Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very ...early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock.
A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h.
Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (00-510 vs. 1500650-2300 mL, p < 0.001) and during the first 8 h of resuscitation (1100500-1900 vs. 26001600-3800 mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h.
A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.
The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19.
To determine the effect of high-flow oxygen therapy through a nasal ...cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19.
Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021.
Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111).
The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities.
Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women 32.7%). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively.
Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy.
ClinicalTrials.gov Identifier: NCT04609462.
Monocytes and macrophages play a central role in chronic brucellosis. Brucella abortus (Ba) is an intracellular pathogen that survives inside these cells. On the other hand, macrophages could be ...differentiated into classical (M1), alternative (M2) or other less-identified profiles. We have previously shown that Ba RNA (a bacterial viability-associated PAMP or vita-PAMP) is a key molecule by which Ba can evade the host immune response. However, we did not know if macrophages could be polarized by this vita-PAMP. To assess this, we used two different approaches: we evaluated if Ba RNA per se was able to differentiate macrophages to M1 or M2 or, given that Ba survives inside macrophages once a Th1 response is established (i.e., in the presence of IFN-γ), we also analysed if Ba RNA could interfere with M1 polarization. We found that Ba RNA alone does not polarize to M1 or M2 but activates human macrophages instead. However, our results show that Ba RNA does interfere with M1 polarization while they are being differentiated. This vita-PAMP diminished the M1-induced CD64, and MHC-II surface expression on macrophages at 48 h. This phenomenon was not associated with an alternative activation of these cells (M2), as shown by unchanged CD206, DC-SIGN and CD163 surface expression. When evaluating glucose metabolism, we found that Ba RNA did not modify M1 glucose consumption or lactate production. However, production of Nitrogen Reactive Species (NRS) did diminish in Ba RNA-treated M1 macrophages. Overall, our results show that Ba RNA could alter the proper immune response set to counterattack the bacteria that could persist in the host establishing a chronic infection.
Background
Loss of vascular tone is a key pathophysiological feature of septic shock. Combination of gradual diastolic hypotension and tachycardia could reflect more serious vasodilatory conditions. ...We sought to evaluate the relationships between heart rate (HR) to diastolic arterial pressure (DAP) ratios and clinical outcomes during early phases of septic shock.
Methods
Diastolic shock index (DSI) was defined as the ratio between HR and DAP. DSI calculated just before starting vasopressors (Pre-VPs/DSI) in a preliminary cohort of 337 patients with septic shock (January 2015 to February 2017) and at vasopressor start (VPs/DSI) in 424 patients with septic shock included in a recent randomized controlled trial (ANDROMEDA-SHOCK; March 2017 to April 2018) was partitioned into five quantiles to estimate the relative risks (RR) of death with respect to the mean risk of each population (assumed to be 1). Matched HR and DAP subsamples were created to evaluate the effect of the individual components of the DSI on RRs. In addition, time-course of DSI and interaction between DSI and vasopressor dose (DSI*NE.dose) were compared between survivors and non-survivors from both populations, while ROC curves were used to identify variables predicting mortality. Finally, as exploratory observation, effect of early start of vasopressors was evaluated at each Pre-VPs/DSI quintile from the preliminary cohort.
Results
Risk of death progressively increased at gradual increments of Pre-VPs/DSI or VPs/DSI (One-way ANOVA,
p
< 0.001). Progressive DAP decrease or HR increase was associated with higher mortality risks only when DSI concomitantly increased. Areas under the ROC curve for Pre-VPs/DSI, SOFA and initial lactate were similar, while mean arterial pressure and systolic shock index showed poor performances to predict mortality. Time-course of DSI and DSI*NE.dose was significantly higher in non-survivors from both populations (repeated-measures ANOVA,
p
< 0.001). Very early start of vasopressors exhibited an apparent benefit at higher Pre-VPs/DSI quintile.
Conclusions
DSI at pre-vasopressor and vasopressor start points might represent a very early identifier of patients at high risk of death. Isolated DAP or HR values do not clearly identify such risk. Usefulness of DSI to trigger or to direct therapeutic interventions in early resuscitation of septic shock need to be addressed in future studies.
To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory ...flows in endotoxic shock.
Animal experimental study.
University translational research laboratory.
Fifteen Landrace pigs.
Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.
Hypotension was significantly shorter in i-NE group (7.5 min 5.5-22.0 min vs 49.3 min 29.5-60.0 min; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).
In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
Many health systems have initiated electronic consultation (e-consultation) programs, although little is known about their impact on accessibility, safety, and satisfaction. The aim of this study was ...to assess the clinical impact of the implementation of an outpatient care model that includes an initial e-consultation and to compare it with a one-time face-to-face consultation model.
We selected patients who visited the cardiology service at least once between 2010 and 2019. Using an interrupted time series regression model, we analyzed the impact of incorporating e-consultation into the health care model (started in 2013), and evaluated waiting times, emergency services, hospital admissions, and mortality.
We analyzed 47 377 patients: 61.9% were attended in e-consultation and 38.1% in one-time face-to-face consultations. The waiting time for care was shorter in the e-consultation model (median IQR: 7 5-13 days) than in the face-to-face model (median IQR: 33 14-81 days), P<.001. The interrupted time series regression model showed that the introduction of e-consultation substantially decreased waiting times, which held steady at around 9 days, although with slight oscillations. Patients evaluated via e-consultation had fewer hospital admissions (0.9% vs 1.2%, P=.0017) and lower mortality (2.5% vs 3.9%, P<.001).
An outpatient care program that includes an e-consultation reduced waiting times significantly and was safe, with a lower rate of hospital admissions and mortality in the first year.
Muchos sistemas sanitarios han iniciado programas de consulta electrónica, aunque poco se conoce de su impacto en acceso, seguridad y satisfacción. El objetivo de este estudio es evaluar el impacto clínico de la puesta en marcha de un modelo de atención ambulatoria que incluye una consulta electrónica (e-consulta) inicial comparándolo con un modelo presencial de acto único.
Se seleccionó a pacientes con al menos 1 consulta al servicio de cardiología entre 2010 y 2019. Mediante un modelo de regresión de series temporales interrumpidas, se analizó el impacto de la incorporación de la e-consulta en el modelo asistencial (iniciado en 2013), evaluando: tiempo de espera de la atención, asistencias a urgencias, ingresos hospitalarios y mortalidad.
Se analizó a 47.377 pacientes: el 61,9% de ellos atendidos incorporando la e-consulta y el 38,1% en el modelo de consulta presencial de acto único. La mediana intervalo intercuartílico de la demora a la atención en el modelo de e-consulta, 7 5-13 días, fue menor que en el modelo presencial: 33 14-81 días (p<0,001). El modelo de regresión para series temporales interrumpidas mostró que la incorporación de la e-consulta aporta una disminución muy importante en la demora de la atención, que se mantiene en torno a los 9 días, aunque con ligeras oscilaciones. Los pacientes valorados vía e-consulta tuvieron menos ingresos hospitalarios (el 0,9 frente al 1,2%; p=0,0017) y mortalidad (el 2,5 frente al 3,9%; p<0,001).
Un programa de atención ambulatoria que incluye una e-consulta ha mostrado importantes reducciones en los tiempos de espera y es un modelo seguro, con menores tasas de ingresos hospitalarios y mortalidad en el primer año.
We study the properties of the dynamical phase transition occurring in neural network models in which a competition between associative memory and sequential pattern recognition exists. This ...competition occurs through a weighted mixture of the symmetric and asymmetric parts of the synaptic matrix. Through a generating functional formalism, we determine the structure of the parameter space at non-zero temperature and near saturation (i.e., when the number of stored patterns scales with the size of the network), identifying the regions of high and weak pattern correlations, the spin-glass solutions, and the order-disorder transition between these regions. This analysis reveals that, when associative memory is dominant, smooth transitions appear between high correlated regions and spurious states. In contrast when sequential pattern recognition is stronger than associative memory, the transitions are always discontinuous. Additionally, when the symmetric and asymmetric parts of the synaptic matrix are defined in terms of the same set of patterns, there is a discontinuous transition between associative memory and sequential pattern recognition. In contrast, when the symmetric and asymmetric parts of the synaptic matrix are defined in terms of independent sets of patterns, the network is able to perform both associative memory and sequential pattern recognition for a wide range of parameter values.
Abstract Background: Wallenberg syndrome (WS) is a classic neurologic disorder secondary to vascular pathology of the vertebrobasilar circulation. Methods: Consecutive patients > 18 years with WS and ...isolated lateral medullary infarction syndrome were included from two Mexican hospitals. Risk factors, initial signs, symptoms, radiological findings, and acute treatment were evaluated; the prognosis was assessed using the Glasgow Outcome Scale. Results: Twenty-six patients were studied in a 26-year period (1988-2014); 17 patients were men (67%); and the average age was 45 years (range 19-77). Fourteen patients were under 45 years old (54%). The most common risk factors were dyslipidemia (41%) and hypertension (37%). The main initial symptoms were vertigo-dizziness (89%) gait ataxia (70%), and crossed-sensory deficit; and the main signs were crossed-sensitive deficit (93%), Horner syndrome (85%), and nystagmus (82%). In the bivariate analysis, age under 45 years was associated with a vertebral arterial dissection (p = 0.001), and age > 45 with atherothrombotic etiology (p = 0.01). About 96% of patients presented good recovery at an average of 17 months follow-up. Conclusion: Non-atherosclerotic vasculopathy was the main cause of WS-ILBI in young people. The clinical characteristics were similar to those reported in other series with a usually benign prognosis.
Background
Supraventricular arrhythmias (SVAs), commonly managed with radiofrequency ablation (RFA), may occur after orthotopic heart transplantation (OHT).
Methods
We retrospectively assessed 514 ...consecutive patients (pts.) undergoing OHT between January 1990 and July 2016 in a single‐center. Patients with SVAs managed with RFA were included. Mechanisms of genesis of SVAs, association with surgical techniques and outcomes, were analyzed.
Results
Of 514 pts undergoing OHT, 53% (272 pts.) were managed with bicaval (BC) technique and 47% (242 pts.) with biatrial (BA) technique. Mean follow‐up 10 ± 8.4 years. Nine pts. (1.7%) developed SVA requiring RFA. The BC technique was performed in 4 pts., 3 pts. presented cavotricuspid isthmus‐dependent atrial flutter (CTI AFL), and 1 pt. double loop AFL. Five pts. were managed with BA technique, 4 pts. presented CTI AFL, and 1 pt. atrial tachycardia (AT). Mean time between OHT and SVA occurrence was 6.6 ± 5.5 years. The procedure was successful in 89% (8 pts.). Arrhythmia recurrence was seen in 3 pts (37%), all with BA technique.
Conclusion
Supraventricular arrhythmias in heart transplantation may be associated with the surgical scar. Identifying the mechanism is vital to choose the appropriate treatment with radiofrequency ablation.
Apatite, Ca
5
(PO
4
)
3
F, concentrate from LKAB in Kiruna, Sweden, has been characterized and pyrometallurgically treated using (i) silicon metal and fluxes to extract phosphorus and transition ...metals at 1600 °C (Part I publication), and (ii) carbon to extract phosphorus without fluxing at temperatures exceeding 1800 °C (Part II publication), with the ultimate objective to recover rare earth elements from the resulting slag/residue phases. A variety of methods (SEM/EDS, EPMA, DTA-TGA, Sessile drop, ICP-MS/OES, and XRD) have been used for the characterization and analysis of both the concentrate and reaction products. Elemental deportment, except for the rare earth metals, is broadly in line with the equilibrium thermodynamic predictions performed using HSC Chemistry
®
. Phase diagrams were predicted using FactSage
®
and a custom phosphate database to explain the observed melting/fluxing behaviors.
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