Background and Purpose-Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) in critically ill patients. The ability to detect loss of autoregulatory vasoreactivity to spontaneous fluctuations in CPP was tested with a new time-domain method that used near-infrared spectroscopic measurements of tissue oxyhemoglobin saturation in an infant animal model. Methods-Piglets were made progressively hypotensive over 4 to 5 hours by inflation of a balloon catheter in the inferior vena cava, and the breakpoint of autoregulation was determined using laser-Doppler flowmetry. The cerebral oximetry index (COx) was determined as a moving linear correlation coefficient between CPP and INVOS cerebral oximeter waveforms during 300-second periods. A laser-Doppler derived time-domain analysis of spontaneous autoregulation with the same parameters (LDx) was also determined. Results-An increase in the correlation coefficient between cerebral oximetry values and dynamic CPP fluctuations, indicative of a pressure-passive relationship, occurred when CPP was below the steady state autoregulatory breakpoint. This COx had 92% sensitivity (73% to 99%) and 63% specificity (48% to 76%) for detecting loss of autoregulation attributable to hypotension when COx was above a threshold of 0.36. The area under the receiver-operator characteristics curve for the COx was 0.89. COx correlated with LDx when values were sorted and averaged according to the CPP at which they were obtained (rϭ0.67). Conclusions-The COx is sensitive for loss of autoregulation attributable to hypotension and is a promising monitoring tool for determining optimal CPP for patients with acute brain injury.

Background and Purpose-The pressure reactivity index (PRx) describes cerebral vessel reactivity by correlation of slow waves of intracranial pressure (ICP) and arterial blood pressure. In theory, slow changes in the relative total hemoglobin (rTHb) measured by near-infrared spectroscopy are caused by the same blood volume changes that cause slow waves of ICP. Our objective was to develop a new index of vascular reactivity, the hemoglobin volume index (HVx), which is a low-frequency correlation of arterial blood pressure and rTHb measured with near-infrared spectroscopy. Methods-Gradual hypotension was induced in piglets while cortical laser-Doppler flux was monitored. ICP was monitored, and rTHb was measured continuously using reflectance near-infrared spectroscopy. The HVx was recorded as a moving linear correlation between slow waves (20 to 300 seconds) of arterial blood pressure and rTHb.

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection. It produces an unusual intracellular infection in which a vegetative form, called the reticulate body (RB), replicates and then converts into an elementary body (EB), which is the infectious form. Here we use quantitative three-dimensional electron microscopy (3D EM) to show that C. trachomatis RBs divide by binary fission and undergo a sixfold reduction in size as the population expands. Conversion only occurs after at least six rounds of replication, and correlates with smaller RB size. These results suggest that RBs only convert into EBs below a size threshold, reached by repeatedly dividing before doubling in size. A stochastic mathematical model shows how replication-dependent RB size reduction produces delayed and asynchronous conversion, which are hallmarks of the Chlamydia developmental cycle. Our findings support a model in which RB size controls the timing of RB-to-EB conversion without the need for an external signal.

Background and Purpose-Clinical application of continuous autoregulation monitoring would benefit from a comparison of curves generated by online monitoring with standard autoregulation curves in animal models. We characterized the accuracy of 3 continuous monitors of autoregulation in a piglet model of hypotension. Methods-Piglets

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

Bacteria in the genus Chlamydia are major human pathogens that cause an intracellular infection. A chlamydial protease, CPAF, has been proposed as an important virulence factor that cleaves or degrades at least 16 host proteins, thereby altering multiple cellular processes. We examined 11 published CPAF substrates and found that there was no detectable proteolysis when CPAF activity was inhibited during cell processing. We show that the reported proteolysis of these putative CPAF substrates was due to enzymatic activity in cell lysates rather than in intact cells. Nevertheless, Chlamydia-infected cells displayed Chlamydia-host interactions, such as Golgi reorganization, apoptosis resistance, and host cytoskeletal remodeling, that have been attributed to CPAF-dependent proteolysis of host proteins. Our findings suggest that other mechanisms may be responsible for these Chlamydia-host interactions, and raise concerns about all published CPAF substrates and the proposed roles of CPAF in chlamydial pathogenesis.

BackgroundNeonates with hypoxic-ischemic encephalopathy (HIE) are at risk of cerebral blood flow dysregulation. Our objective was to describe the relationship between autoregulation and neurologic injury in HIE.MethodsNeonates with HIE had autoregulation monitoring with the hemoglobin volume index (HVx) during therapeutic hypothermia, rewarming, and the first 6 h of normothermia. The 5-mmHg range of mean arterial blood pressure (MAP) with best vasoreactivity (MAPOPT) was identified. The percentage of time spent with MAP below MAPOPT and deviation in MAP from MAPOPT were measured. Neonates received brain MRIs 3–7 days after treatment. MRIs were coded as no, mild, or moderate/severe injury in five regions.ResultsHVx identified MAPOPT in 79% (19/24), 77% (17/22), and 86% (18/21) of neonates during hypothermia, rewarming, and normothermia, respectively. Neonates with moderate/severe injury in paracentral gyri, white matter, basal ganglia, and thalamus spent a greater proportion of time with MAP below MAPOPT during rewarming than neonates with no or mild injury. Neonates with moderate/severe injury in paracentral gyri, basal ganglia, and thalamus had greater MAP deviation below MAPOPT during rewarming than neonates without injury.ConclusionMaintaining MAP within or above MAPOPT may reduce the risk of neurologic injuries in neonatal HIE.

Background and Purpose The limits of cerebral blood flow-pressure autoregulation have not been adequately defined for pediatric patients. Mean arterial blood pressure below these limits might contribute to brain injury during cardiac surgery. The purpose of this pilot study was to assess a novel method of determining the lower limits of pressure autoregulation in pediatric patients supported with cardiopulmonary bypass. Methods A prospective, observational pilot study was conducted in children (n=54) undergoing cardiac surgery with cardiopulmonary bypass for correction of congenital heart defects. Cerebral oximetry index (COx) was calculated as a moving, linear correlation coefficient between slow waves of arterial blood pressure and cerebral oximetry measured with near-infrared spectroscopy. An autoregulation curve was constructed for each patient with averaged COx values sorted by arterial blood pressure. Results Hypotension was associated with increased values of COx (P<0.0001). For 77% of patients, an individual estimate of lower limits of pressure autoregulation could be determined using a threshold COx value of 0.4. The mean lower limits of pressure autoregulation for the cohort using this method was 42±7 mm Hg. Conclusions This pilot study of COx monitoring in pediatric patients demonstrates an association between hypotension during cardiopulmonary bypass and impairment of autoregulation. The COx may be useful to identify arterial blood pressure-dependent limits of cerebral autoregulation during cardiopulmonary bypass. Larger trials with neurological outcomes are indicated.