Prophylactic Antibiotics Delivered Via the Respiratory Tract to Reduce Ventilator-Associated Pneumonia: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the effects of antibiotics delivered via the respiratory tract in preventing ventilator-associated pneumonia (VAP). DATA SOURCES: We searched PubMed, Scopus, the Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 25, 2023. STUDY SELECTION: Adult patients with mechanical ventilation of over 48 h and receiving inhaled or instilled antibiotics (with control group) to prevent VAP were included. DATA EXTRACTION: Two independent groups screened studies, extracted the data, and assessed the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty/quality of the evidence. Results of a random-effects model were reported for overall and predefined subgroup meta-analyses. The analysis was primarily conducted on randomized controlled trials, and observational studies were used for sensitivity analyses. DATA SYNTHESIS: Seven RCTs with 1445 patients were included, of which six involving 1283 patients used nebulizers to deliver antibiotics. No obvious risk of bias was found among the included RCTs for the primary outcome. Compared with control group, prophylactic antibiotics delivery via the respiratory tract significantly reduced the risk of VAP (risk ratio [RR], 0.69 [95% CI, 0.53-0.89]), particularly in subgroups where aminoglycosides (RR, 0.67 [0.47-0.97]) or nebulization (RR, 0.64 [0.49-0.83]) were used as opposed to other antibiotics (ceftazidime and colistin) or intratracheal instillation. No significant differences were observed in mortality, mechanical ventilation duration, ICU and hospital length of stay, duration of systemic antibiotics, need for tracheostomy, and adverse events between the two groups. Results were confirmed in sensitivity analyses. CONCLUSIONS: In adult patients with mechanical ventilation for over 48 h, prophylactic antibiotics delivered via the respiratory tract reduced the risk of VAP, particularly for those treated with nebulized aminoglycosides.

Ictal Central Apnea Is Predictive of Mesial Temporal Seizure Onset: An Intracranial Investigation.

OBJECTIVE: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. METHODS: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. RESULTS: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. INTERPRETATION: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.

Pro-Ictal State in Human Temporal Lobe Epilepsy.

BACKGROUND: Studies of continuous electroencephalography (EEG) suggest that seizures in individuals with focal-onset epilepsies preferentially occur during periods of heightened risk, typified by pathologic brain activities, termed pro-ictal states; however, the presence of (pathologic) pro-ictal states among a plethora of otherwise physiologic (e.g., sleep­wake cycle) states has not been established. METHODS: We studied a prospective, consecutive series of 15 patients with temporal lobe epilepsy who underwent limbic thalamic recordings in addition to routine (cortical) intracranial EEG for seizure localization. For each participant, pro-ictal (45 minutes before seizure onset) and interictal (4 hours removed from all seizures) EEG segments were divided into 10-minute, nonoverlapping windows, which were randomly distributed into training and validation cohorts in a 1:1 ratio. A deep neural classifier was applied to distinguish pro-ictal from interictal brain activities in a patient-specific fashion. RESULTS: We analyzed 1800 patient-hours of continuous thalamocortical EEG. Distinct pro-ictal states were detected in each participant. The median area under the receiver-operating characteristic curve of the classifier was 0.92 (interquartile range, 0.90­0.96). Pro-ictal states were distinguished at least 45 minutes before seizure onset in 13 of 15 participants; in 2 of 15 participants, they were distinguished up to 35 minutes prior. CONCLUSIONS: On the basis of thalamocortical EEG, pro-ictal states ­ pathologic brain activities during periods of heightened seizure risk ­ could be identified in patients with temporal lobe epilepsy and were detected, in our small sample, more than one half hour before seizure onset.

Interictal localization of the epileptogenic zone: Utilizing the observed resonance behavior in the spectral band of surrounding inhibition.

Introduction: The gold standard for identification of the epileptogenic zone (EZ) continues to be the visual inspection of electrographic changes around seizures' onset by experienced electroencephalography (EEG) readers. Development of an epileptogenic focus localization tool that can delineate the EZ from analysis of interictal (seizure-free) periods is still an open question of great significance for improved diagnosis (e.g., presurgical evaluation) and treatment of epilepsy (e.g., surgical outcome). Methods: We developed an EZ interictal localization algorithm (EZILA) based on novel analysis of intracranial EEG (iEEG) using a univariate periodogram-type power measure, a straight-forward ranking approach, a robust dimensional reduction method and a clustering technique. Ten patients with temporal and extra temporal lobe epilepsies, and matching the inclusion criteria of having iEEG recordings at the epilepsy monitoring unit (EMU) and being Engel Class I ≥12 months post-surgery, were recruited in this study. Results: In a nested k-fold cross validation statistical framework, EZILA assigned the highest score to iEEG channels within the EZ in all patients (10/10) during the first hour of the iEEG recordings and up to their first typical clinical seizure in the EMU (i.e., early interictal period). To further validate EZILA's performance, data from two new (Engel Class I) patients were analyzed in a double-blinded fashion; the EZILA successfully localized iEEG channels within the EZ from interictal iEEG in both patients. Discussion: Out of the sampled brain regions, iEEG channels in the EZ were most frequently and maximally active in seizure-free (interictal) periods across patients in specific narrow gamma frequency band (∼60-80 Hz), which we have termed focal frequency band (FFB). These findings are consistent with the hypothesis that the EZ may interictally be regulated (controlled) by surrounding inhibitory neurons with resonance characteristics within this narrow gamma band.