilonRI is expressed in human blood eosinophils, and that the synthesis of FcepsilonRI in purified human blood eosinophils is regulated by fibronectin in combination with IgE, IL-4, both involved in allergic reactions, and by RANTES, a strong chemotactic agent for eosinophils. This provides further evidence for a regulatory effect of IgE on human eosinophils in allergic disease.

Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice.

The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

Pediatric pain management: a research-based clinical pathway.

Nurses want to provide pain management for pediatric patients, but different approaches lead to inconsistent pain management. This article presents a pediatric pain management clinical pathways developed as a result of research in the pediatric intensive care unit and based on pain management research. Using this pathway can help nurses deliver consistent pain management to pediatric patients.

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season.

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001). CONCLUSIONS: Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.

The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness.

The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that blockage of each one of these chemokines reduces both lung leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES (regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1alpha, reduces only slightly lung eosinophilia and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators. These results suggest that different chemokines activate different cellular and molecular pathways that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their individual blockage results in intervention at different levels of these processes.

The effects of clinical pathways for renal transplant on patient outcomes and length of stay.

OBJECTIVES: Clinical pathways have been implemented nationwide but little is understood about their effects on efficiency of care and patient outcomes. The present study examined the effects of both development and implementation of two renal transplant pathways. METHODS: Cohorts of patients at a university hospital were compared before, during, and after the development and implementation of two renal transplant clinical pathways: isolated renal transplant from cadaveric donors (n = 170) or from living donors (n = 178). Clinical pathways for cadaveric and living related donor renal transplants were developed and implemented. Hospital length of stay and complications and infections after renal transplant were determined. RESULTS: Mean length of hospital stay decreased after development and implementation of the cadaveric donor pathway (11.8 days after implementation versus 17.5 days before development). Cadaveric kidney recipients also had statistically fewer complications and infections after both guideline development and guideline implementation (57.1% before, 24.5% during, 18.5% after), but the greatest effect occurred during development. All of these findings persisted after control for demographic and comorbid factors. There were no changes in hospital stay, complications, or infections in the patients who received kidneys from living donors. CONCLUSIONS: The development and use of a clinical pathway for cadaveric donor renal transplant patients was associated with a significant decline in length of stay, complications, and infections, but much of the effect was seen during development rather than during implementation, and a closely related pathway for living related donor patients had no effect. Further understanding of what factors predict an effective pathway and what elements (ie, development or implementation) have an effect should be undertaken.