Explore the vast range of titles available.

Background The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection. Methods For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the “procalcitonin-guided” group) or the current standard of care (the “controls”). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay. Results Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p  = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient −1.19 days, 95% CI −1.73 to −0.66; p  <  0.001). Conclusion Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.

Background Use of serum procalcitonin (PCT), an inflammatory biomarker for bacterial infections, has shown promising results for early stopping antibiotic treatment among patients with respiratory infections and sepsis. There is need for additional data regarding effectiveness and safety of this concept among patients with cancer. Methods Individual data of patients with a documented diagnosis of cancer and proven or suspected respiratory infection and/or sepsis were extracted from previous trials where adult patients were randomized to receive antibiotic treatment based on a PCT protocol or usual care (control group). The primary efficacy and safety endpoints were antibiotic exposure and 28-day all-cause mortality. Results This individual-patient data meta-analysis included 777 patients with a diagnosis of cancer from 15 randomized-controlled trials. Regarding efficacy, there was a 18% reduction in antibiotic exposure in patients randomized to PCT-guided care compared to usual care ([days] 8.2 ± 6.6 vs. 9.8 ± 7.3; adjusted difference, − 1.77 [95% CI, − 2.74 to − 0.80]; p  < 0.001). Regarding safety, there were 72 deaths in 379 patients in the PCT-guided group (19.0%) compared to 91 deaths in 398 participants in the usual care group (22.9%) resulting in an adjusted OR of 0.78 (95% CI, 0.60 to 1.02). A subgroup analysis showed a significant reduction in mortality in patients younger than 70 years (adjusted OR, 0.58 [95% CI, 0.40 to 0.86]). Conclusion Result of this individual patient meta-analysis from 15 previous trials suggests that among patients with cancer and suspected or proven respiratory infection or sepsis, use of PCT to guide antibiotic treatment decisions results in reduced antibiotic exposure with a possible reduction in mortality, particularly among younger patients.

In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (pinteractions>0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI −2·71 to −2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. National Institute for Health Research.

Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of PCT-guided antibiotic management in patients with bacteremia. We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days. Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days [95% confidence interval [CI], -4.88 to -.84]; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections. This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.

Background The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients. Methods A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics. Results One hundred thirty patients were included in the CRP ( n  = 64) and control ( n  = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0–8.8) days in the CRP and 7.0 (7.0–11.3) days in the control ( p  = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode ( p  = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0–8.0) days for the CRP and 7.0 (7.0–10.0) days for the control ( p  = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days. Conclusions Daily monitoring of CRP levels may allow early interruption of antibiotic therapy in a higher proportion of patients, without an effect on total antibiotic consumption. The clinical and microbiological relevance of this finding remains to be demonstrated. Trial registry ClinicalTrials.gov Identifier: NCT02987790 . Registered 09 December 2016.

Mutations in Foxn1 and Prkdc genes lead to nude and severe combined immunodeficiency (scid) phenotypes, respectively. Besides being immunodeficient, previous reports have shown that nude mice have lower gonadotropins and testosterone levels, while scid mice present increased pachytene spermatocyte (PS) apoptosis. Therefore, these specific features make them important experimental models for understanding Foxn1 and Prkdc roles in reproduction. Hence, we conducted an investigation of the testicular function in nude and scid BALB/c adult male mice and significant differences were observed, especially in Leydig cell (LC) parameters. Although the differences were more pronounced in nude mice, both immunodeficient strains presented a larger number of LC, whereas its cellular volume was smaller in comparison to the wild type. Besides these alterations in LC, we also observed differences in androgen receptor and steroidogenic enzyme expression in nude and scid mice, suggesting the importance of Foxn1 and Prkdc genes in androgen synthesis. Specifically in scid mice, we found a smaller meiotic index, which represents the number of round spermatids per PS, indicating a greater cell loss during meiosis, as previously described in the literature. In addition and for the first time, Foxn1 was identified in the testis, being expressed in LC, whereas DNA-PKc (the protein produced by Prkdc ) was observed in LC and Sertoli cells. Taken together, our results show that the changes in LC composition added to the higher expression of steroidogenesis-related genes in nude mice and imply that Foxn1 transcription factor may be associated to androgen production regulation, while Prkdc expression is also important for the meiotic process.

Background: Thermovinification is a non-conventional winemaking practice that replaces the traditional method of grape maceration. Methods: This study evaluated the influence of thermovinification temperature on the quality of Syrah wines. The treatments included traditional winemaking with 7 days of maceration during alcoholic fermentation at 23 °C (TW—control); and thermovinification for 2 h at 55 °C (TV55), 65 °C (TV65), and 75 °C (TV75). The red wines were made through microvinification (10-litre glass). Phenolic compounds (n = 26) were quantified by high-performance liquid chromatography and a colour analysis using the CIELab/CIEL*C*h systems and a sensory analysis was conducted to evaluate the acceptability of the thermovinified wine. Results: The results indicate that thermovinification increased the content of bioactive compounds and intensified the colour of the wine, reducing L* and a*. However, the content of phenolic acids decreased, except for trans-caftaric acid, which was approximately 50 times higher. A higher temperature of thermovinification (75 °C) promoted the degradation of all anthocyanins. Among flavonols, kaempferol-3-O-glucoside, quercetin-3-β-D-glucoside, and isorhamnetin-3-O-glucoside were higher in TV65 and TV75 wines. Greater amounts of stilbenes were quantified in TV65. Among the flavan-3-ols, TV75 stood out, especially for (+)-catechin, (−)-epicatechin, procyanidin A2, and procyanidin B1. Conclusions: The thermovinification at 65 °C is optimal for minimising anthocyanin degradation and improving Syrah wine quality.

Hemophagocytic syndrome (HPS) represents a critical and often overlooked hyperinflammatory condition that can lead to rapid multi-organ failure and high mortality rates, particularly in adults. This article presents a compelling case study of a 45-year-old male with a complex clinical presentation, highlighting the diagnostic challenges posed by HPS, including its nonspecific symptoms and the necessity for a high index of suspicion. We underscore the paramount importance of early recognition, thorough differential diagnosis, and prompt initiation of treatment to improve patient outcomes. This case not only illustrates the intricacies of diagnosing HPS but also advocates for increased awareness among healthcare providers to mitigate the risks associated with this life-threatening syndrome.

Objectives: The central nervous system plays a fundamental role in chronic pain; however, its behavior in this condition remains unclear, especially when associated with interventions such as kinesiotaping (KT). This study aimed to analyze the effects of KT on the somatosensory cortex of women with chronic low back pain. Methods: This case series involved 15 women with chronic low back pain. Participants underwent a progressive-tension KT protocol for 8 weeks, and electroencephalogram recordings were performed in two positions, namely sitting and standing while load bearing (10% of body weight), in the first and eighth weeks. The following instruments were employed: Oswestry lumbar disability index, fear avoidance beliefs questionnaire, and the numerical pain intensity scale. Results: All participants showed significant pain improvement and a reduction in Oswestry disability index scores from moderate to minimal. Additionally, activity in the alpha band within the somatosensory cortex and insula (central region—represented by the electrode Cz) decreased. This was confirmed by reduced power spectral density, indicating diminished cortical activity in these regions. Conclusions: KT positively affects women with chronic low back pain, providing pain reduction and improved functional capacity, as indicated by the fear avoidance beliefs questionnaire and numerical pain intensity scale. Moreover, KT reduces cortical activity in the somatosensory cortex, which is related to the progression of painful sensations, described above after the intervention.

Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival. Despite having high GLS levels, we verified that several breast cancer cells (including TN cells) express endogenous GLS2, defying its role as a bona fide tumor suppressor. Moreover, ectopic GLS2 expression rescued cell proliferation, TCA anaplerosis, redox balance, and mitochondrial function after GLS inhibition by the small molecule currently in clinical trials CB-839 or GLS knockdown of GLS-dependent cell lines. In several cell lines, GLS2 knockdown decreased cell proliferation and glutamine-linked metabolic phenotypes. Strikingly, long-term treatment of TN cells with another GLS-exclusive inhibitor bis-2′-(5-phenylacetamide-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) selected for a drug-resistant population with increased endogenous GLS2 and restored proliferative capacity. GLS2 was linked to enhanced in vitro cell migration and invasion, mesenchymal markers (through the ERK-ZEB1-vimentin axis under certain conditions) and in vivo lung metastasis. Of concern, GLS2 amplification or overexpression is linked to an overall, disease-free and distant metastasis-free worse survival prognosis in breast cancer. Altogether, these data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer and provide an initial framework for exploring GLS2 as a novel therapeutic target.