Impact of recanalisation by mechanical thrombectomy in mild acute ischemic stroke with large anterior vessel occlusion.

BACKGROUND: The net clinical benefit of mechanical thrombectomy (MT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) and mild neurological deficit is uncertain. AIMS: To investigate efficacy and safety of MT in patients with acute AIS-LVO and mild neurological deficit by evaluating i) the influence of recanalisation on three-month outcome and ii) mortality, symptomatic intracerebral hemorrhage (sICH) and procedural complications. METHODS: We included consecutive patients with acute AIS-LVO and National Institute of Stroke Scale (NIHSS) score<8, treated by MT at Lille University Hospital. Recanalisation was graded according to modified thrombolysis in cerebral infarction (mTICI) score, mTICI 2b/2c/3 being considered successful. We recorded procedural complications and classified intra-cerebral hemorrhages (ICH) and sICH according with European Cooperative Acute Stroke Study (ECASS) and ECASS2 criteria. Three-month outcome was evaluated by modified Rankin scale (mRS). Excellent and favourable outcomes were respectively defined as mRS 0-1 and 0-2 (or similar to pre-stroke). RESULTS: We included 95 patients. At three months, 56 patients (59. 0%) achieved an excellent outcome and 69 (72, 6%) a favourable outcome, both being more frequent in patients with successful recanalisation than in patients without (excellent outcome 71, 1% versus 10, 5%, P<0.001 and favourable outcome 82.9% versus 31.6%, P<0.001). The difference remained unchanged after adjustment for age and pre-MT infarct volume. Similar results were observed in patients with pre-MT NIHSS ≤5. Death occurred in five patients (5.3%), procedural complications in 12 (12.6%), any ICH in 38 (40.0%), including 3 (3.2%) sICH. CONCLUSIONS: Achieving successful recanalisation appears beneficial and safe in acute AIS-LVO patients with NIHSS<8 before MT.

Cerebral ischaemia with unknown onset: Outcome after recanalization procedure.

BACKGROUND: Stroke of unknown time of onset (UTOS) accounts for one-third of contra-indications for revascularization procedures. With modern neuroimaging techniques it is possible to differentiate the core infarcts and the presence of penumbra. OBJECTIVE: To evaluate outcomes in patients with UTOS, treated with intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA), mechanical thrombectomy (MT), or both. METHOD: We conducted this observational study in patients treated by i.v. rt-PA, MT, or both, selected by a diffusion-weighted image/fluid-attenuated inversion recovery mismatch. We evaluated outcomes with the modified Rankin scale (mRS) at 3 months. RESULTS: Of 992 consecutive patients (522 women, 52.6%; median age 76 years; median baseline national institutes of health stroke scale [NIHSS] 10), 153 (15.4%) had UTOS, including 101 with wake-up strokes. Compared to other patients, they were more likely to have pre-existing mRS scores >2 (P=0.022), multiple infarcts (P<0.001), middle cerebral artery occlusions (P=0.023), and to undergo MT (P=0.003), and less likely to receive i.v. rt-PA (P<0.001). They had higher NIHSS scores (P<0.001) and longer discovery to treatment initiation times (P<0.001). They were more likely to develop pulmonary (P=0.001) and urinary (P=0.006) infections, and pulmonary embolism (P=0.019), and tended to have a higher mortality rate (P=0.052) within 7 days. After adjustment, there was no association of UTOS with any of these outcome measures anymore. CONCLUSION: Patients with UTOS have more severe strokes and more comorbidities, but after adjustment, their outcomes did not differ from those of other patients.

Access to mechanical thrombectomy for cerebral ischaemia: A population-based study in the North-of-France.

BACKGROUND AND PURPOSE: Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area. METHOD: We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS. RESULTS: During the study period (2016-2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72-90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234-264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay. CONCLUSION: The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay.

Endovascular Stroke Therapy with a Novel 6-French Aspiration Catheter.

BACKGROUND AND PURPOSE: Direct thrombus aspiration is increasingly used as a first-line therapy in acute ischemic stroke with large vessel occlusion. We assessed the performance and safety of a novel aspiration catheter available: the 6-French AXS Catalyst catheter. MATERIALS AND METHODS: We conducted a cohort study from a prospective clinical registry of consecutive stroke patients treated by mechanical thrombectomy between March 2016 and July 2016. Baseline clinical and imaging characteristics, recanalization rates, complications, and clinical outcomes were analyzed. RESULTS: Among the 60 patients included, 30 were treated using aspiration alone, 14 were treated using aspiration and then stent retriever as a rescue therapy, and 16 were treated using aspiration combined with a stent retriever straightaway. Successful recanalization (mTICI2b/3) was achieved in 85% patients and functional independence in 48.3%. We observed one intracranial perforation and one vertebral artery dissection. Symptomatic intracranial hemorrhage occurred in 5% and mortality in 21.7%. CONCLUSION: Endovascular stroke therapy using the AXS Catalyst catheter seems safe and effective, with similar performance than other reperfusion catheters.

Characterization and predicted role of the microRNA expression profile in amnion from obese pregnant women.

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. We have studied the microRNA (miRNA) expression profile in amnion from obese and control women at delivery to investigate if a specific miRNA signature is associated with obesity. The expression profile of 365 human miRNAs was evaluated with the TaqMan Array in amnion from 10 obese and 5 control (prepregnancy body mass index (BMI) >30 and <25 kg m(-2), respectively) women at delivery. Target genes and miRNA-regulated pathways were predicted by bioinformatics. Anthropometric and biochemical parameters were also measured in mothers and newborns. Seven miRNAs were expressed only in obese women (miR-422b, miR-219, miR-575, miR-523, miR-579, miR-618 and miR-659), whereas 13 miRNAs were expressed at a higher level and 12 miRNAs at a lower level in obese women than in controls. MicroRNAs significantly downregulated the neurotrophin, cancer/ErbB, mammalian target of rapamycin, insulin, adipocytokine, actin cytoskeleton and mitogen-activated protein kinase signaling pathways. In conclusion, we show that the miRNA profile is altered in amnion during obesity and hypothesize that this could affect pathways important for placental growth and function, thereby contributing to an increase in the newborn's risk of future metabolic diseases.

Deadly diving? Physiological and behavioural management of decompression stress in diving mammals.

Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N(2)) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N(2) tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N(2) loading to management of the N(2) load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.

The feasibility of pharmacological mitigation of nitrogen narcosis during submarine escapes from depths down to 1,000 fsw.

INTRODUCTION: Nitrogen (N2) narcosis could interfere with deep submarine escapes, particularly in the escape trunk, where simple but essential tasks are required in order to leave the submarine and start rapid ascent. In a previous study, we had suggested that prolongation of lungs-to-brain circulation time (LBct) may have a protective effect on N2 narcosis, a hypothesis tested in the present study. MATERIALS AND METHODS: Computer software was designed to assess the effects of changes in circulation times on N2 uptake and distribution during the extremely rapid pressure changes typical of submarine escapes. Simulations of escapes from 600 to 1,000 fsw (with 200-fsw steps) were performed, with varying dwell times (DT) in the escape trunk (from 10 to 60 seconds, in 10-second steps). Baseline cardiac output (CO) was set at 5 liters/minute, and it was varied through changes in heart rate from 50% to 200% in the escape simulations. LBct was assumed to vary inversely with CO. RESULTS: The risk of N2 narcosis was expressed as equivalent narcosis depth (END) in fsw, corresponding to N2 pressure in the brain after five minutes of air diving at that equivalent depth. The effects of changing CO on the highest END values (corresponding to the peak N2 pressures) reached while in the escape trunk or during entire escapes were tabulated. Depths at which peak N2 occurred were also analyzed. Prolonging LBct appeared to have two advantageous effects: 1. It reduced peak N2 reached both in the escape trunk and during the entire course of the escape 2. It delayed peak N2 to later stages of escapes (i.e., closer to the surface during ascent). These effects were more evident at greater escape depths and with longer DTs. CONCLUSIONS: Prolongation of LBct could protect against N2 narcosis and it could plausibly be achieved with the oral administration of a beta-blocker, such as propranolol, prior to deep submarine escape. Animal experiments should be conducted to validate this pharmacological approach.

Cardiovascular aspects of glossopharyngeal insufflation and exsufflation.

Breath-hold divers use glossopharyngeal breathing to inhale above total lung capacity (glossopharyngeal insufflation, GI) or exhale below residual volume (glossopharyngeal exsufflation, GE). In these maneuvers, air is moved using glossopharyngeal rather than respiratory muscle activity. Four competitive divers performed several GI and GE maneuvers in sitting or standing position, while cardiovascular parameters were measured with a photoplethysmographic method; echocardiography was also performed during GE. During GI, the divers showed a 48% drop in mean arterial pressure (MAP) to 50 mmHg, with a 88% decrease in pulse pressure (PP), while heart rate (HR) increased by 36% to 103 beats/min and cardiac output (CO) dropped by 79% to 1.3 l/min. The increase in intrathoracic pressure during GI, measured in separate experiments, is probably responsible for these hemodynamic changes, by impeding venous return into the chest. Associated with the drop in MAP during GI were various neurological signs and symptoms, including dizziness, tunnel vision, involuntary twitching of facial muscles and one brief episode of loss of consciousness. During GE, initially MAP and PP increased by 36% and 61%, to 149 and 95 mmHg respectively; later HR decreased by 37% to 45 beats/min and CO dropped by 37% to 4.3 l/min. The early cardiovascular changes of GE may be related to a decrease in intrathoracic pressure, enhancing venous return, as shown by a 6 to 15% increase in end-diastolic diameter; later changes are similar to the responses to apnea at low lung volumes. Because of their hemodynamic effects, these breathing maneuvers should be performed with caution, particularly in the case of GI.

Pneumomediastinum after lung packing.

Lung packing (glossopharyngeal insufflation) consists of forcing air into the lungs, using glossopharyngeal muscle contractions similar to swallowing. Breath-hold divers perform this technique after a maximal inhalation prior to diving, thus increasing initial lung volume. However, as suggested by previous authors, this breathing maneuver could theoretically lead to lung rupture. Here we report a pneumomediastinum found on chest CT scan in a diver during a physiological study, when glossopharyngeal insufflation increased the volume of gas in the lungs by 1,040 ml (over his total lung capacity); at the same time, his transpulmonary pressures increased up to 4.1 kPa. We discuss the possibility that the very high transpulmonary pressures during lung packing caused this pneumomediastinum.

Gastric emptying in infants: epigastric impedance versus scintigraphy.

AIM: To compare epigastric impedance versus scintigraphy in monitoring the gastric emptying of the same adapted milk formula in infants. METHODS: Seven infants with clinical symptoms of gastric motility disease underwent scintigraphy with 99mTc sulphur colloid for the 90 min following the ingestion of the same adapted milk formula, in order to evaluate gastric emptying. A bio-impedance device, connected to a PC, was prepared for this purpose with four standard electrodes placed anteriorly on the upper part of the body. The obtained graphs were compared to those of the scintigraphic method. Statistical analysis was performed using Pearson correlation. The confidence limits were set at 95%. Parental consent was obtained before each analysis. RESULTS: The gastric emptying patterns obtained with epigastric impedance were closely correlated to those shown by the scintigraphy (r = 0.86 +/- 0.08; p < 0.05). A significant correlation between the gastric emptying velocity measured by the two techniques was found (r = 0.94; p = 0.002). CONCLUSIONS: Epigastric impedance in infants provided estimates of gastric emptying that were closely correlated with scintigraphy. However, the limits derived from the epigastric impedance suggest that, at the moment, the two methods should not be used interchangeably.

[Stomatologic approach in patients with congenital coagulation deficit]. / Approccio stomatologico in pazienti affetti da deficit coagulativi congeniti.

BACKGROUND: The purpose of the present paper was to resolve postoperative bleeding after oral surgery in patients with congenital coagulative defects, avoid transfusion of clotting factors and improve the patient's quality of life. METHODS: Since 1988, 1598 oral surgery procedures have been performed on patients with congenital coagulative defects treated with a protocol including pre- and postoperative tranexamic acid rinses. RESULTS: The use of tranexamic acid mouth washing has obtained effective hemostasis in 86% of cases and only 4% of surgical procedures required clotting factor transfusions. CONCLUSIONS: The results suggest that mouth washing with tranexamic acid prevents excessive oral bleeding in patients with congenital deficit of the coagulation system. Furthermore, a total elimination of the granulation tissue, that reduces the possibility of activation of the fibrinolytic mechanism, is also important.

A stage of change approach to addiction in the medical setting.

Despite recent advances in its understanding and treatment, addiction remains a difficult challenge for clinicians within medical settings such as the general hospital. The use of single, traditional paradigms (disciplinary, therapeutic, educational, or libertarian) for approaching addiction-related problems have often failed to embrace the complexity of the patients' motivation to change. Prochaska and DiClemente's [7] stage of change model offers a realistic, practical, and broadly applicable means by which clinicians can facilitate behavioral change from the stage of denial (precontemplation) through that of sustained recovery (maintenance). Clinicians can help addicted individuals to move from precontemplation to contemplation by enhancing their ambivalence; from contemplation to preparation by considering their history of change; from preparation to action by flexibly intervening based on this understanding; and from action to maintenance by evaluating the outcomes of these interventions. A stage of change model is also useful in understanding the process of change in clinicians' own approaches to patients with substance use disorders.

Cardiovascular changes during deep breath-hold dives in a pressure chamber.

Electrocardiogram, cardiac output, and blood lactate accumulation were recorded in three elite breath-hold divers diving to 40-55 m in a pressure chamber in thermoneutral (35 degrees C) or cool (25 degrees C) water. In two of the divers, invasive recordings of arterial blood pressure were also obtained during dives to 50 m in cool water. Bradycardia during the dives was more pronounced and developed more rapidly in the cool water, with heart rates dropping to 20-30 beats/min. Arrhythmias occurred, particularly during the dives in cool water, when they were often more frequent than sinus beats. Because of bradycardia, cardiac output decreased during the dives, especially in cool water (to <3 l/min in 2 of the divers). Arterial blood pressure increased dramatically, reaching values as high as 280/200 and 290/150 mmHg in the two divers, respectively. This hypertension was secondary to peripheral vasoconstriction, which also led to anaerobic metabolism, reflected in increased blood lactate concentration. The diving response of these divers resembles the one described for diving animals, although the presence of arrhythmias and large increases in blood pressure indicate a less perfect adaptation in humans.

Ventilatory responses to hypercapnia and hypoxia in elite breath-hold divers.

It was recently hypothesized that elite breath-hold divers may display blunted ventilatory responses to hypoxia and/or hypercapnia (Ferretti et al., J. Appl. Physiol. 70: 794-802, 1991). To test this hypothesis, the following measurements were made on three elite breath-hold divers (members of the same family), and on 9 healthy untrained control subjects (C): (1) Steady-state pulmonary ventilation (VE) at rest in the supine posture while breathing room air or normoxic CO2-enriched mixtures. (2) Breath-by-breath VE changes (delta VE), with respect to baseline conditions, after 4 breaths of 100% O2, under the following conditions: normoxia (PIO2 = 146 Torr) at rest (NR); normoxic exercise (60 watt on a bicycle ergometer) (NE); hypoxia (PIO2 = 77 Torr) at rest (HR); hypoxic exercise (HE). The results were as follows: (1) In hypercapnic experiments VE (normalized per unit of body surface area) was significantly lower in the divers than in C (4.32 +/- 0.04 [mean +/- SD]L.min-1.m-2 vs. 5.31 +/- 0.62 at FICO2 = 1.5%; 5.21 +/- 0.17 vs. 7.72 +/- 1.39 at FICO2 = 3%; 8.86 +/- 0.76 vs. 13.14 +/- 2.27 at FICO2 = 5%), as well as than in subjects described by previous authors as being characterized by 'low CO2 sensitivity'. (2) The 100% O2-breathing maneuvers did not induce significant delta VE both in NR and in HR, whereas peak delta VE were -6.73 +/- 1.38 L.min-1 (divers) vs. -5.24 +/- 3.10 (C) in NE, and -17.39 +/- 4.92 (divers) vs. -17.52 +/- 6.32 (C) in HE (no significant differences). It is concluded that the divers, compared to C, had a blunted ventilatory response to hypercapnia, but not to hypoxia. The former may represent an adaptive or genetically inherited phenomenon.

Alveolar gas exchange during simulated breath-hold diving to 20 m.

Alveolar gas exchange, as affected by changes in pulmonary blood flow, was studied in five subjects performing breath holds lasting 75 s at the surface and during compression to 20 m in a hyperbaric chamber. After reaching the maximal depth, VO2 started to increase, compared to control, reaching a maximum of 346 +/- 66 (SE) ml (STPD).min-1.m2 (body surface area) at 50 s, i.e., early in the ascent; it exceeded the 50-s surface breath-hold value by 214 +/- 9 ml.min-1.m2. During descent, CO2 was absorbed from the alveoli into the blood, initially at 140 +/- 24 ml.min-1.m2; during ascent CO2 was transferred back into the lungs. These changes reflected compression and expansion of lung air. The increase in VO2 during the dives, which are not steady states, may be explained by an increasing cardiac output at depth. An augmented cardiac output had earlier been observed under identical conditions and explained by a drop in transthoracic pressure, enhancing venous return. Upon surfacing, the PAO2 was about 20 mmHg lower than after surface breath holds, reflecting the effects of changes in cardiac output.

Electrocardiogram during deep breath-hold dives by elite divers.

A portable ECG recorder was used during breath-hold dives at sea by 3 elite divers to 65 and 45 m. ECG was also recorded during nonimmersed maximal breath holds in the divers and 8 control subjects. Heart rate in the dives decreased rapidly to 20-24 beats.min(-1). During the surface experiments in the divers, bradycardia was much slower in onset, reaching 28-36 beats.min(-1) at the end of the breath holds. The divers showed a more consistent bradycardial response than the controls. The difference in temporal pattern of bradycardia, in the dives and in the breath holds by the divers, may have been due to face immersion in cold water, chest compression, and/or redistribution of blood into the chest with concomitant stimulation of cardiac and other mechanoreceptors. Arrhythmias, mostly supraventricular and ventricular premature complexes, were observed coincidently with the lowest heart rates, presumably reflecting a high vagal tone. In addition, cardiac distention at depth might have made the heart more prone to arrhythmias, while in the surface breath holds hypoxia might have accounted for a similar effect.

Alveolar gas composition and exchange during deep breath-hold diving and dry breath holds in elite divers.

End tidal O2 and CO2 (PETCO2) pressures, expired volume, blood lactate concentration ([Lab]), and arterial blood O2 saturation [dry breath holds (BHs) only] were assessed in three elite breath-hold divers (ED) before and after deep dives and BH and in nine control subjects (C; BH only). After the dives (depth 40-70 m, duration 88-151 s), end-tidal O2 pressure decreased from approximately 140 Torr to a minimum of 30.6 Torr, PETCO2 increased from approximately 25 Torr to a maximum of 47.0 Torr, and expired volume (BTPS) ranged from 1.32 to 2.86 liters. Pulmonary O2 exchange was 455-1,006 ml. CO2 output approached zero. [Lab] increased from approximately 1.2 mM to at most 6.46 mM. Estimated power output during dives was 513-929 ml O2/min, i.e. approximately 20-30% of maximal O2 consumption. During BH, alveolar PO2 decreased from approximately 130 to less than 30 Torr in ED and from 125 to 45 Torr in C. PETCO2 increased from approximately 30 to approximately 50 Torr in both ED and C. Contrary to C, pulmonary O2 exchange in ED was less than resting O2 consumption, whereas CO2 output approached zero in both groups. [Lab] was unchanged. Arterial blood O2 saturation decreased more in ED than in C. ED are characterized by increased anaerobic metabolism likely due to the existence of a diving reflex.

Simulated breath-hold diving to 20 meters: cardiac performance in humans.

Cardiac performance was assessed in six subjects breath-hold diving to 20 m in a hyperbaric chamber, while nonsubmersed or submersed in a thermoneutral environment. Cardiac index and systolic time intervals were obtained with impedance cardiography and intrathoracic pressure with an esophageal balloon. Breath holding at large lung volume (80% vital capacity) decreased cardiac index, probably by increasing intrathoracic pressure and thereby impeding venous return. During diving, cardiac index increased (compared with breath holding at the surface) by 35.1% in the nonsubmersed and by 29.5% in the submersed condition. This increase was attributed to a fall in intrathoracic pressure. Combination of the opposite effects of breath holding and diving to 20 m left cardiac performance unchanged during the dives (relative to the surface control). A larger intrathoracic blood redistribution probably explains a smaller reduction in intrathoracic pressure observed during submersed compared with nonsubmersed diving. Submersed breath-hold diving may entail a smaller risk of thoracic squeeze (lesser intrathoracic pressure drop) but a greater risk of overloading the central circulation (larger intrathoracic blood pooling) than simulated nonsubmersed diving.

Cardiac performance in humans during breath holding.

The effects on cardiac performance of high and low intrathoracic pressures induced by breath holding at large and small lung volumes have been investigated. Cardiac index and systolic time intervals were recorded from six resting subjects with impedance cardiography in both the nonimmersed and immersed condition. A thermoneutral environment (air 28 degrees C, water 35 degrees C) was used to eliminate the cold-induced circulatory component of the diving response. Cardiac performance was enhanced during immersion compared with nonimmersion, whereas it was depressed by breath holding at large lung volume. The depressed performance was apparent from the decrease in cardiac index (24.1% in the immersed and 20.9% in the nonimmersed condition) and from changes in systolic time intervals, e.g., shortening of left ventricular ejection time coupled with lengthening of preejection period. In the absence of the cold water component of the diving response, breath holding at the large lung volume used by breath-hold divers tends to reduce cardiac performance presumably by impeding venous return.