Use of ECMO in Sepsis and Septic Shock

The use of extracorporeal membrane oxygenation (ECMO) has always been controversial in the past. Evidence was mainly build up in neonates and much controversy remained in adults. The main adult indications were mechanical support (e.g., in cardiogenic shock) or respiratory support (e.g., in the field of acute respiratory distress syndrome (ARDS)). Sepsis was historically often considered as a contraindication. As a consequence of several worldwide flu outbreaks, the use of ECMO in infectious diseases increased. Besides in these viral infections, there was also growing interest for its use in bacterial septicemia, although often as escape therapy. In the recent years, other techniques gained increasing interest like for example, immunoadsorption, implemented in dialysis or ECMO circuits. In this chapter, we resume the available literature on the use of ECMO in septic shock including the use of immunoadsorption techniques

Altering the sex pheromone cyclo(L-Pro-L-Pro) of the diatom Seminavis robusta towards a chemical probe

As a major group of algae, diatoms are responsible for a substantial part of the primary production on the planet. Pennate diatoms have a predominantly benthic lifestyle and are the most species-rich diatom group, with members of the raphid clades being motile and generally having heterothallic sexual reproduction. It was recently shown that the model species Seminavis robusta uses multiple sexual cues during mating, including cyclo(l-Pro-l-Pro) as an attraction pheromone. Elaboration of the pheromone-detection system is a key aspect in elucidating pennate diatom life-cycle regulation that could yield novel fundamental insights into diatom speciation. This study reports the synthesis and bio-evaluation of seven novel pheromone analogs containing small structural alterations to the cyclo(l-Pro-l-Pro) pheromone. Toxicity, attraction, and interference assays were applied to assess their potential activity as a pheromone. Most of our analogs show a moderate-to-good bioactivity and low-to-no phytotoxicity. The pheromone activity of azide- and diazirine-containing analogs was unaffected and induced a similar mating behavior as the natural pheromone. These results demonstrate that the introduction of confined structural modifications can be used to develop a chemical probe based on the diazirine- and/or azide-containing analogs to study the pheromone-detection system of S. robusta

Mating type specific transcriptomic response to sex inducing pheromone in the pennate diatom Seminavis robusta

Sexual reproduction is a fundamental phase in the life cycle of most diatoms. Despite its role as a source of genetic variation, it is rarely reported in natural circumstances and its molecular foundations remain largely unknown. Here, we integrate independent transcriptomic datasets to prioritize genes responding to sex inducing pheromones (SIPs) in the pennate diatomSeminavis robusta. We observe marked gene expression changes associated with SIP treatment in both mating types, including an inhibition of S phase progression, chloroplast division, mitosis, and cell wall formation. Meanwhile, meiotic genes are upregulated in response to SIP, including a sexually induced diatom specific cyclin. Our data further suggest an important role for reactive oxygen species, energy metabolism, and cGMP signaling during the early stages of sexual reproduction. In addition, we identify several genes with a mating type specific response to SIP, and link their expression pattern with physiological specialization, such as the production of the attraction pheromone diproline in mating type - (MT-) and mate-searching behavior in mating type + (MT+). Combined, our results provide a model for early sexual reproduction in pennate diatoms and significantly expand the suite of target genes to detect sexual reproduction events in natural diatom populations

Target-Controlled Infusion of Cefepime in Critically Ill Patients:single center experience

Attainment of appropriate pharmacokinetic-pharmacodynamic (PK-PD) targets for antimicrobial treatment is challenging in critically ill patients, particularly for cefepime, which exhibits a relative narrow therapeutic-toxic window compared to other beta-lactam antibiotics. Target-controlled infusion (TCI) systems, which deliver drugs to achieve specific target drug concentrations, have successfully been implemented for improved dosing of sedatives and analgesics in anesthesia. We conducted a clinical trial in an intensive care unit (ICU) to investigate the performance of TCI for adequate target attainment of cefepime. Twenty-one patients treated with cefepime according to the standard of care were included. Cefepime was administered through continuous infusion using TCI for a median duration of 4.5 days. TCI was based on a previously developed population PK model incorporating the estimated creatinine clearance based on the Cockcroft-Gault formula as the input variable to calculate cefepime clearance. A cefepime blood concentration of 16 mg/liter was targeted. To evaluate the measured versus predicted plasma concentrations, blood samples were taken (median of 10 samples per patient), and total cefepime concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. The performance of the TCI system was evaluated using Varvel criteria. Half (50.3%) of the measured cefepime concentrations were within +/- 30% around the target value of 16 mg liter(-1). The wobble was 11.4%, the median performance error (MdPE) was 21.1%, the median absolute performance error (MdAPE) was 32.0%, and the divergence was -3.72% h(-1). Based on these results, we conclude that TCI is useful for dose optimization of cefepime in ICU patients

Distinctive growth and transcriptional changes of the diatom Seminavis robusta in response to quorum sensing related compounds

In aquatic habitats, diatoms are frequently found in association with Proteobacteria, many members of which employ cell-to-cell communication via N-acyl homoserine lactones (AHLs). It has been suggested that diatoms could distinguish between beneficial and algicidal bacteria in their surroundings by sensing AHLs. Although some microalgae can interfere with AHL signaling, e.g., by releasing AHL mimics or degrading them, molecular responses to AHLs in microalgae are still unclear. Therefore, we tested the effects of short-chained AHLs, i.e., N-hexanoyl homoserine lactone (C6-HSL), N-3-hydroxyhexanoyl homoserine lactone (OH-C6-HSL), and N-3-oxohexanoyl homoserine lactone (oxo-C6-HSL) and long-chained AHLs, i.e., N-tetradecanoyl homoserine lactone (C14-HSL), N-3-hydroxytetradecanoyl homoserine lactone (OH-C14-HSL), and N-3-oxotetradecanoyl homoserine lactone (oxo-C14-HSL), on growth of the benthic diatom Seminavis robusta. All tested short-chained AHLs did not affect diatom growth, while long-chained AHLs promoted (C14-HSL) or inhibited (OH-C14-HSL and oxo-C14-HSL) growth. To investigate the physiological effects of these long-chained AHLs in more detail, an RNA-seq experiment was performed during which S. robusta was treated with the growth-promoting C14-HSL and the growth-inhibiting oxo-C14-HSL. One tetramic acid was also tested (TA14), a structural rearrangement product of oxo-C14-HSL, which also induced growth inhibition in S. robusta. After 3 days of treatment, analysis revealed that 3,410 genes were differentially expressed in response to at least one of the compounds. In the treatment with the growth-promoting C14-HSL many genes involved in intracellular signaling were upregulated. On the other hand, exposure to growth-inhibiting oxo-C14-HSL and TA14 triggered a switch in lipid metabolism towards increased fatty acid degradation. In addition, oxo-C14-HSL led to downregulation of cell cycle genes, which is in agreement with the stagnation of cell growth in this treatment. Combined, our results indicate that bacterial signaling molecules with high structural similarity induce contrasting physiological responses in S. robusta

Borderline ovarian tumor frozen section diagnoses with features suspicious of invasive cancer:a retrospective study

Abstract Background A frozen section diagnosis of a borderline ovarian tumor with suspicious features of invasive carcinoma (“at least borderline” or synonymous descriptions) presents us with the dilemma of whether or not to perform a full ovarian cancer staging procedure. Quantification of this dilemma may help us with the issue of this clinical decision. The present study assessed and compared both the prevalence of straightforward borderline and “at least borderline” frozen section diagnoses and the proportion of these women with a final histopathological diagnosis of invasive carcinoma, with a special interest in histologic subtypes. Methods A retrospective cohort study was performed in three hospitals in The Netherlands. All women that underwent ovarian surgery with perioperative frozen section evaluation in one of these hospitals between January 2007 and July 2018 were identified and included in case of a borderline or “at least borderline” frozen section diagnosis and a borderline ovarian tumor or invasive carcinoma as a final diagnosis. Results A total of 223 women were included, of which 41 women (18.4%) were diagnosed with “at least borderline” at frozen section. Thirteen of forty-one women (31.7%) following “at least borderline” frozen section diagnosis and 14 of 182 women (7.7%) following a straightforward borderline frozen section diagnosis were diagnosed with invasive carcinoma at paraffin section evaluation (p < 0.001). When compared to straightforward borderline frozen section diagnoses, the proportion of women diagnosed with invasive carcinoma increased from 3.1 to 35.7% for serous tumors (p = 0.001), 10.0 to 21.7% for mucinous tumors (p = 0.129) and 50.0 to 75.0% (p = 0.452) in case of other histologic subtypes following an “at least borderline” frozen section diagnosis. Conclusions Overall, when compared to women with a decisive borderline frozen section diagnosis, women diagnosed with “at least borderline” frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis (7.7% vs 31.7%). Especially in the serous subtype, full staging during initial surgery might be considered after preoperative consent to prevent a second surgical procedure or chemotherapy in unstaged women. Further studies are needed to evaluate whether additional sampling in case of an “at least borderline” diagnosis may decrease the risk of surgical over-treatment

Frozen section diagnosis of borderline ovarian tumors with suspicious features of invasive cancer is a devil's dilemma for the surgeon:A systematic review and meta-analysis

Introduction Frozen section diagnoses of borderline ovarian tumors are not always straightforward and a borderline frozen section diagnosis with suspicious features of invasive carcinoma (reported as "at least borderline" or synonymous descriptions) presents us with the dilemma of whether or not to perform a full surgical staging procedure. By performing a systematic review and meta-analysis, the prevalence of straightforward borderline and "at least borderline" frozen section diagnoses, as well as proportion of patients with a final diagnosis of invasive carcinoma in these cases, were assessed and compared, as quantification of this dilemma may help us with the issue of this clinical decision. Material and methods PubMed, EMBASE and Cochrane library databases were searched and studies discussing "at least borderline" frozen section diagnoses were included in the review. Numbers of specific frozen section diagnoses and subsequent final histological diagnoses were extracted and pooled analysis was performed to compare the proportion of patients diagnosed with invasive carcinoma following borderline and "at least borderline" frozen section diagnoses, presented as risk ratio and risk difference with 95% confidence intervals (95% CI). Results Of 4940 screened records, eight studies were considered eligible for quantitative analysis. A total of 921 women was identified and 230 (25.0%) of these women were diagnosed with "at least borderline" ovarian tumor at the time of frozen section. Final histological diagnoses were reported in five studies, including 61 women with an "at least borderline" diagnosis and 290 women with a straightforward borderline frozen section diagnosis. Twenty-five of 61 women (41.0%) of the "at least borderline" group had invasive cancer at final diagnosis, compared with 28 of 290 women (9.7%) of the straightforward borderline frozen section group (risk difference -0.34, 95% CI -0.53 to -0.15; relative risk 0.25, 95% CI 0.13-0.50). Conclusions Women diagnosed with "at least borderline" frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis when compared with women with a straightforward borderline frozen section diagnosis (41.0% vs 9.7%). Especially in the serous subtype, and after preoperative consent, full staging during initial surgery might be considered in these cases to prevent a second surgical procedure

Borderline tumours of the ovary:Common practice in the Netherlands

Objectives: Discordance between frozen section diagnosis and the definite histopathological diagnosis and the fact that the frozen section result is not always unambiguous, may contribute to differences in clinical practice regarding perioperative treatment and follow-up of borderline ovarian tumours (BOTs) patients amongst gynaecologic oncologists, which may lead to over- and undertreatment. The aim of the study was to map the Dutch gynaecologists' preferred treatment and follow-up strategy in case of BOTs. Methods: A questionnaire was sent to all Dutch gynaecologists involved in ovarian surgery with perioperative frozen section analysis, and the outcomes were assessed using descriptive statistics. Results: Nearly half of the respondents (41.0%) would not perform a staging procedure in case of a BOT. In case of an ambiguous frozen section diagnosis, tending towards invasive carcinoma, a considerable number (sBOT 56.4%; mBOT 30.8%) would perform a lymph node sampling as part of the staging procedure. A relaparotomy/relaparoscopy, to perform a lymph node sampling in case of a serous or mucinous carcinoma after a BOT frozen section diagnosis, would be performed by 97.4% and 48.7% of the respondents, respectively. Conclusions: A considerable number of gynaecologists would perform a staging procedure that is recommended for ovarian cancer in case of an ambiguous BOT frozen section diagnosis, especially for serous tumours. In addition, nearly all gynaecologists would perform a second procedure including a lymph node sampling in case of a serous invasive carcinoma after a BOT frozen section diagnosis, which applies to half of the gynaecologists in case of a mucinous carcinoma. Keywords: Borderline tumours of the ovary, Staging procedure, Frozen section analysis, Questionnaire, Gynaecologic oncologist, Semi-specialized gynaecologist