Risk Factors and Outcomes Associated With the Development of Persistent Acute Kidney Injury in Non-Renal Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Persistent acute kidney injury (pAKI), compared with acute kidney injury (AKI) that resolves in <72 h, is associated with worse prognosis in critically ill patients. Definitions and prognosis of pAKI are not well characterized in solid organ transplant patients. Our aims were to investigate (a) definitions and incidence of pAKI; (b) association with clinical outcomes; and (c) risk factors for pAKI among heart, lung, and liver transplant recipients. We systematically reviewed the literature including PubMed, Embase, Web of Science, and Cochrane from inception to 8/1/2023 for human prospective and retrospective studies reporting on the development of pAKI in heart, lung, or liver transplant recipients. We assessed heterogeneity using Cochran's Q and I2. We identified 25 studies including 6330 patients. AKI (8%-71.6%) and pAKI (2.7%-55.1%) varied widely. Definitions of pAKI included 48-72 h (six studies), 7 days (three studies), 14 days (four studies), or more (12 studies). Risk factors included age, body mass index (BMI), diabetes, preoperative chronic kidney disease (CKD), intraoperative vasopressor use, and intraoperative circulatory support. pAKI was associated with new onset of CKD (odds ratio [OR] 1.41-11.2), graft dysfunction (OR 1.81-8.51), and long-term mortality (OR 3.01-13.96), although significant heterogeneity limited certainty of CKD and graft dysfunction outcome analyses. pAKI is common and is associated with worse mortality among liver and lung transplant recipients. Standardization of the nomenclature of AKI will be important in future studies (PROSPERO CRD42022371952).

Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI).

INTRODUCTION: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI. METHODS AND ANALYSIS: Blind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis. TRIAL REGISTRATION NUMBER: NCT05900284.

Laterality of lower extremity deep vein thrombosis after colectomy: A retrospective study using the national inpatient sample.

BACKGROUND AND AIMS: Deep venous thrombosis (DVT) is known to occur preferentially on the left lower extremity. The renowned surgeon Denis Burkitt advanced the theory that a heavy sigmoid colon would compress the left pelvic veins and predispose to DVT. Our study aimed to evaluate this hypothesis by comparing the laterality distributions with and without a prior colectomy. METHODS: We conducted a retrospective analysis of the 2016 National Inpatient Sample database by stratifying the patients at any age with acute DVT of lower extremity by history of prior colectomy, thereby eliminating local gut mechanical factors in the development of DVT. We compared the laterality distribution (i.e., left, right, bilateral, and unspecified) between the patients with and without a prior colectomy. We also conducted a subgroup analysis by the sex category to examine the difference in laterality distribution for male and female patients. Chi-square test for independence was used. P value ≤0.05 was considered statistically significant. RESULTS: We found an estimated total of 342,525 cases. Among patients without a prior colectomy, 136,605 (41.6%) were left-sided DVT versus 119,555 (36.4%) right-sided, with 55,555 bilateral and 16,865 unspecified. Among patients with a prior colectomy, 5,750 (41.2%) were left-sided, 5,000 (35.9%) were right-sided, 2,345 were bilateral and 850 were unspecified. The laterality distribution between the two groups was not significantly different (p = .167). The left-side predominance disappeared only in males with a prior colectomy (37.1% for left vs. 38.9% for right, p = .027). CONCLUSIONS: Our findings did not confirm the Burkitt's hypothesis. The left-side predominance of lower extremity DVT was attenuated only in male patients with a prior colectomy.

Continuous renal replacement therapy in critically ill patients with acute on chronic liver failure and acute kidney injury: A retrospective cohort study
.

BACKGROUND: Incident acute kidney injury (AKI) in critically ill patients with acute on chronic liver failure (ACLF) is associated with poor prognosis. The role of continuous renal replacement therapy (CRRT) is not well established for patients with ACLF and AKI. MATERIALS AND METHODS: We conducted a retrospective cohort study to examine clinical outcomes in 66 patients with ACLF and AKI requiring CRRT. RESULTS: All-cause hospital mortality was 89.4%. Five (7.6%) patients were listed for liver transplantation, of whom 1 (1.5%) was eventually subjected to transplantation. Etiology of AKI included type 1 hepatorenal syndrome (HRS) with or without some degree of acute tubular necrosis (ATN) in 20 (30.3%) patients, and primarily ATN in 46 (69.7%) patients. When evaluated at the time of CRRT initiation, Child-Pugh-Turcotte (CPT) and Model for End-stage Liver Disease (MELD) (area under the receiver operating characteristics curve (AUROC) 0.67 for both) had fair performance for prediction of mortality, whereas Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure (CLIF)-SOFA performed better for the prediction of mortality (AUROC 0.87 for both). SOFA and CLIF-SOFA also performed well when determined at the time of ICU admission (AUROC 0.86 and 0.85, respectively). Etiology of liver disease or AKI did not influence prognosis. CONCLUSION: Critically ill patients with ACLF and AKI requiring CRRT have poor hospital survival, even with provision of extracorporeal support therapy. SOFA and CLIF-SOFA are good prognostic tools of mortality in this susceptible population.

Rattlesnakes bites in the Brazilian Amazon: Clinical epidemiology, spatial distribution and ecological determinants.

Crotalus bites are considered a public health problem especially in Latin America. This study was performed to describe the epidemiology, spatial distribution and environmental determinants of Crotalus durissus bites in the Brazilian Amazon. Crotalus durissus envenomings official database included cases reported from 2010 to 2015. A total of 70,816 snakebites were recorded in the Amazon Region, 3058 (4.3%) cases being classified as crotalid, with a mean incidence rate of 11.1/100,000 inhabitants/year. The highest mean incidence rates were reported in Roraima, Tocantins and Maranhão. Area covered by water bodies, precipitation and soil humidity were negatively associated to rattlesnake encountering. Rattlesnake bites incidence was positively associated to tree canopy loss and altitude. In the Amazon, severe manifestations at admission, delayed medical assistance, lack of antivenom administration and ages ≥61 and 0-15 years were predictors of death in C. durissus snakebites. Spatial distribution of rattlesnake bites across the Brazilian Amazon showed higher incidence in areas of transition from the equatorial forest to the savanna, and in the savanna itself. Such results may aid focused policy-making in order to mitigate the burden, clinical complications and death as well as to manage Crotalus rattlesnake populations in the Brazilian Amazon.

Stepping into a dangerous quagmire: Macroecological determinants of Bothrops envenomings, Brazilian Amazon.

Despite significant and successful efforts in Brazil regarding snakebites in the areas of research, antivenom manufacture and quality control, training of health professionals in the diagnosis and clinical management of bites, little is known about determinants of snakebites incidence in order to further plan interventions to reduce the impact of this medical condition. Understanding the complexity of ecological interactions in a geographical region is important for prediction, prevention and control measures of snakebites. This investigation aims to describe spatial distribution and identify environmental determinants of human envenoming by lancehead pit vipers (Bothrops genus), in the Brazilian Amazon. Aggregated data by the municipality was used to analyze the spatial distribution of Bothrops bites cases and its relationship with geographic and environmental factors. Eight geo-environmental factors were included in the analysis as independent variables: (1) tree canopy loss increase; (2) area with vegetation cover; (3) area covered by water bodies; (4) altitude; (5) precipitation; (6) air relative humidity; (7) soil moisture; and (8) air temperature. Human envenoming by lancehead pit vipers (Bothrops genus) in the Amazon region is more incident in lowlands [Adjusted regression coefficient [ARC] -0.0007 (IC95%: -0.001; -0.0006), p<0.0001], with high preserved original vegetation cover [ARC 0.0065 (IC95%: 0.0071; 0.0060), p<0.0001], with heaviest rainfall [ARC 0.0001 (IC95%: 0.00009; 0.0001), p<0.0001] and higher air relative humidity [ARC 0.0082 (IC95%: 0.0108; 0.0056), p<0.0001]. This association is interpreted as the result of the higher prey availability and further abundance of pit vipers in such landscapes.

Uso de tonometria arterial periférica - hiperemia reativa e biomarcadores séricos para predição prognóstica na sepse / Use of reactive hyperemia - peripheral arterial tonometry and circulating biological markers to predict outcomes in sepsis

RESUMO Objetivo: Avaliar a utilidade e o valor prognóstico da tonometria arterial periférica - hiperemia reativa em pacientes com sepse, e investigar a associação dos resultados deste exame com os níveis séricos de algumas moléculas inflamatórias. Métodos: Estudo prospectivo, realizado em uma unidade de terapia intensiva para pacientes adultos com 18 leitos. Os critérios de exclusão foram imunossupressão grave ou tratamento com antibióticos iniciado mais de 48 horas antes da avaliação. Aplicamos o exame de tonometria arterial periférica - hiperemia reativa quando da inclusão (dia 1) e no dia 3. Avaliamos os níveis de interleucina 6, interleucina 10, proteínas do grupo 1 de mobilidade alta e de ST2 solúvel no sangue obtido quando da inclusão. Resultados: Dos 79 pacientes incluídos, 17 (21,6%) tiveram os sinais da tonometria arterial periférica - hiperemia reativa considerados tecnicamente não confiáveis, tendo sido excluídos do estudo. Assim, incluímos na análise final 62 pacientes, que foram submetidos a 95 exames de tonometria arterial periférica - hiperemia reativa dentro das primeiras 48 horas após sua inclusão. A média de idade foi de 51,5 (DP: 18,9), e 49 (62%) dos pacientes eram do sexo masculino. Os índices de hiperemia reativa dos dias 1 e 3 não se associaram com necessidade de vasopressores, SOFA, APACHE II ou mortalidade aos 28 dias. Dentre os pacientes que morreram, em comparação aos sobreviventes, houve aumento significante nos índices de hiperemia reativa no dia 3 em comparação ao dia 1 (p = 0,0045). Ocorreu fraca correlação negativa entre o índice obtido por tonometria arterial periférica - hiperemia reativa no dia 1 e os níveis de proteínas do grupo 1 de mobilidade alta (r = -0,287). Conclusão: Dificuldades técnicas e falta de associações claras dos resultados do exame com a gravidade clínica e com o desfecho foram fortes limitantes da utilidade do exame de tonometria arterial periférica - hiperemia reativa em pacientes sépticos admitidos à unidade de terapia intensiva.

ABSTRACT Objective: To evaluate the usefulness and prognostic value of reactive hyperemia - peripheral arterial tonometry in patients with sepsis. Moreover, we investigated the association of reactive hyperemia - peripheral arterial tonometry results with serum levels of certain inflammatory molecules. Methods: Prospective study, conducted in an 18-bed mixed intensive care unit for adults. The exclusion criteria included severe immunosuppression or antibiotic therapy initiated more than 48 hours before assessment. We measured the reactive hyperemia - peripheral arterial tonometry on inclusion (day 1) and on day 3. Interleukin-6, interleukin-10, high-mobility group box 1 protein and soluble ST2 levels were measured in the blood obtained upon inclusion. Results: Seventeen of the 79 patients (21.6%) enrolled were determined to have reactive hyperemia - peripheral arterial tonometry signals considered technically unreliable and were excluded from the study. Thus, 62 patients were included in the final analysis, and they underwent a total of 95 reactive hyperemia - peripheral arterial tonometry exams within the first 48 hours after inclusion. The mean age was 51.5 (SD: 18.9), and 49 (62%) of the patients were male. Reactive hyperemia indexes from days 1 and 3 were not associated with vasopressor need, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, or 28-day mortality. Among the patients who died, compared with survivors, there was a significant increase in the day 3 reactive hyperemia index compared with day 1 (p = 0.045). There was a weak negative correlation between the day 1 reactive hyperemia - peripheral arterial tonometry index and the levels of high-mobility group box 1 protein (r = -0.287). Conclusion: Technical difficulties and the lack of clear associations between the exam results and clinical severity or outcomes strongly limits the utility of reactive hyperemia - peripheral arterial tonometry in septic patients admitted to the intensive care unit.

Use of reactive hyperemia - peripheral arterial tonometry and circulating biological markers to predict outcomes in sepsis. / Uso de tonometria arterial periférica - hiperemia reativa e biomarcadores séricos para predição prognóstica na sepse.

OBJECTIVE:: To evaluate the usefulness and prognostic value of reactive hyperemia - peripheral arterial tonometry in patients with sepsis. Moreover, we investigated the association of reactive hyperemia - peripheral arterial tonometry results with serum levels of certain inflammatory molecules. METHODS:: Prospective study, conducted in an 18-bed mixed intensive care unit for adults. The exclusion criteria included severe immunosuppression or antibiotic therapy initiated more than 48 hours before assessment. We measured the reactive hyperemia - peripheral arterial tonometry on inclusion (day 1) and on day 3. Interleukin-6, interleukin-10, high-mobility group box 1 protein and soluble ST2 levels were measured in the blood obtained upon inclusion. RESULTS:: Seventeen of the 79 patients (21.6%) enrolled were determined to have reactive hyperemia - peripheral arterial tonometry signals considered technically unreliable and were excluded from the study. Thus, 62 patients were included in the final analysis, and they underwent a total of 95 reactive hyperemia - peripheral arterial tonometry exams within the first 48 hours after inclusion. The mean age was 51.5 (SD: 18.9), and 49 (62%) of the patients were male. Reactive hyperemia indexes from days 1 and 3 were not associated with vasopressor need, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, or 28-day mortality. Among the patients who died, compared with survivors, there was a significant increase in the day 3 reactive hyperemia index compared with day 1 (p = 0.045). There was a weak negative correlation between the day 1 reactive hyperemia - peripheral arterial tonometry index and the levels of high-mobility group box 1 protein (r = -0.287). CONCLUSION:: Technical difficulties and the lack of clear associations between the exam results and clinical severity or outcomes strongly limits the utility of reactive hyperemia - peripheral arterial tonometry in septic patients admitted to the intensive care unit.

Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer.

BACKGROUND: Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis. RESULTS: The number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR=3.08, 95% CI=1.74 to 5.45, p<10-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p=0.04) and intestinal metaplasia (p=0.007). Furthermore, patients infected by cagA strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer. CONCLUSIONS: Our results demonstrate that infection with H. pylori strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer.Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.

dupA polymorphisms and risk of Helicobacter pylori-associated diseases.

The dupA of Helicobacter pylori has been suggested as a virulence marker associated with the development of duodenal ulcer disease. However, the studies performed in different geographical areas have shown that there are variations in the prevalence of dupA and its association with H. pylori clinical outcomes. Our group did not observe associations between the presence of dupA and H. pylori clinical outcomes in Brazil. On the other hand, we observed 2 mutations in the sequence of dupA that lead to stop codons: a deletion of an adenine at position 1311 and an insertion of an adenine at position 1426 of the gene. Our aim was to evaluate associations of the presence of dupA with duodenal ulcer and gastric cancer, considering dupA-positive only those H. pylori strains that do not have the mutations in the gene sequence. We also evaluated the effect of infection with a strain carrying an intact dupA on the gastric mucosa histology and IL-8 gastric levels. Colonization with strains that had the intact dupA was negatively associated with gastric carcinoma (p=0.001, OR=0.32, 95% CI=0.16-0.66). The presence of dupA was also associated with an increased degree of antral mucosa inflammation (p=0.01) and with decreased corpus atrophy (p<0.01) as well as with increased gastric mucosa IL-8 levels (p=0.04). In conclusion, the infection with a H. pylori strain containing the dupA without the stop codon polymorphisms is associated with a lower risk of development of gastric carcinoma in Brazilian subjects.

Avaliação dos prognósticos de precipitação simulada pelo modelo BRAMS na Amazônia Ocidental na estação chuvosa / Evaluation of prognostic of rainfall model BRAMS in Western Amazonia during the wet season

O objetivo deste estudo é avaliar o modelo de previsão numérica do tempo BRAMS (Brazilian Regional Atmospheric Modelling System), a partir da comparação entre os valores preditos e os observados (dados do NCEP/NOAA (National Centers of Environmental Predictions/ National Oceanic and Atmospheric Administration) e do satélite TRMM (Tropical Rainfall Measuring Mission)). O modelo foi assimilado com dados do modelo global do NCEP/NOAA e do CPTEC/INPE. Foram realizadas comparações entre os valores preditos e os observados através da raiz do erro quadrático médio (RMSE) e do erro médio (ME) para os prognósticos de precipitação para os horizontes de 24, 48, 72 e 96 horas, do período de novembro de 2008 a março de 2009. Os resultados mostraram que o modelo BRAMS teve uma performance melhor quando assimilado com dados do modelo global do NCEP/NOAA comparado com as saídas a partir das assimilações do modelo global do CPTEC/INPE.

The objective of this study is to evaluate the model of numerical forecast BRAMS (Brazilian Regional Atmospheric Modelling System) from the comparison between the forecast and observed rainfall (data of NCEP/NOAA (National Centers of Environmental Predictions/ National Oceanic and Atmospheric Administration) and of TRMM satellite (Tropical Rainfall Measuring Mission)). The model used the initial conditions of global model of NCEP/NOAA e do CPTEC/INPE. Comparisons between predicted values and observed through were the root medium square error (RMSE) and of medium error (ME) for the forecast of rainfall of 24, 48, 72 and 96 hours, of the period November of 2008 to March of 2009. The results showed that the BRAMS model had better performance when treated with global model data from NCEP / NOAA compared with the outputs from the assimilation of the global model of CPTEC / INPE.

Helicobacter pylori transiently in the mouth may participate in the transmission of infection.

Helicobacter pylori infection is associated with peptic ulcer and gastric carcinoma. The oral cavity may be a reservoir for H. pylori; however, the results of studies on this subject are controversial. We employed single-step and nested polymerase chain reactions (PCR) to detect the presence of the vacA, ureA and 16S rDNA genes of H. pylori in the stomach, saliva and dental plaque of 30 subjects. The results were confirmed by sequencing. Nested 16S rDNA and ureA amplification was achieved in 80% of gastric, 30% of saliva and 20% of dental plaque specimens. Sequencing of 10, seven and four 16S rDNA products from stomach, saliva and dental plaque, respectively, showed > 99% identity with H. pylori. Sequencing of the other four oral cavity PCR products showed similarity with Campylobacter and Wolinella species. Additionally, the vacA genotype identified in the samples of different sites was the same within a given subject.H. pylori may be found in the oral cavity of patients with gastric infection, thus it could be a source of transmission. However, results obtained with detection methods based only on PCR should be interpreted with caution because other microorganisms that are phylogenetically very close to H. pylori are also present in the mouth.

Helicobacter pylori transiently in the mouth may participate in the transmission of infection

Helicobacter pylori infection is associated with peptic ulcer and gastric carcinoma. The oral cavity may be a reservoir for H. pylori; however, the results of studies on this subject are controversial. We employed single-step and nested polymerase chain reactions (PCR) to detect the presence of the vacA, ureA and 16S rDNA genes of H. pylori in the stomach, saliva and dental plaque of 30 subjects. The results were confirmed by sequencing. Nested 16S rDNA and ureA amplification was achieved in 80 percent of gastric, 30 percent of saliva and 20 percent of dental plaque specimens. Sequencing of 10, seven and four 16S rDNA products from stomach, saliva and dental plaque, respectively, showed > 99 percent identity with H. pylori. Sequencing of the other four oral cavity PCR products showed similarity with Campylobacter and Wolinella species. Additionally, the vacA genotype identified in the samples of different sites was the same within a given subject.H. pylori may be found in the oral cavity of patients with gastric infection, thus it could be a source of transmission. However, results obtained with detection methods based only on PCR should be interpreted with caution because other microorganisms that are phylogenetically very close to H. pylori are also present in the mouth.

Helicobacter pylori virulence factors as tools to study human migrations.

Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA and vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.

IL2-330G polymorphic allele is associated with decreased risk of Helicobacter pylori infection in adulthood.

We evaluated whether polymorphisms in genes coding molecules linked to the innate and adaptive immune response are associated with susceptibility to Helicobacter pylori infection. IL1B-511C-->T, IL1B-31T-->C, IL1RN allele 2, IL2-330T-->G, TNFA-307G-->A, TLR2Arg677Trp, TLR2Arg753Gln, TLR4Asp299Gly, and TLR5(392STOP) polymorphisms were determined in 541 blood donors. IL2-330T-->G allele carriers had a decreased H. pylori infection risk (OR=0.63, 95% CI=0.43-0.93) after adjustment for demographic and environmental factors. Hence, we investigated whether the polymorphism is functional by evaluating IL-2 serum concentration in 150 blood donors and 100 children. IL-2 pro-inflammatory and anti-inflammatory properties were indirectly investigated by determining serum IFN-gamma and IL-10/TGF-beta levels. The polymorphism was associated with increased mean IL-2 levels in H. pylori-positive adults (2.65 pg/mL vs. 7.78 pg/mL) and children (4.19 pg/mL vs. 8.03 pg/mL). Increased IL-2 was associated with pro-inflammatory activity in adults (IFN-gamma=18.61 pg/mL vs. 25.71 pg/mL), and with anti-inflammatory activity in children (IL-10=6.99 vs. 14.17 pg/mL, TGF-beta=45.88 vs. 93.44 pg/mL) (p<10(-3) for all). In conclusion, in the context of H. pylori infection, IL2-330 T-->G polymorphism is functional and is associated with decreased risk of infection in adults.

Immune response and gene polymorphism profiles in Crohn's disease and ulcerative colitis.

BACKGROUND: Polymorphisms in genes linked to the innate and adaptive immune response may be involved in inflammatory bowel disease pathogenesis. Our aim was to investigate associations among IL1B-511, IL1B-31, IL1RN, TNFA-307, TLR-2, TLR-4, IL2-330, NOD2 G908R, NOD2 L1007fsinsC polymorphisms and both Crohn's disease (CD) and ulcerative colitis (UC) in a Brazilian population. METHODS: We studied 43 patients with CD, 42 with UC, and 541 blood donors. Polymorphisms were evaluated by PCR, PCR-CTPP, or PCR-RFLP. Data were analyzed in multivariate models adjusting for confounding factors. RESULTS: IL1RN VNTR (P = 0.00, odds ratio [OR] = 2.43, 95% confidence interval [CI] = 1.50-3.90), as well as TNFA-307 polymorphic allele (P = 0.05, OR = 1.70, 95% CI = 1.00-2.94) were associated with UC. Both NOD2 mutations (G908R, P = 0.02, OR = 6.83, 95% CI = 1.62-25.45, and L1007fsinsC, P = 0.00, OR = 20.00, 95% CI = 3.21-124.69) were associated with CD. CONCLUSIONS: Our analyses showed positive associations between proinflammatory polymorphisms at IL1RN and TNFA-307 loci and UC, as well as polymorphisms in the NOD2 gene and CD. These results highlight the importance of different genetic profiles associated with CD and UC.

IL1RN polymorphic gene and cagA-positive status independently increase the risk of noncardia gastric carcinoma.

Helicobacter pylori cagA-positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL-1 gene cluster and tumor necrosis factor-alpha (TNFA)-307 polymorphisms, as well as cagA-positive status, are associated with gastric carcinoma in a non-Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori-positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme-linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B-511/-31, IL1RN (interleukin-1 receptor antagonist) and TNFA-307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2-pair primers. We found that the IL1RN2 polymorphic allele (OR = 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA-positive status was the strongest independent factor associated with gastric carcinoma (OR = 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA-positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma.