Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Supplementary Figure 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

Supplementary Figure 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination</jats:p

Data from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

&lt;div&gt;Abstract&lt;p&gt;The translocation t(11;18)(q21;q21) that generates an API2-MALT1 fusion protein is the most common structural abnormality among the genetic defects reported in mucosa-associated lymphoid tissue (MALT)-type lymphomas, and its presence correlates with the apparent lack of further genetic instability or chromosomal imbalances. Hence, constitutive nuclear factor-κB (NF-κB) activation induced by the API2-MALT1 fusion protein is considered essential for B-cell transformation. To examine its role in B-cell development and lymphomagenesis, Eμ-API2-MALT1 transgenic mice were produced. Our data show that expression of the API2-MALT1 fusion protein alone is not sufficient for the development of lymphoma masses within 50 weeks. Nevertheless, API2-MALT1 expression affected B-cell maturation in the bone marrow and triggered the specific expansion of splenic marginal zone B cells. Polyubiquitination of IκB kinase γ (IKKγ), indicative for enhanced NF-κB activation, was increased in splenic lymphocytes and promoted the survival of B cells &lt;i&gt;ex vivo&lt;/i&gt;. In addition, we show that the API2-MALT1 fusion resided in the cholesterol- and sphingolipid-enriched membrane microdomains, termed lipid rafts. We provide evidence that association of the MALT1 COOH terminal with the lipid rafts, which is mediated by the API2 portion, is sufficient to trigger NF-κB activation via enhanced polyubiquitination of IKKγ. Taken together, these data support the hypothesis that the API2-MALT1 fusion protein can contribute to MALT lymphoma formation via increased NF-κB activation. (Cancer Res 2006; 66(10): 5270-7)&lt;/p&gt;&lt;/div&gt;</jats:p

Supplementary Table 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

Supplementary Table 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination</jats:p

Supplementary Table 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

Supplementary Table 1 from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination</jats:p

Data from Selective Expansion of Marginal Zone B Cells in Eμ-API2-MALT1 Mice Is Linked to Enhanced IκB Kinase γ Polyubiquitination

&lt;div&gt;Abstract&lt;p&gt;The translocation t(11;18)(q21;q21) that generates an API2-MALT1 fusion protein is the most common structural abnormality among the genetic defects reported in mucosa-associated lymphoid tissue (MALT)-type lymphomas, and its presence correlates with the apparent lack of further genetic instability or chromosomal imbalances. Hence, constitutive nuclear factor-κB (NF-κB) activation induced by the API2-MALT1 fusion protein is considered essential for B-cell transformation. To examine its role in B-cell development and lymphomagenesis, Eμ-API2-MALT1 transgenic mice were produced. Our data show that expression of the API2-MALT1 fusion protein alone is not sufficient for the development of lymphoma masses within 50 weeks. Nevertheless, API2-MALT1 expression affected B-cell maturation in the bone marrow and triggered the specific expansion of splenic marginal zone B cells. Polyubiquitination of IκB kinase γ (IKKγ), indicative for enhanced NF-κB activation, was increased in splenic lymphocytes and promoted the survival of B cells &lt;i&gt;ex vivo&lt;/i&gt;. In addition, we show that the API2-MALT1 fusion resided in the cholesterol- and sphingolipid-enriched membrane microdomains, termed lipid rafts. We provide evidence that association of the MALT1 COOH terminal with the lipid rafts, which is mediated by the API2 portion, is sufficient to trigger NF-κB activation via enhanced polyubiquitination of IKKγ. Taken together, these data support the hypothesis that the API2-MALT1 fusion protein can contribute to MALT lymphoma formation via increased NF-κB activation. (Cancer Res 2006; 66(10): 5270-7)&lt;/p&gt;&lt;/div&gt;</jats:p