Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Mechanical properties of tissue adhesives used for retaining extraoral silicone prostheses in maxillofacial defects: A systematic review.

STATEMENT OF PROBLEM: Different tissue adhesives are available for retaining extraoral silicone prostheses in maxillofacial defects. Comparative assessment of their mechanical properties will help the clinician select the right product for a specific clinical situation, but a systematic review is lacking. PURPOSE: The purpose of this systematic review was to analyze the existing data in the literature regarding 5 mechanical properties of tissue adhesives for extraoral silicone prostheses: peel strength, tensile strength, shear strength, torsional strength, and tack. MATERIAL AND METHODS: A manual and electronic search was performed in appropriate databases to identify relevant publications with specific inclusion and exclusion criteria. The retrieved studies were screened for eligibility using the title, abstract, and published full texts. To evaluate the risk of bias, a methodological quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklists for Randomized Controlled Trials. A custom data extraction template was used, and the results pooled using descriptive methods. RESULTS: After screening, 15 articles, 5 in vitro studies, and 10 clinical studies were eligible for data extraction. In vitro studies assessed tack and peel bond strength. In contrast, clinical studies assessed peel strength, tensile strength, shear strength, and torsional strength through direct comparisons and in diverse settings. CONCLUSIONS: The assessed studies showed considerable methodological heterogeneity. When silicone-based tissue adhesives (Secure2 Medical Adhesive; Factor II, Hollister Colostomy Adhesive; Hollister Inc, Dow Corning 355 Medical adhesives; Dow Corning Europe Inc) were compared with water-based adhesives (Pros-Aide Adhesive; ADM Tronics Inc, PSA 1; Cosmedica Ltd, Daro adhesive; Factor II, Epithane-3; Daro Products), the silicone-based adhesives showed a higher peel bond strength (PBS), while double-sided medical adhesive tapes showed lower PBS. A few studies evaluated variations in the PBS as being affected by the addition of stone wool fibers, immersion in water, application of skin protective dressings and adhesive removers, application of multiple layers of adhesive, and usage of urethane liner.

Micronutrient intake to protect against osteoporosis during and after critical illness.

PURPOSE OF REVIEW: Improved survival from critical illness has enhanced the focus on ways to augment functional outcomes following discharge from the Intensive Care Unit. An area that is gaining increased attention is the effect of critical illness on bone health and fragility fractures following the episode. This review discusses the micronutrients that may play a role in bone metabolism and the potential benefits of their supplementation to prevent osteoporosis. These include calcium, phosphorous, magnesium, vitamin D, vitamin C, vitamin K, and certain trace elements. FINDINGS: Although there is sound physiological basis for the involvement of these micronutrients in bone health and fracture prevention, there are few clinically relevant publications in this area with calcium and vitamin D being the best studied to date. SUMMARY: In the absence of high-quality evidence in critically ill populations, attention to measurement and supplementation of these micronutrients as per current guidelines outlining micronutrient requirements in enteral and parenteral nutrition might mitigate bone loss and its sequelae in the recovery phase from critical illness.

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group.

BACKGROUND: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. METHODS: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. RESULTS: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. CONCLUSIONS: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.

Mechanical ventilation post-bilateral lung transplantation: A scoping review.

BACKGROUND: Evidence from lung protective ventilation (LPV) in the acute respiratory distress syndrome has commonly been applied to guide periprocedural ventilation in lung transplantation. However, this approach may not adequately consider the distinctive features of respiratory failure and allograft physiology in the lung transplant recipient. This scoping review was conducted to systematically map the research describing ventilation and relevant physiological parameters post-bilateral lung transplantation with the aim to identify any associations with patient outcomes and gaps in the current knowledge base. METHODS: To identify relevant publications, comprehensive literature searches of electronic bibliographic databases were conducted with the guidance of an experienced librarian in MEDLINE, EMBASE, SCOPUS and the Cochrane Library. The search strategies were peer-reviewed using the PRESS (Peer Review of Electronic Search Strategies) checklist. The reference lists of all relevant review articles were surveyed. Publications were included in the review if they described relevant ventilation parameters in the immediate post-operative period, published between 2000 and 2022 and involved human subjects undergoing bilateral lung transplantation. Publications were excluded if they included animal models, only single-lung transplant recipients or only patients managed with extracorporeal membrane oxygenation. RESULTS: A total of 1212 articles were screened, 27 were subject to full-text review and 11 were included in the analysis. The quality of the included studies was assessed to be poor with no prospective multi-centre randomised controlled trials. The frequency of reported retrospective LPV parameters was as follows: tidal volume (82%), tidal volume indexed to both donor and recipient body weight (27%) and plateau pressure (18%). Data suggest that undersized grafts are at risk of unrecognised higher tidal volume ventilation indexed to donor body weight. The most reported patient-centred outcome was graft dysfunction severity in the first 72 h. CONCLUSION: This review has identified a significant knowledge gap that indicates uncertainty regarding the safest ventilation practice in lung transplant recipients. The risk may be greatest in patients with established high-grade primary graft dysfunction and undersized allografts, and these factors may define a sub-group that warrants further investigation.

Quality care close to home: Objectives and early outcomes of a second paediatric heart transplant service in Australia.

AIM: We describe the experience of a new paediatric heart transplant (HT) centre in Australia. New South Wales offers quaternary paediatric cardiac services including comprehensive care pre- and post-HT; however, perioperative HT care has previously occurred at the national paediatric centre or in adult centres. Internationally, perioperative HT care is highly protocol-driven and a majority of HT occurs in low volume centres. Establishing a low volume paediatric HT centre in New South Wales offers potential for quality HT care close to home. METHODS: Retrospective review of programme data for the first 12 months was undertaken. Patient selection was audited against the programme's intended initiation criteria. Longitudinal patient data on outcomes and complications were obtained from patient medical records. RESULTS: The programme's initial phase offered HT to children with non-congenital heart disease and no requirement for durable mechanical circulatory support. Eight patients met criteria for HT referral. Three underwent interstate transfer to the national paediatric centre. Five children (13-15 years, weight 36-85 kg) underwent HT in the new programme. Individual predicted 90-day mortality was 1.3-11.6%, with increased risk for recipients transplanted from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and with restrictive/hypertrophic cardiomyopathies. Survival at 90 days and for duration of follow-up is 100%. Observed programme benefits include mitigation of family dislocation and improved continuity of care within a family-centred programme. CONCLUSION: Audit of the first 12 months' activity of a second paediatric HT centre in Australia demonstrates adherence to proposed patient selection criteria and excellent 90-day patient outcomes. The programme demonstrates feasibility of care close to home, providing continuity for all patients including those requiring increased rehabilitation and psychosocial support post-transplantation.

Pulse pressure within the first 2 days of veno-arterial extracorporeal membrane oxygenation is predictive of death prior to hospital discharge, renal dysfunction requiring dialysis and pulmonary oedema.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) flows are titrated to achieve adequate perfusion while attempting to ideally maintain arterial pulse pressure (PP). We assessed risk in patients with low PP defined as <10 mmHg within the first 2 days of support. METHODS: Demographics, haemodynamics, echocardiographic and radiological findings were recorded retrospectively in cases conducted between 2014 and 2016. Outcomes were hospital mortality, requirement for renal replacement therapy (RRT) and severe pulmonary oedema (PO). RESULTS: Of 101 patients, 66.3% were male, mean age was 56 (range 18-71 years), mean duration of support was 6.3 days ± 4.1 days, 37.6% died prior to hospital discharge, 39.6% needed RRT and 11.9% had severe PO. Areas under the receiver operating curves of PP at 48 h for hospital mortality, RRT and severe PO were (respectively): 0.69 (95% CI 0.58-0.80, p = .001), 0.64 (95% CI 0.50-0.77, p = .044), 0.69 (95% CI 0.55-0.82, p = .009). The odds ratio for mortality, RRT, severe PO for those with low PP were (respectively) 2.8 (95% CI 1.01-7.5, p = .04), 3.1 (95% CI 1.11-8.40, p = .026), 7.6 (95% CI 2.06-27.89, p = .001). Central venous pressure, mean arterial pressure were not predictive. CONCLUSION: PP during the first 2 days of support is predictive of clinically important outcomes in patients supported with VA-ECMO.

Results and lessons from dual extraction of DNA and RNA from formalin-fixed paraffin-embedded breast tumor tissues for a large Cancer epidemiologic study.

BACKGROUND: The use of archived formalin-fixed paraffin-embedded (FFPE) tumor tissues has become a common practice in clinical and epidemiologic genetic research. Simultaneous extraction of DNA and RNA from FFPE tissues is appealing but can be practically challenging. Here we report our results and lessons learned from processing FFPE breast tumor tissues for a large epidemiologic study. METHODS: Qiagen AllPrep DNA/RNA FFPE kit was adapted for dual extraction using tissue punches or sections from breast tumor tissues. The yield was quantified using Qubit and fragmentation analysis by Agilent Bioanalyzer. A subset of the DNA samples were used for genome-wide DNA methylation assays and RNA samples for sequencing. The QC metrices and performance of the assays were analyzed with pre-analytical variables. RESULTS: A total of 1859 FFPE breast tumor tissues were processed. We found it critical to adjust proteinase K digestion time based on tissue volume to achieve balanced yields of DNA and RNA. Tissue punches taken from tumor-enriched regions provided the most reliable output. A median of 1475 ng DNA and 1786 ng RNA per sample was generated. The median DNA integrity number (DIN) was 3.8 and median DV200 for RNA was 33.2. Of 1294 DNA samples used in DNA methylation assays, 97% passed quality check by qPCR and 92% generated data deemed high quality. Of the 130 RNA samples with DV200 ≥ 20% used in RNA-sequencing, all but 5 generated usable transcriptomic data with a mapping rate ≥ 60%. CONCLUSIONS: Dual DNA/RNA purification using Qiagen AllPrep FFPE extraction protocol is feasible for clinical and epidemiologic studies. We recommend tissue punches as a reliable source material and fine tuning of proteinase K digestion time based on tissue volume. IMPACT: Our protocol and recommendations may be adapted by future studies for successful extraction of archived tumor tissues.

Metabolic engineering of E. coli for ß-alanine production using a multi-biosensor enabled approach.

ß-alanine is an important biomolecule used in nutraceuticals, pharmaceuticals, and chemical synthesis. The relatively eco-friendly bioproduction of ß-alanine has recently attracted more interest than petroleum-based chemical synthesis. In this work, we developed two types of in vivo high-throughput screening platforms, wherein one was utilized to identify a novel target ribonuclease E (encoded by rne) as well as a redox-cofactor balancing module that can enhance de novo ß-alanine biosynthesis from glucose, and the other was employed for screening fermentation conditions. When combining these approaches with rational upstream and downstream module engineering, an engineered E. coli producer was developed that exhibited 3.4- and 6.6-fold improvement in ß-alanine yield (0.85 mol ß-alanine/mole glucose) and specific ß-alanine production (0.74 g/L/OD600), respectively, compared to the parental strain in a minimal medium. Across all of the strains constructed, the best yielding strain exhibited 1.08 mol ß-alanine/mole glucose (equivalent to 81.2% of theoretic yield). The final engineered strain produced 6.98 g/L ß-alanine in a batch-mode bioreactor and 34.8 g/L through a whole-cell catalysis. This approach demonstrates the utility of biosensor-enabled high-throughput screening for the production of ß-alanine.

HIV Stigma and Health Care Discrimination Experienced by Hispanic or Latino Persons with HIV - United States, 2018-2020.

Hispanic or Latino (Hispanic) persons with HIV experience disparities in HIV health outcomes compared with some other racial and ethnic groups. A previous report found that the percentages of Hispanic persons who received HIV care, were retained in care, and were virally suppressed were lower than those among non-Hispanic White persons with HIV (1). HIV stigma and discrimination are human rights issues associated with adverse HIV outcomes; eliminating stigma and discrimination among persons with HIV is a national priority*,†,§ (2,3). CDC analyzed data from the Medical Monitoring Project (MMP), an annual, cross-sectional study designed to report nationally representative estimates of experiences and outcomes among adults with diagnosed HIV. Data from the 2018-2020 cycles were analyzed to assess self-reported stigma and health care discrimination using adapted versions of validated multi-component scales among 2,690 adult Hispanic persons with HIV in the United States overall and by six characteristics.¶ The median HIV stigma score on a scale of 0-100 was 31.7, with women (35.6) and American Indian or Alaska Native (AI/AN) persons (38.9) reporting the highest scores among Hispanic persons with HIV. HIV stigma was primarily attributed to disclosure concerns (e.g., fearing others will disclose one's HIV status and being careful about who one tells about one's HIV status). Nearly one in four (23%) Hispanic persons with HIV experienced health care discrimination. Health care discrimination was experienced more frequently by Hispanic men (23%) than by Hispanic women (18%) and by Black or African American (Black) Hispanic persons (28%) than by White Hispanic persons (21%). Understanding disparities in experiences of stigma and discrimination is important when designing culturally appropriate interventions to reduce stigma and discrimination.

Care for adults with COVID-19: living guidelines from the National COVID-19 Clinical Evidence Taskforce.

INTRODUCTION: The Australian National COVID-19 Clinical Evidence Taskforce was established in March 2020 to maintain up-to-date recommendations for the treatment of people with coronavirus disease 2019 (COVID-19). The original guideline (April 2020) has been continuously updated and expanded from nine to 176 recommendations, facilitated by the rapid identification, appraisal, and analysis of clinical trial findings and subsequent review by expert panels. MAIN RECOMMENDATIONS: In this article, we describe the recommendations for treating non-pregnant adults with COVID-19, as current on 1 August 2022 (version 61.0). The Taskforce has made specific recommendations for adults with severe/critical or mild disease, including definitions of disease severity, recommendations for therapy, COVID-19 prophylaxis, respiratory support, and supportive care. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: The Taskforce currently recommends eight drug treatments for people with COVID-19 who do not require supplemental oxygen (inhaled corticosteroids, casirivimab/imdevimab, molnupiravir, nirmatrelvir/ritonavir, regdanvimab, remdesivir, sotrovimab, tixagevimab/cilgavimab) and six for those who require supplemental oxygen (systemic corticosteroids, remdesivir, tocilizumab, sarilumab, baricitinib, casirivimab/imdevimab). Based on evidence of their achieving no or only limited benefit, ten drug treatments or treatment combinations are not recommended; an additional 42 drug treatments should only be used in the context of randomised trials. Additional recommendations include support for the use of continuous positive airway pressure, prone positioning, and endotracheal intubation in patients whose condition is deteriorating, and prophylactic anticoagulation for preventing venous thromboembolism. The latest updates and full recommendations are available at www.covid19evidence.net.au.

Development of an academic-practice partnership model to anchor care coordination and population health.

The National Academy of Medicine's The Future of Nursing 2020-2030 recommends the expansion of the role of nurses throughout the continuum of health care in an effort to improve the health of the nation while decreasing costs. To accomplish this goal, nursing students and nurses must be well prepared to perform at their highest capacity to meet health care demands. Currently the U.S. health care delivery system is undergoing rapid changes that affect approaches to delivering care services. These changes call for education and practice reforms in nursing. This article introduces an innovative academic-practice partnership model (the University of Maryland Nursing [UMNursing] Care Coordination Implementation Collaborative), including its background, development, and blueprint for a large implementation project. The implementation model integrates nursing education and practice in areas of care co-ordination and population health, which have a significant impact on the Triple Aim of health. The project also uniquely integrates education, practice, and research, with the ultimate outcome of higher quality patient care.

CNS Complications in Adult Patients Treated With Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the incidence and outcomes of radiologically confirmed acute CNS complications in extracorporeal membrane oxygenation patients at an Australian extracorporeal membrane oxygenation referral center and identify associated patient characteristics. DESIGN: Retrospective cohort study. SETTING: Single-center tertiary institution. PATIENTS: Four-hundred twelve consecutive adult patients supported with extracorporeal membrane oxygenation from 2009 to 2017. RESULTS: Fifty-five patients (13.3%) had a CNS complication confirmed by CT or MRI, including ischemic stroke (7.0%), intracerebral hemorrhage (3.4%), hypoxic ischemic encephalopathy (3.6%), and spinal cord injury (1.2%). CNS complication rates in the venoarterial, venovenous, and veno-pulmonary artery extracorporeal membrane oxygenation subgroups were 18.0%, 4.6%, and 13.6%, respectively. Neurologic complications were independently associated with the use of venoarterial extracorporeal membrane oxygenation (p = 0.002) and renal replacement therapy (p = 0.04). Sixty-five percent of patients with a neurologic complication died during their hospital admission compared with 32% of patients without this complication (p < 0.001). Venoarterial extracorporeal membrane oxygenation, renal replacement therapy, and days of extracorporeal membrane oxygenation support were also associated with hospital mortality and remained so after adjustment in a multivariable regression model (p = 0.01, p < 0.001, and p = 0.003, respectively). CONCLUSIONS: CNS complications appear to occur more frequently in patients requiring circulatory as opposed to respiratory support on extracorporeal membrane oxygenation and are independently associated with mortality. It remains unclear if these complications are causative of a poor outcome or a marker of severity of the underlying condition. Further research is required to better elucidate modifiable or preventable aspects through better patient selection and change in ongoing care.

Development of a growth coupled and multi-layered dynamic regulation network balancing malonyl-CoA node to enhance (2S)-naringenin biosynthesis in Escherichia coli.

Metabolic heterogeneity and dynamic changes in metabolic fluxes are two inherent characteristics of microbial fermentation that limit the precise control of metabolisms, often leading to impaired cell growth and low productivity. Dynamic metabolic engineering addresses these challenges through the design of multi-layered and multi-genetic dynamic regulation network (DRN) that allow a single cell to autonomously adjust metabolic flux in response to its growth and metabolite accumulation conditions. Here, we developed a growth coupled NCOMB (Naringenin-Coumaric acid-Malonyl-CoA-Balanced) DRN with systematic optimization of (2S)-naringenin and p-coumaric acid-responsive regulation pathways for real-time control of intracellular supply of malonyl-CoA. In this scenario, the acyl carrier protein was used as a novel critical node for fine-tuning malonyl-CoA consumption instead of direct repression of fatty acid synthase commonly employed in previous studies. To do so, we first engineered a multi-layered DRN enabling single cells to concurrently regulate acpH, acpS, acpT, acs, and ACC in malonyl-CoA catabolic and anabolic pathways. Next, the NCOMB DRN was optimized to enhance the synergies between different dynamic regulation layers via a biosensor-based directed evolution strategy. Finally, a high producer obtained from NCOMB DRN approach yielded a 8.7-fold improvement in (2S)-naringenin production (523.7 ± 51.8 mg/L) with a concomitant 20% increase in cell growth compared to the base strain using static strain engineering approach, thus demonstrating the high efficiency of this system for improving pathway production.

Endoscopic management of high-grade biliary strictures complicating living donor liver transplantation using soehendra stent retrievers.

BACKGROUND: Biliary strictures following living donor liver transplantation (LDLT) are usually managed by endoscopic retrograde cholangiography (ERC) with stricture dilation and stent placement. While current endoscopic techniques are successful in most cases, high-grade biliary strictures (HGBS) pose a challenge using currently employed techniques which have a low rate of technical success. AIMS: In this study, we have explored the safety and efficacy of Soehendra stent retrievers (SSR) for the dilation of HGBS complicating LDLT. METHODS: This was a prospective cohort study where all patients with anastomotic biliary strictures following LDLT from January 2016 till February 2018 were included. Patients with HGBS defined as the exclusive passage of 0.018-inch guidewire, were included in Group 1. In these patients, 5 Fr Soehendra stent retrievers were used to dilate HGBS over guidewire, using torsional movements. Technical success, safety and clinical response was compared with patients who required Per-cutaneous transhepatic cholangiography (PTC) with rendezvous procedure due to a failed ERC, before the commencement of the study (Group 2). RESULTS: Ten patients with HGBS were included into Group 1. Technical success defined as successful placement of a biliary stent across the stricture was achieved in all the patients in group 1. Favorable response to endotherapy was higher in group 1(8/10 patients (80%)) as compared to group 2(6/14 patients (42.8%)). There were no post procedure complications in patients of group 1, while 3 patients developed cholangitis in group 2. CONCLUSIONS: HGBS can be successfully treated with SSR for stricture dilation. It is safe with no significant complications and requires fewer procedures.

Metabolic support in sepsis: corticosteroids and vitamins: the why, the when, the how.

PURPOSE OF REVIEW: Sepsis is a global health issue, and there is a need for effective, low-cost adjunct metabolic treatments. Corticosteroids have been investigated in many trials for decades, and recently the administration of vitamin C, thiamine (vitamin B1), and vitamin D have been proposed as novel therapies in patients with sepsis. RECENT FINDINGS: APROCCHSS (N = 1241) and ADRENAL (N = 3800) trial reported inconsistent results in mortality outcome; however, both demonstrated a decreased duration of shock with low-dose corticosteroids. The CITRIS-ALI trial (N = 170) examined the effects of intravenous vitamin C 200 mg/kg/day and reported no effect on organ dysfunction or biomarkers. The VITAMINS trial (N = 216) compared combination therapy of vitamin C 6 g/day, thiamine 200 mg/day, and hydrocortisone 200 mg/day with hydrocortisone alone to find that the combination did not increase vasopressor free time. A single trial (N = 88) evaluating the effect of thiamine in patients with sepsis reported a neutral result. Two randomized trials (N = 475 and N = 1360) on the supplementation of vitamin D in the critically ill patients did not identify statistically significant reduction in mortality. SUMMARY: Evidence from high-quality research is still insufficient to support the use of vitamin C, thiamine, and vitamin D as metabolic support in sepsis treatment.

COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ).

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

Restaurant Characteristics Associated With the Use of Specific Food-Cooling Methods.

Pathogen growth caused by improper or slow cooling of hot foods was a contributing factor in 504 of restaurant- and deli-related outbreaks in the U.S. from 1998-2008. Little is known, however, about restaurant cooling practices. To fill this gap, the Centers for Disease Control and Prevention's Environmental Health Specialists Network (EHS-Net) conducted an observational study to identify and understand factors that might determine which methods restaurants follow to rapidly cool food. These methods include refrigerating food at ≤41 °F, at shallow depths, and in containers that are ventilated, unstacked, and have space around them. EHS-Net personnel collected data through manager interviews and observation of cooling processes in 420 randomly selected restaurants. Regression analyses revealed characteristics of restaurants most likely to use the cooling methods assessed. These characteristics included ownership by restaurant chains, manager food safety training and certification, few foods cooled at a time, many meals served daily, and a high ratio of workers to managers. These findings suggest that regulatory food safety programs and the retail industry might improve cooling methods-and reduce outbreaks-by providing and encouraging manager food safety training and certification, and by focusing intervention efforts on independent and smaller restaurants.

Characterization of a class III peroxidase from Artemisia annua: relevance to artemisinin metabolism and beyond.

KEY MESSAGE: A class III peroxidase from Artemisia annua has been shown to indicate the possibility of cellular localization-based role diversity, which may have implications in artemisinin catabolism as well as lignification. Artemisia annua derives its importance from the antimalarial artemisinin. The -O-O- linkage in artemisinin makes peroxidases relevant to its metabolism. Earlier, we identified three peroxidase-coding genes from A. annua, whereby Aa547 showed higher expression in the low-artemisinin plant stage whereas Aa528 and Aa540 showed higher expression in the artemisinin-rich plant stage. Here we carried out tertiary structure homology modelling of the peroxidases for docking studies. Maximum binding affinity for artemisinin was shown by Aa547. Further, Aa547 showed greater binding affinity for post-artemisinin metabolite, deoxyartemisinin, as compared to pre-artemisinin metabolites (dihydroartemisinic hydroperoxide, artemisinic acid, dihydroartemisinic acid). It also showed significant binding affinity for the monolignol, coniferyl alcohol. Moreover, Aa547 expression was related inversely to artemisinin content and directly to total lignin content as indicated by its transient silencing and overexpression in A. annua. Artemisinin reduction assay also indicated inverse relationship between Aa547 expression and artemisinin content. Subcellular localization using GFP fusion suggested that Aa547 is peroxisomal. Nevertheless, dual localization (intracellular/extracellular) of Aa547 could not be ruled out due to its effect on both, artemisinin and lignin. Taken together, this indicates possibility of localization-based role diversity for Aa547, which may have implications in artemisinin catabolism as well as lignification in A. annua.

Hemodynamic and morphological characteristics of a growing cerebral aneurysm.

The growth of cerebral aneurysms is linked to local hemodynamic conditions, but the driving mechanisms of the growth are poorly understood. The goal of this study was to examine the association between intraaneurysmal hemodynamic features and areas of aneurysm growth, to present the key hemodynamic parameters essential for an accurate prediction of the growth, and to gain a deeper understanding of the underlying mechanisms. Patient-specific images of a growing cerebral aneurysm in 3 different growth stages acquired over a period of 40 months were segmented and reconstructed. A unique aspect of this patient-specific case study was that while one side of the aneurysm stayed stable, the other side continued to grow. This unique case enabled the authors to examine their aims in the same patient with parent and daughter arteries under the same inlet flow conditions. Pulsatile flow in the aneurysm models was simulated using computational fluid dynamics and was validated with in vitro experiments using particle image velocimetry measurements. The authors' detailed analysis of intrasaccular hemodynamics linked the growing regions of aneurysms to flow instabilities and complex vortex structures. Extremely low velocities were observed at or around the center of the unstable vortex structure, which matched well with the growing regions of the studied cerebral aneurysm. Furthermore, the authors observed that the aneurysm wall regions with a growth greater than 0.5 mm coincided with wall regions of lower (< 0.5 Pa) time-averaged wall shear stress (TAWSS), lower instantaneous (< 0.5 Pa) wall shear stress (WSS), and high (> 0.1) oscillatory shear index (OSI). To determine which set of parameters can best identify growing and nongrowing aneurysms, the authors performed statistical analysis for consecutive stages of the growing CA. The results demonstrated that the combination of TAWSS and the distance from the center of the vortical structure has the highest sensitivity and positive predictive value, and relatively high specificity and negative predictive value. These findings suggest that an unstable, recirculating flow structure within the aneurysm sac created in the region adjacent to the aneurysm wall with low TAWSS may be introduced as an accurate criterion to explain the hemodynamic conditions predisposing the aneurysm to growth. The authors' findings are based on one patient's data set, but the study lays out the justification for future large-scale verification. The authors' findings can assist clinicians in differentiating stable and growing aneurysms during preinterventional planning.