Baroreflex dynamics during the rest to exercise transient in acute normobaric hypoxia in humans.

PURPOSE: We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A1) due to lower vagal activity in H than N. METHODS: Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O2 = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method. RESULTS: Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg-1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg-1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg-1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg-1 (p < 0.01 vs. rest). CO-A1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min-1 in N and H, respectively (p = 0.06). HR-A1 was 7.7 ± 4.6 and 7.1 ± 5.9 min-1 in N and H, respectively (p = 0.81). CONCLUSION: The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive.

Changing the stroke network during pandemic scenarios does not affect the management of patients with a positive Cincinnati prehospital stroke scale.

INTRODUCTION: Time plays a crucial role in the management of stroke, and changing the prehospital emergency network, altering the HUB and spoke relationship in pandemic scenarios, might have an impact on time to fibrinolysis or thrombectomy. The aim of this study was to evaluate the time-dependent stroke emergency network in Lombardy region (Italy) by comparing 2019 with 2020 and early 2021. Three parameters were investigated: (i) time of arrival of the first vehicle at the scene, (ii) overall duration of missions, and (iii) number of patients transported by emergency vehicles. METHODS: Data analysis process conducted using the SAS-AREU portal (SAS Institute, USA). RESULTS: The number of patients with a positive CPSS was similar among the different pandemic waves. Mission duration increased from a mean time (SD) of 52.9 (16.1) min in 2019 to 64.1 (19.7) in 2020 and 55.0 (16.8) in 2021. Time to first vehicle on scene increased to 15.7 (8.4) min in 2020 and 16.0 (7.0) in 2021 compared to 2019, 13.6 (7.2) (P < 0.05). The number of hospital with available stroke units decreased from 46 in 2019 to 10 during the first pandemic wave. CONCLUSIONS: The pandemic forced changes in the clinical mission of many hospitals by reducing the number of stroke units. Despite this, the organization of the emergency system allowed to identify strategic hospitals and thus avoid excessive transport time. The result was an adequate time for fibrinolysis/thrombectomy, in agreement with the guidelines. Coordinated management in emergency situations makes it possible to maintain service quality standards, despite the unfavorable scenario.

Effectiveness of Cardiopulmonary Resuscitation at the Workplace.

BACKGROUND: Out-of-Hospital Cardiac Arrest (OHCA) is a medical emergency whose chances of survival can be increased by rapid Cardiopulmonary Resuscitation (CPR) and early use of Public Access Defibrillators (PAD). Basic Life Support (BLS) training became mandatory in Italy to spread knowledge of resuscitation maneuvers in the workplace. Basic Life Support (BLS) training became mandatory according to the DL 81/2008 law. To improve the level of cardioprotection in the workplace, the national law DL 116/2021 increased the number of places required to be provided with PADs. The study highlights the possibility of a Return to spontaneous circulation in OHCA in the workplace. METHODS: A multivariate logistic regression model was fitted to the data to extrapolate associations between ROSC and the dependent variables. The associations' robustness was evaluated through sensitivity analysis. RESULTS: The chance to receive CPR (OR 2.3; 95% CI:1.8-2.9), PAD (OR 7.2; 95% CI:4.9 - 10.7), and achieve Return to spontaneous circulation (ROSC) (crude OR 2.2; 95% CI:1.7-3.0, adjusted OR 1.6; 95% CI:1.2-2.2) is higher in the workplace compared to all other places. CONCLUSION: The workplace could be considered cardioprotective, although further research is necessary to understand the causes of missed CPRs and identify the best places to increase BLS and defibrillation training to help policymakers implement correct programming on the activation of PAD projects.

Comparison of resting energy expenditure measured with metabolic cart and calculated with predictive formulas in critically ill patients on mechanical ventilation.

INTRODUCTION: The purpose was to compare the resting energy expenditure (REE) measured with the Q-NRG™+ metabolic-cart (MREE) with REE predicted by equations (the Harris-Benedict formula and an equation developed in ward, REE-HB and REE-W, respectively). We also aimed to assess the agreement of the measurements of oxygen consumption (V̇O2) and carbon dioxide production (V̇CO2) at different inspired fractions of oxygen (FiO2). METHODS: 27 mechanically ventilated ICU patients were enrolled. V̇O2 and V̇CO2 were measured by Q-NRG™+ during breathing 40% and 60% FiO2. MREE was compared with REE-W and REE-HB normalized for body weight. RESULTS: V̇O2 was 233.0 (95.2) ml/min and 217.5 (89.8) ml/min at FiO2 40% and 60%, respectively (NS). V̇CO2 was 199.0 (91.7) ml/min at FiO2 40%, and 197.5 (85.5) ml/min at FiO2 60% (NS). The REE estimated from the equations was significantly different from the MREE. The best agreement was found for the Harris-Benedict equation without correction for stress-factors. Harris-Benedict equation corrected overestimates REE. CONCLUSIONS: This new metabolic cart Q-NRG™+ provides a concordance of values for V̇O2 and V̇CO2 when measured at different FiO2, and is a reliable tool for estimating energy expenditure and assessing the nutritional needs of the patient. This study demonstrates that the estimation of REE using predictive formulas does not allow accurate calculation of metabolic demands in ventilated intensive care patient. However, predictive equations allow for a rapid assessment of REE and calculation of the amount of energy derived from different substrates.

Changes to the Major Trauma Pre-Hospital Emergency Medical System Network before and during the 2019 COVID-19 Pandemic.

Objectives: During the coronavirus disease 2019 pandemic, emergency medical services (EMSs) were among the most affected; in fact, there were delays in rescue and changes in time-dependent disease networks. The aim of the study is to understand the impact of COVID-19 on the time-dependent trauma network in the Lombardy region. Methods: A retrospective analysis on major trauma was performed by analysing all records saved in the EmMa database from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Age, gender, time to first emergency vehicle on scene and mission duration were collected. Results: In 2020, compared to 2019, there was a reduction in major trauma diagnoses in March and April, during the first lockdown, OR 0.59 (95% CI 0.49−0.70; p < 0.0001), and a reduction in road accidents and accidents at work, while injuries related to falls from height and violent events increased. There was no significant increase in the number of deaths in the prehospital setting, OR 1.09 (95% CI 0.73−1.30; p = 0.325). Conclusions: The COVID-19 pandemic has changed the epidemiology of major trauma, but in the Lombardy region there was no significant change in mortality in the out-of-hospital setting.

The Impact of COVID-19 on Lombardy Region ST-Elevation Myocardial Infarction Emergency Medical System Network-A Three-Year Study.

Objectives: The COVID-19 pandemic had a significant impact on emergency medical systems (EMS). Regarding the ST-elevation myocardial infarction (STEMI) dependent time network, however, there is little evidence linked to the post-pandemic phase regarding this issue. Such information could prove to be of pivotal importance regarding STEMI clinical management, especially pre-hospital clinical protocols such as fibrinolysis. Methods: A retrospective observational cohort study of all STEMI rescues recorded in the Lombardy EMS registry from the 1st of January 2019 to the 30th of December 2021. Results: Regarding the number of STEMI diagnoses, March 2020 (first pandemic wave in Italy) saw a reduction compared to March 2019 (OR 0.76 [0.60-0.93], p = 0.011). The average time of the entire mission increased to 63.1 min in 2021, reaching 64.7 min in 2020, compared with 57.7 min in 2019. The number of HUBs for STEMI patients saw a reduction, falling from 52 HUBs in the pre-pandemic phase to 13 HUBs during the first wave. Conclusions: During the pandemic phase, there was an increase in the transportation times of STEMI patients from home to the hospital. Such changes did not alter the clinical approach in the out-of-hospital phase. Indeed, the implementation of fibrinolysis was not required.

Smart-working policies during COVID-19 pandemic: a way to reduce work-related traumas?

Eighth of March 2020, the Italian government introduced a national lockdown to counter the exponential increase in the number of COVID-19 cases; this decision avoided putting a strain on the health system. During the lockdown all non-essential services were stopped and a "stay at home" order was imposed. The purpose is to evaluate the impact of COVID-19 lockdown on Emergency Department (ED) visits due to work-related traumas in the Lombardy region. We performed a retrospective analysis on trauma admissions to the ED registered through the regional portal (EUOL), from 1st January 2019 to 31st December 2019 and from 1st January 2020 to 31st December 2020. The number of ED admissions for traumatic injury and work-related traumas dropped by 32% between 2019 and 2020. A remarkable reduction of work-related traumas was recorded during the two pandemic waves, from March to June and in October and November. The percentage of patient in critical condition in ED slightly raised. These results are probably a consequence of the unprecedented measures imposed by the Italian government to cope with the spread of COVID-19, with important implications for work contexts. This analysis should be considered to optimise the organisation of the emergency system in other critical scenarios. We speculate that the different epidemiology of occupational injuries during the lockdown period is a consequence of smart-working policies that can be held responsible for the drastic reduction of work-related traumas.

Dynamics of cardiovascular and baroreflex readjustments during a light-to-moderate exercise transient in humans.

PURPOSE: We hypothesised that, during a light-to-moderate exercise transient, compared to an equivalent rest-to-exercise transient, (1) a further baroreflex sensitivity (BRS) decrease would be slower, (2) no rapid heart rate (HR) response would occur, and (3) the rapid cardiac output (CO) response would have a smaller amplitude (A1). Hence, we analysed the dynamics of arterial baroreflexes and the HR and CO kinetics during rest-to-50 W (0-50 W) and 50-to-100 W (50-100 W) exercise transients. METHODS: 10 subjects performed three 0-50 W and three 50-100 W on a cycle ergometer. We recorded arterial blood pressure profiles (photo-plethysmography) and R-to-R interval (RRi, electrocardiography). The former were analysed to obtain beat-by-beat mean arterial pressure (MAP) and stroke volume (SV). CO was calculated as SV times HR. BRS was measured by modified sequence method. RESULTS: During 0-50 W, MAP transiently fell (- 9.0 ± 5.7 mmHg, p < 0.01) and BRS passed from 15.0 ± 3.7 at rest to 7.3 ± 2.4 ms mmHg-1 at 50 W (p < 0.01) promptly (first BRS sequence: 8.1 ± 4.6 ms mmHg-1, p < 0.01 vs. rest). During 50-100 W, MAP did not fall and BRS passed from 7.2 ± 2.6 at 50 W to 3.3 ± 1.3 ms mmHg-1 at 100 W (p < 0.01) slowly (first BRS sequence: 5.3 ± 3.1 ms mmHg-1, p = 0.07 vs. 50 W). A1 for HR was 9.2 ± 6.0 and 6.0 ± 4.5 min-1 in 0-50 W and 50-100 W, respectively (p = 0.19). The corresponding A1 for CO were 2.80 ± 1.54 and 0.91 ± 0.55 l∙min-1 (p < 0.01). CONCLUSION: During 50-100 W, with respect to 0-50 W, BRS decreased more slowly, in absence of a prompt pressure decrease. BRS decrease and rapid HR response in 50-100 W were unexpected and ascribed to possible persistence of some vagal tone at 50 W.

Cardiopulmonary resuscitation missed by bystanders: Collateral damage of coronavirus disease 2019.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic changed the time-dependent cardiac arrest network. This study aims to understand whether the rescue standards of cardiopulmonary resuscitation (CPR) and out-of-hospital cardiac arrest (OHCA) were handled differently during pandemic compared to the previous year. METHODS: Data for the years 2019 and 2020 were provided by the records of the Lombardy office of the Regional Agency for Emergency and Urgency. We analysed where the cardiac arrest occurred, when CPR started and whether the bystanders used public access to defibrillation (PAD). RESULTS: During 2020, there was a reduction in CPRs performed by bystanders (odds ratio [OR] = 0.936 [95% confidence interval (CI95% ) 0.882-0.993], p = .029) and in the return of spontaneous circulation (ROSC) (OR = 0.621 [CI95% 0.563-0.685], p < .0001), while there was no significant reduction in the use of PAD. Analysing only March, the period of the first wave in Lombardy, the comparison shows a reduction in bystanders CPRs (OR = 0.727 [CI95% 0.602-0.877], p = .0008), use of PAD (OR = 0.441 [CI95% 0.272-0.716], p = .0009) and in ROSC (OR = 0.179 [CI95% 0.124-0.257], p < .0001). These phenomena could be influenced by the different settings in which the OHCAs occurred; in fact, those that occurred in public places with a mandatory PAD were strongly reduced (OR = 0.49 [CI95% , 0.44-0.55], p < .0001). CONCLUSIONS: COVID-19 had a profound impact on the time-dependant OHCA network. During the first pandemic wave, CPR and PAD used by bystanders decreased. The different contexts in which OHCAs occurred may partially explain these differences.

A century of exercise physiology: key concepts on coupling respiratory oxygen flow to muscle energy demand during exercise.

After a short historical account, and a discussion of Hill and Meyerhof's theory of the energetics of muscular exercise, we analyse steady-state rest and exercise as the condition wherein coupling of respiration to metabolism is most perfect. The quantitative relationships show that the homeostatic equilibrium, centred around arterial pH of 7.4 and arterial carbon dioxide partial pressure of 40 mmHg, is attained when the ratio of alveolar ventilation to carbon dioxide flow ([Formula: see text]) is - 21.6. Several combinations, exploited during exercise, of pertinent respiratory variables are compatible with this equilibrium, allowing adjustment of oxygen flow to oxygen demand without its alteration. During exercise transients, the balance is broken, but the coupling of respiration to metabolism is preserved when, as during moderate exercise, the respiratory system responds faster than the metabolic pathways. At higher exercise intensities, early blood lactate accumulation suggests that the coupling of respiration to metabolism is transiently broken, to be re-established when, at steady state, blood lactate stabilizes at higher levels than resting. In the severe exercise domain, coupling cannot be re-established, so that anaerobic lactic metabolism also contributes to sustain energy demand, lactate concentration goes up and arterial pH falls continuously. The [Formula: see text] decreases below - 21.6, because of ensuing hyperventilation, while lactate keeps being accumulated, so that exercise is rapidly interrupted. The most extreme rupture of the homeostatic equilibrium occurs during breath-holding, because oxygen flow from ambient air to mitochondria is interrupted. No coupling at all is possible between respiration and metabolism in this case.

Missed training, collateral damage from COVID 19?

BACKGROUND: during the COVID-19 pandemic a total lockdown was enforced all over Italy starting on March 9th. This resulted in the shrinking of economic activities. In addition, all formal occupational security-training courses were halted, among them the 81/08 law lectures and Basic Life Support-Defibrillation (BLS-D) laymen training courses. The aim of the study was to evaluate the impact of the pandemic on BLS-D laymen training courses in the Lombardy region. METHODS: BLS-D training courses records for the Lombardy region were analysed. The analysis was conducted from 2016 to 2020 as part of the Hippo project. RESULTS: between 2017 and 2019 BLS-D trained laymen kept increasing, moving from 53,500 trained individuals up to 74,700. In 2020 a stark reduction was observed with only 22,160 individuals trained. Formal courses were not halted completely during 2020. Still, in the months available for training, the number of individuals enrolled showed a sharp 50% reduction. CONCLUSIONS: laymen training courses for emergency management are a fundamental component of primary prevention practice. The 81/08 and 158/12 Italian laws have decreed this practice mandatory on the workplace. Following the enforcement of the lockdown and the subsequent interruption of emergency management courses, efforts will be necessary to re-establish and guarantee the high quality training of the pre-pandemic period.

Effectiveness of massive transfusion protocol activation in pre-hospital setting for major trauma.

INTRODUCTION: Hemorrhage in major trauma is life-threatening and the activation of the Massive Transfusion Protocol (MTP) was found to reduce the time to transfusion and mortality. The purpose was (i) to verify whether MTP activation identifies patients that require massive transfusions once admitted to the Emergency Department (ED), (ii) to establish whether pre-hospital MTP activation reduces the time to transfusion on arrival at the ED, (iii) to identify the variable that best predicts MTP activation. MATERIALS AND METHODS: This is a retrospective, single-center study. The MTP was implemented at the end of 2012; it was activated for major trauma in pre-hospital setting on the basis on established criteria. Pre-hospital MTP activation aimed to make blood products available prior to the patients' arrival at the ED. The blood products are transfused when the patient arrives at the hospital. RESULTS: The MTP was activated in pre-hospital setting in 219 patients. On arrival at the hospital, the Trauma Team Leader confirmed MTP activation in 146 (66.7%) patients. Patients with MTP criteria received a higher amount of blood products than the patients without MTP criteria, median 7 (IQR 2-13) units versus 2 (0-6) units, respectively (P < 0.001). At the same time, patients with a Shock Index ≥ 0.9 received more transfusions (5.5 [2-13] units) compared with patients characterized by a lower SI (2 [0-7.25] units, P = 0.009). 146 patients were transfused in the first hour of ED admission. Poisson's multiple regression shows that the SI is the variable that better predicted MTP activation compared to age, gender and the number of injured sites. CONCLUSIONS: Pre-hospital MTP activation is useful to identify patients that require an urgent blood transfusion on arrival at the ED. Further analysis should be considered to evaluate the implementation of the Shock Index as a criterion to activate MTP.

A closed-loop approach to the study of the baroreflex dynamics during posture changes at rest and at exercise in humans.

We hypothesized that during rapid uptilting at rest, due to vagal withdrawal, arterial baroreflex sensitivity (BRS) may decrease promptly and precede the operating point (OP) resetting, whereas different kinetics are expected during exercise steady state, due to lower vagal activity than at rest. To test this, eleven subjects were rapidly (<2 s) tilted from supine (S) to upright (U) and vice versa every 3 min, at rest and during steady-state 50 W pedaling. Mean arterial pressure (MAP) was measured by finger cuff (Portapres) and R-to-R interval (RRi) by electrocardiography. BRS was computed with the sequence method both during steady and unsteady states. At rest, BRS was 35.1 ms·mmHg-1 (SD = 17.1) in S and 16.7 ms·mmHg-1 (SD = 6.4) in U (P < 0.01), RRi was 901 ms (SD = 118) in S and 749 ms (SD = 98) in U (P < 0.01), and MAP was 76 mmHg (SD = 11) in S and 83 mmHg (SD = 8) in U (P < 0.01). During uptilt, BRS decreased promptly [first BRS sequence was 19.7 ms·mmHg-1 (SD = 5.0)] and was followed by an OP resetting (MAP increase without changes in RRi). At exercise, BRS and OP did not differ between supine and upright positions [BRS was 7.7 ms·mmHg-1 (SD = 3.0) and 7.7 ms·mmHg-1 (SD = 3.5), MAP was 85 mmHg (SD = 13) and 88 mmHg (SD = 10), and RRi was 622 ms (SD = 61) and 600 ms (SD = 70), respectively]. The results support the tested hypothesis. The prompt BRS decrease during uptilt at rest may be ascribed to a vagal withdrawal, similarly to what occurs at exercise onset. The OP resetting may be due to a slower control mechanism, possibly an increase in sympathetic activity.

Vagal blockade suppresses the phase I heart rate response but not the phase I cardiac output response at exercise onset in humans.

PURPOSE: We tested the vagal withdrawal concept for heart rate (HR) and cardiac output (CO) kinetics upon moderate exercise onset, by analysing the effects of vagal blockade on cardiovascular kinetics in humans. We hypothesized that, under atropine, the φ1 amplitude (A1) for HR would reduce to nil, whereas the A1 for CO would still be positive, due to the sudden increase in stroke volume (SV) at exercise onset. METHODS: On nine young non-smoking men, during 0-80 W exercise transients of 5-min duration on the cycle ergometer, preceded by 5-min rest, we continuously recorded HR, CO, SV and oxygen uptake ([Formula: see text]O2) upright and supine, in control condition and after full vagal blockade with atropine. Kinetics were analysed with the double exponential model, wherein we computed the amplitudes (A) and time constants (τ) of phase 1 (φ1) and phase 2 (φ2). RESULTS: In atropine versus control, A1 for HR was strongly reduced and fell to 0 bpm in seven out of nine subjects for HR was practically suppressed by atropine in them. The A1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A1 for CO in atropine. A2 did not differ between control and atropine. No effect on τ1 and τ2 was found. These patterns were independent of posture. CONCLUSION: The results are fully compatible with the tested hypothesis. They provide the first direct demonstration that vagal blockade, while suppressing HR φ1, did not affect φ1 of CO.

A reappraisal of the strength-duration test to assess neuromuscular impairment of critically ill patients.

INTRODUCTION: Neuromuscular impairment (NMI) affects almost half of critically ill patients. The purpose was to investigate the role of neuromuscular electrical stimulation (NMES) to gain more insight into the nature of the NMI associated with ICU admission. To this aim, we analyzed the strength-duration (S-D) curves of the rectus femoris muscles of ICU patients compared to healthy volunteers. METHODS: S-D curves were recorded from 44 healthy volunteers and 29 ICU patients. Three electrophysiological parameters were used to classify the neuromuscular function, from grade 0 (normal function), to grade 3 (no evocable muscle contraction). ICU patients underwent electroneurographic peroneal nerve testing (PENT) to analyze NMI by electroneurography (ENG). RESULTS: Three patients were classified as Grade 0; nine as mild NMI (Grade 1), 13 as Grade 2, and four showed unexcitable muscles (Grade 3). Mean CMAP amplitudes were 6.1, 3.4, 2.9 and 0.81 mV from Grade 0 to Grade 3, respectively. CMAP was inversely correlated to NMI grade (-1.7 mV, R2 = 0.946, p < 0.05). CONCLUSIONS: The normative parameters of the S-D curves obtained by NMES in healthy volunteers allowed identification of NMI in ICU patients. NMES was an affordable tool to evaluate NMI in ICU patients, providing additional information to that obtained by ENG.

Effects of the Level and Duration of Mobilization Therapy in the Surgical ICU on the Loss of the Ability to Live Independently: An International Prospective Cohort Study.

OBJECTIVES: It is unclear whether early mobilization in the surgical ICU helps improve patients' functional recovery to a level that enables independent living. We assessed dose of mobilization (level + duration). We tested the research hypotheses that dose of mobilization predicts adverse discharge and that both duration of mobilization and maximum mobilization level predict adverse discharge. DESIGN: International, prospective cohort study. SETTING: Study conducted in five surgical ICUs at four different institutions. PATIENTS: One hundred fifty patients who were functionally independent before admission (Barthel Index ≥ 70) and who were expected to stay in the ICU for greater than or equal to 72 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mobilization was quantified daily, and treatments from all healthcare providers were included. We developed and used the Mobilization Quantification Score that quantifies both level and duration of mobilization. We assessed the association between the dose of mobilization (level + duration; exposure) and adverse discharge disposition (loss of the ability to live independently; primary outcome). There was wide variability in the dose of mobilization across centers and patients, which could not be explained by patients' comorbidity or disease severity. Dose of mobilization was associated with reduced risk of adverse discharge (adjusted odds ratio, 0.21; 95%CI, 0.09-0.50; p < 0.001). Both level and duration explained variance of adverse discharge (adjusted odds ratio, 0.28; 95% CI, 0.12-0.65; p = 0.003; adjusted odds ratio, 0.14; 95% CI, 0.06-0.36; p < 0.001, respectively). Duration compared with the level of mobilization tended to explain more variance in adverse discharge (area under the curve duration 0.73; 95% CI, 0.64-0.82; area under the curve mobilization level 0.68; 95% CI, 0.58-0.77; p = 0.10). CONCLUSIONS: We observed wide variability in dose of mobilization treatment applied, which could not be explained by patients' comorbidity or disease severity. High dose of mobilization is an independent predictor of patients' ability to live independently after discharge. Duration of mobilization sessions should be taken into account in future quality improvement and research projects.

The Lombardy Emergency Medical System Faced with COVID-19: The Impact of Out-of-Hospital Outbreak.

OBJECTIVE: The Lombardy region was among the areas most affected by COVID-19 infection worldwide; the Lombardy Emergency Medical System (EMS) responded immediately to this emergency. We analyzed several critical aspects to understand what occurred in that region. METHODS: This retrospective study compares the events managed by the dispatch center and the characteristics of the patients transported to the hospital -age, sex, SpO2, deaths- managed by the EMS in Brescia and Bergamo provinces between March-April 2020 and March-April 2019. Ambulances' waiting time at the hospitals before discharging patients and the patients' severity at emergency department admission were also analyzed. RESULTS: EMS managed 37,340 events in March-April 2020, +51.5% versus 2019. "Breathing" or "Infective" events reported to the dispatch center increased more than ten-fold (OR 25.1, p < 0.0001) in March 2020 and two-fold in April 2020 compared to 2019 (OR 3, p < 0.0001). Deaths increased +246% (OR 1.7, p < 0.0001), and patients not transported to hospital +481% (OR 2.9, p < 0.0001) in March 2020 compared to 2019. In some hospitals, ambulances waited more than one hour before discharging the patients, and the emergency departments doubled the admission of critically ill patients. Transported patients for "Breathing" or "Infective" events were primarily males (OR 1.5, p < 0.0001). The patients had lower SpO2 in 2020 than in 2019 and they were younger. CONCLUSIONS: The Lombardy region experienced an unexpected outbreak in an extremely short timeframe and in a limited area. The EMS coped with this pandemic, covering an extremely higher number of requests, with a ten-fold increase in the number of events managed.

Baroreflex responses during dry resting and exercise apnoeas in air and pure oxygen.

PURPOSE: We analysed the characteristics of arterial baroreflexes during the first phase of apnoea (φ1). METHODS: 12 divers performed rest and exercise (30 W) apnoeas (air and oxygen). We measured beat-by-beat R-to-R interval (RRi) and mean arterial pressure (MAP). Mean RRi and MAP values defined the operating point (OP) before (PRE-ss) and in the second phase (φ2) of apnoea. Baroreflex sensitivity (BRS, ms·mmHg-1) was calculated with the sequence method. RESULTS: In PRE-ss, BRS was (median [IQR]): at rest, 20.3 [10.0-28.6] in air and 18.8 [13.8-25.2] in O2; at exercise 9.2[8.4-13.2] in air and 10.1[8.4-13.6] in O2. In φ1, during MAP decrease, BRS was lower than in PRE-ss at rest (6.6 [5.3-11.4] in air and 7.7 [4.9-14.3] in O2, p < 0.05). At exercise, BRS in φ1 was 6.4 [3.9-13.1] in air and 6.7 [4.1-9.5] in O2. After attainment of minimum MAP (MAPmin), baroreflex resetting started. After attainment of minimum RRi, baroreflex sequences reappeared. In φ2, BRS at rest was 12.1 [9.6-16.2] in air, 12.9 [9.2-15.8] in O2. At exercise (no φ2 in air), it was 7.9 [5.4-10.7] in O2. In φ2, OP acts at higher MAP values. CONCLUSION: In apnoea φ1, there is a sudden correction of MAP fall via baroreflex. The lower BRS in the earliest φ1 suggests a possible parasympathetic mechanism underpinning this reduction. After MAPmin, baroreflex resets, displacing its OP at higher MAP level; thus, resetting may not be due to central command. After resetting, restoration of BRS suggests re-establishment of vagal drive.

High-mobility group box-1 protein as a novel biomarker to diagnose healthcare-associated ventriculitis and meningitis: a pilot study.

BACKGROUND: The diagnosis of healthcare-associated ventriculitis and meningitis (HAVM) is challenging in the ICU setting. Traditional cerebrospinal fluid (CSF) markers and clinical signs of infection fail to diagnose HAVM in the critically ill setting. We sought to determine the diagnostic accuracy of measuring levels of high-mobility group box 1 (HMGB1) protein in cerebrospinal fluid (CSF) for the diagnosis of HAVM. METHODS: In this prospective observational cohort study, we enrolled 29 patients with an implanted external ventricular drainage (EVD). We tested the accuracy of CSF-HMGB1 as a diagnostic test for HAVM when compared to standard CSF parameters. RESULTS: HAVM was diagnosed in 11/29 (37.9%) patients. These patients had significantly higher CSF-HMGB1 levels compared to patients without HAVM (median [IQR] 43.39 [83.51] ng/mL vs 6.46 ng/mL [10.94]; P<0.001). CSF-HMGB1 and CSF-glucose were independently related to HAVM, with OR's (95% CI) of 15.43 (15.37 to 15.48, P<0.0001) and 0.31 (0.30 to 0.32, P<0.0001), respectively. The AUC [CI] of CSF-HMGB1 to predict HAVM was 0.83 [0.72 to 0.94]. CONCLUSIONS: HMGB1 is an accurate marker of HAVM and it adds incremental diagnostic value when paired with CSF-glucose measurements. Future larger and multicenter studies should assess the incremental diagnostic value of HMGB1 data when used alongside other established CSF markers of infection, and the external validity of these preliminary results.