Findings Predictive of Poor Outcome in Grade 5 Subarachnoid Hemorrhage: A Cohort Study.

BACKGROUND: Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to "self-fulfilling prophecy," where withdrawal of life-sustaining measures (WLSM) is invariably followed by death. METHODS: We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM. RESULTS: Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02). CONCLUSIONS: We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from "self-fulfilling prophecy." Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Exploratory Evaluation of the Relationship Between iNKT Cells and Systemic Cytokine Profiles of Critically Ill Patients with Neurological Injury.

BACKGROUND: Neurological injury can alter the systemic immune system, modifying the functional capacity of immune cells and causing a dysfunctional balance of cytokines, although mechanisms remain incompletely understood. The objective of this study was to assess the temporal relationship between changes in the activation status of circulating invariant natural killer T (iNKT) cells and the balance of plasma cytokines among critically ill patients with neurological injury. METHODS: We conducted an exploratory prospective observational study of adult (18 years or older) intensive care unit (ICU) patients with acute neurological injury (n = 20) compared with ICU patients without neurological injury (n = 22) and healthy controls (n = 10). Blood samples were collected on days 1, 2, 4, 7, 14, and 28 following ICU admission to analyze the activation status of circulating iNKT cells by flow cytometry and the plasma concentration of inflammation-relevant immune mediators, including T helper 1 (TH1) and T helper 2 (TH2) cytokines, by multiplex bead-based assay. RESULTS: Invariant natural killer T cells were activated in both ICU patient groups compared with healthy controls. Neurological patients had decreased levels of multiple immune mediators, including TH1 cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-12p70), indicative of immunosuppression. This led to a greater than twofold increase in the ratio of TH2/TH1 cytokines early after injury (days 1 - 2) compared with healthy controls, a shift that was also observed for ICU controls. Systemic TH2/TH1 cytokine ratios were positively associated with iNKT cell activation in the neurological patients and negatively associated in ICU controls. These relationships were strongest for the CD4+ iNKT cell subset compared with the CD4- iNKT cell subset. The relationships to individual cytokines similarly differed between patient groups. Forty percent of the neurological patients developed an infection; however, differences for the infection subgroup were not identified. CONCLUSIONS: Critically ill patients with neurological injury demonstrated altered systemic immune profiles early after injury, with an association between activated peripheral iNKT cells and elevated systemic TH2/TH1 cytokine ratios. This work provides further support for a brain-immune axis and the ability of neurological injury to have far-reaching effects on the body's immune system.

Decompressive Craniectomy in Patients with Traumatic Brain Injury: Are the Usual Indications Congruent with Those Evaluated in Clinical Trials?

BACKGROUND: In patients with traumatic brain injury (TBI), multicenter randomized controlled trials have assessed decompressive craniectomy (DC) exclusively as treatment for refractory elevation of intracranial pressure (ICP). DC reliably lowers ICP but does not necessarily improve outcomes. However, some patients undergo DC as treatment for impending or established transtentorial herniation, irrespective of ICP. METHODS: We performed a population-based cohort study assessing consecutive patients with moderate-severe TBI. Indications for DC were compared with enrollment criteria for the DECRA and RESCUE-ICP trials. RESULTS: Of 644 consecutive patients, 51 (8 %) were treated with DC. All patients undergoing DC had compressed basal cisterns, 82 % had at least temporary preoperative loss of ≥1 pupillary light reflex (PLR), and 80 % had >5 mm of midline shift. Most DC procedures (67 %) were "primary," having been performed concomitantly with evacuation of a space-occupying lesion. ICP measurements influenced the decision to perform DC in 18 % of patients. Only 10 and 16 % of patients, respectively, would have been eligible for the DECRA and RESCUE-ICP trials. DC improved basal cistern compression in 76 %, and midline shift in 94 % of patients. Among patients with ≥1 absent PLR at admission, DC was associated with lower mortality (46 vs. 68 %, p = 0.03), especially when the admission Marshall CT score was 3-4 (p = 0.0005). No patients treated with DC progressed to brain death. Variables predictive of poor outcome following DC included loss of PLR(s), poor motor score, midline shift ≥11 mm, and development of perioperative cerebral infarcts. CONCLUSIONS: DC is most often performed for clinical and radiographic evidence of herniation, rather than for refractory ICP elevation. Results of previously completed randomized trials do not directly apply to a large proportion of patients undergoing DC in practice.

ICU Care Team's Perception of Clinical Research in the ICU: A Cross-Sectional Study.

OBJECTIVES: Adequate recruitment is essential for successful clinical research. ICU nurses play a crucial role in identifying eligible patients, introducing research teams, facilitating informed consent, and caring for enrolled patients. However, a larger group of multidisciplinary healthcare professionals (the ICU care team) is equally important in promoting clinical research participation.To describe the ICU care team's experiences in ongoing clinical research, identifying perceived barriers and enablers to their participation, and apply a behavior framework to enhance research engagement. DESIGN: Cross-sectional survey study. SETTING: Four adult ICUs and one PICU between June 2021 and March 2023. SUBJECTS: We recruited nurses, physicians, nurse practitioners, allied health professionals, and unit clerks. MEASUREMENT AND MAIN RESULTS: We developed and validated a cross-sectional survey based on the Capability, Opportunity, Motivation, Behavior model. This survey included: 1) demographic questions (n = 7); 2) research experience questions (n = 6), 3) capability questions (n = 8); 4) opportunity questions (n = 11); 5) and motivation questions (n = 13).A total of 172 ICU care team members completed the survey. Results showed differences in capabilities, opportunities, and motivations among ICU care team members. For example, fellow/attending physicians and nurse practitioners reported higher confidence in discussing research with patients/families, while registered nurses and allied health professionals expressed less confidence. CONCLUSIONS: ICU care team members face multiple barriers that impact their involvement with the conduct of ICU research. To effectively engage healthcare professionals in this process, it is essential to address their capabilities (research knowledge and skills to communicate research with patients/families), create opportunities (collaboration/communication with research team, discuss research during multidisciplinary rounds), and motivate them (recognize their help and share the results of the research being conducted at their site) to improve ICU care team engagement in the conduct of ICU research.

Time required to initiate outbreak and pandemic observational research.

PURPOSE: Observational research focused upon emerging infectious diseases such as Ebola virus, Middle East respiratory syndrome, and Zika virus has been challenging to quickly initiate. We aimed to determine the duration of start-up procedures and barriers encountered for an observational study focused upon such infectious outbreaks. MATERIALS AND METHODS: At 1 pediatric and 5 adult intensive care units, we measured durations from protocol receipt to a variety of outbreak research milestones, including research ethics board (REB) approval, data sharing agreement (DSA) execution, and patient study screening initiation. RESULTS: The median (interquartile range) time from site receipt of the protocol to REB submission was 73 (30-126) days; to REB approval, 158 (42-188) days; to DSA completion, 276 (186-312) days; and to study screening initiation, 293 (269-391) days. The median time from REB submission to REB approval was 43 (13-85) days. The median time for all start-up procedures was 335 (188-335) days. CONCLUSIONS: There is a lengthy start-up period required for outbreak-focused research. Completing DSAs was the most time-consuming step. A reactive approach to newly emerging threats such as Ebola virus, Middle East respiratory syndrome, and Zika virus will likely not allow sufficient time to initiate research before most outbreaks are advanced.

Efficacy and safety of active negative pressure peritoneal therapy for reducing the systemic inflammatory response after damage control laparotomy (the Intra-peritoneal Vacuum Trial): study protocol for a randomized controlled trial.

BACKGROUND: Damage control laparotomy, or abbreviated initial laparotomy followed by temporary abdominal closure (TAC), intensive care unit resuscitation, and planned re-laparotomy, is frequently used to manage intra-abdominal bleeding and contamination among critically ill or injured adults. Animal data suggest that TAC techniques that employ negative pressure to the peritoneal cavity may reduce the systemic inflammatory response and associated organ injury. The primary objective of this study is to determine if use of a TAC dressing that affords active negative pressure peritoneal therapy, the ABThera Open Abdomen Negative Pressure Therapy System, reduces the extent of the systemic inflammatory response after damage control laparotomy for intra-abdominal sepsis or injury as compared to a commonly used TAC method that provides potentially less efficient peritoneal negative pressure, the Barker's vacuum pack. METHODS/DESIGN: The Intra-peritoneal Vacuum Trial will be a single-center, randomized controlled trial. Adults will be intraoperatively allocated to TAC with either the ABThera or Barker's vacuum pack after the decision has been made by the attending surgeon to perform a damage control laparotomy. The study will use variable block size randomization. On study days 1, 2, 3, 7, and 28, blood will be collected. Whenever possible, peritoneal fluid will also be collected at these time points from the patient's abdomen or TAC device. Luminex technology will be used to quantify the concentrations of 65 mediators relevant to the inflammatory response in peritoneal fluid and plasma. The primary endpoint is the difference in the plasma concentration of the pro-inflammatory cytokine IL-6 at 24 and 48 h after TAC dressing application. Secondary endpoints include the differential effects of these dressings on the systemic concentration of other pro-inflammatory cytokines, collective peritoneal and systemic inflammatory mediator profiles, postoperative fluid balance, intra-abdominal pressure, and several patient-important outcomes, including organ dysfunction measures and mortality. DISCUSSION: Results from this study will improve understanding of the effect of active negative pressure peritoneal therapy after damage control laparotomy on the inflammatory response. It will also gather necessary pilot information needed to inform design of a multicenter trial comparing clinical outcomes among patients randomized to TAC with the ABThera versus Barker's vacuum pack. TRIAL REGISTRATION: ClinicalTrials.gov identifier http://www.clicaltrials.gov/ct2/show/NCT01355094.

Recurrent sixth nerve palsy associated with a hypoplastic Dorello's canal.

Recurrent sixth nerve palsies are usually idiopathic, although they have been postulated to be caused by a postinflammatory insult or abnormal cerebral circulation. We report the case a 9-month-old boy who had 2 episodes of a left abduction deficit that resolved spontaneously. A 3-dimensional high-resolution T2-weighted sequence magnetic resonance imaging scan of the head revealed a hypoplastic left 6th nerve and a small left Dorello's canal.

Laser-assisted subepithelial keratectomy and photorefractive keratectomy for post-penetrating keratoplasty myopia and astigmatism in adults.

PURPOSE: To evaluate whether laser-assisted subepithelial keratectomy (LASEK) and photorefractive keratectomy (PRK) achieve effective targeted correction and the extent of post-treatment corneal haze after corneal transplantation. SETTING: Nonhospital surgical facility, Calgary, Alberta, Canada. DESIGN: Evidence-based manuscript. METHODS: This study evaluated visual acuity, refractive error correction, and potential complications after LASEK or PRK to eliminate refractive error differences after penetrating keratoplasty in adults. A Nidek EC-5000 or Technolas 217 excimer laser was used in all treatments. RESULTS: At last follow-up (mean 20.50 months post laser), the mean spherical equivalent (SE) decreased from -2.71 diopters (D) ± 4.17 (SD) to -0.54 ± 3.28 D in the LASEK group and from -4.87 ± 3.90 D to -1.82 ± 3.34 D in the PRK group. The mean preoperative uncorrected distance visual acuity (UDVA) was 1.63 ± 0.53 and 1.45 ± 0.64, respectively, and the mean postoperative UDVA, 0.83 ± 0.54 and 0.90 ± 0.55, respectively. The improvement in SE and UDVA was statistically significant in both groups (P < .01). The mean haze (0 to 3 scale) at the last follow-up was 0.46 ± 0.708 in the LASEK group and 0.58 ± 0.776 in the PRK group. CONCLUSIONS: The UDVA improved and refractive errors were effectively reduced after LASEK or PRK in eyes with previous PKP. There was no significant difference in the change in SE, UDVA, or corrected distance visual acuity between LASEK and PRK. Some patients had evidence of corneal haze, although the difference between the groups was not significant.