Cyclic workflow to improve implementation of learning points from morbidity and mortality meetings.

BACKGROUND: Morbidity and mortality meetings (M&MMs) are organized in most hospital departments with an educational purpose to learn from adverse events (AEs) to improve patient care. M&MMs often lack effectiveness due to unsuccessful systematic follow-up of areas of improvement. This can have an effect on improving patient safety and care. Therefore, a new strategy that focuses on implementing areas of improvement into daily practice is necessary. The study aim is to see if we could improve the implementation of meeting outcomes from the M&MM by using a cyclic workflow, and which factors are important to achieve its implementation. METHODS: This prospective study took place at the department of gynecologic oncology of a university hospital. Research was conducted with a participatory action research (PAR) approach using 10 consecutive M&MMs in 2019 and 2020. The cyclical workflow consisted of an action list based on the PDCA-cycle, a check of the implementation of areas for improvement at the next M&MM and regular monitoring of tasks. Each M&MM was observed and each professional with an assigned task was interviewed and gave their informed consent. Thematic content analysis was performed with the program Atlas.ti 8.4.20. RESULTS: Out of the 39 tasks that resulted from 10 M&MMs, 37 (94.8%) followed all the steps in the PDCA-cycle and were implemented. In total, 16 interviews were conducted with consultants, nurses, registrars and residents. Five main factors were important to achieve follow-up of areas for improvement: organizational culture, motivation, commitment, communication to mobilize employees and skills. Repetition of the cyclic workflow at the M&MM and an external person who reminded professionals of their assigned task(s) was important to change habits and motivate professionals. CONCLUSION: Cyclical tools can support the implementation of areas for improvement to optimize the M&MM. A M&MM with an organizational culture where attendees can discuss openly and freely may motivate attendees to take on tasks successfully. A positive stimulant to reach commitment of professionals is team participation. Integrating new habits of reflection may lead to a deeper level of learning from the PDCA-cycle and of the M&MM. Creating a learning environment outside of the M&MM may support professionals to take on actions and engage in improvement practices. Future research may focus on including a comparative analysis to show a success rate of the implementation of learning points from the M&MM more clearly.

The effect of opportunistic salpingectomy for primary prevention of ovarian cancer on ovarian reserve: a systematic review and meta-analysis.

BACKGROUND: Opportunistic salpingectomy (OS) is an attractive method for primary prevention of ovarian cancer. Although OS has not been associated with a higher complication rate, it may be associated with earlier onset of menopause. OBJECTIVE: To provide a systematic review and meta-analysis of the effect of OS on both age at menopause and ovarian reserve. METHODS: A search was conducted in the Cochrane Library, Embase and MEDLINE databases from inception until March 2022. We included randomized clinical trials and cohort studies investigating the effect of OS on onset of menopause and/or ovarian reserve through change in anti-Müllerian hormone (AMH), antral follicle count (AFC), estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH). Data was extracted independently by two researchers. Random-effects meta-analyses were conducted to estimate the pooled effect of OS on ovarian reserve. RESULTS: The initial search yielded 1047 studies. No studies were found investigating the effect of OS on age of menopause. Fifteen studies were included in the meta-analysis on ovarian reserve. Meta-analyses did not result in statistically significant differences in mean change in AMH (MD -0.07 ng/ml, 95%CI -0.18;0.05), AFC (MD 0.20 n, 95 % CI -4.91;5.30), E2 (MD 3.97 pg/ml, 95%CI -0.92;8.86), FSH (MD 0.33mIU/ml, 95%CI -0.15;0.81) and LH (MD 0.03mIU/ml; 95%CI -0.47;0.53). CONCLUSION: Our study shows that OS does not result in a significant reduction of ovarian reserve in the short term. Further research is essential to confirm the absence of major effects of OS on menopausal onset since clear evidence on this subject is lacking. Registration number PROSPERO CRD42021260966.

Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke.

Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen-glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1ß and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1ß and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.

Expression of Nav1.8 sodium channels perturbs the firing patterns of cerebellar Purkinje cells.

The sensory neuron specific sodium channel Na(v)1.8/SNS exhibits depolarized voltage-dependence of inactivation, slow inactivation and rapid repriming, which differentiate it from other voltage-gated sodium channels. Na(v)1.8 is normally selectively expressed at high levels in sensory ganglion neurons, but not within the CNS. However, expression of Na(v)1.8 mRNA and protein are upregulated within cerebellar Purkinje cells in animal models of multiple sclerosis (MS), and in human MS. To examine the effect of expression of Na(v)1.8 on the activity pattern of Purkinje cells, we biolistically introduced Na(v)1.8 cDNA into these cells in vitro. We report here that Na(v)1.8 can be functionally expressed at physiological levels (similar to the levels in DRG neurons where Na(v)1.8 is normally expressed) within Purkinje cells, and that its expression alters the activity of these neurons in three ways: first, by increasing the amplitude and duration of action potentials; second, by decreasing the proportion of action potentials that are conglomerate and the number of spikes per conglomerate action potential; and third, by contributing to the production of sustained, pacemaker-like impulse trains in response to depolarization. These results provide support for the hypothesis that the expression of Na(v)1.8 channels within Purkinje cells, which occurs in MS, may perturb their function.

Caspase-3 activation and DNA fragmentation in primary hippocampal neurons following glutamate excitotoxicity.

Excitotoxic glutamate CNS stimulation can result in neuronal cell death. Contributing mechanisms and markers of cell death are the activation of caspase-3 and DNA fragmentation. It remains to be resolved to which extent both cellular reactions overlap and/or indicate different processes of neurodegeneration. In this study, mixed neuronal cultures from newborn mice pubs (0-24 h) were stimulated with glutamate, and the co-localization of active caspase-3 and DNA fragmentation was investigated by immunocytochemistry and the TUNEL nick-end labelling. In untreated cultures, 8% scattered neurons (marked by MAP-2) displayed activated caspase-3 at different morphological stages of degeneration. TUNEL staining was detected in 5% of cell nuclei including GFAP-positive astrocytes. However, co-localization of active caspase-3 with TUNEL was less than 2%. After glutamate stimulation (125 microM), the majority of neurons was dying between 12 and 24 h. The absolute number of active caspase-3 neurons increased only moderately but in relation of surviving neurons after 24 h from 8 to 36% (125 microM), to 53% (250 microM) or to 32% (500 microM). TUNEL staining also increased after 24 h following glutamate treatment to 37% but the co-localization with active caspase-3 remained at the basal low level of 2%. In our system, glutamate-mediated excitotoxicity effects the DNA fragmentation and caspase-3 activation. Co-localization of both parameters, however, is very poor. Active caspase-3 in the absence of TUNEL indicates a dynamic degenerative process, whereas TUNEL marks the end stage of severe irreversible cell damage regardless to the origin of the cell.