CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.

A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

Bladder Neck Obstruction: Experience and Management in a Sperm Bank.

Primary Bladder Neck Obstruction (PBNO) management provides medical and surgical treatment, such as transurethral incisions that can lead to retrograde ejaculation. The aim of this study was to investigate the maintenance of anterograde ejaculation and semen quality before and after this surgical procedure. A retrospective evaluation was carried out between 2011 and 2020. A total of 73 patients diagnosed with PBNO were recruited. Ejaculatory function, semen quality, and the fertility of recruited subjects were evaluated. Semen parameters-Baseline, 8.2% of patients were oligozoospermic and 12.3% had a semen volume below the WHO 2010 fifth percentile. Post-surgery, 20% of patients were oligozoospermic. We detected a significant decrease in total sperm number, a significant increase in the number of abnormal forms, and a reduction in the leukocyte concentration. Ejaculatory function-A total of 7.7% of patients reported anejaculation after transurethral incision of the bladder neck. Fertility-9.2% of the patients already had children before surgery; 13.8% had naturally conceived children in the years following surgery; 76.9% had no desire for paternity at the time. Our data have important implications for sperm bank management. The alterations in semen parameters and the risk of anejaculation suggest that the use of sperm cryopreservation before surgery for PBNO should be encouraged.

COVID-19 and its treatments: lights and shadows on testicular function.

PURPOSE: The SARS-CoV-2 pandemic has rapidly spread worldwide and, among the others, the male gender was quickly recognized as an independent risk factor for both the disease and its consequences. Since the possibility of long-term hormonal axis changes and male gamete impairment have been hypothesized but a relatively low levels of evidence has been reached, we focused this narrative mini-review on summarizing key state-of-the-art knowledge on male reproductive effects of COVID-19 as a quick reference for reproductive health specialists. METHODS: A comprehensive Medline/PubMed and Embase search was performed selecting all relevant, peer-reviewed papers in English published from 2020. Other relevant papers were selected from the reference lists. RESULTS: Available evidence indicates that the likelihood of direct testicular damage from SARS-CoV-2 is somewhat low, but there are many indirect ways (fever, cytokine imbalance, and drugs) through which the pituitary-gonadal axis and spermatogenesis may be disrupted. These alterations are probably transient, but as available evidence is low quality, it cannot be excluded that previous pathologies or comorbidities might modulate the risk of their persistence. On the other hand, available evidence shows high safety regarding andrological health for available vaccines, although studies are mainly focused on mRNA vaccines. CONCLUSION: A careful andrological evaluation of men recovering from COVID-19 is highly recommended. Since available evidence is relatively scarce, a careful andrological follow-up and counseling of these patients are mandatory.

Connectivity Alterations in Emotional and Cognitive Networks During a Manic State Induced by Direct Electrical Stimulation.

Mania is characterized by affective and cognitive alterations, with heightened external and self-awareness that are opposite to the alteration of awareness during epileptic seizures. Electrical stimulations carried out routinely during stereotactic intracerebral EEG (SEEG) recordings for presurgical evaluation of epilepsy may represent a unique opportunity to study the pathophysiology of such complex emotional-behavioral phenomenon, particularly difficult to reproduce in experimental setting. We investigated SEEG signals-based functional connectivity between different brain regions involved in emotions and in consciousness processing during a manic state induced by electrical stimulation in a patient with drug-resistant focal epilepsy. The stimulation inducing manic state and an asymptomatic stimulation of the same site, as well as a seizure with alteration of awareness (AOA) were analyzed. Functional connectivity analysis was performed by measuring interdependencies (nonlinear regression analysis based on the h2 coefficient) between broadband SEEG signals and within typical sub-bands, before and after stimulation, or before and during the seizure with AOA, respectively. Stimulation of the right lateral prefrontal cortex induced a manic state lasting several hours. Its onset was associated with significant increase of broadband-signal functional coupling between the right hemispheric limbic nodes, the temporal pole and the claustrum, whereas significant decorrelation between the right lateral prefrontal and the anterior cingulate cortex was observed in theta-band. In contrast, ictal alteration of awareness was associated with increased broadband and sub-bands synchronization within and between the internal and external awareness networks, including the anterior and middle cingulate, the mesial and lateral prefrontal, the inferior parietal and the temporopolar cortex. Our data suggest the existence of network- and frequency-specific functional connectivity patterns during manic state. A transient desynchronization of theta activity between the external and internal awareness network hubs is likely to increase awareness, with potential therapeutic effect.

Genetic generalized epilepsy and generalized onset seizures with focal evolution (GOFE).

"Generalized Onset with Focal Evolution" (GOFE) is an underrecognized seizure type defined by an evolution from generalized onset to focal activity during the same ictal event. We aimed to discuss electroclinical aspects of GOFE and to emphasize its link with Genetic Generalized Epilepsy (GGE). Patients were identified retrospectively over 10 years, using the video-EEG data base from the Epilepsy Unit of Strasbourg University Hospital. GOFE was defined, as previously reported, from an EEG point of view with an evolution from generalized onset to focal activity during the same ictal event. Three male patients with GOFE were identified among 51 patients with recorded tonic-clonic seizures. Ages at onset of seizures were 13, 20 and 22 years. Focal clinical features (motor asymmetric phenomenology) could be identified. EEG showed generalized interictal discharges with focal evolution of various localization. Four seizures were recorded characterized by 2-3 s of generalized abnormalities followed by focal (parieto-occipital or frontal) discharges. There were initially uncontrolled seizures with lamotrigine, but all patients reported a good outcome with valproate monotherapy. We emphasize that GOFE presents many similarities with GGE. Recognition of the GOFE entity could bring a therapeutic interest avoiding misdiagnosis of focal epilepsy and consequently inappropriate use of narrow spectrum anti-seizure medicine.

From the Operating Room to the Front Lines: Shared Experiences of Nurse Anesthetists During the Coronavirus Pandemic.

Coronavirus disease 2019 (COVID-19) has resulted in severe health, economic, social, political, and cultural consequences while thrusting Certified Registered Nurse Anesthetists (CRNAs) at the forefront of battling an often invisible enemy. A mixed-methods study was conducted to assess the impact of the COVID-19 pandemic on CRNA practice. The purpose of the qualitative component of the study, a focused ethnography, was to use personal and group interviews to determine the shared experiences of CRNAs who worked during the COVID-19 pandemic. Six themes were identified: (1) CRNAs are part of the solution, (2) doing whatever it takes, (3) CRNAs are valued contributors, (4) removal of barriers promotes positive change, (5) trying times, and (6) expertise revealed. The quantitative component of the study will be discussed in a separate article.

Three Different FDG Patterns in Periventricular Nodular Heterotopia Correlated to Video Stereoelectroencephalography.

ABSTRACT: A 40-year-old woman with a drug-resistant focal epilepsy underwent cerebral FDG PET in phase 1 presurgical epilepsy study. MRI essentially showed multiple periventricular nodular heterotopias. The stereoelectroencephalography coupled to MRI and FDG PET helped to define the anatomofunctional correlation of the epileptogenic zone network. This procedure brought to light 3 distinct patterns of FDG consumption, corresponding to different anatomoelectroclinical features. This pattern was already found in a previous FDG PET reflecting a "stable" permanent intralesional intercritical stereoelectroencephalography activity, an electrical "signature" of the lesion. Finally, functional imaging improved thermocoagulation in this patient and emphasized the use of FDG in drug-resistant epilepsy.

Exome sequencing in 57 patients with self-limited focal epilepsies of childhood with typical or atypical presentations suggests novel candidate genes.

OBJECTIVE: Self-limited focal epilepsies of childhood (SFEC) are amongst the best defined and most frequent epilepsy syndromes affecting children with usually normal developmental milestones. They include core syndromes such as Rolandic epilepsy or "Benign" epilepsy with Centro-Temporal Spikes and the benign occipital epilepsies, the early onset Panayiotopoulos syndrome and the late-onset Gastaut type. Atypical forms exist for all of them. Atypical Rolandic epilepsies are conceptualized as belonging to a continuum reaching from the "benign" RE to the severe end of the Landau-Kleffner (LKS) and Continuous Spike-Waves during Sleep syndromes (CSWS). GRIN2A has been shown to cause the epilepsy-aphasia continuum that includes some patients with atypical Rolandic epilepsy with frequent speech disorders, LKS and CSWS. In the present study, we searched novel genes causing SFEC with typical or atypical presentations. METHODS: Exome sequencing was performed in 57 trios. Patients presented with typical or atypical SFEC, negative for GRIN2A pathogenic variant. RESULTS: We found rare candidate variants in 20 patients. Thirteen had occurred de novo and were mostly associated to atypical Rolandic Epilepsy. Two of them could be considered as disease related: a null variant in GRIN2B and a missense variant in CAMK2A. Others were considered good candidates, including a substitution affecting a splice site in CACNG2 and missense variants in genes encoding enzymes involved in chromatin remodeling. SIGNIFICANCE: Our results further illustrate the fact that atypical SFEC are more likely to have Mendelian inheritance than typical SFEC.

Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia.

Cause of complex dyskinesia remains elusive in some patients. A homozygous missense variant leading to drastic decrease of PDE2A enzymatic activity was reported in one patient with childhood-onset choreodystonia preceded by paroxysmal dyskinesia and associated with cognitive impairment and interictal EEG abnormalities. Here, we report three new cases with biallelic PDE2A variants identified by trio whole-exome sequencing. Mitochondria network was analyzed after Mitotracker™ Red staining in control and mutated primary fibroblasts. Analysis of retrospective video of patients' movement disorder and refinement of phenotype was carried out. We identified a homozygous gain of stop codon variant c.1180C>T; p.(Gln394*) in PDE2A in siblings and compound heterozygous variants in young adult: a missense c.446C>T; p.(Pro149Leu) and splice-site variant c.1922+5G>A predicted and shown to produce an out of frame transcript lacking exon 22. All three patients had cognitive impairment or developmental delay. The phenotype of the two oldest patients, aged 9 and 26, was characterized by childhood-onset refractory paroxysmal dyskinesia initially misdiagnosed as epilepsy due to interictal EEG abnormalities. The youngest patient showed a proven epilepsy at the age of 4 months and no paroxysmal dyskinesia at 15 months. Interestingly, analysis of the fibroblasts with the biallelic variants in PDE2A variants revealed mitochondria network morphology changes. Together with previously reported case, our three patients confirm that biallelic PDE2A variants are a cause of childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy.

Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy.

OBJECTIVE: Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by hypermotor seizures and may be caused by gain-of-function mutations affecting the nicotinic acetylcholine receptor (nAChR). Benefit from nicotine consumption has been reported in adult patients with this disorder. For the first time, the effect of transdermal nicotine is evaluated in children. METHODS: Transdermal nicotine was applied to three boys, two aged 10 years (7 mg/24 h) and one six years (3.5 mg/24 h). Autosomal dominant sleep-related hypermotor epilepsy was caused by the p.S280F-CHRNA4 (cholinergic receptor, nicotinic, alpha polypeptide 4) mutation. The children suffered from frequent, persistent nocturnal seizures and had developed educational and psychosocial problems. Seizure frequency and cognitive and behavioral parameters were assessed before and after treatment. RESULTS: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions. SIGNIFICANCE: Nicotine appears to be a mechanistic treatment for this specific disorder, probably because of desensitization of the mutated receptors. It may control seizures resistant to conventional drugs for epilepsy and impact socioeducational function in children. This mode of precision therapy should receive more attention and should be available to more patients with uncontrolled CHRNA4-related ADSHE across the age span.

It's Never Just a Block: An Analysis of Regional Anesthesia Closed Claims.

Anesthesia care increasingly includes use of regional anesthesia techniques, either as a primary anesthetic or to reduce the patient's postoperative pain. Both neuraxial anesthesia and peripheral nerve blockade have several noteworthy functions. These functions include diminishing sensory sensation to pain and potentially producing a motor blockade, both of which may facilitate the surgical procedure. The desire to reduce reliance on opioid medications, protocols to enhance and accelerate patient recovery from surgery, and patient expectations all contribute to the likelihood that use of regional anesthesia will continue to gain popularity. As such, it is essential to understand whether an association exists between regional anesthesia and adverse outcomes of care. The American Association of Nurse Anesthetists Foundation Closed Claim Research Team searched the most current database of closed claims that involved adverse outcomes when either a peripheral nerve block or a neuraxial block was a component of care in the claims. Although there were only 32 claims in the dataset, a thematic analysis resulted in the identification of 3 themes: errors in cognitive decision making, ineffective communication patterns, and production pressure.

Can histologically normal epileptogenic zone share common electrophysiological phenotypes with focal cortical dysplasia? SEEG-based study in MRI-negative epileptic patients.

OBJECTIVE: We aimed to assess stereoelectroencephalography (SEEG) seizure-onset and interictal patterns associated with MRI-negative epilepsy and investigate their possible links with histology, extent of the epileptogenic zone (EZ) and surgical outcome. METHODS: We retrospectively analysed a cohort of 59 consecutive MRI-negative surgical candidates, who underwent SEEG recordings followed by cortectomy between 2000 and 2016. RESULTS: Most of the eight distinct seizure-onset patterns could be encountered both in confirmed focal cortical dysplasia (FCD) and in histologically non-specific or normal cases. We found strong correlation (p = 0.008) between seizure-onset pattern and histology for: (1) slow-wave/DC-shift prior to low voltage fast activity (LVFA), associated with normal/non-specific histology, and (2) bursts of polyspikes prior to LVFA, exclusively observed in FCD. Three interictal patterns were identified: periodic slow-wave/gamma burst, sub-continuous rhythmic spiking and irregular spikes. Both "periodic" patterns were more frequent in but not specific to FCD. Surgical outcome depended on the EZ complete removal, regardless electrophysiological features. CONCLUSIONS: Histologically normal and FCD-associated epileptogenic zones share distinct interictal and ictal electrophysiological phenotypes, with common patterns between FCD subtypes and between dysplastic and apparently normal brain. SIGNIFICANCE: Some specific seizure-onset patterns seem to be predictive of the underlying histology and may help to detect an MRI-invisible FCD.

Comparison of Functional Deficit Zone Defined by FDG PET to the Epileptogenic Zones Described in Stereo-Electroencephalograph in Drug-Resistant Epileptic Patients Treated by Surgery.

INTRODUCTION: The purpose of presurgical assessment is to delimit the epileptogenic zone and the functional deficit zone with a brain MRI, an electroencephalograph or even a stereo-electroencephalograph (SEEG), neuropsychological evaluation, and a cerebral FDG PET. Several studies concur that the hypometabolism of FDG PET seems to be consistent with epileptogenic zones. We compared the functional deficit zone defined by FDG PET with the results of the SEEG, for each cluster electrode contact (CEC) located in the gray matter. METHODS: The electrode diagram of the 15 patients (486 CECs) operated on for drug-resistant epilepsy was merged with MRI and FDG PET. The metabolisms of FDG PET and SEEG were compared using a logistic regression test. RESULTS: The presence of hypometabolism resulted in a significantly higher risk of being in the seizure onset zone and the irritative zone, particularly when it was intense. Of the deeply hypometabolic CECs, 47% were in the seizure onset zone and 76% in the irritative zone. Normal metabolism resulted in a significantly higher probability of being in the healthy zone. CONCLUSIONS: This study demonstrated an association between the presence of normal metabolism and the location of CECs in the healthy zone, and between the presence of pathological metabolism and the location of CECs in the seizure onset zone and the irritative zone, with metabolism abnormalities progressively more present and more intense near the seizure onset zone.

Illusory own body perceptions mapped in the cingulate cortex-An intracranial stimulation study.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug-resistant epilepsy, explored by stereo-electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high-frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h2 coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi-body. High-frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.

High-frequency oscillations and spikes running down after SEEG-guided thermocoagulations in the epileptogenic network of periventricular nodular heterotopia.

OBJECTIVE: Epilepsy associated with periventricular nodular heterotopia (PNH) is characterized by complex relationships between the heterotopic and the normotopic cortex during the interictal state and at seizure onset. High-frequency oscillations (HFO) have been proposed as a marker of epileptogenicity that might reflect disease activity. The effects of thermocoagulations on epileptogenicity in this context remain unknown. We aimed to investigate the interictal HFO- and spike profiles of different cortical structures before and after two consecutive SEEG-guided thermocoagulations, in correlation with seizure outcome, in a patient with PNH-related drug-resistant epilepsy. METHODS: The epileptogenic zone (EZ) was defined by SEEG analysis based on the Epileptogenicity Index. Interictal spikes, ripples (80-250 Hz) and fast ripples (FR, 250-330 Hz) were analyzed within the heterotopia, the temporal neocortex and the hippocampus. RESULTS: The SEEG recordings revealed a distributed EZ involving the heterotopia and the posterior temporal neocortex. Both structures were targeted by thermocoagulations. Background spikes, ripples and FR-rates were significantly higher in PNH compared to the normotopic cortex. A drastic reduction of spikes (by over 80%) and absence of FR were demonstrated both in the PNH and in the neocortex during the second SEEG exploration 6 months after the first thermocoagulation, whereas no significant difference was observed in the posterior hippocampus. Ripples were significantly reduced by the first and suppressed by the second thermocoagulation within the three structures. Seizures relapsed after two months but decreased in frequency after the first thermocoagulation. Sustained seizure-freedom was achieved only after the second procedure. CONCLUSIONS: Our data demonstrate the running down of interictal HFO and spikes within the epileptogenic network following thermocoagulations of heterotopic and normotopic sites involved at seizure onset. This dynamics was in good correlation with significantly improved seizure control. SIGNIFICANCE: Combination of ictal and different interictal markers of epileptogenicity, including HFO and spike analysis, is important to get the full picture of the epileptogenic zone and could help to evaluate the disease activity.

Preventable Closed Claims in the AANA Foundation Closed Malpractice Claims Database.

Medical errors are among the top 3 causes of patient deaths in the United States, with up to 400,000 preventable deaths occurring in hospitalized patients each year. Although improvements have been made in anesthesia patient safety, adverse outcomes continue to occur. This study used thematic analysis to examine anesthesia closed claims that were associated with preventable morbidity and mortality. Investigators determined that 123 closed malpractice claims files from the American Association of Nurse Anesthetists (AANA) Foundation closed claims database involved events that the involved Certified Registered Nurse Anesthetist could have prevented. Factors that were associated with preventable closed claims included communication failures, violations of the AANA Standards for Nurse Anesthesia Practice, and errors in judgment.

Interpretation of SEEG recordings.

The interpretation of SEEG recordings is a crucial step. It must be carried out by an epileptologist/neurophysiologist with sufficient training and qualification in this field. The objectives of the interpretation are to define the brain topography of interictal activities (irritative zone) and the epileptogenic zone, defined as the site of primary organization of ictal discharges. Several patterns of seizure onset are possible, the most typical including fast discharges. The interpretation of the SEEG is based on the recording of spontaneous activity but also on the results of intracerebral electrical stimulation. It must be done with accurate anatomical information on the location of the electrodes in terms of the patient's anatomy. Quantification of interictal activities (spikes, high frequency oscillations) and ictal activity (epileptogenicity index) is recommended. The interpretation of the SEEG must also take into account functional data and will be the basis for the final decision on the operability and type of intervention chosen.

Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure.

OBJECTIVE: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information. RESULTS: Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy.

Improving Patient Outcomes Through Closed-Claims Analysis: Salient Characteristics and Patterns Associated With Respiratory Events.

A retrospective, exploratory research design was used to analyze salient characteristics and patterns associated with closed claims involving Certified Registered Nurse Anesthetists (CRNAs) in which a respiratory event caused the adverse outcome. Alleged malpractice acts found in these claims occurred between 2003 and 2012. Respiratory events were the most frequent cause of adverse outcomes in the current database (34%). The respiratory adverse outcomes often resulted in mortality or significant and permanent morbidity (69%) and were largely preventable (81%). Of these respiratory outcomes, inadequate ventilation and oxygenation associated with respiratory depressant medications accounted for 37% of the adverse outcomes (hypoventilation = 27.4%; respiratory arrest = 9.5%). In every hypoventilation claim, regardless of the type of anesthetic technique, a failure to optimally monitor the patient's ventilation was identified as a sentinel, contributory practice pattern. Payouts for CRNAs were made in 55% of respiratory claims and averaged $282,840. Claims judged to have an AANA standard-of-practice guideline violation that directly contributed to the adverse outcome were more likely to result in a payout vs those involving no violation (P <.01). Costs to defend against the malpractice allegation for all respiratory event claims averaged $51,996 (SD = $52,658) and ranged from $525 to $227,153.

A Content and Thematic Analysis of Closed Claims Resulting in Death.

The analyses of malpractice closed claims conducted by the AANA Foundation Closed Claims Research Team are scientific studies of adverse anesthetic events where a Certified Registered Nurse Anesthetist was identified as potentially contributing to the outcome. From July 2013 to March 2014, the AANA Foundation Closed Claims Researchers evaluated 245 closed claims from the CNA Insurance Companies spanning from 2003 to 2012. An adverse event leading to death occurred in 87 of the claims. This article describes the use of content and thematic analysis in the evaluation of these closed claims. The purpose of the study was to establish themes that would provide unique insights into the events leading up to death with a focus on the role anesthesia may or may not have had in the outcome. Major themes identified include: (1) patient factors, (2) provider factors, (3) environmental factors, and (4) team/group factors.