Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVE: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). DESIGN: Retrospective cohort study with prospectively collected data. SETTING: Eighteen Level-1 Trauma Centers, United States. PATIENTS: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). CONCLUSION: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Role of Blood-Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults.

OBJECTIVE: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients. METHODS: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR). RESULTS: Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = -0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [-0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03-1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09-1.22, p < 0.001). INTERPRETATION: Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024-1035.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking. OBJECTIVE: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI. METHODS: We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB+). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication. RESULTS: A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB+ group compared to the BB- group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB+ group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality. CONCLUSION: In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population.

Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States. METHODS: We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes. RESULTS: The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66). CONCLUSIONS: Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population.

Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

Prognostic Factors and Clinical Outcomes in Extraskeletal Ewing Sarcoma: A Cohort Study.

BACKGROUND: Extraskeletal Ewing sarcoma (ESE) is a lesser-known, rarer counterpart of Ewing sarcoma of bone. This single-center study sought to evaluate the prognosticators and outcomes following multimodality therapy in patients with ESE. METHODS: Forty-seven patients with ESE, treated between 2013 and 2018 with a standardized protocol and multimodality therapy using established doxorubicin-based regimens, were followed-up to assess outcomes. RESULTS: Median age at diagnosis was 20 (range 7-56) years, and 57.4% were male. Median tumor size was 7 (range 2-21) cm. The symptom-duration ranged from 1 to 8 (median 4) months. Tumor-site was trunkal in 61.7%, extremity in 23.4%, and head and neck 14.9%. Of the 35 patients with nonmetastatic disease at presentation, 13 underwent upfront surgery. The rest received chemotherapy followed by local treatment, which was surgical in 15 and radiotherapy in 5. At median follow-up of 24 (range 5-98) months, 55.3% patients had experienced events, and 29.8% had died of progressive disease. Three-year event-free survival was 41.1%, and overall survival was 53%. On univariate analysis, trunkal location, upfront surgery, and positive surgical margins were associated with inferior EFS. Trunkal tumors and upfront surgery were also associated with poorer OS. On multivariate analysis, trunkal location and margin-positive resections retained statistical significance for adverse EFS. CONCLUSIONS: Unless clearly resectable upfront, ESE should be downstaged with chemotherapy before local treatment. A margin-negative resection should be the objective when performing surgery. Definitive radiotherapy is an alternative in tumors not amenable for complete excision or when anticipated postoperative morbidity precludes radical surgery.

Transcranial direct current stimulation (tDCS) combined with cognitive training in adolescent boys with ADHD: a double-blind, randomised, sham-controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) could be a side-effect-free alternative to psychostimulants in attention-deficit/hyperactivity disorder (ADHD). Although there is limited evidence for clinical and cognitive effects, most studies were small, single-session and stimulated left dorsolateral prefrontal cortex (dlPFC). No sham-controlled study has stimulated the right inferior frontal cortex (rIFC), which is the most consistently under-functioning region in ADHD, with multiple anodal-tDCS sessions combined with cognitive training (CT) to enhance effects. Thus, we investigated the clinical and cognitive effects of multi-session anodal-tDCS over rIFC combined with CT in double-blind, randomised, sham-controlled trial (RCT, ISRCTN48265228). METHODS: Fifty boys with ADHD (10-18 years) received 15 weekday sessions of anodal- or sham-tDCS over rIFC combined with CT (20 min, 1 mA). ANCOVA, adjusting for baseline measures, age and medication status, tested group differences in clinical and ADHD-relevant executive functions at posttreatment and after 6 months. RESULTS: ADHD-Rating Scale, Conners ADHD Index and adverse effects were significantly lower at post-treatment after sham relative to anodal tDCS. No other effects were significant. CONCLUSIONS: This rigorous and largest RCT of tDCS in adolescent boys with ADHD found no evidence of improved ADHD symptoms or cognitive performance following multi-session anodal tDCS over rIFC combined with CT. These findings extend limited meta-analytic evidence of cognitive and clinical effects in ADHD after 1-5 tDCS sessions over mainly left dlPFC. Given that tDCS is commercially and clinically available, the findings are important as they suggest that rIFC stimulation may not be indicated as a neurotherapy for cognitive or clinical remediation for ADHD.

Perioperative changes in neurocognitive and Alzheimer's disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance.

BACKGROUND: Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans. METHODS: This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively. RESULTS: There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aß), tau, or phospho-tau181p levels, or on the tau/Aß or p-tau181p/Aß ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses. CONCLUSIONS: Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults. CLINICAL TRIAL REGISTRATION: NCT01993836.

Utilization and Outcomes of Extracorporeal Membrane Oxygenation Following Traumatic Brain Injury in the United States.

Objectives: Describe contemporary ECMO utilization patterns among patients with traumatic brain injury (TBI) and examine clinical outcomes among TBI patients requiring ECMO. Design: Retrospective cohort study. Setting: Premier Healthcare Database (PHD) between January 2016 to June 2020. Subjects: Adult patients with TBI who were mechanically ventilated and stratified by exposure to ECMO. Results: Among patients exposed to ECMO, we examined the following clinical outcomes: hospital LOS, ICU LOS, duration of mechanical ventilation, and hospital mortality. Of our initial cohort (n = 59,612), 118 patients (0.2%) were placed on ECMO during hospitalization. Most patients were placed on ECMO within the first 2 days of admission (54.3%). Factors associated with ECMO utilization included younger age (OR 0.96, 95% CI (0.95-0.97)), higher injury severity score (ISS) (OR 1.03, 95% CI (1.01-1.04)), vasopressor utilization (2.92, 95% CI (1.90-4.48)), tranexamic acid utilization (OR 1.84, 95% CI (1.12-3.04)), baseline comorbidities (OR 1.06, 95% CI (1.03-1.09)), and care in a teaching hospital (OR 3.04, 95% CI 1.31-7.05). A moderate degree (ICC = 19.5%) of variation in ECMO use was explained at the individual hospital level. Patients exposed to ECMO had longer median (IQR) hospital and ICU length of stay (LOS) [26 days (11-36) versus 9 days (4-8) and 19.5 days (8-32) versus 5 days (2-11), respectively] and a longer median (IQR) duration of mechanical ventilation [18 days (8-31) versus 3 days (2-8)]. Patients exposed to ECMO experienced a hospital mortality rate of 33.9%, compared to 21.2% of TBI patients unexposed to ECMO. Conclusions: ECMO utilization in mechanically ventilated patients with TBI is rare, with significant variation across hospitals. The impact of ECMO on healthcare utilization and hospital mortality following TBI is comparable to non-TBI conditions requiring ECMO. Further research is necessary to better understand the role of ECMO following TBI and identify patients who may benefit from this therapy.

A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist.

BACKGROUND: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines. OBJECTIVE: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist. DESIGN: A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group. SETTING: International collaboration. PARTICIPANTS: A total of 119 professionals participated in the development process. MEASUREMENTS: Participants' consensus on items in the checklist. RESULTS: The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience. LIMITATION: The RIGHT-Ad@pt checklist requires further validation in real-life use. CONCLUSION: The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations. PRIMARY FUNDING SOURCE: None.

Recommendations to improve maternal health equity among Black women in "The South": A position paper from the SNRS minority health research interest & implementation group.

Black women in the United States experience a higher maternal mortality rate compared to other racial groups. The maternal mortality rate among non-Hispanic Black women is 3.5 times that of non-Hispanic White women and is higher in the South compared to other regions. The majority of pregnancy-related deaths in Black women are deemed to be preventable. Healthy People 2030 directs healthcare providers to advance health equity through societal efforts to address avoidable inequalities, historical and contemporary injustices, and the elimination of health and healthcare disparities. The Southern Nursing Research Society has put forward this position paper to provide recommendations to improve maternal health equity among Black women. Recommendations for nurses, multidisciplinary healthcare providers, policymakers, and researchers are discussed.

Life cycle assessment of greenhouse gas emission from the dairy production system - review.

Climate change is altering ecological systems and poses a serious threat to human life. Climate change also seriously influences on livestock production by interfering with growth, reproduction, and production. Livestock, on the other hand, is blamed for being a significant contributor to climate change, emitting 8.1 gigatonnes of CO2-eq per year and accounting for two-thirds of global ammonia emissions. Methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2) are three major greenhouse gases (GHG) that are primarily produced by enteric fermentation, feed production, diet management, and total product output. Ruminants account for three-quarters of total CO2-equivalent (CO2-eq) emissions from the livestock sector. The global dairy sector alone emits 4.0% of global anthropogenic GHG emissions. Hence, dairy farming needs to engage in environmental impact assessment. Public concern for a sustainable and environmentally friendly farming system is growing, resulting in the significant importance of food-based life cycle assessment (LCA). Over the last decade, LCA has been used in agriculture to assess total GHG emissions associated with products such as milk and manure. It includes the production of farm inputs, farm emissions, milk processing, transportation, consumer use, and waste. LCA studies on milk production would assist us in identifying the specific production processes/areas that contribute to excessive greenhouse gas emissions when producing milk and recommending appropriate mitigation strategies to be implemented for a clean, green, and resilient environment.

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Relationship Between Depression/Anxiety and Cognitive Function Before and 6 Weeks After Major Non-Cardiac Surgery in Older Adults.

OBJECTIVE: To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults. METHODS: Observational prospective cohort study in 103 surgical patients age ≥ 60 years old. All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa. RESULTS: Lower global cognition before surgery was associated with greater baseline depression severity (Spearman's r = -0.30, p = 0.002) and baseline anxiety severity (Spearman's r = -0.25, p = 0.010), and these associations were similar following surgery (r = -0.36, p < 0.001; r = -0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change. CONCLUSIONS: Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.

Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

Next-generation sequencing analysis suggests varied multistep mutational pathogenesis for endocrine mucin-producing sweat gland carcinoma with comments on INSM1 and MUC2 suggesting a conjunctival origin.

Endocrine mucin-producing sweat gland carcinoma is a low-grade eyelid tumor. Small biopsies and insensitive immunohistochemistry predispose to misdiagnosis. We aimed to identify clarifying immunohistochemical markers, molecular markers, or both. Clinicopathologic data (22 cases) were reviewed. Immunohistochemistry (insulinoma-associated protein 1, BCL-2, mucin 2 [MUC2], mucin 4, androgen receptor, ß-catenin, and Merkel cell polyomavirus) and next-generation sequencing (Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets, 468 genes) were performed (3 cases). Female patients (n = 15) and male patients (n = 7) (mean age 71.8 years; range 53-88 years) had eyelid or periorbital tumors (>90%) with mucin-containing solid or cystic neuroendocrine pathology. Immunohistochemistry (insulinoma-associated protein 1, BCL2, androgen receptor, retinoblastoma-associated protein 1, and ß-catenin) was diffusely positive (5/5), MUC2 partial, mucin 4 focal, and Merkel cell polyomavirus negative. Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets identified 12 single-nucleotide variants and 1 in-frame deletion in 3 cases, each with DNA damage response or repair (BRD4, PPP4R2, and RTEL1) and tumor-suppressor pathway (BRD4, TP53, TSC1, and LATS2) mutations. Microsatellite instability, copy number alterations, and structural alterations were absent. Insulinoma-associated protein 1 and MUC2 are positive in endocrine mucin-producing sweat gland carcinoma. MUC2 positivity suggests conjunctival origin. Multistep pathogenesis involving DNA damage repair and tumor-suppressor pathways may be implicated.

Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.

BACKGROUND: Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to support blood pressure after TBI. However, guidelines do not specify vasopressor type, resulting in variation in clinical practice. We describe early vasopressor utilization patterns in critically ill patients with TBI and examine the association between utilization of norepinephrine, compared to phenylephrine, with hospital mortality after sTBI. METHODS: We conducted a retrospective cohort study of US hospitals participating in the Premier Healthcare Database between 2009 and 2018. We examined adult patients (>17 years of age) with a primary diagnosis of sTBI who were treated in an intensive care unit (ICU) after injury. The primary exposure was vasopressor choice (phenylephrine versus norepinephrine) within the first 2 days of hospital admission. The primary outcome was in-hospital mortality. Secondary outcomes examined included hospital length of stay (LOS) and ICU LOS. We conducted a post hoc subgroup analysis in all patients with intracranial pressure (ICP) monitor placement. Regression analysis was used to assess differences in outcomes between patients exposed to phenylephrine versus norepinephrine, with propensity matching to address selection bias due to the nonrandom allocation of treatment groups. RESULTS: From 2009 to 2018, 24,718 (37.1%) of 66,610 sTBI patients received vasopressors within the first 2 days of hospitalization. Among these patients, 60.6% (n = 14,991) received only phenylephrine, 10.8% (n = 2668) received only norepinephrine, 3.5% (n = 877) received other vasopressors, and 25.0% (n = 6182) received multiple vasopressors. In that time period, the use of all vasopressors after sTBI increased. A moderate degree of variation in vasopressor choice was explained at the individual hospital level (23.1%). In propensity-matched analysis, the use of norepinephrine compared to phenylephrine was associated with an increased risk of in-hospital mortality (OR, 1.65; CI, 1.46-1.86; P < .0001). CONCLUSIONS: Early vasopressor utilization among critically ill patients with sTBI is common, increasing over the last decade, and varies across hospitals caring for TBI patients. Compared to phenylephrine, norepinephrine was associated with increased risk of in-hospital mortality in propensity-matched analysis. Given the wide variation in vasopressor utilization and possible differences in efficacy, our analysis suggests the need for randomized controlled trials to better inform vasopressor choice for patients with sTBI.