Procalcitonin (PCT) was shown to be related to the severity of bacterial infection and is recommended as a new parameter of inflammation and infection. To evaluate the prognostic value in septic ...shock, PCT levels were repeatedly determined and compared with tumour necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6 bioactivity as well as with C-reactive protein (CRP) serum levels.
Twenty-four surgical patients with septic shock were included. Eight patients died within the study period of 14 days.
Serum levels of TNF-(WEHI 164) and IL-6 (B13-29 subclone 9) bioactivity, CRP and PCT were determined on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock.
Survivors and non-survivors were comparable in terms of age and severity of sepsis characterized by the APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP was constantly elevated with no difference between the groups. In nonsurvivors PCT remained increased, while the course of survivors was characterized by decreased values which were significantly lower (P<0.05) at every time point compared with those patients who died. A significant correlation could be found on day 1 (P<0.05) and at the end of the observation period (P<0.01) when comparing PCT levels with the multiple-organ-failure score.
PCT seems to be a more reliable prognostic parameter in septic shock than IL-6, while TNF and CRP did not show any difference between survivors and non-survivors. These data indicate that PCT may represent a valuable parameter not only in the diagnosis of sepsis but also in the clinical course of the disease.
Gender Differences in Human Sepsis Schröder, Jörg; Kahlke, Volker; Staubach, Karl-Hermann ...
Archives of surgery (Chicago. 1960),
11/1998, Letnik:
133, Številka:
11
Journal Article
Odprti dostop
BACKGROUND In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE In a prospective ...study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING Surgical intensive care unit of a university hospital. PATIENTS Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS In a prospective study, tumor necrosis factor α and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-β estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.-->
Summary
Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle‐aged women. It usually lasts for several years (> 1 year in 25–75% of patients) and often ...takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1‐antihistamines, even at higher doses, and third‐ and fourth‐line therapies (omalizumab and ciclosporin) control the disease only in two‐thirds of H1‐antihistamine‐resistant patients. Here we review the impact of CU on different aspects of patients’ quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health‐related quality of life (HRQoL), particularly when CSU is associated with angio‐oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio‐oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients’ performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
Plain language summary available online
The incidence of fungal infection as well as fungal sepsis has increased dramatically during the last decade. Changes of local microbial flora after broad-spectrum antibiotic therapy allow overgrowth ...of Candida species. Prophylactic strategies to lower fungal infection and sepsis include adequate and restrictive antibiotic therapy. Concerning the treatment of the septic syndrome, supportive as well as adjunctive strategies like early-goal-directed cardiovascular therapy, hydrocortisone replacement therapy, intense insulin application to achieve normoglycemia as well as the application of activated Protein C besides a consequent source control regimen and standard intensive care therapy, are able to improve significantly the outcome of septic patients.
This evidence‐ and consensus‐based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working ...group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU‐founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell‐driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.
Background: Major vascular surgery with aortic cross-clamping is
associated with temporary ischaemia of the lower limb due to lack of tissue blood
flow. The present study was designed to determine if ...the short-term changes in
cellular metabolism occurring during this situation can be detected by subcutaneous
microdialysis. It was also hoped to ascertain if this new technique is useful in the
continuous bedside monitoring of metabolism during aortic surgery.
Methods: In a controlled clinical study 20 patients undergoing elective
aortic surgery were monitored using microdialysis probes that were inserted in the
subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder).
Interstitial fluid was obtained and the concentrations of glucose and lactate during
lower limb ischaemia and during reperfusion were measured and compared with
concentrations observed in fluid obtained from the non-ischaemic control tissue.
Results: Circulatory occlusion caused an immediate and significant
decrease in the glucose/lactate ratio from 3·1±1·3 to 0·48±0·5 (P<0·05) that
returned to preocclusion values within 2 h of commencing reperfusion.
Conclusion: We suggest that microdialysis may be used both to assess
acute changes in tissue metabolism during ischaemic periods and also to act as an
additional tool for the detection of peri-operative acute variations in limb blood
flow.
Lipopolysaccharide (LPS) has been shown to induce proliferation of human T‐lymphocytes only in the presence of monocytes and CD34+ hematopoietic cells (HCs) from peripheral blood. This finding ...provided evidence of an active role of CD34+ HCs during inflammation and immunological events. To investigate mechanisms by which CD34+ HCs become activated and exert their immune‐modulatory function, we used the human CD34+ acute myeloid leukemia cell line KG‐1a and CD34+ bone marrow cells (BMCs). We showed that culture supernatants of LPS‐stimulated mononuclear cells (SUPLPS) as well as tumor necrosis factor α (ΤNF‐α), but not LPS alone, can activate nuclear factor‐κB in KG‐1a cells. By cDNA subtraction and multiplex polymerase chain reaction, we revealed differential expression of cellular inhibitor of apoptosis protein‐1, inhibitor of κB (IκB)/IκBα (MAD‐3), and intercellular adhesion molecule‐1 (ICAM‐1) in SUPLPS‐stimulated KG‐1a cells and up‐regulation of interferon (IFN)‐inducible T cell‐chemoattractant, interleukin (IL)‐8, macrophage‐inflammatory protein‐1α (MIP‐1α), MIP‐1β, RANTES, CD70, granulocyte macrophage‐colony stimulating factor, and IL‐1β in stimulated KG‐1a cells and CD34+ BMCs. Although monokine induced by IFN‐γ, IFN‐inducible protein 10, and IFN‐γ were exclusively up‐regulated in KG‐1a cells, differential expression of monocyte chemoattractant protein‐1 (MCP‐1), macrophage‐derived chemokine, myeloid progenitor inhibitory factor‐2, and IL‐18 receptor was only detectable in CD34+ BMCs. More importantly, CD34+ BMCs stimulated by TNF‐α also showed enhanced secretion of MCP‐1, MIP‐1α, MIP‐1β, and IL‐8, and increased ICAM‐1 protein expression could be detected in stimulated KG‐1a cells and CD34+ BMCs. Furthermore, we revealed that T cell proliferation can be induced by TNF‐α‐stimulated KG‐1a cells, which is preventable by blocking anti‐ICAM‐1 monoclonal antibodies. Our results demonstrate that CD34+ HCs have the potential to express a variety of immune‐regulatory mediators upon stimulation by inflammatory cytokines including TNF‐α, which may contribute to innate‐ and adaptive‐immune processes.
A percutaneous osseointegrated anchoring device for above-knee implantation designed to enable permanent attachment of an artificial limb is described. In addition to a technical description, the ...two-stage operative procedure, together with the rehabilitation process in an 18-year-old man, is also detailed. Following amputation and complete healing of the soft tissues, a surface-structured metal pin capable of supporting large loads, is driven into the medullary canal of the thigh bone. A metal sleeve having an identical surface structure serves to close off the medullary canal and provide an interface with the soft tissues. Screwed to the end of the pin is a conical metal adapter to which is attached a silicone cylinder whose right-angled distal end is located subcutaneously and ends in a titanium mesh. The first part of the implantation procedure is concluded by closing the silicone cylinder with a plastic plug for 6 weeks to permit osseous integration and the ingrowth of tissue into the mesh. In a second step, the plastic plug is removed via a skin incision, and the permanent load-bearing metal adapter fitted. In the above-mentioned patient wound healing at the metal/tissue interface was complication-free, since the implanted silicone cylinder prevented the "wedge effect" caused by the build-up of "luxuriant" tissue. After a further healing phase of 6 weeks, rehabilitation with an exoprosthesis took only 2 weeks, after which time, the patient was able to walk without a walking aid, and returned to work.
This guideline, together with its sister guideline on the management of urticaria Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA²LEN/EDF/WAO ...Guideline: Management of urticaria. Allergy, 2009; 64:1427-1443 is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life-time prevalence for any subtype of urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors, and pathomechanisms. In addition, it outlines evidence-based diagnostic approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).
Background
Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high‐affinity receptor ...(FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU.
Methods
This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti‐FcεRI and IgG anti‐IgE; IgG‐anti‐thyroperoxidase (IgG anti‐TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA).
Results
Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti‐FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non‐aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti‐TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively.
Conclusions
aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.
Autoimmune chronic spontaneous urticaria (aiCSU) is defined by IgG anti‐IgE or FcεRI, a positive basophil activation test (BAT) and a positive autologous serum skin test (ASST). 14% of ASST+ patients have aiCSU with low IgE levels and elevated levels of anti‐thyroperoxidase. Positive BAT and basophil histamine release assays (BHRA) were 69% and 88% predictive of aiCSU and, therefore, are biomarkers.
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