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Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in an attempt to clear the invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later in sepsis, a paradoxical immunosuppression occurs, where the host is unable to clear the preexisting infection and is susceptible to secondary infections. A major issue with sepsis treatment is that it is difficult for physicians to ascertain which stage of sepsis the patient is in. Sepsis treatment will depend on the patient’s immune status across the spectrum of the disease, and these immune statuses are nearly polar opposites in the early and late stages of sepsis. Furthermore, there is no approved treatment that can resolve inflammation without contributing to immunosuppression within the host. Here, we review the major mechanisms of sepsis-induced immunosuppression and the biomarkers of the immunosuppressive phase of sepsis. We focused on reviewing three main mechanisms of immunosuppression in sepsis. These are lymphocyte apoptosis, monocyte/macrophage exhaustion, and increased migration of myeloid-derived suppressor cells (MDSCs). The biomarkers of septic immunosuppression that we discuss include increased MDSC production/migration and IL-10 levels, decreased lymphocyte counts and HLA-DR expression, and increased GPR18 expression. We also review the literature on the use of specialized pro-resolving mediators (SPMs) in different models of infection and/or sepsis, as these compounds have been reported to resolve inflammation without being immunosuppressive. To obtain the necessary information, we searched the PubMed database using the keywords sepsis, lymphocyte apoptosis, macrophage exhaustion, MDSCs, biomarkers, and SPMs.

Human milk is essential for the initial development of newborns, as it provides all nutrients and vitamins, such as vitamin D, and represents a great source of commensal bacteria. Here we explore the microbiota network of colostrum and mature milk of Italian and Burundian mothers using the auto contractive map (AutoCM), a new methodology based on artificial neural network (ANN) architecture. We were able to demonstrate the microbiota of human milk to be a dynamic, and complex, ecosystem with different bacterial networks among different populations containing diverse microbial hubs and central nodes, which change during the transition from colostrum to mature milk. Furthermore, a greater abundance of anaerobic intestinal bacteria in mature milk compared with colostrum samples has been observed. The association of complex mathematic systems such as ANN and AutoCM adopted to metagenomics analysis represents an innovative approach to investigate in detail specific bacterial interactions in biological samples.

Anomalies in the abundance measurements of short lived radionuclides in meteorites indicate that the protosolar nebulae was irradiated by a large number of energetic particles (E≳ 10 MeV), often called solar cosmic rays. The particle flux of the contemporary Sun cannot explain these anomalies, but, similar to T Tauri stars, the young Sun was more active and probably produced enough high energy particles. However, the stellar particle (SP) flux of young stars is essentially unknown. We model the impact of high-energy ionization sources on the chemistry of the circumstellar environment (disks and envelopes). The model includes X-ray radiative transfer and makes use of particle transport models to calculate the individual molecular hydrogen ionization rates. We study the impact on the chemistry via the ionization tracers HCO+ and N2H+. We argue that spatially resolved observations of those molecules combined with detailed models allow for disentangling the contribution of the individual high-energy ionization sources and to put constraints on the SP flux in young stars.

ObjectiveTo assess accuracy and repeatability of a modified echocardiographic approach to quantify superior vena cava (SVC) flow volume that uses a short-axis view to directly measure SVC area and a suprasternal view to measure flow velocity, both at the level of the right pulmonary artery.SettingThree tertiary-level neonatal intensive care units.DesignThis was a multicentre, prospective, observational study. Accuracy of the traditional and modified approach was first assessed by comparing echo measurements according to both techniques with Phase contrast MRI (PCMRI) assessments, in a cohort of 10 neonates. In a second cohort of 40 neonates, intraobserver scan–rescan repeatability and interobserver analysis–reanalysis repeatability were assessed by repeated SVC flow echo measurements, according to both techniques.ResultsThe traditional echocardiographic approach to assessment of SVC flow had a moderate agreement with PCMRI (r2 0.259), a scan–rescan intraobserver repeatability index (RI) of 37% (limits of agreement (LOA) −47/+51 mL/kg/min) and an interobserver analysis–reanalysis RI of 31% (LOA −38/+40 mL/kg/min). The modified approach showed a stronger agreement with PCMRI (r2 0.775), an improved intraobserver scan–rescan repeatability (RI 22%, LOA −24/+18 mL/kg/min) and improved interobserver analysis–reanalysis repeatability (RI 18%, LOA −18/+20 mL/kg/min).ConclusionsEchocardiographic assessment of SVC flow volume by tracing area from a short-axis view and measuring velocity–time integral from a suprasternal view offered an improvement in accuracy and repeatability, building on the traditional approach previously described.

Colostrum is produced in the first days postpartum. It is a known source of immune mediators for a newborn within the first week of life. Although it is still unclear if colostrum composition varies between populations, recent data suggest differences. Hepatocyte growth factor (HGF); transforming growth factor-β (TGF-β) 1, 2, and 3; and immunoglobulin A (IgA) are key immunological components of colostrum that stimulate neonatal gastrointestinal and immune system development. We aimed to investigate the differences in the concentration between immune markers in the colostrum of mothers living in Burundi and Italy, and to identify the factors associated with differences. In this cross-sectional birth cohort study, a total of 99 colostrum samples from Burundian (n = 23) and Italian (n = 76) women were collected at 0 to 6 days postpartum. A clinical chemistry analyser was used for IgA quantification and electro-chemiluminescence, for HGF and TGFβ1-3 assessment. A univariate analysis and multivariate linear regression model were used for statistical testing. The concentrations of TGF-β2 (p = 0.01) and IgA (p < 0.01) were significantly higher in the colostrum from the women residing in Burundi than in Italy, both in a univariate analysis and upon the adjustment for confounding factors. A similar trend is seen for HGF, reaching statistical significance upon a multivariate analysis. We found a moderate to strong positive correlation between the TGF-β isoforms and IgA concentration in both countries (p < 0.01), with stronger concentration in the colostrum from Burundi. The results of this study are in support of previous data, suggesting that concentration of the immune active molecules is higher in the human milk of women residing in developing countries. However, with a small sample size, caution must be applied, as the findings require further confirmation. Future work should also be focused on other factors (e.g., lipid and microbial composition), as well as the investigation into colostrum and between populations comparison, adjusting for potential confounders.

Cosmic rays are the main agents in controlling the chemical evolution and setting the ambipolar diffusion time of a molecular cloud. We summarise the processes causing the energy degradation of cosmic rays due to their interaction with molecular hydrogen, focusing on the magnetic effects that influence their propagation. Making use of magnetic field configurations generated by numerical simulations, we show that the increase of the field line density in the collapse region results in a reduction of the cosmic-ray ionisation rate. As a consequence the ionisation fraction decreases, facilitating the decoupling between the gas and the magnetic field.

This case describes a rare instance of reversible dilated cardiomyopathy (DCM) in a 65-year-old Caucasian male with a significant past medical history of inflammatory rheumatoid arthritis (RA) controlled with rituximab and hydroxychloroquine (HCQ). The patient presented with acute onset of dyspnea on exertion and palpitations and was diagnosed with congestive heart failure in the context of DCM. Despite having no prior cardiac abnormalities, an EKG revealed a new left bundle branch block, and an echocardiogram demonstrated a severely reduced left ventricular ejection fraction (LVEF) of 10-15%. Left heart catheterization and coronary angiography revealed no evidence of coronary artery disease. Given the absence of an overt cause, drug-induced DCM was suspected; hence, rituximab and HCQ were discontinued. Other common causes of DCM, including alcohol abuse and virus-induced DCM, were excluded based on relevant testing. Seven to nine months after cessation of HCQ and rituximab, the patient's RA progressed, and treatment was initiated with IV tocilizumab, resulting in a good clinical response. At the 26-month follow-up, a repeat echocardiogram revealed mild mitral regurgitation with an LVEF which improved to 55%. At this point, Takotsubo cardiomyopathy was considered a potential cause of this patient's DCM due to its reversible nature. This case highlights the importance of comprehensive cardiac monitoring in symptomatic patients at high risk for cardiovascular disease, such as this patient with long-standing inflammatory disease. Physicians should work together to closely monitor and consider the serious potential risks of all treatment regimens.

ObjectiveThe objective was to evaluate the association between age-related comorbidities (ARCs) and 5-year HIV-related excess mortality in people living with HIV aged ≥60 years.DesignCohort study using relative survival analysis (Estève’s model).SettingThe French multicentre prospective Dat’AIDS cohort that involves 12 French hospitals.ParticipantsInclusion of 1415 HIV-1 infected patients actively followed aged ≥60 years on January 2008, with a 5-year follow-up period in the late combination antiretroviral therapy era.ResultsAmong 1415 patients included, 154 died. By multivariable analysis, factors predictive of 5-year HIV-related excess mortality were non-AIDS-related cancer (adjusted excess HR (aEHR)=2.94; 95% CI 1.32 to 6.57), cardiovascular disease (aEHR=6.00; 95% CI 2.45 to 14.65), chronic renal disease (aEHR=4.86; 95% CI 2.24 to 10.53), cirrhosis (aEHR=3.58; 95% CI 1.25 to 10.28), hepatitis C co-infection (aEHR=3.63; 95% CI 1.44 to 9.12), body mass index<18.5 kg/m² (aEHR=4.10; 95% CI 1.61 to 10.48) and having a CD4 cell count ≤200/mm3 (aEHR=5.79; 95% CI 2.28 to 14.69).ConclusionsARCs, particularly cardiovascular disease and chronic renal disease, are predictive of HIV-related excess mortality, with an increase in hazard similar to that of CD4 cell count.Trial registration number NCT02898987.

Carotid stenting is a potential alternative to carotid endarterectomy but whether this technique is as safe as surgery and whether the long-term protection against stroke is similar to that of surgery are unclear. We previously reported that in patients in the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the rate of any stroke or death within 30 days after the procedure was higher with stenting than with endarterectomy. We now report the results up to 4 years. In this follow-up study of a multicentre, randomised, open, assessor-blinded, non-inferiority trial, we compared outcome after stenting with outcome after endarterectomy in 527 patients who had carotid stenosis of at least 60% that had recently become symptomatic. The primary endpoint of the EVA-3S trial was the rate of any periprocedural stroke or death (ie, within 30 days after the procedure). The prespecified main secondary endpoint was a composite of any periprocedural stroke or death and any non-procedural ipsilateral stroke during up to 4 years of follow-up. Other trial outcomes were any stroke or periprocedural death, any stroke or death, and the above endpoints restricted to disabling or fatal strokes. This trial is registered with ClinicalTrials.gov, number NCT00190398. 262 patients were randomly assigned to endarterectomy and 265 to stenting. The cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke after 4 years of follow-up was higher with stenting than with endarterectomy (11·1% vs 6·2%, hazard ratio [HR] 1·97, 95% CI 1·06–3·67; p=0·03). The HR for periprocedural disabling stroke or death and non-procedural fatal or disabling ipsilateral stroke was 2·00 (0·75–5·33; p=0·17). A hazard function analysis showed the 4-year differences in the cumulative probabilities of outcomes between stenting and endarterectomy were largely accounted for by the higher periprocedural (within 30 days of the procedure) risk of stenting compared with endarterectomy. After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups. For any stroke or periprocedural death, the HR was 1·77 (1·03–3·02; p=0·04). For any stroke or death, the HR was 1·39 (0·96–2·00; p=0·08). The results of this study suggest that carotid stenting is as effective as carotid endarterectomy for middle-term prevention of ipsilateral stroke, but the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy in patients with symptomatic carotid stenosis. French Ministry of Health.

In this communication we describe the finding of a Bacillus circulans strain resistant to vancomycin and carrying the vanA gene in a case of catheter-related infection. The patient was a three-month-old baby transferred to the pediatric department of the Verona University Hospital from the General Hospital of Trento, Italy, because of sequelae of Escherichia coli meningitis. He received treatment with chloramphenicol, aztreonam and ceftazidime. The day after admission, a short peripheral vascular catheter was removed and sent with a blood sample to the microbiology laboratory for routine bacteriological analysis. Bacillus spp. are ubiquitous in nature and are frequently discounted as contaminants in cultures of clinical materials. However, several serious infections caused by this organism, including endocarditis, sepsis, meningitis, endophthalmitis and surgical wound infections, have been described. Clinical isolates of Bacillus spp. are reported to be susceptible in vitro to a number of antibiotics, as was our isolate. Thus, the natural acquisition of vancomycin resistance by these organisms would not actually represent a serious therapeutical challenge. However, the evidence we provided of the enterococcal vancomycin-resistance determinant spreading among clinically relevant isolates of other species has to be viewed with great concern.