Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.

BACKGROUND AND AIMS: Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. METHODS: A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. RESULTS: In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. CONCLUSIONS: Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

Pan AMPK Activation Protects Tubules in Rat Ischemic Acute Kidney Injury.

Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI. We developed a selective potent small molecule pan AMPK activator, compound 1, and tested its ability to increase AMPK activity and preserve kidney function during ischemia/reperfusion injury in rats. A single administration of 1 caused sustained activation of AMPK for at least 24 hours, protected against acute tubular necrosis, and reduced clinical markers of tubular injury such as NephroCheck and Fractional Excretion of Sodium (FENa). Reduction in plasma creatinine and increased Glomerular Filtration Rate (GFR) indicated preservation of kidney function. Surprisingly, we observed a strong diuretic effect of AMPK activation associated with natriuresis both with and without AKI. Our findings demonstrate that activation of AMPK leads to protection of tubular function under hypoxic/ischemic conditions which holds promise as a potential novel therapeutic approach for AKI. Significance Statement No approved pharmacological therapies currently exist for acute kidney injury. We developed Compound 1 which dose-dependently activated AMPK in the kidney and protected kidney function and tubules after ischemic renal injury in the rat. This was accompanied by natriuresis in injured as well as uninjured rats.

How I use platelet transfusions.

Platelet transfusions are commonly administered for the prevention or treatment of bleeding in patients with acquired thrombocytopenia across a range of clinical contexts. Recent data, including randomized trials, have highlighted uncertainties in the risk-benefit balance of this therapy, which is the subject of this review. Hemovigilance systems report that platelets are the most frequently implicated component in transfusion reactions. There is considerable variation in platelet count increment after platelet transfusion, and limited evidence of efficacy for clinical outcomes, including prevention of bleeding. Bleeding events commonly occur despite the different policies for platelet transfusion prophylaxis. The underlying mechanisms of harm reported in randomized trials may be related to the role of platelets beyond hemostasis, including mediating inflammation. Research supports the implementation of a restrictive platelet transfusion policy. Research is needed to better understand the impact of platelet donation characteristics on outcomes, and to determine the optimal thresholds for platelet transfusion before invasive procedures or major surgery (eg, laparotomy). Platelet transfusion policies should move toward a risk-adapted approach that does not focus solely on platelet count.

Temporal changes in erythroid progenitors in critically ill patients: a prospective cohort study.

Not available.

A Robust and Efficient Method to Purify DNA-Scaffolded Nanostructures by Gravity-Driven Size Exclusion Chromatography.

In recent decades, nucleic acid self-assemblies have emerged as popular nanomaterials due to their programmable and robust assembly, prescribed geometry, and versatile functionality. However, it remains a challenge to purify large quantities of DNA nanostructures or DNA-templated nanocomplexes for various applications. Commonly used purification methods are either limited by a small scale or incompatible with functionalized structures. To address this unmet need, we present a robust and scalable method of purifying DNA nanostructures by Sepharose resin-based size exclusion. The resin column can be manually packed in-house with reusability. The separation is driven by a low-pressure gravity flow in which large DNA nanostructures are eluted first followed by smaller impurities of ssDNA and proteins. We demonstrated the efficiency of the method for purifying DNA origami assemblies and protein-immobilized DNA nanostructures. Compared to routine agarose gel electrophoresis that yields 1 µg or less of purified products, this method can purify ∼100-1000 µg of DNA nanostructures in less than 30 min, with the overall collection yield of 50-70% of crude preparation mixture. The purified nanocomplexes showed more precise activity in evaluating enzyme functions and antibody-triggered activation of complement protein reactions.

Iron Deficiency in Anemic Children Surviving Critical Illness: Post Hoc Analysis of a Single-Center Prospective Cohort in Canada, 2019-2022.

OBJECTIVES: Many children leave the PICU with anemia. The mechanisms of post-PICU anemia are poorly investigated, and treatment of anemia, other than blood, is rarely started during PICU. We aimed to characterize the contributions of iron depletion (ID) and/or inflammation in the development of post-PICU anemia and to explore the utility of hepcidin (a novel iron marker) at detecting ID during inflammation. DESIGN: Post hoc analysis of a single-center prospective study (November 2019 to September 2022). SETTING: PICU, quaternary center, Canada. PATIENTS: Children admitted to PICU with greater than or equal to 48 hours of invasive or greater than or equal to 96 hours of noninvasive ventilation. We excluded patients with preexisting conditions causing anemia or those admitted after cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hematological and iron profiles were performed at PICU discharge on 56 participants of which 37 (37/56) were diagnosed with anemia. Thirty-three children (33/56; 59%) were younger than 2 years. Median Pediatric Logistic Organ Dysfunction score was 11 (interquartile range, 6-16). Twenty-four of the 37 anemic patients had repeat bloodwork 2 months post-PICU. Of those, four (4/24; 16%) remained anemic. Hematologic profiles were categorized as: anemia of inflammation (AI), iron deficiency anemia (IDA), IDA with inflammation, and ID (low iron stores without anemia). Seven (7/47; 15%) had AI at discharge, and one had persistent AI post-PICU. Three patients (3/47; 6%) had IDA at discharge; of which one was lost to follow-up and the other two were no longer anemic but had ID post-PICU. Eleven additional patients developed ID post-PICU. In the exploratory analysis, we identified a diagnostic cutoff value for ID during inflammation from the receiver operating characteristic curve for hepcidin of 31.9 pg/mL. This cutoff would increase the detection of ID at discharge from 6% to 34%. CONCLUSIONS: The burden of ID in children post-PICU is high and better management strategies are required. Hepcidin may increase the diagnostic yield of ID in patients with inflammation.

Hypertonic Saline Versus Other Intracranial-Pressure-Lowering Agents for Patients with Acute Traumatic Brain Injury: A Systematic Review and Meta-analysis.

Acute traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Intracranial pressure (ICP)-lowering is a critical management priority in patients with moderate to severe acute TBI. We aimed to evaluate the clinical efficacy and safety of hypertonic saline (HTS) versus other ICP-lowering agents in patients with TBI. We conducted a systematic search from 2000 onward for randomized controlled trials (RCTs) comparing HTS vs. other ICP-lowering agents in patients with TBI of all ages. The primary outcome was the Glasgow Outcome Scale (GOS) score at 6 months (PROSPERO CRD42022324370). Ten RCTs (760 patients) were included. Six RCTs were included in the quantitative analysis. There was no evidence of an effect of HTS on the GOS score (favorable vs. unfavorable) compared with other agents (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.48-1.40; n = 406; 2 RCTs). There was no evidence of an effect of HTS on all-cause mortality (RR 0.96, 95% CI 0.60-1.55; n = 486; 5 RCTs) or total length of stay (RR 2.36, 95% CI - 0.53 to 5.25; n = 89; 3 RCTs). HTS was associated with adverse hypernatremia compared with other agents (RR 2.13, 95% CI 1.09-4.17; n = 386; 2 RCTs). The point estimate favored a reduction in uncontrolled ICP with HTS, but this was not statistically significant (RR 0.52, 95% CI 0.26-1.04; n = 423; 3 RCTs). Most included RCTs were at unclear or high risk of bias because of lack of blinding, incomplete outcome data, and selective reporting. We found no evidence of an effect of HTS on clinically important outcomes and that HTS is associated with adverse hypernatremia. The included evidence was of low to very low certainty, but ongoing RCTs may help to the reduce this uncertainty. In addition, heterogeneity in GOS score reporting reflects the need for a standardized TBI core outcome set.

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial.

BACKGROUND: Anaemia is common and associated with poor outcomes in survivors of critical illness. However, the optimal treatment strategy is unclear. METHODS: We conducted a multicentre, feasibility RCT to compare either a single dose of ferric carboxymaltose 1000 mg i.v. or usual care in patients being discharged from the ICU with moderate or severe anaemia (haemoglobin ≤100 g L-1). We collected data on feasibility (recruitment, randomisation, follow-up), biological efficacy, and clinical outcomes. RESULTS: Ninety-eight participants were randomly allocated (49 in each arm). The overall recruitment rate was 34% with 6.5 participants recruited on average per month. Forty-seven of 49 (96%) participants received the intervention. Patient-reported outcome measures were available for 79/93 (85%) survivors at 90 days. Intravenous iron resulted in a higher mean (standard deviation [sd]) haemoglobin at 28 days (119.8 [13.3] vs 106.7 [14.9] g L-1) and 90 days (130.5 [15.1] vs 122.7 [17.3] g L-1), adjusted mean difference (10.98 g L-1; 95% confidence interval [CI], 4.96-17.01; P<0.001) over 90 days after randomisation. Infection rates were similar in both groups. Hospital readmissions at 90 days post-ICU discharge were lower in the i.v. iron group (7/40 vs 15/39; risk ratio=0.46; 95% CI, 0.21-0.99; P=0.037). The median (inter-quartile range) post-ICU hospital stay was shorter in the i.v. iron group but did not reach statistical significance (5.0 [3.0-13.0] vs 9.0 [5.0-16.0] days, P=0.15). CONCLUSION: A large, multicentre RCT of i.v. iron to treat anaemia in survivors of critical illness appears feasible and is necessary to determine the effects on patient-centred outcomes. CLINICAL TRIAL REGISTRATION: ISRCTN13721808 (www.isrctn.com).

The Use of Wearable Pulse Oximeters in the Prompt Detection of Hypoxemia and During Movement: Diagnostic Accuracy Study.

BACKGROUND: Commercially available wearable (ambulatory) pulse oximeters have been recommended as a method for managing patients at risk of physiological deterioration, such as active patients with COVID-19 disease receiving care in hospital isolation rooms; however, their reliability in usual hospital settings is not known. OBJECTIVE: We report the performance of wearable pulse oximeters in a simulated clinical setting when challenged by motion and low levels of arterial blood oxygen saturation (SaO2). METHODS: The performance of 1 wrist-worn (Wavelet) and 3 finger-worn (CheckMe O2+, AP-20, and WristOx2 3150) wearable, wireless transmission-mode pulse oximeters was evaluated. For this, 7 motion tasks were performed: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia exposure followed, in which inspired gases were adjusted to achieve decreasing SaO2 levels at 100%, 95%, 90%, 87%, 85%, 83%, and 80%. Peripheral oxygen saturation (SpO2) estimates were compared with simultaneous SaO2 samples to calculate the root-mean-square error (RMSE). The area under the receiver operating characteristic curve was used to analyze the detection of hypoxemia (ie, SaO2<90%). RESULTS: SpO2 estimates matching 215 SaO2 samples in both study phases, from 33 participants, were analyzed. Tapping, rubbing, turning pages, and using a tablet degraded SpO2 estimation (RMSE>4% for at least 1 device). All finger-worn pulse oximeters detected hypoxemia, with an overall sensitivity of ≥0.87 and specificity of ≥0.80, comparable to that of the Philips MX450 pulse oximeter. CONCLUSIONS: The SpO2 accuracy of wearable finger-worn pulse oximeters was within that required by the International Organization for Standardization guidelines. Performance was degraded by motion, but all pulse oximeters could detect hypoxemia. Our findings support the use of wearable, wireless transmission-mode pulse oximeters to detect the onset of clinical deterioration in hospital settings. TRIAL REGISTRATION: ISRCTN Registry 61535692; http://www.isrctn.com/ISRCTN61535692. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-034404.

Outcome measures in solid organ donor management research: a systematic review.

AIM: We systematically reviewed published outcome measures across randomised controlled trials (RCTs) of donor management interventions. METHODS: The systematic review was conducted in accordance with recommendations by the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched MEDLINE, Embase, CENTRAL, Web of Science, and trial databases from 1980 to February 2021 for RCTs of donor management interventions. RESULTS: Twenty-two RCTs (n=3432 donors) were included in our analysis. Fourteen RCTs (63.6%) reported a primary outcome relating to a single organ only. Eight RCTs primarily focused on aspects of donor optimisation in critical care. Thyroid hormones and methylprednisolone were the most commonly evaluated interventions (five and four studies, respectively). Only two studies, focusing on single organs (e.g. kidney), evaluated outcomes relating to other organs. The majority of studies evaluated physiological or biomarker-related outcomes. No study evaluated recipient health-related quality of life. Only one study sought consent from potential organ recipients. CONCLUSIONS: The majority of RCTs evaluating donor management interventions only assessed single-organ outcomes or effects on donor stability in critical care. There is a need for an evaluation of patient-centred recipient outcomes and standardisation and reporting of outcome measures for future donor management RCTs.

Evidence cornered: Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT trial).

CLINICAL QUESTION: Does intravenous iron given to anaemic patients (haemoglobin [Hb] <130 g/L for men and 120 g/L for women) before major elective open abdominal surgery reduce the need for blood transfusions or death within 30 days of surgery? EVIDENCE FROM TRIAL: There were no significant differences in the rates of blood transfusion or death at 30 days after the index operation between anaemic patients who received intravenous iron preoperatively and those who did not.

A Chest Patch for Continuous Vital Sign Monitoring: Clinical Validation Study During Movement and Controlled Hypoxia.

BACKGROUND: The standard of care in general wards includes periodic manual measurements, with the data entered into track-and-trigger charts, either on paper or electronically. Wearable devices may support health care staff, improve patient safety, and promote early deterioration detection in the interval between periodic measurements. However, regulatory standards for ambulatory cardiac monitors estimating heart rate (HR) and respiratory rate (RR) do not specify performance criteria during patient movement or clinical conditions in which the patient's oxygen saturation varies. Therefore, further validation is required before clinical implementation and deployment of any wearable system that provides continuous vital sign measurements. OBJECTIVE: The objective of this study is to determine the agreement between a chest-worn patch (VitalPatch) and a gold standard reference device for HR and RR measurements during movement and gradual desaturation (modeling a hypoxic episode) in a controlled environment. METHODS: After the VitalPatch and gold standard devices (Philips MX450) were applied, participants performed different movements in seven consecutive stages: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia was then induced, and the participants' oxygen saturation gradually reduced to 80% in a controlled environment. The primary outcome measure was accuracy, defined as the mean absolute error (MAE) of the VitalPatch estimates when compared with HR and RR gold standards (3-lead electrocardiography and capnography, respectively). We defined these as clinically acceptable if the rates were within 5 beats per minute for HR and 3 respirations per minute (rpm) for RR. RESULTS: Complete data sets were acquired for 29 participants. In the movement phase, the HR estimates were within prespecified limits for all movements. For RR, estimates were also within the acceptable range, with the exception of the sit-to-stand and turning page movements, showing an MAE of 3.05 (95% CI 2.48-3.58) rpm and 3.45 (95% CI 2.71-4.11) rpm, respectively. For the hypoxia phase, both HR and RR estimates were within limits, with an overall MAE of 0.72 (95% CI 0.66-0.78) beats per minute and 1.89 (95% CI 1.75-2.03) rpm, respectively. There were no significant differences in the accuracy of HR and RR estimations between normoxia (≥90%), mild (89.9%-85%), and severe hypoxia (<85%). CONCLUSIONS: The VitalPatch was highly accurate throughout both the movement and hypoxia phases of the study, except for RR estimation during the two types of movements. This study demonstrated that VitalPatch can be safely tested in clinical environments to support earlier detection of cardiorespiratory deterioration. TRIAL REGISTRATION: ISRCTN Registry ISRCTN61535692; https://www.isrctn.com/ISRCTN61535692.

Exploring adult critical illness survivors' experiences of fatigue: A qualitative study.

AIMS: To explore adult experiences of fatigue after discharge from an intensive care unit and identify potential management strategies. DESIGN: An exploratory qualitative study. METHODS: One to one audio-recorded semi-structured interviews with 17 adult survivors of critical illness in the United Kingdom, lasting up to 1 h, between September 2019 and January 2020. Anonymised and verbatim-transcribed interview data underwent a standard process of inductive thematic analysis as described by Braun and Clarke. FINDINGS: Three themes were identified: fatigue is different for everyone; complex interrelating interactions; and personalised fatigue strategies. Fatigue was described as a distressing symptom, unique to the individual that causes an array of complex, often long-term interrelating impacts on the survivor and their wider family, made worse by a lack of understanding, empathy and support resources. Support from others, alongside interventions such as exercise, good nutrition, information and alternative therapies are used by survivors with variable degrees of success. CONCLUSIONS: This qualitative study reports peoples' experiences of fatigue after critical illness. Findings highlight the significant impact it has on people's lives and those of their family and friends.

The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks.

The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigan-type (FPLD2), a lipodystrophic syndrome complicated by early onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2. Genome modeling in fibroblasts from patients with FPLD2 caused by the lamin A R482W mutation reveals repositioning of the mesodermal regulator T/Brachyury locus towards the nuclear center relative to normal fibroblasts, suggesting enhanced activation propensity of the locus in a developmental model of FPLD2. Addressing this issue, we report phenotypic and transcriptional alterations in mesodermal and endothelial differentiation of induced pluripotent stem cells we generated from a patient with R482W-associated FPLD2. Correction of the LMNA mutation ameliorates R482W-associated phenotypes and gene expression. Transcriptomics links endothelial differentiation defects to decreased Polycomb-mediated repression of the T/Brachyury locus and over-activation of T target genes. Binding of the Polycomb repressor complex 2 to T/Brachyury is impaired by the mutated lamin A network, which is unable to properly associate with the locus. This leads to a deregulation of vascular gene expression over time. By connecting a lipodystrophic hotspot lamin A mutation to a disruption of early mesodermal gene expression and defective endothelial differentiation, we propose that the mutation rewires the fate of several lineages, resulting in multi-tissue pathogenic phenotypes.

PML protein organizes heterochromatin domains where it regulates histone H3.3 deposition by ATRX/DAXX.

Maintenance of chromatin homeostasis involves proper delivery of histone variants to the genome. The interplay between different chaperones regulating the supply of histone variants to distinct chromatin domains remains largely undeciphered. We report a role of promyelocytic leukemia (PML) protein in the routing of histone variant H3.3 to chromatin and in the organization of megabase-size heterochromatic PML-associated domains that we call PADs. Loss of PML alters the heterochromatic state of PADs by shifting the histone H3 methylation balance from K9me3 to K27me3. Loss of PML impairs deposition of H3.3 by ATRX and DAXX in PADs but preserves the H3.3 loading function of HIRA in these regions. Our results unveil an unappreciated role of PML in the large-scale organization of chromatin and demonstrate a PML-dependent role of ATRX/DAXX in the deposition of H3.3 in PADs. Our data suggest that H3.3 loading by HIRA and ATRX-dependent H3K27 trimethylation constitute mechanisms ensuring maintenance of heterochromatin when the integrity of these domains is compromised.

Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study.

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Transfusion in critical care: Past, present and future.

Anaemia and coagulopathy are common in critically ill patients and are associated with poor outcomes, including increased risk of mortality, myocardial infarction, failure to be liberated from mechanical ventilation and poor physical recovery. Transfusion of blood and blood products remains the corner stone of anaemia and coagulopathy treatment in critical care. However, determining when the benefits of transfusion outweigh the risks of anaemia may be challenging in some critically ill patients. Therefore, the European Society of Intensive Care Medicine prioritised the development of a clinical practice guideline to address anaemia and coagulopathy in non-bleeding critically ill patients. The aims of this article are to: (1) review the evolution of transfusion practice in critical care and the direction for future developments in this important area of transfusion medicine and (2) to provide a brief synopsis of the guideline development process and recommendations in a format designed for busy clinicians and blood bank staff. These clinical practice guidelines provide recommendations to clinicians on how best to manage non-bleeding critically ill patients at the bedside. More research is needed on alternative transfusion targets, use of transfusions in special populations (e.g., acute neurological injury, acute coronary syndromes), use of anaemia prevention strategies and point-of-care interventions to guide transfusion strategies.

Infectious Diseases Specialty Intervention Is Associated With Better Outcomes Among Privately Insured Individuals Receiving Outpatient Parenteral Antimicrobial Therapy.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) can be managed by specialists in infectious diseases (ID) or by other physicians. Better management of OPAT can reduce the likelihood of readmission or emergency department (ED) use. The relative success of ID specialists and other physicians in managing OPAT has received little study. METHODS: We analyzed a national database of insurance claims for privately insured individuals under age 65, locating inpatient acute-care stays in 2013 and 2014 that were followed by OPAT. Through propensity scoring, patients who received outpatient ID intervention (ID-led OPAT) were matched 1-to-1 with those who did not (Other OPAT). We estimated regression models of hospital and ED admissions and of total healthcare payments over the first 30 days after discharge. RESULTS: The final analytic sample of 8200 observations was well balanced on clinical and demographic characteristics. Soft-tissue infection and osteomyelitis were the most common infections in the index event, each affecting more than 40% of individuals. Relative to those with Other OPAT, people with ID-led OPAT had lower odds of an ED admission (odds ratio [OR] 0.449, 95% confidence interval [CI] 0.311-0.645) or hospitalization (OR 0.661, 95% CI 0.557-0.791) over 30 days, and they accumulated $1488 less in total healthcare payments (95% CI -2 688.56--266.58). CONCLUSIONS: Among privately insured individuals below age 65, ID consultations during OPAT are associated with large and significant reductions in the rates of ED admission and hospital admission in the 30 days after index events, as well as lower total healthcare spending.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.