Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis.

The FUT2 α1,2fucosyltransferase contributes to the synthesis of fucosylated glycans used as attachment factors by several pathogens, including noroviruses and rotaviruses, that can induce life-threatening gastroenteritis in young children. FUT2 genetic polymorphisms impairing fucosylation are strongly associated with resistance to dominant strains of both noroviruses and rotaviruses. Interestingly, the wild-type allele associated with viral gastroenteritis susceptibility inversely appears to be protective against several inflammatory or autoimmune diseases for yet unclear reasons, although a FUT2 influence on microbiota composition has been observed. Here, we studied a cohort of young healthy adults and showed that the wild-type FUT2 allele was associated with the presence of anti-RVA antibodies, either neutralizing antibodies or serum IgA, confirming its association with the risk of RVA gastroenteritis. Strikingly, it was also associated with the frequency of gut microbiota-induced regulatory T cells (Tregs), so-called DP8α Tregs, albeit only in individuals who had anti-RVA neutralizing antibodies or high titers of anti-RVA IgAs. DP8α Tregs specifically recognize the human symbiont Faecalibacterium prausnitzii, which strongly supports their induction by this anti-inflammatory bacterium. The proportion of F. prausnitzii in feces was also associated with the FUT2 wild-type allele. These observations link the FUT2 genotype with the risk of RVA gastroenteritis, the microbiota and microbiota-induced DP8α Treg cells, suggesting that the anti-RVA immune response might involve an induction/expansion of these T lymphocytes later providing a balanced immunological state that confers protection against inflammatory diseases.

Faecal Microbiota Composition Varies between Patients with Breast Cancer and Healthy Women: A Comparative Case-Control Study.

The intestinal microbiota plays an essential role in many diseases, such as obesity, irritable bowel disease (IBD), and cancer. This study aimed to characterize the faecal microbiota from early-stage breast cancer (BC) patients and healthy controls. Faeces from newly diagnosed breast cancer patients, mainly for an invasive carcinoma of no specific type (HR+ and HER2-), before any therapeutic treatment and healthy controls were collected for metabarcoding analyses. We show that the Shannon index, used as an index of diversity, was statistically lower in the BC group compared to that of controls. This work highlights a reduction of microbial diversity, a relative enrichment in Firmicutes, as well as a depletion in Bacteroidetes in patients diagnosed with early BC compared to those of healthy women. A tendency towards a decreased relative abundance of Odoribacter sp., Butyricimonas sp., and Coprococcus sp. was observed. This preliminary study suggests that breast cancer patients may differ from healthy subjects in their intestinal bacterial composition.

Feasibility and postoperative opioid sparing effect of an opioid-free anaesthesia in adult cardiac surgery: a retrospective study.

BACKGROUND: No previous study investigated the dexmedetomidine-based opioid-free anesthesia (OFA) protocol in cardiac surgery. The main objective of this study was to evaluate the feasibility and the postoperative opioid-sparing effect of dexmedetomidine-based OFA in adult cardiac surgery patients. METHODS: We conducted a single-centre and retrospective study including 80 patients above 18 years old who underwent on-pump cardiac surgery between November 2018 and February 2020. Patients were divided into two groups: OFA (lidocaine, ketamine, dexmedetomidine, MgSO4) or opioid-based anaesthesia (remifentanil and anti-hyperalgesic medications such as ketamine and/or MgSO4 and/or lidocaine at the discretion of the anesthesiologist). The primary endpoint was the total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours. Secondary outcomes included perioperative hemodynamics, post-operative maximal pain at rest and during coughing and adverse outcomes. Data are expressed as median [interquartile range]. RESULTS: Patients in the OFA-group had a higher EuroSCORE II, with more diabetes, more dyslipidemia and more non-elective surgery but fewer smoking history. In the OFA group, the median loading dose of dexmedetomidine was 0.6 [0.4-0.6] µg.kg- 1 while the median maintenance dose was 0.11 µg.kg- 1.h- 1 [0.05-0.20]. In 10 (25%) patients, dexmedetomidine was discontinued for a drop of mean arterial pressure below 55 mmHg. The median total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours was lower in the OFA group (15.0 mg [8.5-23.5] versus 30.0 mg [17.3-44.3], p < 0.001). While no differences were seen with rest pain (2.0 [0.0-3.0] versus 0.5 [0.0-5.0], p = 0.60), the maximal pain score during coughing was lower in OFA group (3.5 [2.0-5.0] versus 5.5 [3.0-7.0], p = 0.04). In OFA group the incidence of atrial fibrillation (18% versus 40%, p = 0.03) and non-invasive ventilation use (25% versus 48%, p = 0.04) were lower. The incidence of bradycardia and the intraoperative use of norepinephrine were similar between both groups. CONCLUSION: Dexmedetomidine-based OFA in cardiac surgery patients is feasible and could be associated with a lower postoperative morphine consumption and better postoperative outcomes. Further randomized studies are required to confirm these promising results and determine the optimal associations, dosages, and infusion protocols during cardiac surgery.

Characterization of Bacterial Communities of Cold-Smoked Salmon during Storage.

Cold-smoked salmon is a widely consumed ready-to-eat seafood product that is a fragile commodity with a long shelf-life. The microbial ecology of cold-smoked salmon during its shelf-life is well known. However, to our knowledge, no study on the microbial ecology of cold-smoked salmon using next-generation sequencing has yet been undertaken. In this study, cold-smoked salmon microbiotas were investigated using a polyphasic approach composed of cultivable methods, V3-V4 16S rRNA gene metabarcoding and chemical analyses. Forty-five cold-smoked salmon products processed in three different factories were analyzed. The metabarcoding approach highlighted 12 dominant genera previously reported as fish spoilers: Firmicutes Staphylococcus, Carnobacterium, Lactobacillus, ß-Proteobacteria Photobacterium, Vibrio, Aliivibrio, Salinivibrio, Enterobacteriaceae Serratia,Pantoea, γ-Proteobacteria Psychrobacter, Shewanella and Pseudomonas. Specific operational taxonomic units were identified during the 28-day storage study period. Operational taxonomic units specific to the processing environment were also identified. Although the 45 cold-smoked salmon products shared a core microbiota, a processing plant signature was found. This suggest that the bacterial communities of cold-smoked salmon products are impacted by the processing environment, and this environment could have a negative effect on product quality. The use of a polyphasic approach for seafood products and food processing environments could provide better insights into residential bacteria dynamics and their impact on food safety and quality.

Impact of DNA extraction and sampling methods on bacterial communities monitored by 16S rDNA metabarcoding in cold-smoked salmon and processing plant surfaces.

Amplicon sequencing approaches have been widely used in food bacterial ecology. However, choices regarding the methodology can bias results. In this study, bacterial communities associated with cold-smoked salmon products and their processing plant surfaces were monitored via sequencing of the V3-V4 region of the 16S rRNA gene. The impact of DNA extraction protocols, sampling methods (swabbing or sponging) and surface materials on bacterial communities were investigated. α and ß diversity analyses revealed that DNA extraction methods mainly influence the observed cold-smoked salmon microbiota composition. Moreover, different DNA extraction methods revealed significant differences in observed community richness and evenness. ß-Proteobacteria: Photobacterium, Serratia and Firmicutes: Brochothrix, Carnobacterium and Staphylococcus were identified as the dominant genera. Surface microbiota richness, diversity and composition were mainly affected by cleaning and disinfection procedures but not by DNA extraction methods. Surface community richness and evenness appeared higher when sampled by sponging compared to swabbing. ß-diversity analyses highlighted that surface topology, cleaning and disinfection and sampling devices seemed to affect the bacterial community composition. The dominant surface bacteria identified were mainly Flavobacteriaceae, ß-Proteobacteria and γ-Proteobacteria described as fish spoilers such as Acinetobacter, Pseudomonas and Shewanella. DNA extraction and sampling methods can have an impact on sequencing results and the ecological analysis of bacterial community structures. This study confirmed the importance of methodology standardization and the need for analytical validation before 16S rDNA metabarcoding surveys.

Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models.

Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota's role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown. The objective of this study was to evaluate the impact of pemetrexed and the tumor graft on the gut microbiota composition in immunodeficient mice. The faecal microbiota composition was studied with metabarcoding before, 24-h and one week after treatment. The colon epithelial barrier integrity was evaluated by histological examination, intestinal permeability measurement, and selected cytokines quantification. The tumor graft induced some variations in the microbiota composition. Pemetrexed further increased the relative abundance of Enterobacteriaceae and 3 families from the Firmicutes phylum: Enterococcaceae, Lactobacillaceae and Streptococcaceae. Pemetrexed also significantly altered the epithelial barrier integrity, which was associated with early inflammation. This pilot study shows that the association of a lung tumor graft with pemetrexed causes an alteration in the microbiota composition. Such information increases our knowledge about the impact of chemotherapy on the microbiota, which could help to minimize side effects and improve therapeutic effectiveness in the future.

Independent risk factors for ICU mortality after left ventricular assist device implantation.

Left ventricular assist devices (LVADs) are used as an alternative therapy for heart transplantation in patients with advanced heart failure. However, the mortality rate of these patients remains relatively high. A large proportion of deaths after LVAD implantation occur during intensive care unit (ICU) stay. We conducted a retrospective study to identify the risk factors for all-cause ICU mortality in patients with an implanted LVAD. Between January 1, 2008 and December 31, 2016, 70 consecutive patients who had received an LVAD were analyzed. The median ICU length of stay was 14 days (IQR: 8-31) and 16 patients (22.9% [95%CI: 13.1-32.7]) died in the ICU. The 90-day mortality rate was 25.7% (95%CI: 15.5-35.9). The main causes of ICU mortality were: multiple organ failure, stroke, and hemorrhagic events. The univariate analysis identified the following perioperative risk factors for all-cause ICU mortality: hypertension, preoperative platelet count, preoperative white cell count, inotropic support before LVAD implantation, mechanical ventilation before LVAD implantation, renal replacement therapy before LVAD implantation, short-term mechanical support before LVAD implantation, INTERMACS class 1 to 2, low intraoperative platelet count, low early postoperative hemoglobin level, low early postoperative platelet count, low early postoperative pH, and massive perioperative blood transfusion. In the multivariate logistic regression analysis, only mechanical ventilation before LVAD implantation was retained as an independent risk factor for ICU mortality (OR = 11.96 [95%CI: 2.67-53.45], P < .01). These findings confirm that most deaths after LVAD implantation occur in the ICU. Patients that receive mechanical ventilation preoperatively have the highest risk of death. This confirms the need to actively treat respiratory failure and to wean patients from respiratory support before LVAD implantation. Such a strategy offers the best opportunity to initiate active rehabilitation.

Glycemic Index and Insulinemic Index of Foods: An Interlaboratory Study Using the ISO 2010 Method.

An official method for determining food glycemic index (GI) was published by the Organization for International Standardization (ISO) in 2010, but its performance has not been assessed. Therefore, we aimed to determine the intra- and inter-laboratory variation of food GI values measured using the 2010 ISO method. Three laboratories (Australia, Canada and France) determined the GI and insulinemic-index (II) of six foods in groups of 13-15 participants using the 2010 ISO method and intra- and inter-laboratory Standard Deviations (SDs) were calculated. Overall mean food GIs varied from 47 to 86 (p < 0.0001) with no significant difference among labs (p = 0.57) and no food × laboratory interaction (p = 0.20). Within-laboratory SD was similar among foods (range, 17.8-22.5; p = 0.49) but varied among laboratories (range 17.5-23.1; p = 0.047). Between-laboratory SD of mean food GI values ranged from 1.6 to 6.7 (mean, 5.1). Mean glucose and insulin responses varied among foods (p < 0.001) with insulin (p = 0.0037), but not glucose (p = 0.054), varying significantly among labs. Mean II varied among foods (p < 0.001) but not among labs (p = 0.94). In conclusion, we found that using the 2010 ISO method, the mean between-laboratory SD of GI was 5.1. This suggests that the ISO method is sufficiently precise to distinguish a mean GI = 55 from a mean GI ≥ 70 with 97-99% probability.

Intraoperative changes in blood lactate levels are associated with worse short-term outcomes after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: A high perioperative blood lactate level has been reported to be associated with poor outcomes after cardiac surgery. More than isolated peaks of lactate values, it should be more interesting to take into account changes in intraoperative blood lactate level (∆Lact). This large-scale retrospective study evaluated the relationship between ∆Lact and overall intensive care unit morbidity and 30-day all-cause mortality. METHODS: Perioperative data from consecutive patients undergoing on-pump cardiac surgery between September 2010 and June 2016 were retrospectively analysed through our institutional database including clinical, transfusion and laboratory test results implemented prospectively by physicians. Blood lactate levels were initially measured after induction of anaesthesia (baseline) and periodically during the surgery. The ∆Lact was defined as the difference between the highest intraoperative blood lactate and the baseline lactate level and offered the opportunity to stratify patients into four subgroups: ⩽0, 0.1-0.9, 1-1.9 and ⩾2 mmol L-1. RESULTS: From the 7,795 patients found eligible during the study period, 7,447 patients were analysed. The median ∆Lact of our patients was 0.6 (0.3-1) mmol L-1. Most of the studied patients (65.9%) exhibited a ∆Lact between 0.1 and 0.9 mmol L-1. A concentration-dependent relationship was observed between ∆Lact and intensive care unit morbidity and 30-day mortality. After adjustment for co-variables, all ∆Lact > 0 was associated with an increase in overall intensive care unit morbidity. An independent relationship was also found between ∆Lact and 30-day mortality as of a 1 mmol L-1 increase. CONCLUSION: Our results suggest that ∆Lact is associated with poor short-term outcomes in adult cardiac surgical patients.

The use of next generation sequencing for improving food safety: Translation into practice.

Next Generation Sequencing (NGS) combined with powerful bioinformatic approaches are revolutionising food microbiology. Whole genome sequencing (WGS) of single isolates allows the most detailed comparison possible hitherto of individual strains. The two principle approaches for strain discrimination, single nucleotide polymorphism (SNP) analysis and genomic multi-locus sequence typing (MLST) are showing concordant results for phylogenetic clustering and are complementary to each other. Metabarcoding and metagenomics, applied to total DNA isolated from either food materials or the production environment, allows the identification of complete microbial populations. Metagenomics identifies the entire gene content and when coupled to transcriptomics or proteomics, allows the identification of functional capacity and biochemical activity of microbial populations. The focus of this review is on the recent use and future potential of NGS in food microbiology and on current challenges. Guidance is provided for new users, such as public health departments and the food industry, on the implementation of NGS and how to critically interpret results and place them in a broader context. The review aims to promote the broader application of NGS technologies within the food industry as well as highlight knowledge gaps and novel applications of NGS with the aim of driving future research and increasing food safety outputs from its wider use.

Benefits of intraoperative analgesia guided by the Analgesia Nociception Index (ANI) in bariatric surgery: An unmatched case-control study.

INTRODUCTION: Analgesia Nociception Index (ANI) has been proposed for the evaluation of the nociception-antinociception balance in the perioperative period. In obese patients, where the management of analgesia may be rendered difficult by pharmacological changes, we hypothesised that the monitoring of analgesia with ANI would reduce intraoperative opioid consumption during bariatric surgery. METHODS: This monocentric, observational, unmatched case-control study aimed to compare perioperative data from obese subjects (body mass index ≥35kgm-2) during bariatric surgery with or without the use of ANI monitoring (ANI+ group versus ANI- group). Intraoperative analgesia was provided by injection of sufentanil, which was performed according to the clinician's assessment in the ANI- group or to the ANI value in the ANI+ group. The primary outcome was the mean hourly intraoperative sufentanil requirement. Secondary outcomes included the need for postoperative morphine titration, incidence of nausea and vomiting, respiratory distress and pain scores in the first 24hours. RESULTS: Between December 2013 and September 2016, 60 obese patients (i.e. 30 per group) were included. The mean hourly consumption of sufentanil was significantly lower in the ANI+ group (0.15±0.05µgkg-1h-1 versus 0.17±0.05µgkg-1h-1, P=0.038). We found no difference between groups regarding the incidence of nausea and vomiting, acute respiratory distress, the need for postoperative morphine titration, or pain scores in the first 24 postoperative hours. CONCLUSION: The use of ANI monitoring might reduce intraoperative consumption of sufentanil during bariatric surgery but does not appear to be accompanied by a reduction in its side effects.

Transcatheter aortic valve implantation: General anesthesia using transesophageal echocardiography does not decrease the incidence of paravalvular leaks compared to sedation alone.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a valid option for patients with severe aortic stenosis judged to be at high surgical risk. For this procedure, there is no agreement on the appropriate type of anesthesia. Sedation offers several advantages, but general anesthesia (GA) leads to less paravalvular leaks (PVLs) probably because of the transesophageal echocardiography (TEE) guidance. The objective was to compare the incidence of PVL among patients receiving conscious sedation (TAVI-S) and patients receiving GA (TAVI-GA). We made the hypothesis that a referral center does not necessitate TAVI-GA to reduce the incidence of moderate-to-severe PVL. AIM: The primary outcome was the incidence of moderate-to-severe PVL at 30 days after the implantation. DESIGN AND SETTING: This study design was a retrospective observational trial in a university hospital. METHODS: The TAVI-S group underwent the procedure under conscious sedation. In the TAVI-GA group, an endotracheal tube and a TEE probe were inserted. After the valve deployment, PVL was assessed by hemodynamic and fluoroscopic measurements in the TAVI-S group. TEE was also used in the TAVI-GA group to evaluate the presence of PVL. When PVL was moderate or severe according to the Valve Academic Research Consortium criteria. RESULTS: TAVI-S and TAVI-GA were accomplished in 168 (67.5%) and 81 (32.5%) patients, respectively. Our results show no difference between the two groups regarding the incidence and grade of PVL. CONCLUSION: Performing TAVI under GA with TEE guidance is not associated with a lower incidence of moderate and severe PVL.

Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis.

AIM: To confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management. METHODS: An individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline ("IBS-C ≥ 2 subpopulation"). RESULTS: S. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as "normal" compared to Placebo (respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation (Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009). CONCLUSION: This meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations.

The Feasibility of a Completely Automated Total IV Anesthesia Drug Delivery System for Cardiac Surgery.

BACKGROUND: In this pilot study, we tested a novel automatic anesthesia system for closed-loop administration of IV anesthesia drugs for cardiac surgical procedures with cardiopulmonary bypass. This anesthesia drug delivery robot integrates all 3 components of general anesthesia: hypnosis, analgesia, and muscle relaxation. METHODS: Twenty patients scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Propofol, remifentanil, and rocuronium were administered using closed-loop feedback control. The main objective was the feasibility of closed-loop anesthesia defined as successful automated cardiac anesthesia without manual override by the attending anesthesiologist. Secondary qualitative observations were clinical and controller performances. The clinical performance of hypnosis control was the efficacy to maintain a bispectral index (BIS) of 45. To evaluate the hypnosis performance, BIS values were stratified into 4 categories: "excellent," "good," "poor," and "inadequate" hypnosis control defined as BIS values within 10%, ranging from 11% to 20%, ranging from 21% to 30%, or >30% of the target value, respectively. The clinical performance of analgesia was the efficacy to maintain NociMap values close to 0. The analgesia performance was assessed classifying the NociMap values in 3 pain control groups: -33 to +33 representing excellent pain control, -34 to -66 and +34 to +66 representing good pain control, and -67 to -100 and +67 to +100 representing insufficient pain control. The controller performance was calculated using the Varvel parameters. RESULTS: Robotic anesthesia was successful in 16 patients, which is equivalent to 80% (97.5% confidence interval [CI], 53%-95%) of the patients undergoing cardiac surgery. Four patients were excluded from the final analysis because of technical problems with the automated anesthesia delivery system. The secondary qualitative observations revealed that the clinical performance of hypnosis allowed an excellent and good control during 70% (97.5% CI, 63%-76%) of maintenance time and an insufficient clinical performance of analgesia for only 3% (97.5% CI, 1%-6%) of maintenance time. CONCLUSIONS: The completely automated closed-loop system tested in this investigation could be used successfully and safely for cardiac surgery necessitating cardiopulmonary bypass. The results of the present trial showed satisfactory clinical performance of anesthesia control.

Kinetic eGFR and Novel AKI Biomarkers to Predict Renal Recovery.

BACKGROUND AND OBJECTIVES: Prompt recognition of severe renal impairment could improve the early management of critically ill patients. We compared the value of kinetic eGFR, plasma neutrophil gelatinase-associated lipocalin (NGAL), and urine tissue inhibitor of metalloproteinase-2 and urine insulin-like growth factor-binding protein 7 ([TIMP-2]*[IGFBP7]) in predicting short-term recovery from AKI and major adverse kidney events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: During the 6-month study period, 245 patients were admitted to our intensive care unit. This study included 57 consecutive patients presenting with AKI within the first 24 hours after admission. AKI markers were evaluated at inclusion (day 0) and 24 hours later (day 1). Kinetic eGFR was calculated on day 1 according to serum creatinine evolution. Renal recovery was defined as normalization of serum creatinine with reversal of oliguria within 48 hours. Major adverse kidney events included death, need for RRT, or persistence of renal dysfunction at hospital discharge. RESULTS: Plasma NGAL and [TIMP-2]*[IGFBP7] predicted renal recovery, with area under the receiver-operating characteristic curve (AUC-ROC) values between 0.70 and 0.79 at inclusion. Although plasma NGAL values frequently reached the maximal measurement range, their decrease on day 1 predicted recovery. The kinetic eGFR calculation after initial resuscitation provided the best AUC-ROC value for renal recovery, at 0.87. The best predictions for major adverse kidney events were provided by [TIMP-2]*[IGFBP7] and kinetic eGFR (equal AUC-ROCs of 0.81). Combining AKI markers in addition to clinical prediction models improved the discrimination and reclassification of patients who will recover from AKI or suffer from major adverse kidney events. CONCLUSIONS: Biomarkers of kidney damage predicted short-term renal recovery and major adverse kidney events for an unselected cohort of critically ill patients. Calculating the kinetic eGFR imposed a delay after initial resuscitation but provided a good diagnostic and prognostic approach. The utility of functional and damage AKI marker combinations in addition to clinical information requires validation in larger prospective studies.

Accuracy of determining hemoglobin level using occlusion spectroscopy in patients with severe gastrointestinal bleeding.

BACKGROUND: In patients presenting with severe hemorrhage, the authors conducted an equivalence trial that compared noninvasive occlusion spectroscopy and the capillary blood method to determine hemoglobin level. METHODS: This prospective observational study included patients admitted to their intensive care unit for gastrointestinal bleeding. A ring-shaped sensor, connected to a NBM-200MP (OrSense, Nes Ziona, Israel), was fitted onto the patient's thumb to intermittently measure hemoglobin (SotHb). During the first 24 h after admission, venous hemoglobin level, considered as the reference method, was determined at the laboratory every 8 h and was compared to SotHb and the capillary blood method. The primary endpoint was the proportion of inaccurate measurements, defined as greater than 15% difference compared with reference values or their unavailability for any technical reason. RESULTS: The study was scheduled to include 68 patients but was stopped prematurely after an interim analysis of 34 patients. The proportion of inaccuracies revealed that SotHb could not be considered equivalent to the capillary blood method (47% [95% CI, 43-51] and 24% [95% CI, 20-28]). Considering venous hemoglobin level as a reference method, the mean biases for SotHb (n = 133) and the capillary blood method (n = 135) were, respectively, -0.4 ± 2.0 and 0.8 ± 1.2 g/dl (P < 0.05). SotHb was associated with an increased incidence of failed transfusion. The inaccuracy of SotHb tended to be increased in patients receiving vasopressor agents. CONCLUSIONS: Noninvasive determination of hemoglobin level based on occlusion spectroscopy lacks accuracy in patients presenting with severe gastrointestinal bleeding and cannot be considered equivalent to the capillary-based method. This inaccuracy seems to be moderately influenced by the infusion of vasopressor agents.

Recording of the full-field electroretinogram in minipigs.

PURPOSE: To test a simple electroretinographic protocol on a representative sample of minipigs. ANIMAL STUDIED: Minipig. PROCEDURES: Electroretinogram recordings were conducted on 162 healthy minipigs (81 males and 81 females) aged 4-6 months. After a 1.5-h light-adaptation period, the animals were anesthetized with general anesthesia. First, binocular full-field photopic electroretinogram recordings were conducted under photopic conditions. Subsequently, scotopic electroretinogram recordings were conducted during dark-adaptation periods every 4 min for a 20-min period. At the end of this period, the maximal combined rod-cone response was recorded by measuring the retinal response to a single high-intensity flash. We used sclerocorneal clip electrodes as active electrodes and needle electrodes as reference and ground electrodes. RESULTS: The a-wave and b-wave peak times and amplitudes have been measured and statistically analyzed. For each of the statistical comparisons, normality and homogeneity of variances were evaluated. No significant gender differences were observed, with the exception of a higher b-wave amplitude for the photopic ERG recordings observed in females when compared to males (48.14 ± 12.909 µV vs. 42.88 ± 10.666 µV; P = 0.005). The process of dark adaptation was evaluated, and the maximal combined rod-cone response was measured (a- and b-waves amplitude and peak time). CONCLUSIONS: We conducted photopic and scotopic electroretinogram recordings from a protocol based on light adaptation followed by dark adaptation using sclerocorneal clip electrodes, which allows quick assembly and examination.

Regulators of cerebellar granule cell development act through specific signaling pathways.

The proper development of the central nervous system depends upon a finely tuned balance between cell proliferation and programmed cell death (PCD). Although PCD was initially believed to depend solely on the inability of certain neurons to obtain access to a limited supply of trophic factors, it has become apparent that the local production of death signals is also critical. In this Viewpoint, we discuss several pathways implicated in the survival of cerebellar granule cells- both pathways that protect from apoptosis and pathways that promote apoptosis-and describe how these disparate pathways converge on the final common mediators of PCD. Information on other important pathways implicated in granule cell survival may be found in the Connections Maps.