Early risk factors for prolonged mechanical ventilation in patients with severe blunt thoracic trauma: A retrospective cohort study.

BACKGROUND: A significant proportion of patients with severe chest trauma require mechanical ventilation (MV). Early prediction of the duration of MV may influence clinical decisions. We aimed to determine early risk factors for prolonged MV among adults suffering from severe blunt thoracic trauma. METHODS: This retrospective, single-center, cohort study included all patients admitted between January 2014 and December 2020 due to severe blunt chest trauma. The primary outcome was prolonged MV, defined as invasive MV lasting more than 14 days. Multivariable logistic regression was performed to identify independent risk factors for prolonged MV. RESULTS: The final analysis included 378 patients. The median duration of MV was 9.7 (IQR 3.0-18.0) days. 221 (58.5 %) patients required MV for more than 7 days and 143 (37.8 %) for more than 14 days. Male gender (aOR 3.01, 95 % CI 1.63-5.58, p < 0.001), age (aOR 1.40, 95 % CI 1.21-1.63, p < 0.001, for each category above 30 years), presence of severe head trauma (aOR 3.77, 95 % CI 2.23-6.38, p < 0.001), and transfusion of >5 blood units on admission (aOR 2.85, 95 % CI 1.62-5.02, p < 0.001) were independently associated with prolonged MV. The number of fractured ribs and the extent of lung contusions were associated with MV for more than 7 days, but not for 14 days. In the subgroup of 134 patients without concomitant head trauma, age (aOR 1.63, 95 % CI 1.18-2.27, p = 0.004, for each category above 30 years), respiratory comorbidities (aOR 9.70, 95 % CI 1.49-63.01, p = 0.017), worse p/f ratio during the first 24 h (aOR 1.55, 95 % CI 1.15-2.09, p = 0.004), and transfusion of >5 blood units on admission (aOR 5.71 95 % CI 1.84-17.68, p = 0.003) were independently associated with MV for more than 14 days. CONCLUSIONS: Several predictors have been identified as independently associated with prolonged MV. Patients who meet these criteria are at high risk for prolonged MV and should be considered for interventions that could potentially shorten MV duration and reduce associated complications. Hemodynamically stable, healthy young patients suffering from severe thoracic trauma but no head injury, including those with extensive lung contusions and rib fractures, have a low risk of prolonged MV.

Automating medical simulations.

OBJECTIVE: This study aims to explore speech as an alternative modality for human activity recognition (HAR) in medical settings. While current HAR technologies rely on video and sensory modalities, they are often unsuitable for the medical environment due to interference from medical personnel, privacy concerns, and environmental limitations. Therefore, we propose an end-to-end, fully automatic objective checklist validation framework that utilizes medical personnel's uttered speech to recognize and document the executed actions in a checklist format. METHODS: Our framework records, processes, and analyzes medical personnel's speech to extract valuable information about performed actions. This information is then used to fill the corresponding rubrics in the checklist automatically. RESULTS: Our approach to activity recognition outperformed the online expert examiner, achieving an F1 score of 0.869 on verbal tasks and an ICC score of 0.822 with an offline examiner. Furthermore, the framework successfully identified communication failures and medical errors made by physicians and nurses. CONCLUSION: Implementing a speech-based framework in medical settings, such as the emergency room and operation room, holds promise for improving care delivery and enabling the development of automated assistive technologies in various medical domains. By leveraging speech as a modality for HAR, we can overcome the limitations of existing technologies and enhance workflow efficiency and patient safety.

Association Between Admission Ionized Calcium Level and Neurological Outcome of Patients with Isolated Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Pathophysiological processes following initial insult are complex and not fully understood. Ionized calcium (Ca++) is an essential cofactor in the coagulation cascade and platelet aggregation, and hypocalcemia may contribute to the progression of intracranial bleeding. On the other hand, Ca++ is an important mediator of cell damage after TBI and cellular hypocalcemia may have a neuroprotective effect after brain injury. We hypothesized that early hypocalcemia might have an adverse effect on the neurological outcome of patients suffering from isolated severe TBI. In this study, we aimed to evaluate the relationship between admission Ca++ level and the neurological outcome of these patients. METHODS: This was a retrospective, single-center, cohort study of all patients admitted between January 2014 and December 2020 due to isolated severe TBI, which was defined as head abbreviated injury score ≥ 4 and an absence of severe (abbreviated injury score > 2) extracranial injuries. The primary outcome was a favorable neurological status at discharge, defined by a modified Rankin Scale of 0-2. Multivariable logistic regression was performed to determine whether admission hypocalcemia (Ca++ < 1.16 mmol L-1) is an independent predictor of neurological status at discharge. RESULTS: The final analysis included 201 patients. Hypocalcemia was common among patients with isolated severe TBI (73.1%). Most of the patients had mild hypocalcemia (1 < Ca++ < 1.16 mmol L-1), and only 13 (6.5%) patients had Ca++ ≤ 1.00 mmol L-1. In the entire cohort, hypocalcemia was independently associated with higher rates of good neurological status at discharge (adjusted odds ratio of 3.03, 95% confidence interval 1.11-8.33, p = 0.03). In the subgroup of 81 patients with an admission Glasgow Coma Scale > 8, 52 (64.2%) had hypocalcemia. Good neurological status at discharge was recorded in 28 (53.8%) of hypocalcemic patients compared with 14 (17.2%) of those with normal Ca++ (p = 0.002). In multivariate analyses, hypocalcemia was independently associated with good neurological status at discharge (adjusted odds ratio of 6.67, 95% confidence interval 1.39-33.33, p = 0.02). CONCLUSIONS: Our study demonstrates that among patients with isolated severe TBI, mild admission hypocalcemia is associated with better neurological status at hospital discharge. The prognostic value of Ca++ may be greater among patients with admission Glasgow Coma Scale > 8. Trials are needed to investigate the role of hypocalcemia in brain injury.

Outcomes of basic versus advanced prehospital life support in severe pediatric trauma.

OBJECTIVE: The role of basic life support (BLS) vs. advanced life support (ALS) in pediatric trauma is controversial. Although ALS is widely accepted as the gold standard, previous studies have found no advantage of ALS over BLS care in adult trauma. The objective of this study was to evaluate whether ALS transport confers a survival advantage over BLS among severely injured children. METHODS: A retrospective cohort study of data included in the Israeli National Trauma Registry from January 1, 2011, through December 31, 2020 was conducted. All the severely injured children (age < 18 years and injury severity score [ISS] ≥16) were included. Patient survival by mode of transport was analyzed using logistic regression. RESULTS: Of 3167 patients included in the study, 65.1% were transported by ALS and 34.9% by BLS. Significantly more patients transported by ALS had ISS ≥25 as well as abnormal vital signs at admission. The ALS and BLS cohorts were comparable in age, gender, mechanism of injury, and prehospital time. Children transported by ALS had higher in-hospital mortality (9.2% vs. 0.9%, p < 0.001). Following risk adjustment, patients transported by ALS teams were significantly more likely to die than patients transported by BLS (adjusted OR 2.27, 95% CI 1.05-5.41, p = 0.04). Patients with ISS ≥50 had comparable mortality rates in both groups (45.9% vs. 55.6%, p = 0.837) while patients with GCS <9 transported by ALS had higher mortality (25.9% vs. 11.5%, p = 0.019). Admission to a level II trauma center vs. a level I hospital was also associated with increased mortality (adjusted OR 2.78 (95% CI 1.75-4.55, p < 0.001). CONCLUSIONS: Among severely injured children, prehospital ALS care was not associated with lower mortality rates relative to BLS care. Because of potential confounding by severity in this retrospective analysis, further studies are warranted to validate these results.

Connected consciousness after tracheal intubation in young adults: an international multicentre cohort study.

BACKGROUND: Connected consciousness, assessed by response to command, occurs in at least 5% of general anaesthetic procedures and perhaps more often in young people. Our primary objective was to establish the incidence of connected consciousness after tracheal intubation in young people aged 18-40 yr. The secondary objectives were to assess the nature of these responses, identify relevant risk factors, and determine their relationship to postoperative outcomes. METHODS: This was an international, multicentre prospective cohort study using the isolated forearm technique to assess connected consciousness shortly after tracheal intubation. RESULTS: Of 344 enrolled subjects, 338 completed the study (mean age, 30 [standard deviation, 6.3] yr; 232 [69%] female). Responses after intubation occurred in 37/338 subjects (11%). Females (13%, 31/232) responded more often than males (6%, 6/106). In logistic regression, the risk of responsiveness was increased with female sex (odds ratio [ORadjusted]=2.7; 95% confidence interval [CI], 1.1-7.6; P=0.022) and was decreased with continuous anaesthesia before laryngoscopy (ORadjusted=0.43; 95% CI, 0.20-0.96; P=0.041). Responses were more likely to occur after a command to respond (and not to nonsense, 13 subjects) than after a nonsense statement (and not to command, four subjects, P=0.049). CONCLUSIONS: Connected consciousness occured after intubation in 11% of young adults, with females at increased risk. Continuous exposure to anaesthesia between induction of anaesthesia and tracheal intubation should be considered to reduce the incidence of connected consciousness. Further research is required to understand sex-related differences in the risk of connected consciousness.

Indications for prehospital intubation among severely injured children and the prevalence of significant traumatic brain injury among those intubated due to impaired level of consciousness.

BACKGROUND: Prehospital endotracheal intubation (PEI) of head injured children with impaired level of consciousness (LOC) aims to minimize secondary brain injury. However, PEI is controversial in otherwise stable children. We aimed to investigate the indications for PEI among pediatric trauma patients and the prevalence of clinically significant traumatic brain injury (csTBI) among those intubated solely due to impaired consciousness. METHODS: This is a multicenter retrospective cohort study of children who underwent PEI in northern Israel between January 2014 and December 2020 by six EMS agencies and were transported to two trauma centers in the area. We extracted data from EMS records and trauma registries. RESULTS: PEI was attempted in 179/986 (18.2%) patients and was successful in 92.2% of cases. Common indications for PEI were hypoxemia not corrected by supplemental oxygen (n = 30), traumatic cardiac arrest (n = 16), and facial injury compromising the airway (n = 13). 112 patients (62.6%) were intubated solely due to impaired or deteriorating LOC. Among these patients, 68 (62.4%) suffered csTBI. The prevalence of csTBI among those with field Glasgow Coma Scale (GCS) of 3, 4-8, and > 8 was 81.4%, 55.8%, and 28.6%, respectively (p < 0.001). Among children ≤ 10 years old intubated due to impaired LOC, 50% had csTBI. CONCLUSION: Impaired LOC is a major indication for PEI. However, a significant proportion of these patients do not suffer csTBI. Older age and lower pre-intubation GCS are associated with more accurate field classification. Our data indicate that further investigation and better characterization of patients who may benefit from PEI is necessary.

Thalamic deep brain stimulation paradigm to reduce consciousness: Cortico-striatal dynamics implicated in mechanisms of consciousness.

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes of abnormally long, vacant staring with low-frequency oscillations here termed vacant, perturbed consciousness (VPC). DBS modulated VPC likelihood in a frequency-specific manner. VPC events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), proposed indices of consciousness, and substantial changes to communication in CST circuits. During VPC, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of VPC and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method-but at different stimulation frequencies-can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of other consciousness disorders.

Admission hypocalcemia in pediatric major trauma patients-An uncommon phenomenon associated with an increased need for urgent blood transfusion.

BACKGROUND: Hemorrhage is a leading cause of death among children. Recent data from adult trauma suggests that early, transfusion-unrelated, hypocalcemia is common and that it is associated with an increased need for blood transfusion, mortality, and coagulopathy. The objectives of this study are to evaluate the prevalence of admission hypocalcemia in severely injured children and its correlation with urgent blood transfusion. STUDY DESIGN AND METHODS: This is a retrospective cohort study of all severely injured (Injury Severity Score [ISS] > 15) pediatric (<18 years) trauma patients admitted to Rambam Health Care Campus, Israel between 2012 and 2020. We excluded patients transferred from other facilities and those who received blood before determining calcium levels. Severe hypocalcemia was defined as ionized calcium (Ca++ ) < 1.0 mmol/L and mild hypocalcemia as 1.0 mmol/L ≤ Ca++  < 1.1 mmol/L. The primary outcome was urgent blood transfusion (transfusion in the emergency department [ED]). RESULTS: Six hundred seventy-three severely injured children were admitted from the field. Ca++ levels were determined before blood transfusion in 457 patients. Severe hypocalcemia was found in three patients (0.7%) and mild hypocalcemia in additional 21 patients (4.6%). Hypocalcemic patients required more urgent blood transfusion (29.2% vs. 6.5%, p < .001) and had higher ISS (29 [interquartile range, IQR: 22-35] vs. 25 [IQR: 19-34], p = .05). Multivariable logistic regression analysis identified Ca++  < 1.1 mmol/L as an independent predictor of the need for blood transfusion, odds ratio 5.44 (95% confidence interval 1.44-20.58), p = .01. DISCUSSION: Contrary to adults, admission hypocalcemia is uncommon in severely injured children. However, it may be associated with an increased risk of blood transfusion in the ED.

Spatiotemporal patterns of population response in the visual cortex under isoflurane: from wakefulness to loss of consciousness.

Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Isoflurane is a commonly used anesthetic drug; however, its effects on cortical sensory processing, in particular around LOC, are not well understood. Using voltage-sensitive dye imaging, we measured visually evoked neuronal population response from the visual cortex in awake and anesthetized mice at 3 increasing concentrations of isoflurane, thus controlling the level of anesthesia from wakefulness to deep anesthesia. At low concentration of isoflurane, the effects on neuronal measures were minor relative to the awake condition. These effects augmented with increasing isoflurane concentration, while around LOC point, they showed abrupt and nonlinear changes. At the network level, we found that isoflurane decreased the stimulus-evoked intra-areal spatial spread of local neural activation, previously reported to be mediated by horizontal connections, and also reduced intra-areal synchronization of neuronal population. The synchronization between different visual areas decreased with higher isoflurane levels. Isoflurane reduced the population response amplitude and prolonged their latencies while higher visual areas showed increased vulnerability to isoflurane concentration. Our results uncover the changes in neural activity and synchronization at isoflurane concentrations leading to LOC and suggest reverse hierarchical shutdown of cortical areas.

Dexmedetomidine depresses neuronal activity in the subthalamic nucleus during deep brain stimulation electrode implantation surgery.

Background: Micro-electrode recordings are often necessary during electrode implantation for deep brain stimulation of the subthalamic nucleus. Dexmedetomidine may be a useful sedative for these procedures, but there is limited information regarding its effect on neural activity in the subthalamic nucleus and on micro-electrode recording quality. Methods: We recorded neural activity in five patients undergoing deep brain stimulation implantation to the subthalamic nucleus. Activity was recorded after subthalamic nucleus identification while patients received dexmedetomidine sedation (loading - 1 µg kg-1 over 10-15 min, maintenance - 0.7 µg kg-1 h-1). We compared the root-mean square (RMS) and beta band (13-30 Hz) oscillation power of multi-unit activity recorded by microelectrode before, during and after recovery from dexmedetomidine sedation. RMS was normalised to values recorded in the white matter. Results: Multi-unit activity decreased during sedation in all five patients. Mean normalised RMS decreased from 2.8 (1.5) to 1.6 (1.1) during sedation (43% drop, p = 0.056). Beta band power dropped by 48.4%, but this was not significant (p = 0.15). Normalised RMS values failed to return to baseline levels during the time allocated for the study (30 min). Conclusions: In this small sample, we demonstrate that dexmedetomidine decreases neuronal firing in the subthalamic nucleus as expressed in the RMS of the multi-unit activity. As multi-unit activity is a factor in determining the subthalamic nucleus borders during micro-electrode recordings, dexmedetomidine should be used with caution for sedation during these procedures. Clinical trial number: NCT01721460.

Prevalence of significant traumatic brain injury among patients intubated in the field due to impaired level of consciousness.

OBJECTIVE: Current guidelines advocate prehospital endotracheal intubation (ETI) in patients with suspected severe head injury and impaired level of consciousness. However, the ability to identify patients with traumatic brain injury (TBI) in the prehospital setting is limited and prehospital ETI carries a high complication rate. We investigated the prevalence of significant TBI among patients intubated in the field for that reason. METHODS: Data were retrospectively collected from emergency medical services and hospital records of trauma patients for whom prehospital ETI was attempted and who were transferred to Rambam Health Care Campus, Israel. The indication for ETI was extracted. The primary outcome was significant TBI (clinical or radiographic) among patients intubated due to suspected severe head trauma. RESULTS: In 57.3% (379/662) of the trauma patients, ETI was attempted due to impaired consciousness. 349 patients were included in the final analysis: 82.8% were male, the median age was 34 years (IQR 23.0-57.3), and 95.7% suffered blunt trauma. 253 patients (72.5%) had significant TBI. In a multivariable analysis, Glasgow Coma Scale>8 and alcohol intoxication were associated with a lower risk of TBI with OR of 0.26 (95% CI 0.13-0.51, p < 0.001) and 0.16 (95% CI 0.06-0.46, p < 0.001), respectively. CONCLUSION: Altered mental status in the setting of trauma is a major reason for prehospital ETI. Although most of these patients had TBI, one in four of them did not suffer a significant TBI. Patients with a higher field GCS and those suffering from intoxication have a higher risk of misdiagnosis. Future studies should explore better tools for prehospital assessment of TBI and ways to better define and characterize patients who may benefit from early ETI.

Differences in the thermal properties and surface temperature of prehospital antihypothermia devices: an in vitro study.

BACKGROUND: Preventing and treating hypothermia in prehospital settings is crucial. Several products have been developed to prevent heat loss and actively warm patients in prehospital settings. We compared the efficacy and the surface temperature of different antihypothermia products, using a fluid-based model at two ambient temperatures. METHODS: We tested five active (Blizzard Heat with active pads, Ready-Heat, Ready-Heat-II, Hypothermia Prevention and Management Kit (HPMK), Bair Hugger) and five passive (Blizzard Heat, Heat Reflective Shell, sleeping bag, 'space blanket', wool blanket) antihypothermia products. A torso model consisting of four 8 L bags of fluid preheated to 36°C±0.5°C (97±0.5°F) was used to compare the devices' performances at 20°C (68°F) and 8°C (46°F). Inner and surface temperatures were recorded for up to 480 min. RESULTS: We found significant differences in heat loss in fluid bags among the tested devices at both temperatures (p<0.001). At 20°C, only HPMK and Ready-Heat-II increased the inner temperature for 480 min while Blizzard Heat with active pads prevented heat loss. Ready-Heat prevented heat loss for 90 min. All the other devices did not prevent heat loss beyond 30 min. At 8°C, none of the products heated the model. Bair Hugger, HPMK, Ready-Heat II and sleeping bag prevented heat loss for 30 min. At 60, 90 and 120 min HPMK, Ready-Heat II and Bair Hugger were the most effective. Over 480 min, Bair Hugger was most effective, with a heat loss of 2.3°C±0.4°C. The surface temperature exceeded 44°C (111°F) for all the exothermic warming devices when used for a prolonged period of time. CONCLUSION: At 20°C, HPMK and Ready-Heat-II increased fluid temperature in the model, while the other devices decreased heat loss. At 8°C, none of the tested devices increased the temperature. However, active heating devices prevented heat loss slightly better than passive methods. A protective insulation layer should be used with all active heating blankets.

Association Between Ionized Calcium Level and Neurological Outcome in Endovascularly Treated Patients with Spontaneous Subarachnoid Hemorrhage: A Retrospective Cohort Study.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SSAH) is associated with significant morbidity and mortality. Pathophysiological processes following initial bleeding are complex and not fully understood. In this study, we aimed to determine whether a low level of ionized calcium (Ca++), an essential cofactor in the coagulation cascade and other cellular processes, is associated with adverse neurological outcome, development of early hydrocephalus, and symptomatic vasospasm among patients with SSAH. METHODS: This was a retrospective single-center cohort study of all patients admitted for SSAH between January 1, 2009, and April 31, 2020. The primary outcome was an unfavorable neurological status at discharge, defined as a modified Rankin Scale score greater than or equal to 3. Secondary outcomes were the development of early hydrocephalus and symptomatic vasospasm. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these outcomes. RESULTS: A total of 255 patients were included in the final analysis. Hypocalcemia, older age, admission Glasgow Coma Scale (GCS) score, and admission Hunt-Hess classification scale (H&H) grades IV and V were independently associated with unfavorable neurological outcome, with adjusted odds ratios (ORs) of 1.93 (95% confidence interval [CI] 1.1-3.4; p = 0.02) for each 0.1 mmol L-1 decrease in the Ca++ level, 1.04 (95% CI 1.01-1.08; p = 0.02) for each year increase, 0.82 (95% CI 0.68-0.99; p = 0.04), and 6.29 (95% CI 1.14-34.6; p = 0.03), respectively. Risk factors for the development of hydrocephalus were hypocalcemia and GCS score, with ORs of 1.85 (95% CI 1.26-2.71; p = 0.002) for each 0.1 mmol L-1 decrease in the Ca++ level and 0.83 (95% CI 0.73-0.94; p = 0.005), respectively. Ca++ was not associated with symptomatic vasospasm (OR 1.04 [95% CI 0.76-1.41]; p = 0.81). Among patients with admission H&H grade I-III bleeding, hypocalcemia was independently associated with unfavorable neurological outcome at discharge, with an adjusted OR of 1.99 (95% CI 1.03-3.84; p = 0.04) for each 0.1 mmol L-1 decrease in the Ca++ level. Hypocalcemia was also an independent risk factor for the development of early hydrocephalus, with an adjusted OR of 2.95 (95% CI 1.49-5.84; p = 0.002) for each 0.1 mmol L-1 decrease in the Ca++ level. Ca++ was not associated with symptomatic vasospasm. No association was found between Ca++ and predefined outcomes among patients with admission H&H grade IV and V bleeding. CONCLUSIONS: Our study shows that hypocalcemia is associated with worse neurological outcome at discharge and development of early hydrocephalus in endovascularly treated patients with SSAH. Potential mechanisms include calcium-induced coagulopathy and higher blood pressure. Trials are needed to assess whether correction of hypocalcemia will lead to improved outcomes.

Neurons in the Nonhuman Primate Amygdala and Dorsal Anterior Cingulate Cortex Signal Aversive Memory Formation under Sedation.

BACKGROUND: Anesthetics aim to prevent memory of unpleasant experiences. The amygdala and dorsal anterior cingulate cortex participate in forging emotional and valence-driven memory formation. It was hypothesized that this circuitry maintains its role under sedation. METHODS: Two nonhuman primates underwent aversive tone-odor conditioning under sedative states induced by ketamine or midazolam (1 to 8 and 0.1 to 0.8 mg/kg, respectively). The primary outcome was behavioral and neural evidence suggesting memory formation. This study simultaneously measured conditioned inspiratory changes and changes in firing rate of single neurons in the amygdala and the dorsal anterior cingulate cortex in response to an expected aversive olfactory stimulus appearing during acquisition and tested their retention after recovery. RESULTS: Aversive memory formation occurred in 26 of 59 sessions under anesthetics (16 of 29 and 10 of 30, 5 of 30 and 21 of 29 for midazolam and ketamine at low and high doses, respectively). Single-neuron responses in the amygdala and dorsal anterior cingulate cortex were positively correlated between acquisition and retention (amygdala, n = 101, r = 0.51, P < 0.001; dorsal anterior cingulate cortex, n = 121, r = 0.32, P < 0.001). Neural responses during acquisition under anesthetics were stronger in sessions exhibiting memory formation than those that did not (amygdala median response ratio, 0.52 versus 0.33, n = 101, P = 0.021; dorsal anterior cingulate cortex median response ratio, 0.48 versus 0.32, n = 121, P = 0.012). The change in firing rate of amygdala neurons during acquisition was correlated with the size of stimuli-conditioned inspiratory response during retention (n = 101, r = 0.22 P = 0.026). Thus, amygdala and dorsal anterior cingulate cortex responses during acquisition under anesthetics predicted retention. Respiratory unconditioned responses to the aversive odor anesthetics did not differ from saline controls. CONCLUSIONS: These results suggest that the amygdala-dorsal anterior cingulate cortex circuit maintains its role in acquisition and maintenance of aversive memories in nonhuman primates under sedation with ketamine and midazolam and that the stimulus valence is sufficient to drive memory formation.

Consciousness depends on integration between parietal cortex, striatum, and thalamus.

The neural substrates of consciousness remain elusive. Competing theories that attempt to explain consciousness disagree on the contribution of frontal versus posterior cortex and omit subcortical influences. This lack of understanding impedes the ability to monitor consciousness, which can lead to adverse clinical consequences. To test substrates and measures of consciousness, we recorded simultaneously from frontal cortex, parietal cortex, and subcortical structures, the striatum and thalamus, in awake, sleeping, and anesthetized macaques. We manipulated consciousness on a finer scale using thalamic stimulation, rousing macaques from continuously administered anesthesia. Our results show that, unlike measures targeting complexity, a measure additionally capturing neural integration (Φ∗) robustly correlated with changes in consciousness. Machine learning approaches show parietal cortex, striatum, and thalamus contributed more than frontal cortex to decoding differences in consciousness. These findings highlight the importance of integration between parietal and subcortical structures and challenge a key role for frontal cortex in consciousness.

Hypocalcemia is associated with adverse clinical course in patients with upper gastrointestinal bleeding.

Acute non-variceal upper gastrointestinal bleeding (NV-UGIB) is associated with significant morbidity and mortality. Early and efficient risk stratification can facilitate management and improve outcomes. We aimed to determine whether the level of ionized calcium (Ca++), an essential co-factor in the coagulation cascade, is associated with the severity of bleeding and the need for advanced interventions among these patients. This was a retrospective single-center cohort study of all patients admitted due to NV-UGIB. The primary outcome was transfusion of ≥ 2 packed red blood cells, arterial embolization, or emergency surgery. Secondary outcomes included (1) transfusion of ≥ 2 packed red blood cells, (2) arterial embolization, or emergency surgery, and (3) all-cause in-hospital mortality. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these adverse outcomes. 1345 patients were included. Hypocalcemia was recorded in 604 (44.9%) patients. The rates of primary adverse outcome were significantly higher in the hypocalcemic group, 14.4% vs. 5.1%, p < 0.001. Secondary outcomes-multiple transfusions, need for angiography or surgery, and mortality were also increased (9.9% vs. 2.3%, p < 0.001, 5.3% vs. 2.8%, p = 0.03, and 33.3% vs. 24.7%, p < 0.001, respectively). Hypocalcemia was an independent predictor of primary and all the secondary outcomes, except mortality. Hypocalcemia in high-risk hospitalized patients with NV-UGIB is common and independently associated with adverse outcomes. Ca++ monitoring in this population may facilitate the rapid identification of high-risk patients. Trials are needed to assess whether correction of hypocalcemia will lead to improved outcomes.

Return to training in the COVID-19 era: The physiological effects of face masks during exercise.

COVID-19 outbreak has a profound impact on almost every aspect of life. Universal masking is recommended as a means of source control. Routinely exercising in a safe environment is an important strategy for healthy living during this crisis. As sports clubs and public spaces may serve a source of viral transmission, masking may become an integral part of physical activity. This study aimed to assess the physiological effects of wearing surgical masks and N95 respirators during short-term strenuous workout. This was a multiple cross-over trial of healthy volunteers. Using a standard cycle ergometry ramp protocol, each subject performed a maximal exercise test without a mask, with a surgical mask, and with an N95 respirator. Physiological parameters and time to exhaustion were compared. Each subject served his own control. Sixteen male volunteers (mean age and BMI of 34 ± 4 years and 28.72 ± 3.78 kg/m2 , respectively) completed the protocol. Heart rate, respiratory rate, blood pressure, oxygen saturation, and time to exhaustion did not differ significantly. Exercising with N95 mask was associated with a significant increase in end-tidal carbon dioxide (EtCO2 ) levels. The differences were more prominent as the load increased, reaching 8 mm Hg at exhaustion (none vs N95, P = .001). In conclusion, in healthy subjects, short-term moderate-strenuous aerobic physical activity with a mask is feasible, safe, and associated with only minor changes in physiological parameters, particularly a mild increase in EtCO2 . Subjects suffering from lung diseases should have a cautious evaluation before attempting physical activity with any mask.

Association between ionised calcium and severity of postpartum haemorrhage: a retrospective cohort study.

BACKGROUND: Postpartum haemorrhage (PPH) is often complicated by impaired coagulation. We aimed to determine whether the level of ionised calcium (Ca2+), an essential coagulation co-factor, at diagnosis of PPH is associated with bleeding severity. METHODS: This was a retrospective cohort study of women diagnosed with PPH during vaginal delivery between January 2009 and April 2020. Ca2+ levels at PPH diagnosis were compared between women who progressed to severe PPH (primary outcome) and those with less severe bleeding. Severe PPH was defined by transfusion of ≥2 blood units, arterial embolisation or emergency surgery, admission to ICU, or death. Associations between other variables (e.g. fibrinogen concentration) and bleeding severity were also assessed. RESULTS: For 436 patients included in the analysis, hypocalcaemia was more common among patients with severe PPH (51.5% vs 10.6%, P<0.001). In a multivariable logistic regression model, Ca2+ and fibrinogen were the only parameters independently associated with PPH severity with odds ratios of 1.14 for each 10 mg dl-1 decrease in fibrinogen (95% confidence interval [CI], 1.05-1.24; P=0.002) and 1.97 for each 0.1 mmol L-1 decrease in Ca2+ (95% CI, 1.25-3.1; P=0.003). The performance of Ca2+ or fibrinogen was not significantly different (area under the curve [AUC]=0.79 [95% CI, 0.75-0.83] vs AUC=0.86 [95% CI, 0.82-0.9]; P=0.09). The addition of Ca2+ to fibrinogen improved the model, leading to AUC of 0.9 (95% CI, 0.86-0.93), P=0.03. CONCLUSIONS: Ca2+ level at the time of diagnosis of PPH was associated with risk of severe bleeding. Ca2+ monitoring may facilitate identification and treatment of high-risk patients.

Sedative drugs modulate the neuronal activity in the subthalamic nucleus of parkinsonian patients.

Microelectrode recording (MER) is often used to identify electrode location which is critical for the success of deep brain stimulation (DBS) treatment of Parkinson's disease. The usage of anesthesia and its' impact on MER quality and electrode placement is controversial. We recorded neuronal activity at a single depth inside the Subthalamic Nucleus (STN) before, during, and after remifentanil infusion. The root mean square (RMS) of the 250-6000 Hz band-passed signal was used to evaluate the regional spiking activity, the power spectrum to evaluate the oscillatory activity and the coherence to evaluate synchrony between two microelectrodes. We compare those to new frequency domain (spectral) analysis of previously obtained data during propofol sedation. Results showed Remifentanil decreased the normalized RMS by 9% (P < 0.001), a smaller decrease compared to propofol. Regarding the beta range oscillatory activity, remifentanil depressed oscillations (drop from 25 to 5% of oscillatory electrodes), while propofol did not (increase from 33.3 to 41.7% of oscillatory electrodes). In the cases of simultaneously recorded oscillatory electrodes, propofol did not change the synchronization while remifentanil depressed it. In conclusion, remifentanil interferes with the identification of the dorsolateral oscillatory region, whereas propofol interferes with RMS identification of the STN borders. Thus, both have undesired effect during the MER procedure.Trial registration: NCT00355927 and NCT00588926.