The Effect of Statins on Mortality in Septic Patients: a Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay. DATA SOURCES AND STUDY SELECTION: Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients. DATA EXTRACTION AND SYNTHESIS: Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found. CONCLUSIONS: Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic

Unoperated ovarian endometriomas and responsiveness to hyperstimulation

There is a growing consensus that ovarian reserve is reduced after surgical excision of ovarian endometriomas. However, it remains to be fully clarified whether this damage precedes or follows surgery. In order to further elucidate this aspect, we evaluated ovarian responsiveness to hyperstimulation in women selected for IVF with unilateral unoperated endometriomas. The main aim of this study was to compare the number of developing follicles in the affected ovary with that in the contralateral intact gonad as a control

Brewers' spent grain as substrates for production of cellulolytic and hemicellulolytic enzymes by different Aspergillus species

Brewers' spent grain (BSG) is the major by-product of the brewing industry, representing around 85% of the total by-products generated. It is a lignocellulosic material containing about 38% cellulose, 29% hemicellulose, chiefly arabinoxylans, and 13% lignin. The production of cellulolytic and hemicellulolytic enzymes using this material as substrate represent an eco-friendly strategy for the lignocellulosic biomass hydrolysis, generating fermentable sugars that can be converted into high- added value products, such as bioethanol, lactic acid, xylitol and others. Thus, this work aimed to evaluate the potential of cellulolytic and hemicellulolytic enzymes production by some Aspergillus species cultivated in BSG. Fungi were grown in minimum media, pH 6.5, with 1% BSG and inoculum was done with 107spores/mL, cultivated at 30°C, 120 rpm, for 5 days. Every 24 hours 2 mL of the samples were collected. The enzymatic activity was performed after the incubation of the crude extract with 1% Linear arabinan, Xylan from beechwood, Xyloglucan, Locust bean gum and CMC, at 50°C for 60 minutes and the reducing sugars were determined using dinitrosalicylic acid (DNS). Synthetic substrates (2 mM of PNP--L-arabinofuranoside, PNP--D-xylopyranoside, PNP--Dglucopyranoside and PNP--D-cellobioside) were also used at the same conditions. The extract from A. niveus showed the best arabinanase (0.284 U/mL) and -glucosidase (0.126 U/mL) activities after 48 and 96 hours of cultivation, respectively. On the other hand, the extract from A. brasiliensis presented the best activities of -L-arabinofuranosidase (0.129 U/mL), -xylosidase (0.265 U/mL) and xylanase (2.15 U/mL) when cultivated for 48 hours. After 72 hours, this fungus also showed the best activities for xyloglucanase (1.06 U/mL), mannanase (0.617 U/mL) and endoglucanase (0.254 U/mL). The extract produced by A. flavus presented the best cellobiohydrolase activity with 0.113 U/mL after 120 hours of cultivation. It is important to mention that A. awamori, A. clavatus and A. terreus also showed good levels of different enzymes produced but they were not the best producers. These data suggest the great potential of different cellulolytic and hemicellulolytic enzymes production using BSG as substrate, which represents an eco-friendly destination for the residues and can generate high-added value products with great biotechnological application.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Institutos Nacionais de Ciência e Tecnologia (INCT)Fundação para a Ciência e a Tecnologia (FCT)info:eu-repo/semantics/publishedVersio

Effect of Pulsed or Continuous Delivery of Salt on Sensory Perception Over Short Time Intervals

Salt in the human diet is a major risk factor for hypertension and many countries have set targets to reduce salt consumption. Technological solutions are being sought to lower the salt content of processed foods without altering their taste. In this study, the approach was to deliver salt solutions in pulses of different concentrations to determine whether a pulsed delivery profile affected sensory perception of salt. Nine different salt profiles were delivered by a Dynataste device and a trained panel assessed their saltiness using time–intensity and single-score sensory techniques. The profile duration (15 s) was designed to match eating conditions and the effects of intensity and duration of the pulses on sensory perception were investigated. Sensory results from the profiles delivered in either water or in a bouillon base were not statistically different. Maximum perceived salt intensities and the area under the time– intensity curves correlated well with the overall perceived saltiness intensity despite the stimulus being delivered as several pulses. The overall saltiness scores for profiles delivering the same overall amount of sodium were statistically not different from one another suggesting that, in this system, pulsed delivery did not enhance salt perception but the overall amount of salt delivered in each profile did affect sensory perception

Production of an enzymatic cocktail by Aspergillus awamori grown on corn straw with stirred tank bioreactor

Increased agroindustrial activity has led to the accumulation of large amounts of lignocellulosic material (LCM). LCM is nature's most abundant source of renewable carbon, representing a valuable industrial substrate with potential for many applications. Thus, the objective of this work was to screen for different holocellulases and to analyze the production of an Aspergillus awamori enzyme cocktail grown in corn straw (CS) using a stirred tank bioreactor. Screening was performed with A. clavatus, A. flavus, A. terreus, A. niveus, A. awamori and A. brasiliensis cultivated in minimal medium (MM), with 1% CS at 30 ºC or 37 ºC (for A. niveus), 120 rpm, for 5 days. Xylanase (XYN) and endoglucanase (EG) activities were evaluated by formation of reducing sugars using dinitrosalicylic acid (DNS). Cellobiohydrolase (CBH), -glucosidase (BGL) and -xylosidase (BXL) were determined by cleavage of PNP--D-cellobioside, PNP--D-glucopyranoside and PNP--D- xylopyranoside, respectively. After screening, a pre-inoculum was prepared with the best enzyme producer using a 500 mL MM flask and incubated at 30 °C, 120 rpm for 48 hours. The increase of enzyme production was performed in a Benchtop BioFlo 310 bioreactor, with 4.5 L of MM and 1% of CS, and was then inoculated the best enzyme producer. Cultivation was performed at 30 °C, pH 6.5, 275 rpm, air flow 2 v.v.m., for 5 days. During the screening, all fungi presented EG, CBH, BGL, XYN and BXL activities. However, A. awamori was chosen to continue the experiments because of its BXL activity which was 12.6 times higher than that produced by A. niveus. At the scale-up stage, XYN production (47.80 U/ mL) increased 4.1-fold compared to flask activity (11.52 U/mL). BXL also showed 1.6-times higher activity, as well as EG, CBH and BGL, which improved 2.3, 3.3 and 1.2 times their activities, respectively. It was concluded that the staggering of cocktail production improved the enzymatic activities and that corn straw is an excellent source of induction. Furthermore, this cocktail has the potential to be applied in the hydrolysis of different LCM due to the range of holocellulases present.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Institutos Nacionais de Ciência e Tecnologia (INCT)Fundação para a Ciência e a Tecnologia (FCT)info:eu-repo/semantics/publishedVersio

Sex-related mortality differences in young adult septic shock patients

Septic shock survival rate and host immune response are intimately interlaced. In the last years, biological and pre-clinical studies demonstrated sex-specific differences in the immune response to infection. In the hypothesis that survival rate is related to the hormonal framework, the aim of the present study was to observe sex-specific differences in 28-day mortality rate between women of childbearing potential and same-age men. This multicenter study was conducted in six Italian intensive care units (ICUs). We enrolled consecutive patients ≤ 55 years old admitted to the Intensive Care Unit from January 2011 to January 2020, who were diagnosed with septic shock at the time of ICU admission or during the ICU stay. We gathered baseline characteristics and outcomes. The primary outcome was 28-day mortality; secondary outcomes included ICU mortality, in-hospital mortality and length of stay in the ICU and in the hospital. Moreover, data from >55 years old patients were collected and analyzed. We enrolled 361 young patients with septic shock: 215 were males (60%) and 146 females (40%). While baseline and ICU characteristics were similar between the two groups, males had a higher 28-day mortality rate (39.5% vs. 29%, p = 0.035), ICU mortality rate (49% vs. 38%, p = 0.040) and hospital mortality rate (61% vs. 50%, p = 0.040) as compared to females. Findings were confirmed in patients with septic shock at ICU admission. Young adult females developed septic shock less frequently than young males, displaying a reduced mortality rate as compared to that of their same-age male counterpart. These findings may stimulate future research and therapies

Synergistic effect of static compliance and d-dimers to predict outcome of patients with covid-19-ards: A prospective multicenter study

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cutoffs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications.

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all