Vaginal Lactoferrin Modulates PGE 2

Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.). Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563

Multidrug Resistant Bacterial Co-Infections in Critically Ill Patients with COVID-19: A Review after Three Years of Pandemic

Secondary bacterial infections and co-infections frequently affect COVID-19 patients. However, bacterial coinfection rates increase in patients admitted in the Intensive Care Units (ICUs), and those diseases can be due to superinfections by Multidrug-Resistant (MDR) bacteria. Most of these infections are related to high-risk carbapenemase-producing clones and occasionally with resistance to new β-lactam-β-lactamase inhibitor combinations. This highlights the urgency to revise frequent and empiric prescription of broad-spectrum antibiotics in COVID-19 patients, with more attention to evidence-based studies and the need to maintain antimicrobial stewardship and infection control programs in pandemic crises. Additionally, the SARS-CoV-2 pandemic highlighted the challenge that an emerging pathogen provides in adapting prevention measures regarding both the risk of exposure to caregivers and the need to maintain quality of care

Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib

Background/aim: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. Patients and methods: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. Results: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. Conclusion: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib

Effects of pre-harvest techniques in the control of berry ripening in grapevine cv. Sauvignon blanc

Due to a variety of reasons (changing climatic conditions, higher photosynthetic efficiency of newly established vineyards, yield restriction imposed by production protocols), there is currently a tendency towards early ripening in grapevines, combined with the production of berries characterized by high sugar content. This tendency conflicts with the general market demand for wines (mostly white wines) with low alcohol level and characterised by a fresh, easy-to-drink taste. We tested two different techniques applied to the canopy (defoliation and the use of an antitranspirant product) with the aim of delaying the ripening process and improving the berry quality of the white cultivar Sauvignon blanc. The defoliation performed at veraison allowed postponement of the ripening process by about 5 days as compared to undefoliated vines, without altering the sugar/acid ratio of the berries. The antitranspirant product delayed ripening by 10 to 15 days. Brix was reduced by 1.5-2.5 degrees in the 2 considered seasons, whereas the effect on acidity was contradicting and needs further research for a full understanding of the mechanisms involved in the process

Myocardial dysfunction and abnormal left ventricular exercise response in autonomic diabetic patients

In diabetic patients, the pathophysiologic mechanisms of exercise-induced left ventricular (LV) dysfunction remain controversial. In this study, the role of myocardial contractility recruitment in determining an abnormal LV response to isometric or dynamic exercise has been investigated in 14 diabetic patients with autonomic dysfunction. Ischemic heart disease was excluded by the absence of LV wall motion abnormalities induced by isotonic and isometric exercise and by coronary angiography. Left ventricular and myocardial function were studied at rest, and during isometric and isotonic exercise, by two-dimensional echocardiography; moreover, recruitment of an inotropic reserve was assessed by postextrasystolic potentiation at rest and at peak handgrip. An abnormal response of LV ejection fraction to isometric (9/14) or to dynamic (8/14) exercise was frequent in study patients. In these patients, baseline myocardial contractility was normal, and the significant increase in ejection fraction by postextrasystolic potentiation indicated a normal contractile reserve (65 +/- 7% vs. 74 +/- 6%, p = 0.001). Nevertheless, the downward displacement of LV ejection fraction-systolic wall stress relationships during exercise suggests an inadequate increase in myocardial contractility. However, the abnormal ejection fraction at peak handgrip was completely reversed by postextrasystolic potentiation (67 +/- 6% vs. 58.1 +/- 10%, p = 0.008), a potent inotropic stimulation independent of the integrity of adrenergic cardiac receptors. A defective inotropic recruitment, despite the presence of a normal LV contractile reserve, plays an important role in deexercise LV dysfunction in diabetic patients with autonomic neuropathy

Expiratory flow limitation in intensive care: prevalence and risk factors

Expiratory flow limitation (EFL) is characterised by a markedly reduced expiratory flow insensitive to the expiratory driving pressure. The presence of EFL can influence the respiratory and cardiovascular function and damage the small airways; its occurrence has been demonstrated in different diseases, such as COPD, asthma, obesity, cardiac failure, ARDS, and cystic fibrosis. Our aim was to evaluate the prevalence of EFL in patients requiring mechanical ventilation for acute respiratory failure and to determine the main clinical characteristics, the risk factors and clinical outcome associated with the presence of EFL

Inspiratory pressure waveform influences time to failure, respiratory muscle fatigue, and metabolism during resistive breathing

Abstract Increased ventilatory work beyond working capacity of the respiratory muscles can induce fatigue, resulting in limited respiratory muscle endurance (Tlim). Previous resistive breathing investigations all applied square wave inspiratory pressure as fatigue‐inducing pattern. Spontaneous breathing pressure pattern more closely approximate a triangle waveform. This study aimed at comparing Tlim, maximal inspiratory pressure (PImax), and metabolism between square and triangle wave breathing. Eight healthy subjects (Wei = 76 ± 10 kg, H = 181 ± 7.9 cm, age = 33.5 ± 4.8 years, sex [F/M] = 1/7) completed the study, comprising two randomized matched load resistive breathing trials with square and triangle wave inspiratory pressure waveform. Tlim decreased with a mean difference of 8 ± 7.2 min (p = 0.01) between square and triangle wave breathing. PImax was reduced following square wave (p = 0.04) but not for triangle wave breathing (p = 0.88). Higher VO2 was observed in the beginning and end for the triangle wave breathing compared with the square wave breathing (p = 0.036 and p = 0.048). Despite higher metabolism, Tlim was significantly longer in triangle wave breathing compared with square wave breathing, showing that the pressure waveform has an impact on the function and endurance of the respiratory muscles

Frailty trajectories in ICU survivors: A comparison between the clinical frailty scale and the Tilburg frailty Indicator and association with 1 year mortality

Purpose: To test the agreement of the Clinical Frailty Scale (CFS) and the Tilburg Frailty Indicator (TFI), their association with 3, 6&nbsp;months and 1-year mortality and the trajectory of frailty in a mixed population of ICU survivors. Material and methods: This is a prospective, multicenter, longitudinal study on ICU survivors ≥18&nbsp;years old with an ICU stay &gt;72&nbsp;h. For each patient, sociodemographic and clinical data were collected. Frailty was assessed during ICU stay and at 3, 6, 12&nbsp;months after ICU discharge, through both CFS and TFI. Results: 124 patients with a mean age of 66&nbsp;years old were enrolled. The baseline prevalence of frailty was 15.3% by CFS and 44.4% by TFI. Baseline CFS and TFI correlated but showed low agreement (Cohen's K&nbsp;=&nbsp;0.23, p&nbsp;&lt;&nbsp;0.001). Baseline CFS score, but not TFI, was significantly associated to 1&nbsp;year mortality. Moreover, CFS score during the follow-up was independently associated 1-year mortality (OR&nbsp;=&nbsp;1.43; 95% CI: 1.18-1.73). Conclusions: CFS and TFI identify different populations of frail ICU survivors. Frail patients before ICU according to CFS have a significantly higher mortality after ICU discharge. The CFS during follow-up is an independent negative prognostic factor of long-term mortality in the ICU population

Transparent decision support for mechanical ventilation using visualization of clinical preferences

BACKGROUND: Systems aiding in selecting the correct settings for mechanical ventilation should visualize patient information at an appropriate level of complexity, so as to reduce information overload and to make reasoning behind advice transparent. Metaphor graphics have been applied to this effect, but these have largely been used to display diagnostic and physiologic information, rather than the clinical decision at hand. This paper describes how the conflicting goals of mechanical ventilation can be visualized and applied in making decisions. Data from previous studies are analyzed to assess whether visual patterns exist which may be of use to the clinical decision maker. MATERIALS AND METHODS: The structure and screen visualizations of a commercial clinical decision support system (CDSS) are described, including the visualization of the conflicting goals of mechanical ventilation represented as a hexagon. Retrospective analysis is performed on 95 patients from 2 previous clinical studies applying the CDSS, to identify repeated patterns of hexagon symbols. RESULTS: Visual patterns were identified describing optimal ventilation, over and under ventilation and pressure support, and over oxygenation, with these patterns identified for both control and support modes of mechanical ventilation. Numerous clinical examples are presented for these patterns illustrating their potential interpretation at the bedside. CONCLUSIONS: Visual patterns can be identified which describe the trade-offs required in mechanical ventilation. These may have potential to reduce information overload and help in simple and rapid identification of sub-optimal settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12938-021-00974-5