Prolonged Infusion of β-Lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-After Study

Septic shock substantially alters the pharmacokinetic properties of β-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of β-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with β-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017–2020 received PI of β-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n = 119/290 vs. IB: 54.8%, n = 68/114; p = 0.0097) and day 90 (PI: 47.9%, n = 139/290 vs. IB: 62.9%, n = 78/124; p = 0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (−10%, p = 0.14). PI was further associated with a reduction in the duration of invasive ventilation and a stronger decrease in SOFA scores within a 14d-observation period. PI of β-lactams was associated with a significant reduction of mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

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Prolonged Infusion of ß-lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-after Study

10.20944/preprints202105.0668.v1 ◽

2021 ◽

Author(s):

Daniel Christoph Richter ◽

Maximilian Dietrich ◽

Lazar Detelinov Lalev ◽

Felix C.F. Schmitt ◽

Mascha Onida Fiedler ◽

...

Keyword(s):

Septic Shock ◽

Invasive Ventilation ◽

Beta Lactam ◽

Unbound Fraction ◽

Improve Patient Survival ◽

Beneficial Effects ◽

Beta Lactam Antibiotics ◽

Pharmacokinetic Properties ◽

Before And After ◽

Improve Patient

Septic shock substantially alters the pharmacokinetic properties of ß-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of ß-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with ß-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017-2020 received PI of ß-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n=119/290 vs. IB: 54.8%, n=68/114; p=0.0097) and day 90 (PI: 47.9%, n=139/290 vs. IB: 62.9%, n=78/124; p=0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (-10%). PI further reduced duration of invasive ventilation. PI of β-lactam antibiotics led to a stronger decrease in SOFA scores within a 14d-observation period. PI of ß-lactams significantly reduces mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

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Effects of High Volume Haemodiafiltration on Inflammatory Response Profile and Microcirculation in Patients with Septic Shock

BioMed Research International ◽

10.1155/2015/125615 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Kadri Tamme ◽

Liivi Maddison ◽

Rein Kruusat ◽

Hans-Erik Ehrlich ◽

Mirjam Viirelaid ◽

...

Keyword(s):

Septic Shock ◽

Kidney Injury ◽

High Volume ◽

Target Range ◽

Sublingual Microcirculation ◽

Cytokine Levels ◽

Before And After ◽

Single Centre Study ◽

The Mean ◽

Improve Patient

Background. High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients.Methods. Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients.Results. The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70–80 mmHg decreased from 0.40 (0.43) μg/kg/min to 0.28 (0.33) μg/kg/min (p= 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF.Conclusions. The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved.

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Changes in Platelet Aggregability after Ovariectomy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657029 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1332-1339 ◽

Cited By ~ 7

Author(s):

Hiroh Yamazaki ◽

Takeshi Motomiya ◽

Minoru Sonoda ◽

Noboru Miyagawa

Keyword(s):

Platelet Count ◽

Platelet Activation ◽

Ovarian Hormones ◽

Control Group ◽

Platelet Aggregability ◽

Appearance Rate ◽

Before And After ◽

The Difference ◽

Induced Aggregation ◽

Observation Period

SummaryChanges in platelets in 48 patients with uterine myoma before and after hysterectomy with and without ovariectomy were examined. Bilateral ovariectomy in 25 cases (ovariec-tomized group) and unilateral or non-ovariectomy in 23 cases (control group) were performed at the hysterectomy. Platelet count and an appearance rate of secondary aggregation decreased at one day after and increased at one week after the operation, similarly in both the ovariectomized and the control group. The appearance rate of secondary aggregation was reflected in an intensity of aggregation at 5 min after the addition of reagent to PRP. At one month after the operation, the appearance rate of secondary aggregation induced by 3 μM ADP showed a statistically significant decrease in comparison with the preoperation value (P <0.05) and the enhancement of 5-min aggregation was still observed in the control group, while ceased in the ovariectomized group. The difference between the two groups was significant (P < 0.05). There was almost no change in the speed and intensity of primary and secondary aggregation during the observation period. No significant differences in collagen-induced aggregation were noted between the two groups. The results suggest that ovarian hormones, mainly estrogen, facilitate platelet activation which is mediated by the so-called secondary aggregation.

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Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽

10.3390/cells10010185 ◽

2021 ◽

Vol 10 (1) ◽

pp. 185

Author(s):

Clara Depommier ◽

Rosa Maria Vitale ◽

Fabio Arturo Iannotti ◽

Cristoforo Silvestri ◽

Nicolas Flamand ◽

...

Keyword(s):

Metabolic Syndrome ◽

Univariate Analysis ◽

Metabolic Effects ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Akkermansia Muciniphila ◽

Beneficial Effects ◽

Daily Ingestion ◽

Before And After ◽

Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

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Reduction in mobility and COVID-19 transmission

Nature Communications ◽

10.1038/s41467-021-21358-2 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 7

Author(s):

Pierre Nouvellet ◽

Sangeeta Bhatia ◽

Anne Cori ◽

Kylie E. C. Ainslie ◽

Marc Baguelin ◽

...

Keyword(s):

Predictive Ability ◽

Control Measures ◽

Social Distancing ◽

Beneficial Effects ◽

Mobility Data ◽

Strict Control ◽

Before And After ◽

Proxy Measure ◽

Lower Transmission ◽

The Relationship

AbstractIn response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts. Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world. Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27–77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49–91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12–48%]) post-relaxation. In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

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Primary Malignant Melanoma of the Vagina without Metastasis: A Rare Case and Review of Literature

Asian Journal of Oncology ◽

10.1055/s-0040-1722110 ◽

2020 ◽

Author(s):

Wilson Bizimana ◽

Gloria Akimana ◽

Arthur Semedo Insumbo ◽

Hounayda Jerguigue ◽

Rachida Latib ◽

...

Keyword(s):

Malignant Melanoma ◽

Patient Survival ◽

Rare Condition ◽

Primary Malignant Melanoma ◽

Imaging Features ◽

Review Of Literature ◽

Pelvic Magnetic Resonance Imaging ◽

Improve Patient Survival ◽

Appropriate Treatment ◽

Improve Patient

AbstractMalignant melanoma of vagina is a rare condition. Its histogenesis has been debated and the positive diagnosis is based on immunohistochemistry. Pelvic magnetic resonance imaging remains the gold standard for assessing locoregional extension status and post-treatment surveillance of melanoma of vagina. The observation concerned a 53-year-old woman with no specific history who presented a primary malignant melanoma of vagina without secondary locations. To date, the case is the second one reported in the literature. Early diagnosis of the malignant melanoma of vagina may improve patient survival because late diagnoses are punctuated by poor prognosis. We have presented epidemiological with etiopathogenic characteristics and described all imaging features to stage the tumor and to conduct the appropriate treatment.

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Brain Training and Sulforaphane Intake Interventions Separately Improve Cognitive Performance in Healthy Older Adults, Whereas a Combination of These Interventions Does Not Have More Beneficial Effects: Evidence from a Randomized Controlled Trial

Nutrients ◽

10.3390/nu13020352 ◽

2021 ◽

Vol 13 (2) ◽

pp. 352

Author(s):

Rui Nouchi ◽

Qingqiang Hu ◽

Toshiki Saito ◽

Natasha Yuriko dos Santos Kawata ◽

Haruka Nouchi ◽

...

Keyword(s):

Older Adults ◽

Active Control ◽

Processing Speed ◽

Cognitive Functions ◽

Controlled Trial ◽

Memory Performance ◽

Brain Training ◽

Beneficial Effects ◽

Before And After ◽

Double Blinded

Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older adults. Methods: In a 12-week double-blinded randomized control trial, 144 older adults were randomly assigned to one of four groups: BT with SFN (BT-S), BT with placebo (BT-P), active control game (AT) with SFN (AT-S), and active control game with placebo (AT-P). We used Brain Age in BT and Tetris in AT. Participants were asked to play BT or AT for 15 min a day for 12 weeks while taking a supplement (SFN or placebo). We measured several cognitive functions before and after the intervention period. Results: The BT (BT-S and BT-P) groups showed more improvement in processing speed than the active control groups (AT-S and AT-P). The SFN intake (BT-S and AT-S) groups recorded significant improvements in processing speed and working memory performance unlike the placebo intake groups (BT-P and AT-P). However, we did not find any evidence of the combined intervention’s beneficial effects on cognition. Discussion: We discussed a mechanism to improve cognitive functions in the BT and SFN alone interventions.

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Hemodynamic Responses in Lower Limb Lymphedema Patients Undergoing Physical Therapy

Biology ◽

10.3390/biology10070642 ◽

2021 ◽

Vol 10 (7) ◽

pp. 642

Author(s):

Bianca Brix ◽

Olivier White ◽

Christian Ure ◽

Gert Apich ◽

Paul Simon ◽

...

Keyword(s):

Physical Therapy ◽

Lymphatic System ◽

Orthostatic Intolerance ◽

Hemodynamic Responses ◽

Stand Test ◽

Beneficial Effects ◽

Sit To Stand ◽

Complete Decongestive Therapy ◽

Before And After ◽

Baseline Values

Background: Lymphedema arises due to a malfunction of the lymphatic system, leading to extensive tissue swelling. Complete decongestive therapy (CDT), which is a physical therapy lasting for 3 weeks and includes manual lymphatic drainages (MLD), leads to fluid mobilization and increases in plasma volume. Here, we investigated hemodynamic responses induced by these fluid shifts due to CDT and MLD. Methods: Hemodynamic parameters were assessed continuously during a sit-to-stand test (5 min baseline, 5 min of standing, and 5 min of recovery). This intervention was repeated on days 1, 2, 7, 14, and 21 of CDT, before and after MLD. Volume regulatory hormones were assessed in plasma samples. Results: A total number of 13 patients took part in this investigation. Resting diastolic blood pressure significantly decreased over three weeks of CDT (p = 0.048). No changes in baseline values were shown due to MLD. However, MLD led to a significant decrease in heart rate during orthostatic loading over all epochs on therapy day 14, as well as day 21. Volume regulatory hormones did not show changes over lymphedema therapy. Conclusion: We did not observe any signs of orthostatic hypotension at rest, as well as during to CDT, indicating that lymphedema patients do not display an elevated risk of orthostatic intolerance. Although baseline hemodynamics were not affected, MLD has shown to have potential beneficial effects on hemodynamic responses to a sit-to-stand test in patients undergoing lymphedema therapy.

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Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00543.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R811-R818 ◽

Cited By ~ 31

Author(s):

Chao-Hung Wang ◽

Wen-Jin Cherng ◽

Ning-I Yang ◽

Chia-Ming Hsu ◽

Chi-Hsiao Yeh ◽

...

Keyword(s):

Critical Role ◽

Serum Levels ◽

Blood Levels ◽

Short Term ◽

Endothelial Progenitor ◽

Beneficial Effects ◽

Dpp Iv ◽

Before And After ◽

Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

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The Usefulness of Impedance Cardiography for Predicting Beneficial Effects of Cardiac Rehabilitation in Patients with Heart Failure

BioMed Research International ◽

10.1155/2013/595369 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Grzegorz Gielerak ◽

Paweł Krzesiński ◽

Ewa Piotrowicz ◽

Ryszard Piotrowicz

Keyword(s):

Heart Failure ◽

Cardiac Rehabilitation ◽

Exercise Tolerance ◽

Impedance Cardiography ◽

The Other ◽

Pronounced Increase ◽

Fluid Content ◽

Beneficial Effects ◽

Patients With Heart Failure ◽

Before And After

Aim. Cardiac rehabilitation (CR) is an important part of heart failure (HF) treatment. The aim of this paper was to evaluate if thoracic fluid content (TFC) measured by impedance cardiography (ICG) is a useful parameter for predicting the outcome of CR.Methods. Fifty HF patients underwent clinical and noninvasive haemodynamic (TFC) assessments before and after 8-week CR.Results. As a result of CR, the patients’ exercise tolerance improved, especially in terms of peak VO2(18.7 versus 20.8 mL × kg−1× min−1;P=0.025). TFC was found to identify patients with significantly improved peak VO2after CR. “High TFC” patients (TFC > 27.0 kOhm−1), compared to those of “low TFC” (TFC < 27.0 kOhm−1), were found to have more pronounced increase in peak VO2(1.3 versus 3.1 mL × kg−1× min−1;P=0.011) and decrease in TFC (4.0 versus 0.7 kOhm−1;P<0.00001). On the other hand, the patients with improved peak VO2(n=32) differed from those with no peak VO2improvement in terms of higher baseline TFC values (28.4 versus 25.3 kOhm−1;P=0.039) and its significant decrease after CR (2.7 versus 0.2 kOhm−1;P=0.012).Conclusions. TFC can be a useful parameter for predicting beneficial effects of CR worth including in the process of patients’ qualification for CR.

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