Tranexamic acid for percutaneous nephrolithotomy: an abridged Cochrane review.

OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

Association Between Adult-Onset Hearing Loss and Income: A Systematic Review.

INTRODUCTION: Hearing loss has been shown to be associated with both negative health outcomes and low socioeconomic position, including lower income. Despite this, a thorough review of the existing literature on this relationship has not yet been performed. OBJECTIVES: To evaluate available literature on the possible association between income and adult-onset hearing loss. DESIGN: A search was conducted in eight databases for all relevant literature using terms focused on hearing loss and income. Studies reporting the presence or absence of an association between income and hearing loss, full-text English-language access, and a predominantly adult population (≥18 years old) were eligible. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. RESULTS: The initial literature search yielded 2994 references with three additional sources added through citation searching. After duplicate removal, 2355 articles underwent title and abstract screening. This yielded 161 articles eligible for full-text review resulting in 46 articles that were included in qualitative synthesis. Of the included studies, 41 of 46 articles found an association between income and adult-onset hearing loss. Due to heterogeneity among study designs, a meta-analysis was not performed. CONCLUSIONS: The available literature consistently supports an association between income and adult-onset hearing loss but is limited entirely to cross-sectional studies with the directionality remaining unknown. An aging population and the negative health outcomes associated with hearing loss, emphasize the importance of understanding and addressing the role of social determinants of health in the prevention and management of hearing loss.

Tranexamic acid for percutaneous nephrolithotomy.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is the gold standard for the treatment of large kidney stones but comes with an increased risk of bleeding compared to other treatments, such as ureteroscopy and shock wave lithotripsy. Tranexamic acid (TXA) is an antifibrinolytic agent that has been used to reduce bleeding complications in other settings. OBJECTIVES: To assess the effects of TXA in individuals with kidney stones undergoing PCNL. SEARCH METHODS: We performed a comprehensive literature search of the Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, other sources of the grey literature, and conference proceedings. We applied no restrictions on the language of publication nor publication status. The latest search date was 11 May 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients ≥ 18 years old. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data. Primary outcomes were: blood transfusion, stone-free rate (SFR), and thromboembolic events (TEEs). Secondary outcomes were: adverse events (AEs), secondary interventions, major surgical complications, minor surgical complications, unplanned hospitalizations or readmissions, and hospital length of stay (LOS). We performed statistical analyzes using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach using a minimally contextualized approach with predefined thresholds for minimally clinically important differences (MCIDs). MAIN RESULTS: We analyzed 10 RCTs assessing the effect of systemic TXA in PCNL versus placebo (or no TXA) with 1883 randomized participants. Eight studies were published as full text. One was published in abstract proceedings, but it was separated into two separate studies for the purpose of our analyzes. Average stone surface area ranged 3.45 to 6.62 cm2. We also found a single RCT published in full text assessing the effects of topical TXA in PCNL versus placebo (or no TXA) with 400 randomized participants, the results of which are further described in the review. Here we focus only on the results of TXA used systemically. Blood transfusion - Based on a representative baseline risk of 5.7% for blood transfusions taken from a large presentative observational studies, systemic TXA may reduce blood transfusions (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.27 to 0.76; I2 = 28%; 9 studies, 1353 participants; low CoE). We assumed an MCID of ≥ 2%. Based on 57 participants per 1000 with placebo (or no TXA) being transfused, this corresponds to 31 fewer (from 42 fewer to 14 fewer) participants being transfused per 1000. Stone-free rate - Based on a representative baseline risk of 75.7% for SFR, systemic TXA may increase SFRs (RR 1.11, 95% CI 0.98 to 1.27; I2 = 62%; 4 studies, 603 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 757 participants per 1000 being stone free with placebo (or no TXA), this corresponds to 83 more (from 15 fewer to 204 more) stone-free participants per 1000. Thromboembolic events - There is probably no difference in TEEs (risk difference (RD) 0.00, 95% CI -0.01 to 0.01; I2 = 0%; 6 studies, 841 participants; moderate CoE). We assumed an MCID of ≥ 2%. Since there were no thromboembolic events in intervention and/or control groups in 5 out of6 studies, we opted to assess a risk difference with systemic TXA for this outcome. Adverse events - Systemic TXA may increase AEs (RR 5.22, 95% CI 0.52 to 52.72; I2 = 75%; 4 studies, 602 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 23 participants per 1000 with placebo (or no TXA) having an adverse event, this corresponds to 98 more (from 11 fewer to 1000 more) participants with adverse events per 1000. Secondary interventions - Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84 to 1.57; I2 = 0%; 2 studies, 319 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 278 participants per 1000 with placebo (or no TXA) having a secondary intervention, this corresponds to 42 more (from 44 fewer to 158 more) participants with secondary interventions per 1000. Major surgical complications - Based on a representative baseline risk for major surgical complications of 4.1%, systemic TXA may reduce major surgical complications (RR 0.36, 95% CI 0.21 to 0.62; I2 = 0%; 5 studies, 733 participants; moderate CoE). We assumed an MCID of ≥ 2%. Based on 41 participants per 1000 with placebo (or no TXA) having a major surgical complication, this corresponds to 26 fewer (from 32 fewer to 16 fewer) participants with major surgical complications per 1000. Minor surgical complications - Systemic TXA may reduce minor surgical complications (RR 0.71, 95% CI 0.45 to 1.10; I2 = 76%; 5 studies, 733 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 396 participants per 1000 with placebo (or no TXA) having a minor surgical complication, this corresponds to 115 fewer (from 218 fewer to 40 more) participants with minor surgical complications per 1000. Unplanned hospitalizations or readmissions - We are very uncertain how unplanned hospitalizations or readmissions are affected (RR 1.55, 95% CI 0.45 to 5.31; I2 = not applicable; 1 study, 189 participants; very low CoE). We assumed an MCID of ≥ 2%. Hospital length of stay - Systemic TXA may reduce hospital LOS (mean difference 0.52 days lower, 95% CI 0.93 lower to 0.11 lower; I2 = 98%; 7 studies, 1151 participants; low CoE). We assumed an MCID of ≥ 0.5 days. AUTHORS' CONCLUSIONS: Based on 10 RCTs with substantial methodological limitations that lowered all CoE of effect, we found that systemic TXA in PCNL may reduce blood transfusions, major and minor surgical complications, and hospital LOS, as well as improve SFRs; however, it may increase AEs. We are uncertain about the effects of systemic TXA on other outcomes. Findings of this review should assist urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

PURPOSE: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. METHODS: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. RESULTS: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR (P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) (P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. CONCLUSIONS: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

Does Medialization Improve Swallowing Function in Patients with Unilateral Vocal Fold Paralysis? A Systematic Review.

Glottal incompetence caused by unilateral vocal fold paralysis (UVFP) is a common cause of dysphagia and aspiration. Treatments targeted at reducing glottal incompetence by injection augmentation or medialization thyroplasty are well established at improving voice outcomes, but improvements in swallowing function are less clear. The objective of this systematic review was to determine the impact of vocal fold medialization on dysphagia outcomes. Six electronic bibliographic databases and one clinical trial registry were searched on 3/13/2020. Our patient population were adult patients with verified UVFP that underwent vocal fold medialization. We limited review to prospective studies that had formal dysphagia assessment both before and after medialization. Nine studies met selection criteria (7 prospective case series and 2 prospective cohort studies) totaling 157 patients. The most common etiology of UVFP was iatrogenic (74/157; 47%). The majority of patients underwent injection augmentation (92/157; 59%), and the remaining underwent medialization thyroplasty. A variety of methods were used to assess changes in dysphagia including patient-reported outcome measures, flexible endoscopic evaluation of swallowing, videofluoroscopic swallow study, and high-resolution manometry. 7/9 studies demonstrated clinically significant improvement in swallowing function following medialization; 4/9 studies demonstrated statistically significant improvement, and three studies did not show statistically significant improvement after intervention. Study participants and outcome measures evaluating swallowing function in this review were heterogeneous. Moreover, the reviewed studies are concerning for multiple risks of bias impacting their conclusions. Taken together, this systematic review demonstrates limited evidence that injection augmentation and medialization thyroplasty improve swallowing function and/or safety.

MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines.

BACKGROUND: Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic stem cell transplant before or soon after symptom onset. We sought to establish evidence-based guidelines detailing the neuroimaging surveillance of boys with neurologically asymptomatic adrenoleukodystrophy. METHODS: To establish the most frequent age and diagnostic neuroimaging modality for CCALD, we completed a meta-analysis of relevant studies published between January 1, 1970 and September 10, 2019. We used the consensus development conference method to incorporate the resulting data into guidelines to inform the timing and techniques for neuroimaging surveillance. Final guideline agreement was defined as >80% consensus. RESULTS: One hundred twenty-three studies met inclusion criteria yielding 1285 patients. The overall mean age of CCALD diagnosis is 7.91 years old. The median age of CCALD diagnosis calculated from individual patient data is 7.0 years old (IQR: 6.0-9.5, n = 349). Ninety percent of patients were diagnosed between 3 and 12. Conventional MRI was most frequently reported, comprised most often of T2-weighted and contrast-enhanced T1-weighted MRI. The expert panel achieved 95.7% consensus on the following surveillance parameters: (a) Obtain an MRI between 12 and 18 months old. (b) Obtain a second MRI 1 year after baseline. (c) Between 3 and 12 years old, obtain a contrast-enhanced MRI every 6 months. (d) After 12 years, obtain an annual MRI. CONCLUSION: Boys with adrenoleukodystrophy identified early in life should be monitored with serial brain MRIs during the period of highest risk for conversion to CCALD.

Laryngeal Injury and Upper Airway Symptoms After Endotracheal Intubation During Surgery: A Systematic Review and Meta-analysis.

Laryngeal injury from intubation can substantially impact airway, voice, and swallowing, thus necessitating multidisciplinary interventions. The goals of this systematic review were (1) to review the types of laryngeal injuries and their patient-reported symptoms and clinical signs resulting from endotracheal intubation in patients intubated for surgeries and (2) to better understand the overall the frequency at which these injuries occur. We conducted a search of 4 online bibliographic databases (ie, PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature [CINAHL], and The Cochrane Library) and ProQuest and Open Access Thesis Dissertations (OPTD) from database inception to September 2019 without restrictions for language. Studies that completed postextubation laryngeal examinations with visualization in adult patients who were endotracheally intubated for surgeries were included. We excluded (1) retrospective studies, (2) case studies, (3) preexisting laryngeal injury/disease, (4) patients with histories of or surgical interventions that risk injury to the recurrent laryngeal nerve, (5) conference abstracts, and (6) patient populations with nonfocal, neurological impairments that may impact voice and swallowing function, thus making it difficult to identify isolated postextubation laryngeal injury. Independent, double-data extraction, and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Collaboration's criteria. Twenty-one articles (1 cross-sectional, 3 cohort, 5 case series, 12 randomized controlled trials) representing 21 surgical studies containing 6140 patients met eligibility criteria. The mean patient age across studies reporting age was 49 (95% confidence interval [CI], 45-53) years with a mean intubation duration of 132 (95% CI, 106-159) minutes. Studies reported no injuries in 80% (95% CI, 69-88) of patients. All 21 studies presented on type of injury. Edema was the most frequently reported mild injury, with a prevalence of 9%-84%. Vocal fold hematomas were the most frequently reported moderate injury, with a prevalence of 4% (95% CI, 2-10). Severe injuries that include subluxation of the arytenoids and vocal fold paralysis are rare (<1%) outcomes. The most prevalent patient complaints postextubation were dysphagia (43%), pain (38%), coughing (32%), a sore throat (27%), and hoarseness (27%). Overall, laryngeal injury from short-duration surgical intubation is common and is most often mild. No uniform guidelines for laryngeal assessment postextubation from surgery are available and hoarseness is neither a good indicator of laryngeal injury or dysphagia. Protocolized screening for dysphonia and dysphagia postextubation may lead to improved identification of injury and, therefore, improved patient outcomes and reduced health care utilization.

Prevalence and Outcome of Acute Respiratory Distress Syndrome in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. DATA SOURCES: PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. DATA EXTRACTION: Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle-Ottawa Scale for cohort and case-control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). DATA SYNTHESIS: We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35-47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13-0.27, I2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2-5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64-0.75; I2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23-0.40; I2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. CONCLUSION: In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted.

Assessing the efficacy of repeat resections in recurrent glioblastoma: a systematic review.

BACKGROUND: The inevitable recurrence of glioblastoma (GBM) results in patients often undergoing multiple resections with questionable benefit to overall survival (OS). OBJECTIVE: To systematically review and analyze prior studies examining the potential added benefit of repeat resection (RR) in recurrent GBM. METHODS: We performed a PRISMA-compliant systematic review of literature published between 1969 to 2019 involving patients undergoing RR at GBM recurrence. RESULTS: The search yielded 3994 non-duplicate citations. Final abstraction included 43 articles, with 2 level II and 41 level III studies. The earliest paper we included was published in 1987 [1], and 35 identified papers (81.4%) were published within the last 10 years. The survival data of 9236 patients (55% male) were analyzed, with a median age of 56; 3726 patients underwent RR. In 31 studies with a comparable single-surgery-only cohort, 20 articles reported a statistically significant increase in OS with RR, 7 reported nonsignificant trends toward increased OS with RR, and 4 reported no significant increase in OS with RR. Twenty-two articles with multivariate analyses of Karnofsky performance scores and 17 articles with extent-of-resection reported these as significant prognostic factors of OS. In 26 studies, median OS among all patients was 17.85 months inclusive of median OS following RR totaling 9.6 months. Notably, in 10 studies with data on subsequent progressions (2+ recurrences), 6 studies reported significant increases in OS with subsequent repeat resection (sRR) compared to those not undergoing sRR. CONCLUSIONS: Recurrent GBM presents a treatment challenge. There appears to be an OS benefit for RR upon first recurrence as well as sRR. Such findings warrant further investigation of the potential benefits of continued surgical intervention after subsequent progressions of GBM.

Pathophysiology of Brain Injury and Neurological Outcome in Acute Respiratory Distress Syndrome: A Scoping Review of Preclinical to Clinical Studies.

Acute respiratory distress syndrome (ARDS) has been associated with secondary acute brain injury (ABI). However, there is sparse literature on the mechanism of lung-mediated brain injury and prevalence of ARDS-associated secondary ABI. We aimed to review and elucidate potential mechanisms of ARDS-mediated ABI from preclinical models and assess the prevalence of ABI and neurological outcome in ARDS with clinical studies. We conducted a systematic search of PubMed and five other databases reporting ABI and ARDS through July 6, 2020 and included studies with ABI and neurological outcome occurring after ARDS. We found 38 studies (10 preclinical studies with 143 animals; 28 clinical studies with 1175 patients) encompassing 9 animal studies (n = 143), 1 in vitro study, 12 studies on neurocognitive outcomes (n = 797), 2 clinical observational studies (n = 126), 1 neuroimaging study (n = 15), and 13 clinical case series/reports (n = 15). Six ARDS animal studies demonstrated evidence of neuroinflammation and neuronal damage within the hippocampus. Five animal studies demonstrated altered cerebral blood flow and increased intracranial pressure with the use of lung-protective mechanical ventilation. High frequency of ARDS-associated secondary ABI or poor neurological outcome was observed ranging 82-86% in clinical observational studies. Of the clinically reported ABIs (median age 49 years, 46% men), the most common injury was hemorrhagic stroke (25%), followed by hypoxic ischemic brain injury (22%), diffuse cerebral edema (11%), and ischemic stroke (8%). Cognitive impairment in patients with ARDS (n = 797) was observed in 87% (range 73-100%) at discharge, 36% (range 32-37%) at 6 months, and 30% (range 25-45%) at 1 year. Mechanisms of ARDS-associated secondary ABI include primary hypoxic ischemic injury from hypoxic respiratory failure, secondary injury, such as lung injury induced neuroinflammation, and increased intracranial pressure from ARDS lung-protective mechanical ventilation strategy. In summary, paucity of clinical data exists on the prevalence of ABI in patients with ARDS. Hemorrhagic stroke and hypoxic ischemic brain injury were commonly observed. Persistent cognitive impairment was highly prevalent in patients with ARDS.

Brain Injury Is More Common in Venoarterial Extracorporeal Membrane Oxygenation Than Venovenous Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Despite the common occurrence of brain injury in patients undergoing extracorporeal membrane oxygenation, it is unclear which cannulation method carries a higher risk of brain injury. We compared the prevalence of brain injury between patients undergoing venoarterial and venovenous extracorporeal membrane oxygenation. DATA SOURCES: PubMed and six other databases from inception to April 2020. STUDY SELECTION: Observational studies and randomized clinical trials in adult patients undergoing venoarterial extracorporeal membrane oxygenation or venovenous extracorporeal membrane oxygenation reporting brain injury. DATA EXTRACTION: Two independent reviewers extracted the data from the studies. Random-effects meta-analyses were used to pool data. DATA SYNTHESIS: Seventy-three studies (n = 16,063) met inclusion criteria encompassing 8,211 patients (51.2%) undergoing venoarterial extracorporeal membrane oxygenation and 7,842 (48.8%) undergoing venovenous extracorporeal membrane oxygenation. Venoarterial extracorporeal membrane oxygenation patients had more overall brain injury compared with venovenous extracorporeal membrane oxygenation (19% vs 10%; p = 0.002). Venoarterial extracorporeal membrane oxygenation patients had more ischemic stroke (10% vs 1%; p < 0.001), hypoxic-ischemic brain injury (13% vs 1%; p < 0.001), and brain death (11% vs 1%; p = 0.001). In contrast, rates of intracerebral hemorrhage (6% vs 8%; p = 0.35) did not differ. Survival was lower in venoarterial extracorporeal membrane oxygenation (48%) than venovenous extracorporeal membrane oxygenation (64%) (p < 0.001). After excluding studies that included extracorporeal cardiopulmonary resuscitation, no significant difference was seen in the rate of overall acute brain injury between venoarterial extracorporeal membrane oxygenation and venovenous extracorporeal membrane oxygenation (13% vs 10%; p = 0.4). However, ischemic stroke (10% vs 1%; p < 0.001), hypoxic-ischemic brain injury (7% vs 1%; p = 0.02), and brain death (9% vs 1%; p = 0.005) remained more frequent in nonextracorporeal cardiopulmonary resuscitation venoarterial extracorporeal membrane oxygenation compared with venovenous extracorporeal membrane oxygenation. CONCLUSIONS: Brain injury was more common in venoarterial extracorporeal membrane oxygenation compared with venovenous extracorporeal membrane oxygenation. While ischemic brain injury was more common in venoarterial extracorporeal membrane oxygenation patients, the rates of intracranial hemorrhage were similar between venoarterial extracorporeal membrane oxygenation and venovenous extracorporeal membrane oxygenation. Further research on mechanism, timing, and effective monitoring of acute brain injury and its management is necessary.

Brain Injury and Neurologic Outcome in Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation has shown survival benefit in select patients with refractory cardiac arrest but there is insufficient data on the frequency of different types of brain injury. We aimed to systematically review the prevalence, predictors of and survival from neurologic complications in patients who have undergone extracorporeal cardiopulmonary resuscitation. DATA SOURCES: MEDLINE (PubMed) and six other databases (EMBASE, Cochrane Library, CINAHL Plus, Web of Science, and Scopus) from inception to August 2019. STUDY SELECTION: Randomized controlled trials and observational studies in patients greater than 18 years old. DATA EXTRACTION: Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for randomized controlled trials, the Newcastle-Ottawa Scale for cohort and case-control studies, and the Murad tool for case series. Random-effects meta-analyses were used to pool data. DATA SYNTHESIS: The 78 studies included in our analysis encompassed 50,049 patients, of which 6,261 (12.5%) received extracorporeal cardiopulmonary resuscitation. Among extracorporeal cardiopulmonary resuscitation patients, the median age was 56 years (interquartile range, 52-59 yr), 3,933 were male (63%), 3,019 had out-of-hospital cardiac arrest (48%), and 2,289 had initial shockable heart rhythm (37%). The most common etiology of cardiac arrest was acute coronary syndrome (n = 1,657, 50% of reported). The median extracorporeal cardiopulmonary resuscitation duration was 3.2 days (interquartile range, 2.1-4.9 d). Overall, 27% (95% CI, 0.17-0.39%) had at least one neurologic complication, 23% (95% CI, 0.14-0.32%) hypoxic-ischemic brain injury, 6% (95% CI, 0.02-0.11%) ischemic stroke, 6% (95% CI, 0.01-0.16%) seizures, and 4% (95% CI, 0.01-0.1%) intracerebral hemorrhage. Seventeen percent (95% CI, 0.12-0.23%) developed brain death. The overall survival rate after extracorporeal cardiopulmonary resuscitation was 29% (95% CI, 0.26-0.33%) and good neurologic outcome was achieved in 24% (95% CI, 0.21-0.28%). CONCLUSIONS: One in four patients developed acute brain injury after extracorporeal cardiopulmonary resuscitation and the most common type was hypoxic-ischemic brain injury. One in four extracorporeal cardiopulmonary resuscitation patients achieved good neurologic outcome. Further research on assessing predictors of extracorporeal cardiopulmonary resuscitation-associated brain injury is necessary.

A systematic review of tumor treating fields therapy for high-grade gliomas.

INTRODUCTION: Tumor treating fields (TTF) is a unique treatment modality that utilizes alternating electric fields to deliver therapy. Treatment effects have been assessed in patients with newly diagnosed and recurrent glioblastoma in clinical trials and retrospective studies. While the results of these studies led to FDA approval for both populations, a portion of the neuro-oncology and neurosurgery community remains skeptical of TTF. Thus, this review aims to systematically summarize and evaluate prior studies investigating the efficacy and safety of TTF in patients with high-grade gliomas. METHODS: A systematic review of the literature was performed according to PRISMA guidelines from database inception through February 2019. To be included, studies must have investigated the efficacy of TTF in adult high-grade glioma patients. RESULTS: In total, 852 studies were initially identified, 9 of which met final inclusion criteria. In total, 1191 patients were identified who received TTF. Included studies consisted of two pilot clinical trials, two randomized clinical trials, and five retrospective studies. In randomized clinical trials, TTF improved survival for newly diagnosed glioblastoma patients but not for recurrent glioblastoma patients. Adverse skin reactions were the primary adverse effect associated with TTF. CONCLUSION: While TTF has been evaluated for safety and efficacy in a number of studies, concerns remain regarding study design, quality of life, and cost of therapy. Further investigation is needed regarding the therapy, and ongoing trials are already underway to provide more data regarding therapy outcomes and interactions in combination regimens.

A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma.

PURPOSE: Due to the infiltrative nature of glioblastoma (GBM) outside of the contrast-enhancing region on MRI, there is interest in exploring supratotal resections (SpTR) that extend beyond the contrast-enhancing portion of the tumor. However, there is currently no consensus on the potential survival benefit of SpTR in GBM compared to gross total resection (GTR). In this study, we compare the impact of SpTR versus GTR on overall survival (OS) of GBM patients. METHODS: We performed a systematic review and meta-analysis of literature published on PubMed, Embase, The Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov, from inception to August 16, 2018, to identify articles comparing OS after SpTR versus GTR. RESULTS: We identified 8902 unique citations, of which 11 articles met study inclusion criteria. 810 patients underwent SpTR out of a total of 2056 patients. 9 of 11 studies demonstrated improved outcomes with SpTR compared to GTR (median improvement in OS of 10.5 months), with no significant difference in postoperative complication rate. Overall study quality was variable, with ten studies presenting level IV evidence and one study presenting level IIIb evidence. Subgroup meta-analysis based on SpTR definition demonstrated a statistically significant 35% lower risk of mortality in patients who underwent anatomical SpTR compared to patients who underwent GTR (Hazard ratio = 0.65, 95% CI 0.47- 0.91, p = 0.003). CONCLUSION: Our systematic review indicates SpTR may be associated with improved OS compared to GTR for GBM, especially with anatomical SpTR. However, this is limited by variable study design and significant clinical and methodological heterogeneity among studies. There is need for prospective clinical data to further guide parameters regarding the use of SpTR in GBM.

Endoscopic endonasal versus transcranial approach to resection of olfactory groove meningiomas: a systematic review.

Despite the increasing utility of the endoscopic endonasal approach (EEA) for management of anterior skull base (ASB) pathologies, the optimal treatment strategy for olfactory groove meningiomas (OGM) remains unclear. This project sought to systematically compare outcomes of EEA management with conventional transcranial approach (TCA) for the treatment of OGMs. A systematic review was performed to identify studies that compared outcomes following EEA and TCA for OGMs. Data extracted from each study included gross total resection (GTR), incidence of cerebrospinal fluid (CSF) leaks, and post-operative complications including anosmia. The results of the search yielded 5 studies which met the criteria for inclusion and analysis. All studies compared TCA (n = 922) with EEA (n = 141) outcomes for OGMs. Overall, the rate of gross total resection (GTR) was lower among the endoscopic group (70.9%) relative to the transcranial group (91.5%). The rate of post-operative CSF leak was 6.3% vs. 25.5% for the transcranial and endoscopic groups, respectively. Post-operative anosmia was higher for patients undergoing EEA (95.9%) compared with patients in the transcranial group (37.4%). In this analysis, EEA was associated with a lower rate of GTR and higher incidences of CSF leaks and post-operative anosmia. However, with increasing surgeon familiarity of the endoscopic anatomy and technique for managing ASB pathologies, a nuanced approach may be used to minimize patient morbidity and widen the spectrum of skull base surgery.

Librarian integration into health care conferences: a case report.

BACKGROUND: Health care continuing education conferences are important educational events that present opportunities for structured learning, interactive sharing, and professional networking. Conference presenters frequently cite published literature, such as clinical trials, to supply an evidence-based foundation, with presenters' slides often shared with conference attendees. By using social media, these conferences can have greater impact, assist in supporting evidence-based clinical practice, and increase stakeholder engagement. CASE PRESENTATION: The authors present a case of embedding a health sciences librarian into the Annual Johns Hopkins Critical Care Rehabilitation Conference. The librarian served multiple roles, including social media ambassador, conference exhibitor, and presenter. We explore how these roles contributed to the field of early rehabilitation research through information dissemination and education. We also address best practices for librarian support of the conference, with a discussion of tools, platforms, and work flows that were beneficial. CONCLUSIONS: Librarian integration facilitated education about bibliographic literature database content, database searching, critical appraisal, and reporting of search methodology. Additionally, the librarian contributed to real-time distribution of scholarly literature through proficiency with web platforms, citation management programs, and social media. Librarians' expertise in information organization and dissemination, as well as various technology platforms, make them a valuable addition to health care conferences.

Head-Mounted Display Use in Surgery: A Systematic Review.

Purpose. We analyzed the literature to determine (1) the surgically relevant applications for which head-mounted display (HMD) use is reported; (2) the types of HMD most commonly reported; and (3) the surgical specialties in which HMD use is reported. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched through August 27, 2017, for publications describing HMD use during surgically relevant applications. We identified 120 relevant English-language, non-opinion publications for inclusion. HMD types were categorized as "heads-up" (nontransparent HMD display and direct visualization of the real environment), "see-through" (visualization of the HMD display overlaid on the real environment), or "non-see-through" (visualization of only the nontransparent HMD display). Results. HMDs were used for image guidance and augmented reality (70 publications), data display (63 publications), communication (34 publications), and education/training (18 publications). See-through HMDs were described in 55 publications, heads-up HMDs in 41 publications, and non-see-through HMDs in 27 publications. Google Glass, a see-through HMD, was the most frequently used model, reported in 32 publications. The specialties with the highest frequency of published HMD use were urology (20 publications), neurosurgery (17 publications), and unspecified surgical specialty (20 publications). Conclusion. Image guidance and augmented reality were the most commonly reported applications for which HMDs were used. See-through HMDs were the most commonly reported type used in surgically relevant applications. Urology and neurosurgery were the specialties with greatest published HMD use.

Early versus deferred standard androgen suppression therapy for advanced hormone-sensitive prostate cancer.

BACKGROUND: Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer. OBJECTIVES: To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer. SEARCH METHODS: For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse. MAIN RESULTS: We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths (95% CI 80 fewer to 31 fewer) per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths (95% CI 32 fewer to 13 fewer) per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events (risk ratio (RR) 1.05, 95% CI 0.95 to 1.16; low-certainty evidence; 10,575 participants) which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time (HR 0.69, 95% CI 0.57 to 0.84; moderate-certainty evidence). This corresponds to 62 fewer prostate cancer deaths per 1000 (95% CI 87 fewer to 31 fewer) at 5 years for the moderate risk group and 24 fewer death from prostate cancer (95% CI 34 fewer to 12 fewer) per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations.Early AST may decrease the rate of skeletal events (RR 0.37, 95% CI 0.17 to 0.80; low-certainty evidence) corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue (RR 1.41, 95% CI 1.23 to 1.62; low-certainty evidence), corresponding to 31 more men with this complaint per 1000 (95% CI 18 more to 48 more). We downgraded for study limitations and imprecision. It may increase the risk of heart failure (RR 1.90, 95% CI 1.09 to 3.33; low-certainty evidence) corresponding to 27 more events per 1000 (95% CI 3 more to 69 more). We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire (mean difference -1.56, 95% CI -4.50 to 1.38; moderate-certainty evidence) with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. AUTHORS' CONCLUSIONS: Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.

Laryngeal Injury and Upper Airway Symptoms After Oral Endotracheal Intubation With Mechanical Ventilation During Critical Care: A Systematic Review.

OBJECTIVES: To systematically review the symptoms and types of laryngeal injuries resulting from endotracheal intubation in mechanically ventilated patients in the ICU. DATA SOURCES: PubMed, Embase, CINAHL, and Cochrane Library from database inception to September 2017. STUDY SELECTION: Studies of adult patients who were endotracheally intubated with mechanical ventilation in the ICU and completed postextubation laryngeal examinations with either direct or indirect visualization. DATA EXTRACTION: Independent, double-data extraction and risk of bias assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias assessment followed the Cochrane Collaboration's criteria. DATA SYNTHESIS: Nine studies (seven cohorts, two cross-sectional) representing 775 patients met eligibility criteria. The mean (SD; 95% CI) duration of intubation was 8.2 days (6.0 d; 7.7-8.7 d). A high prevalence (83%) of laryngeal injury was found. Many of these were mild injuries, although moderate to severe injuries occurred in 13-31% of patients across studies. The most frequently occurring clinical symptoms reported post extubation were dysphonia (76%), pain (76%), hoarseness (63%), and dysphagia (49%) across studies. CONCLUSIONS: Laryngeal injury from intubation is common in the ICU setting. Guidelines for laryngeal assessment and postextubation surveillance do not exist. A systematic approach to more robust investigations could increase knowledge of the association between particular injuries and corresponding functional impairments, improving understanding of both time course and prognosis for resolution of injury. Our findings identify targets for future research and highlight the long-known, but understudied, clinical outcomes from endotracheal intubation with mechanical ventilation in ICU.

Methodologic Innovation in Creating Clinical Practice Guidelines: Insights From the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Guideline Effort.

OBJECTIVES: To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine's 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults. DESIGN: We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges. SETTING/SUBJECTS: Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff. INTERVENTIONS: Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step approach to generating final recommendations; and 4) systematic identification of evidence gaps. MEASUREMENTS AND MAIN RESULTS: Critical illness survivors contributed to prioritizing topics, questions, and outcomes, evidence interpretation, recommendation formulation, and article review to ensure that their values and preferences were considered in the guidelines. Qualitative and semiquantitative approaches supported formulating descriptive statements using comprehensive literature reviews, summaries, and large-group discussion. Experts (including the methodologists and guideline chairs) developed and refined guideline recommendations through monthly topic-specific section conference calls. Recommendations were precirculated to all members, presented to, and vetted by, most members at a live meeting. Final electronic voting provided links to all forest plots, evidence summaries, and "evidence to decision" frameworks. Written comments during voting captured dissenting views and were integrated into evidence to decision frameworks and the guideline article. Evidence gaps, reflecting clinical uncertainty in the literature, were identified during the evidence to decision process, live meeting, and voting and formally incorporated into all written recommendation rationales. Frequent scheduled "check-ins" mitigated communication gaps. CONCLUSIONS: Our multifaceted, interdisciplinary approach and novel methodologic strategies can help inform the development of future critical care clinical practice guidelines.