Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND & AIMS: Several systematic reviews and meta-analyses of randomized controlled trials concluded that probiotics administration in critically ill patients was safe and associated with reduced rates of ventilator-associated pneumonia and diarrhea. However, a recent large multicenter trial found probiotics administration, compared to placebo, was not efficacious and increased adverse events. An updated meta-analysis that controls for type-1 and -2 errors using trial sequential analysis, with a detailed account of adverse events associated with probiotic administration, is warranted to confirm the safety and efficacy of probiotic use in critically ill patients. METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score). RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies). CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients. PROSPERO REGISTRATION: CRD42022302278.

IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients. DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients. DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes. DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C. CONCLUSIONS: IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

A Healthy Diet Is Not More Expensive than Less Healthy Options: Cost-Analysis of Different Dietary Patterns in Mexican Children and Adolescents.

Unhealthy diets are recognized as a major risk factor for many diseases. The decrease in costs of industrialized products, as well as the possible misinformation about a healthy diet, has led to new behaviors in the dietary patterns of the pediatric population. The costs of dietary patterns have not been estimated in our population, so the objective of this study was to determine the cost associated with dietary patterns in Mexican children and adolescents, hypothesizing that a healthy diet is not necessarily more economically expensive. This study analyzed data from a population-based cross-sectional study of healthy children and adolescents in Mexico City. Data were collected from a food frequency questionnaire and the meal cost of habitual food shopping. Eating patterns were obtained by using principal component analysis. A micro-costing technique was performed to obtain the direct costs of each pattern. When comparing the healthy pattern with the transition and non-healthy patterns, it was observed that there were no statistically significant differences between the dietary patterns (p = 0.8293). The cost of the healthy pattern only takes up 16.6% of the total biweekly income of a salaried Mexican. In this study, no differences were observed between the costs of a healthy and a less healthy diet.

Simulated GABA synaptic input and L-type calcium channels form functional microdomains in hypothalamic gonadotropin-releasing hormone neurons.

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons integrate the multiple internal and external cues that regulate sexual reproduction. In contrast to other neurons that exhibit extensive dendritic arbors, GnRH neurons usually have a single dendrite with relatively little branching. This largely precludes the integration strategy in which a single dendritic branch serves as a unit of integration. In the present study, we identify a gradient in L-type calcium channels in dendrites of mouse GnRH neurons and its interaction with GABAergic and glutamatergic inputs. Higher levels of L-type calcium channels are in somata/proximal dendrites (i.e., 0-26 µm) and distal dendrites (∼130 µm dendrite length), but intervening midlengths of dendrite (∼27-130 µm) have reduced L-type calcium channels. Using uncaging of GABA, there is a decreasing GABAergic influence along the dendrite and the impact of GABA(A) receptors is dependent on activation of L-type calcium channels. This results in amplification of proximal GABAergic signals and attenuation of distal dendritic signals. Most interestingly, the intervening dendritic regions create a filter through which only relatively high-amplitude, low-frequency GABAergic signaling to dendrites elicits action potentials. The findings of the present study suggest that GnRH dendrites adopt an integration strategy whereby segments of single nonbranching GnRH dendrites create functional microdomains and thus serve as units of integration.

[Usefulness of the Delphi method for reaching consensus in the allocation of deceased donor kidneys in six Mexican hospitals]. / Utilidad del método Delphi para la construcción de acuerdos en la asignación de riñones de donante fallecido en seis hospitales de México.

OBJECTIVE: To ascertain medical criteria and their priority in the allocation of deceased patient kidneys in pediatrics among members of Internal Transplant Committees of six hospitals. To assess if, by using the Delphi method, it is possible to reach consensus to reduce heterogeneity of criteria in the allocation of renal transplant organs among physicians ascribed to Nephrology and Surgery services in six hospital centers in Mexico. METHODOLOGY: A study was carried out by the Delphi method of independent experts panel, with three stages and two rounds. The method makes possible iteration and controlled feedback from experts to identify behaviors and trends with the synergy of the debate in a group. Kappa index was applied to assess results agreement. RESULTS: Results of first round show the criteria heterogeneity for the allocation of cadaveric origin organs within each hospital, and among hospitals compared to each other. With the results of the second round, consensus increased in four hospitals for the selection of both first and second recipient. Kappa coefficient shows the reliability of results. CONCLUSION: Our Country needs a point-score system to allocate deceased donor organs, ideally including HLA matching. Expecting that the Internal Transplant Committees throughout the Mexican territory may have available a useful tool as this, the Delphi method makes it possible to reach consensus in this task, in order to minimize subjectivity in the staff involved in the decision-making process.

Expanding the range of free calcium regulation in biological solutions.

Many biological systems use ethylene glycol bis (beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) to regulate the free calcium concentration ([Ca(2+)](free)) in the presence of physiological levels of free Mg(2+) ([Mg(2+)](free)). Frequently, it is necessary to work at [Ca(2+)](free) beyond EGTA's buffering capabilities. Therefore, we have developed methods to extend the buffering range by adding nitrilotriacetic acid (NTA) to solutions containing EGTA. This extension results from NTA having a lower K'(dCa) than EGTA. Such equilibria are solved by pCa Calculator, a computer program designed to aid in the study of Ca(2+)-dependent physiological processes while accounting for the effects of pH, temperature, and ionic strength. With multiple chelators and pH buffers from which to choose, pCa Calculator calculates the total concentration of each species required to achieve specified free concentrations of Ca(2+), ATP, and Mg(2+). The program is intuitive, user-friendly, and flexible enough to fix or vary the [Mg-ATP(2-)] and ionic strength. Moreover, it can account for increases in experimental volume from calcium addition. A comparative analysis is reported for testing solutions in the presence and absence of NTA by measuring the calcium binding affinity of fluorescent cardiac troponin C. These findings demonstrate that EGTA, when used in conjunction with NTA, improves and expands the regulation of free calcium in solution.

Narrow-band spectral measurements of EEG during emotional tasks.

The objective of this study was to discover how narrow-band spectral measurements express emotional behavior. Electroencephalographic narrowband absolute and relative spectral powers were calculated for every 1 Hz of frequency from the recordings of 40 healthy male university students during emotional tasks. Sentences evoking positive, negative, and neutral emotional states were used as stimuli. Repeated multivariate analyses of variance were computed with IQ as covariate. The results showed only a few significant relations between absolute power and emotion. Relative power reflected better the differences determined by emotional states. The frequencies between 7.6 and 9.5 Hz showed differences between emotional states over the entire scalp with increased power during neutral state. Interaction between emotional states and cerebral regions revealed that all cerebral areas had an important role, especially frontal, parietal, and temporal regions. Hemispheric differences showed less power in the left hemisphere during positive emotional state (joy of love) in the 8.6 to 9.5 Hz band and in the right hemisphere during negative emotional state (frustration) in the 17.6 to 18.5 Hz band. Significant interaction between states, hemispheres, and electrode positions was observed in the frequency range of 17.6 to 19.5 Hz. As none of our results covered the range of any broad band, we may conclude that narrow-band calculations are more adequate for the study of emotions, because their use reduces the danger that frequency-specific effects go undetected or cancel each other.

Anemia aplástica adquirida familiar / Familial acquired aplastic anemia

Una variedad poco frecuente de la anemia aplástica adquirida (AAA) es la forma familiar. Lo anterior se ejemplifica al considerar que de 200 casos con AAA atendidos en el servicio, sólo dos presentaron la característica de ser integrantes de una misma familia; éstos correspondieron a dos hermanos no gemelos, uno con AAA leve secundaria a derivados del benceno y que curó espontáneamente, y el otro con AAA grave relacionado con cloranfenicol y que falleció por hemorragia del sistema nervioso central. El estudio del sistema HLA mostró los mismos antígenos en ambos pacientes (A2, A28, B16, B40)