Exploring the Collateral Damage of the COVID-19 Pandemic on Stroke Care: A Statewide Analysis.

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Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

Staff Perceptions of Chaplains in a Neurosciences Critical Care Unit.

Hospital chaplains often visit critically ill patients, but neurosciences critical care unit (NCCU) staff beliefs surrounding chaplains have not been characterized. In this study, we used Qualtrics® to survey 70 NCCU healthcare workers about their attitudes toward chaplains in the NCCU. Chaplains were seen positively by staff but were less likely to be viewed as part of the care team by staff with more than five years of NCCU experience. The results of this study will allow chaplaincy programs to target staff education efforts in order to enhance the care provided to patients in critical care settings.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

Medical and Surgical Advances in Intracerebral Hemorrhage and Intraventricular Hemorrhage.

In recent decades, the medical and surgical treatment of intracerebral hemorrhage (ICH) have become the focus of a number of scientific investigations. This effort has been led by an international group of neurologists and neurosurgeons with the goal of studying functional recovery and developing new medical and surgical treatments to facilitate improved clinical outcomes. Currently, two of the most pressing ICH investigational goals are (1) early blood pressure control, and (2) safe hematoma volume reduction. Answering these questions would support decision-making, level-of-care choices, and the global research strategy of developing biologically informed treatments. The authors review the contemporary medical management and the conventional and minimally invasive surgical approaches to spontaneous ICH, as well as discuss the scope of the problem, recent clinical trials, management issues, and relevant questions for future research. They propose the hypothesis that strategies using minimally invasive techniques, including clot aspiration with stereotactic guidance, may give better results with improved clinical outcomes compared with standard open surgical approaches. They also discuss the level of evidence for the variously known approaches.

The SAH Score: a comprehensive communication tool.

BACKGROUND: The Hunt and Hess grade and World Federation of Neurological Surgeons (WFNS) scale are commonly used to predict mortality after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to improve the accuracy of mortality prediction compared with the aforementioned scales by creating the "SAH score." METHODS: The aSAH database at our institution was analyzed for factors affecting in-hospital mortality using multiple logistic regression analysis. Scores were weighted based on relative risk of mortality after stratification of each of these variables. Glasgow Coma Scale (GCS) was subdivided into groups of 3-4 (score = 1), 5-8 (score = 2), 9-13 (score = 3), and 14-15 (score = 4). Age was categorized into 4 subgroups: 18-49 (score = 1), 50-69 (score = 2), 70-79 (score = 3), and 80 years or more (score = 4). Medical comorbidities were subdivided into none (score = 1), 1 (score = 2), or 2 or more (score = 3). RESULTS: In total, 1134 patients were included; all-cause SAH hospital mortality was 18.3%. Admission GCS, age, and medical comorbidities significantly affected mortality after multivariate analysis (P < .05). Summated scores ranged from 0 to 8 with escalating mortality at higher scores (0 = 2%, 1 = 6%, 2 = 8%, 3 = 15%, 4 = 30%, 5 = 58%, 6 = 79%, 7 = 87%, and 8 = 100%). Positive predictive value (PPV) for scores in the range 7-8 was 88.5%, whereas 6-8 was 83%. Negative predictive value (NPV) was 94% for range 0-2 and 92% for 0-3. The area under the curve (AUC) for the SAH score was .821 (good accuracy), compared with the WFNS scale (AUC .777, fair accuracy) and the Hunt and Hess grade (AUC .771, fair accuracy). CONCLUSIONS: The SAH score was found to be more accurate in predicting aSAH mortality compared with the Hunt and Hess grade and WFNS scale.

A scoping review of end-of-life discussions and palliative care: implications for neurological intensive care among Latinos in the U.S.

Goals of care (Goals-of-care) discussions and palliative care (PC) are crucial to providing comprehensive healthcare, particularly for acute neurological conditions requiring admission to a neurological intensive care unit. We identified gaps in the literature and describe insight for future research on end-of-life discussions and PC for U.S. Latinos with acute neurological conditions. We searched 10 databases including peer-reviewed abstracts and manuscripts of hospitalized U.S. Latinos with acute neurological and non-neurological conditions. We included 44 of 3231 publications and identified various themes: PC utilization, pre-established advanced directives in Goals-of-care discussions, Goals-of-care discussion outcomes, tracheostomy or percutaneous gastrostomy tube placement rates among hospitalized Latinos. Our review highlights that Latinos appear to have lower palliative care utilization compared with non-Latino Whites and may be less likely to have pre-established advanced directives, more likely to have gastrostomy or tracheostomy placement and less likely to have do-not-resuscitate status.

Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema.

BACKGROUND AND PURPOSE: Perihematomal edema (PHE) can worsen outcomes after intracerebral hemorrhage (ICH). Reports suggest that blood degradation products lead to PHE. We hypothesized that hematoma evacuation will reduce PHE volume and that treatment with recombinant tissue-type plasminogen activator (rt-PA) will not exacerbate it. METHODS: Minimally invasive surgery and rt-PA in ICH evacuation (MISTIE) phase II tested safety and efficacy of hematoma evacuation after ICH. We conducted a semiautomated, computerized volumetric analysis on computed tomography to assess impact of hematoma removal on PHE and effects of rt-PA on PHE. Volumetric analyses were performed on baseline stability and end of treatment scans. RESULTS: Seventy-nine surgical and 39 medical patients from minimally invasive surgery and rt-PA in ICH evacuation phase II (MISTIE II) were analyzed. Mean hematoma volume at end of treatment was 19.6±14.5 cm(3) for the surgical cohort and 40.7±13.9 cm(3) for the medical cohort (P<0.001). Edema volume at end of treatment was lower for the surgical cohort: 27.7±13.3 cm(3) than medical cohort: 41.7±14.6 cm(3) (P<0.001). Graded effect of clot removal on PHE was observed when patients with >65%, 20% to 65%, and <20% ICH removed were analyzed (P<0.001). Positive correlation between PHE reduction and percent of ICH removed was identified (ρ=0.658; P<0.001). In the surgical cohort, 69 patients underwent surgical aspiration and rt-PA, whereas 10 underwent surgical aspiration only. Both cohorts achieved similar clot reduction: surgical aspiration and rt-PA, 18.9±14.5 cm(3); and surgical aspiration only, 24.5±14.0 cm(3) (P=0.26). Edema at end of treatment in surgical aspiration and rt-PA was 28.1±13.8 cm(3) and 24.4±8.6 cm(3) in surgical aspiration only (P=0.41). CONCLUSIONS: Hematoma evacuation is associated with significant reduction in PHE. Furthermore, PHE does not seem to be exacerbated by rt-PA, making such neurotoxic effects unlikely when the drug is delivered to intracranial clot.

Withdrawal of technological life support following subarachnoid hemorrhage.

BACKGROUND: Prognostication of mortality or severe disability often prompts withdrawal of technological life support in patients following aneurysmal subarachnoid hemorrhage (aSAH). We assessed admission factors impacting decisions to withdraw treatment after aSAH. METHODS: Prospectively collected data of aSAH patients admitted to our institution between 1991 and 2009 were reviewed. Patients given comfort care measures were identified, including early withdrawal of treatment (<72 h after admission). Independent predictors of treatment withdrawal were assessed with multivariable analysis. RESULTS: The study included 1,134 patients, of whom 72 % were female, 58 % white, and 38 % black or African-American. Mean age was 52.5 ± 14.0 years. In-hospital mortality was 18.3 %. Of the 207 patients who died, treatment was withdrawn in 72 (35 %) and comfort measures instituted early in 31 (15 %). Among patients who died, WOLST was associated with older age (63.6 ± 14.2 years, WOLST vs. 55.6 ± 13.7 years, no WOLST, p < 0.001); GCS score <8 (62 % of WOLST vs. 44 % with no WOLST, p = 0.010); HH >3 (72 % of WOLST vs. 53 % with no WOLST, p = 0.008); and hydrocephalus (81 % of WOLST vs. 63 % with no WOLST, p = 0.009). Independent predictors of WOLST were poorer Hunt and Hess grade (AOR 1.520, 95 % CI 1.160-1.992, p = 0.002) and older age (AOR 1.045, 95 % CI 1.022-1.068, p < 0.001) with the latter also impacting early WOLST decisions. CONCLUSIONS: Older age and poor clinical grade on presentation predicted WOLST, and age predicted decisions to withdraw treatment earlier following aSAH. While based on prognosis, and in some cases patient wishes, this may also constitute a self-fulfilling prophecy in others.

Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association.

PURPOSE: The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. RESULTS: Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. CONCLUSIONS: aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.

Impact of pattern of admission on ICH outcomes.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with the highest mortality of all strokes. Admission to a Neurosciences Critical Care Unit (NCCU) compared to a general ICU has been associated with reduced mortality following ICH. Such association has led to several hospitals transferring ICH patients to Neuro-ICUs in tertiary care centers. However, delays in optimizing ICH management prior to and during transfer can lead to deleterious consequences. To compare functional outcomes in ICH patients admitted to our NCCU directly from the ED versus inter-hospital transfer admissions. METHODS: Records of consecutive spontaneous supratentorial ICH patients admitted to The Johns Hopkins Hospital NCCU were reviewed. Patients with ICH related to trauma or underlying lesions (brain tumors, aneurysms, AVM) were excluded. We compared outcomes at discharge in patients admitted directly from the ED and inter-hospital transfers (IHT) using dichotomized modified Rankin Scale (Good outcomes: mRS 0-3). Other factors potentially impacting outcomes such as age, ICH volume, IVH volume, and admission GCS were included in the multiple logistic regression analysis. RESULTS: 125 patients were included in the analysis (ED 61.6%; IHT 38.4%). There were no significant differences between the two groups in mean age (ED 63.4 +/- 13.1; IHT 63.4 +/- 15.2, P = 0.96), ICH volume (ED 31.4 +/- 37.6; IHT 33.5 +/- 42.8, P = 0.76), IVH volume (ED 6.0 +/- 11.2; IHT 8.0 +/- 14.5, P = 0.38), and GCS (ED 11.3 +/- 3.7, IHT 10.9 +/- 3.5; P = 0.44). 57.2% ED patients had good outcomes (mRS 0-3) at discharge compared to 37.5% IHT. This difference was statistically significant following univariate (P = 0.034, 95% CI .2151-.9416) and multivariate analysis (P = 0.028, 95% CI .1338-.8896). Odds (adjusted) of ED admissions having good outcomes was three times higher than IHT. Neurological deterioration (GCS decline 2 or more) was more common in IHT and, in subgroup analysis of IHT patients with warfarin-associated ICH, hematoma enlargement was significantly more likely than in direct ED admissions. CONCLUSIONS: Patients with ICH brought directly to our ED had significantly better outcomes than IHT; we hypothesize this may be caused by delays in optimizing management prior to arrival at the facility with a dedicated Neuro-ICU. Nevertheless, other equally plausible hypotheses need to be prospectively tested.

A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III).

RATIONALE AND HYPOTHESIS: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials. METHODS AND DESIGN: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study. STUDY OUTCOMES: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

Management of spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) has the highest mortality of all cerebrovascular events. Thirty-day mortality approaches 50%, and only 20% of survivors achieve meaningful functional recovery at 6 months. Many clinicians believe that effective therapies are lacking; however, this is changing because of new data on the pathophysiology and treatment of ICH, particularly research establishing the role of medical therapies to promote hematoma stabilization. This article provides updates to a recent publication discussing basic principles of ICH management, including initial stabilization, the prevention of hematoma growth, treatment of complications, and identification of the underlying etiology. Minimally invasive surgery (MIS) to reduce clot size is also discussed, with the goal of preserving neurologic function through reduction in parenchymal damage from edema formation.

Intracerebral Hemorrhage.

PURPOSE OF REVIEW: This article describes the advances in the management of spontaneous intracerebral hemorrhage in adults. RECENT FINDINGS: Therapeutic intervention in intracerebral hemorrhage has continued to focus on arresting hemorrhage expansion, with large randomized controlled trials addressing the effectiveness of rapidly lowering blood pressure, hemostatic therapy with platelet transfusion, and other clotting complexes and clot volume reduction both of intraventricular and parenchymal hematomas using minimally invasive techniques. Smaller studies targeting perihematomal edema and inflammation may also show promise. SUMMARY: The management of spontaneous intracerebral hemorrhage, long relegated to the management and prevention of complications, is undergoing a recent evolution in large part owing to stereotactically guided clot evacuation techniques that have been shown to be safe and that may potentially improve outcomes.

Update on the Treatment of Spontaneous Intraparenchymal Hemorrhage: Medical and Interventional Management.

PURPOSE OF REVIEW: Spontaneous intraparenchymal hemorrhage (IPH) is a prominent challenge faced globally by neurosurgeons, neurologists, and intensivists. Over the past few decades, basic and clinical research efforts have been undertaken with the goal of delineating biologically and evidence-based practices aimed at decreasing mortality and optimizing the likelihood of meaningful functional outcome for patients afflicted with this devastating condition. Here, the authors review the medical and surgical approaches available for the treatment of spontaneous intraparenchymal hemorrhage, identifying areas of recent progress and ongoing research to delineate the scope and scale of IPH as it is currently understood and treated. RECENT FINDINGS: The approaches to IPH have broadly focused on arresting expansion of hemorrhage using a number of approaches. Recent trials have addressed the effectiveness of rapid blood pressure lowering in hypertensive patients with IPH, with rapid lowering demonstrated to be safe and at least partially effective in preventing hematoma expansion. Hemostatic therapy with platelet transfusion in patients on anti-platelet medications has been recently demonstrated to have no benefit and may be harmful. Hemostasis with administration of clotting complexes has not been shown to be effective in reducing hematoma expansion or improving outcomes although correcting these abnormalities as soon as possible remains good practice until further data are available. Stereotactically guided drainage of IPH with intraventricular hemorrhage (IVH) has been shown to be safe and to improve outcomes. Research on new stereotactic surgical methods has begun to show promise. Patients with IPH should have rapid and accurate diagnosis with neuroimaging with computed tomography (CT) and computed tomography angiography (CTA). Early interventions should include control of hypertension to a systolic BP in the range of 140 mmHg for small hemorrhages without intracranial hypertension with beta blockers or calcium channel blockers, correction of any coagulopathy if present, and assessment of the need for surgical intervention. IPH and FUNC (Functional Outcome in Patients with Primary Intracerebral Hemorrhage) scores should be assessed. Patients should be dispositioned to a dedicated neurologic ICU if available. Patients should be monitored for seizures and intracranial pressure issues. Select patients, particularly those with intraventricular extension, may benefit from evacuation of hematoma with a ventriculostomy or stereotactically guided catheter. Once stabilized, patients should be reassessed with CT imaging and receive ongoing management of blood pressure, cerebral edema, ICP issues, and seizures as they arise. The goal of care for most patients is to regain capacity to receive multidisciplinary rehabilitation to optimize functional outcome.

Anti-aging factor, serum alpha-Klotho, as a marker of acute physiological stress, and a predictor of ICU mortality, in patients with septic shock.

PURPOSE: Genetic deletions decreasing serum alpha-Klotho (alpha-KL) have been associated with rapid aging, multi-organ failure and increased mortality in experimental sepsis. We hypothesized that lower alpha-KL obtained at the onset of septic shock correlates with higher mortality. MATERIALS AND METHODS: Prospective cohort of 104 adult patients with septic shock. Alpha-KL was measured via ELISA on serum collected on the day of enrollment (within 72h from the onset of shock). Relationship between alpha-KL and clinical outcome measures was evaluated in uni- and multi-variable models. RESULTS: Median (IQR) alpha-KL was 816 (1020.4) pg/mL and demonstrated a bimodal distribution with two distinct populations, Cohort A [n=97, median alpha-KL 789.3 (767.1)] and Cohort B [n=7, median alpha-KL 4365.1(1374.4), >1.5 IQR greater than Cohort A]. Within Cohort A, ICU non-survivors had significantly higher serum alpha-KL compared to survivors as well as significantly higher APACHE II and SOFA scores, rates of mechanical ventilation, and serum BUN, creatinine, calcium, phosphorus and lactate (all p≤0.05). Serum alpha-KL≥1005, the highest tertile, was an independent predictor of ICU mortality when controlling for co-variates (p=0.028, 95% CI 1.143-11.136). CONCLUSIONS: Elevated serum alpha-KL in patients with septic shock is independently associated with higher mortality. Further studies are needed to corroborate these findings.

Hypothermia: comparing technology.

Hypothermia has recently been shown to be beneficial in certain clinical settings of acute brain injury, such as cardiac arrest. The available technology to induce and maintain this state is advancing quickly. This review will focus on the current state of available technology and devices as well as their limitations in attaining this potentially neuroprotective state. Furthermore, we will present the efficacy of the individual systems as well as potential side effects and complications that are associated with the technology chosen.

ICH aspiration and thrombolysis.

Intracerebral hemorrhage (ICH) is associated with the highest mortality among all forms of stroke. Evolution in the medical management of ICH has not improved patient outcomes while the results of conventional surgery have generally been disappointing. Minimally invasive surgery (MIS) using stereotactic clot aspiration followed by clot lysis is gaining credibility as an alternative management strategy. We review the published data on this methodology in the treatment of ICH.