To assess the potential association of the functional polymorphism rs1801274 in the receptor IIa for the Fc portion of immunoglobin G (FcγRIIa) gene (FCGR2A-H131R) with the susceptibility to and the severity of community-acquired pneumonia (CAP). Multicenter prospective and observational study. Four university hospitals in Spain. FCGR2A-H131R polymorphism was determined in 1,262 patients with CAP and in 1,224 in the subject control group. Severe sepsis was recorded in 366 patients. No significant differences in genotype or allele frequencies were seen among patients with CAP or pneumococcal CAP (PCAP) and controls. Patients with bacteremic PCAP (B-PCAP) had significantly higher frequencies of FCGR2A-H/H131 genotypes than those with nonbacteremic PCAP (p = .00016, odds ratio = 2.9, 95% confidence interval 1.58-5.3). The differences remained significant when adjusting for pneumonia severity index, hospital of origin, and intensive care unit admission (p = .0012, odds ratio = 2.83, 95% confidence interval 1.51-5.32). B-PCAP was associated with a significantly higher severity of the disease, evaluated as sepsis severity (p = .000007, odds ratio = 4.40, 95% confidence interval 2.31-8.39), multiorgan dysfunction syndrome (0.00048, odds ratio = 3.29, 95% confidence interval 1.69-6.41), intensive care unit admission, acute renal failure, and acute respiratory distress syndrome. Our results do not support a role of FCGR2A-H131R polymorphism in susceptibility to CAP or PCAP. However, we provide the insight that homozygosity for FCGR2A-H131 predisposes B-PCAP, which was associated with higher severity in our study.

The role of mannose-binding lectin (MBL) deficiency (MBL2;XA/OandO/Ogenotypes) in host defences remains controversial. The surfactant proteins (SP)-A1, -A2 and -D, other collectins whose genes are located nearMBL2, are part of the first-line lung defence against infection. We analysed the role of MBL on susceptibility to pneumococcal infection and the existence of linkage disequilibrium (LD) among the four genes.We studied 348 patients with pneumococcal community-acquired pneumonia (P-CAP) and 2,110 controls. A meta-analysis ofMBL2genotypes in susceptibility to P-CAP and to invasive pneumococcal disease (IPD) was also performed. The extent of LD ofMBL2withSFTPA1,SFTPA2andSFTPDwas analysed.MBL2genotypes did not associate with either P-CAP or bacteraemic P-CAP in the case–control study. The MBL-deficientO/Ogenotype was significantly associated with higher risk of IPD in a meta-analysis, whereas the other MBL-deficient genotype (XA/O) showed a trend towards a protective role. We showed the existence of LD betweenMBL2and SP genes.The data do not support a role of MBL deficiency on susceptibility to P-CAP or to IPD. LD amongMBL2and SP genes must be considered in studies on the role of MBL in infectious diseases.

Oxygen therapy is currently used as a supportive treatment in septic patients to improve tissue oxygenation. However, oxygen can exert deleterious effects on the inflammatory response triggered by infection. We postulated that the use of high oxygen concentrations may be partially responsible for the worsening of sepsis-induced multiple system organ dysfunction in an experimental clinically relevant model of sepsis. We used Sprague-Dawley rats. Sepsis was induced by cecal ligation and puncture. Sham-septic controls (n = 16) and septic animals (n = 32) were randomly assigned to four groups and placed in a sealed Plexiglas cage continuously flushed for 24 h with medical air (group 1), 40% oxygen (group 2), 60% oxygen (group 3), or 100% oxygen (group 4). We examined the effects of these oxygen concentrations on the spread of infection in blood, urine, peritoneal fluid, bronchoalveolar lavage, and meninges; serum levels of inflammatory biomarkers and reactive oxygen species production; and hematological parameters in all experimental groups. In cecal ligation and puncture animals, the use of higher oxygen concentrations was associated with a greater number of infected biological samples (P < 0.0001), higher serum levels of interleukin-6 (P < 0.0001), interleukin-10 (P = 0.033), and tumor necrosis factor-α (P = 0.034), a marked decrease in platelet counts (P < 0.001), and a marked elevation of reactive oxygen species serum levels (P = 0.0006) after 24 h of oxygen exposure. Oxygen therapy greatly influences the progression and clinical manifestation of multiple system organ dysfunction in experimental sepsis. If these results are extrapolated to humans, they suggest that oxygen therapy should be carefully managed in septic patients to minimize its deleterious effects.

Background: Type 2 diabetes mellitus (T2DM) is a chronic disease in which health outcomes are related to decision making by patients and health care professionals. Objective: This study aims to assess the effectiveness of internet-based multicomponent interventions to support decision making of all actors involved in the care of patients with T2DM in primary care. Methods: The INDICA study is an open, community-based, multicenter trial with random allocation to usual care or the intervention for patients, the intervention for health care professionals in primary care, or the combined intervention for both. In the intervention for patients, participants received an educational group program and were monitored and supported by logs, a web-based platform, and automated SMS. Those in the intervention for professionals also received an educational program, a decision support tool embedded in the electronic clinical record, and periodic feedback about patients’ results. A total of 2334 people with T2DM, regardless of glycated hemoglobin (HbA1c) levels and without diabetes-related complications, were included. The primary end point was change in HbA1c level. The main analysis was performed using multilevel mixed models. Results: For the overall sample, the intervention for patients attained a significant mean reduction in HbA1c levels of ‒0.27 (95% CI ‒0.45 to ‒0.10) at month 3 and ‒0.26 (95% CI ‒0.44 to ‒0.08) at month 6 compared with usual care, which remained marginally significant at month 12. A clinically relevant reduction in HbA1c level was observed in 35.6% (191/537) of patients in the intervention for patients and 26.0% (152/586) of those in usual care at month 12 (P=.006). In the combined intervention, HbA1c reduction was significant until month 18 (181/557, 32.6% vs 140/586, 23.9%; P=.009). Considering the subgroup of patients uncontrolled at baseline, all interventions produced significant reductions in HbA1c levels across the entire study period: ‒0.49 (95% CI ‒0.70 to ‒0.27) for the intervention for patients, ‒0.35 (95% CI ‒0.59 to ‒0.14) for the intervention for professionals, and ‒0.35 (95% CI ‒0.57 to ‒0.13) for the combined intervention. Differences in HbA1c for the area under the curve considering the entire period were significant for the intervention for patients and the combined intervention compared with usual care (P=.03 for both). Compared with usual care, the intervention for professionals and the combined intervention had significant longer-term reductions in systolic and diastolic blood pressure. Conclusions: In uncontrolled patients, the intervention for patients at baseline provided clinically relevant and significant longer-term reductions of HbA1c levels. The intervention for professionals and combined intervention also improved the cardiovascular risk profile of patients. Trial Registration: ClinicalTrials.gov NCT01657227; https://clinicaltrials.gov/ct2/show/NCT01657227

Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarkers among septic patients. Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1β, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7^th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001≤p≤0.022), and with reduced IL-10 (0.012≤p≤0.047) and elevated CRP (0.011≤p≤0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p = 0.017) and ALI (p = 0.050) in a combined analysis with European Americans, suggesting common risk effects among studies. These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis.