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Lactate levels are commonly evaluated in acutely ill patients. Although most often used in the context of evaluating shock, lactate levels can be elevated for many reasons. While tissue hypoperfusion may be the most common cause of elevation, many other etiologies or contributing factors exist. Clinicians need to be aware of the many potential causes of lactate level elevation as the clinical and prognostic importance of an elevated lactate level varies widely by disease state. Moreover, specific therapy may need to be tailored to the underlying cause of elevation. The present review is based on a comprehensive PubMed search between the dates of January 1, 1960, to April 30, 2013, using the search term lactate or lactic acidosis combined with known associations, such as shock, sepsis, cardiac arrest, trauma, seizure, ischemia, diabetic ketoacidosis, thiamine, malignancy, liver, toxins, overdose, and medication. We provide an overview of the pathogenesis of lactate level elevation followed by an in-depth look at the varied etiologies, including medication-related causes. The strengths and weaknesses of lactate as a diagnostic/prognostic tool and its potential use as a clinical end point of resuscitation are discussed. The review ends with some general recommendations on the management of patients with elevated lactate levels.

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early—every minute counts.

To evaluate and summarize the evidence linking balance impairment as a risk factor for falls in community-dwelling older adults. Systematic review and meta-analysis. English language articles in MEDLINE, EMBASE, CINAHL (1988–2009), under keywords of accidental falls, aged, risk factors, and hip, radius, ulna, and humerus fractures; and bibliographies of retrieved articles. Community-dwelling older adults in a prospective study, at least 1-year duration, age more than 60 years, and samples not specific to a single disease-defined population were included. Sample size, inclusion/exclusion criteria, demographics, clinical balance measurement scale, type of fall outcome, method of fall ascertainment, length of follow-up, and odds ratio (OR) or risk ratio (RR) were extracted. Studies must have reported adjustment for confounders. Random effects meta-analysis to generate summary risk estimate was used. A priori evaluation of sources of heterogeneity was performed. Twenty-three studies met the selection criteria. A single summary measure could not be calculated because of the nonequivalence of the OR and RR, producing an overall fall risk of RR of 1.42 (1.08, 1.85) and OR of 1.98 (1.60, 2.46). Balance impairment imparts a moderate increase on fall risk in community-dwelling older adults. The type of fall outcome, the length of follow-up, and the balance measurement tool impact the magnitude of the association. Specific balance measurement scales were identified with associations for an increased fall risk, but further research is required to refine recommendations for their use in clinical practice.

Peroxisome‐localized oxo‐phytodienoic acid (OPDA) reductases (OPR) are enzymes converting 12‐OPDA into jasmonic acid (JA). However, the biochemical and physiological functions of the cytoplasmic non‐JA producing OPRs remain largely unknown. Here, we generated Mutator‐insertional mutants of the maize OPR2 gene and tested its role in resistance to pathogens with distinct lifestyles. Functional analyses showed that the opr2 mutants were more susceptible to the (hemi)biotrophic pathogens Colletotrichum graminicola and Ustilago maydis, but were more resistant to the necrotrophic fungus Cochliobolus heterostrophus. Hormone profiling revealed that increased susceptibility to C. graminicola was associated with decreased salicylic acid (SA) but increased JA levels. Mutation of the JA‐producing lipoxygenase 10 (LOX10) reversed this phenotype in the opr2 mutant background, corroborating the notion that JA promotes susceptibility to this pathogen. Exogenous SA did not rescue normal resistance levels in opr2 mutants, suggesting that this SA‐inducible gene is the key downstream component of the SA‐mediated defences against C. graminicola. Disease assays of the single and double opr2 and lox10 mutants and the JA‐deficient opr7opr8 mutants showed that OPR2 negatively regulates JA biosynthesis, and that JA is required for resistance against C. heterostrophus. Overall, this study uncovers a novel function of a non‐JA producing OPR as a major negative regulator of JA biosynthesis during pathogen infection, a function that leads to its contrasting contribution to either resistance or susceptibility depending on pathogen lifestyle. ZmOPR2 functions as a key component of salicylic acid‐mediated defences via suppressing jasmonic acid biosynthesis during pathogen infection, leading to its contrasting contribution to either resistance or susceptibility depending on pathogen lifestyle.

Background Prescribing pharmacologic therapies for critically ill patients requires a careful balancing of risks and benefits. Defining, monitoring, and reporting harms that occur in clinical trials conducted in critically ill populations, however, is challenging given that the natural history of most critical illnesses includes progressive multiple organ failure and death. In this study, we assessed harms reporting in clinical trials performed in critically ill populations. Methods Randomized, non-industry-sponsored, human clinical trials of pharmacologic interventions in adult critically ill populations published between 2015 and 2018 in high-impact journals were included in this systematic review. Harms data, adherence to Consolidated Standards of Reporting Trials (CONSORT) harms reporting guidelines, and restrictions on harms reporting were recorded. Results A total of 707 abstracts were screened with 40 trials ultimately being included in the analysis. Included trials represent 28,636 randomized patients with a median of 292 (IQR 100–546) patients per trial. The most common disease states were general critical care (33%) and sepsis (28%). Of 18 included CONSORT items, the median number met was 12 (IQR 9, 14). The most commonly missed items were adverse event (AE) severity grading definitions and AE attribution (relationship of AE to study drug), which were only reported in 35 and 38% of manuscripts, respectively. Half of the manuscripts (48%) provided definitions for recorded AEs. There were 5 studies investigating the effects of corticosteroids in sepsis, with the number of AEs reported per analyzed patient ranging from 0.01 to 1.89. AE definitions in studies of similar/equivalent interventions often varied substantially. Study protocols were available for 30/40 (75%) of studies, with 13 (43%) of those not providing any guidance regarding AE attribution. Conclusions Randomized trials of pharmacologic interventions conducted in critically ill populations and published in high impact journals often fail to adequately describe AE definitions, severity, attribution, and collection procedures. Among trials of similar interventions in comparable populations, variation in AE collection and reporting procedures is substantial. These factors may limit a clinician’s ability to accurately balance the potential benefits and harms of an intervention.

Objectives To evaluate whether patients who experience cardiac arrest in hospital receive epinephrine (adrenaline) within the two minutes after the first defibrillation (contrary to American Heart Association guidelines) and to evaluate the association between early administration of epinephrine and outcomes in this population.Design Prospective observational cohort study.Setting Analysis of data from the Get With The Guidelines-Resuscitation registry, which includes data from more than 300 hospitals in the United States.Participants Adults in hospital who experienced cardiac arrest with an initial shockable rhythm, including patients who had a first defibrillation within two minutes of the cardiac arrest and who remained in a shockable rhythm after defibrillation.Intervention Epinephrine given within two minutes after the first defibrillation.Main outcome measures Survival to hospital discharge. Secondary outcomes included return of spontaneous circulation and survival to hospital discharge with a good functional outcome. A propensity score was calculated for the receipt of epinephrine within two minutes after the first defibrillation, based on multiple characteristics of patients, events, and hospitals. Patients who received epinephrine at either zero, one, or two minutes after the first defibrillation were then matched on the propensity score with patients who were “at risk” of receiving epinephrine within the same minute but who did not receive it. Results 2978patients were matched on the propensity score, and the groups were well balanced. 1510 (51%) patients received epinephrine within two minutes after the first defibrillation, which is contrary to current American Heart Association guidelines. Epinephrine given within the first two minutes after the first defibrillation was associated with decreased odds of survival in the propensity score matched analysis (odds ratio 0.70, 95% confidence interval 0.59 to 0.82; P<0.001). Early epinephrine administration was also associated with a decreased odds of return of spontaneous circulation (0.71, 0.60 to 0.83; P<0.001) and good functional outcome (0.69, 0.58 to 0.83; P<0.001).Conclusion Half of patients with a persistent shockable rhythm received epinephrine within two minutes after the first defibrillation, contrary to current American Heart Association guidelines. The receipt of epinephrine within two minutes after the first defibrillation was associated with decreased odds of survival to hospital discharge as well as decreased odds of return of spontaneous circulation and survival to hospital discharge with a good functional outcome.

Plants produce an array of oxylipins implicated in defense responses against various stresses, with about 600 oxylipins identified in plants to date. Most known oxylipins are the products of lipoxygenase (LOX)-mediated oxygenation of polyunsaturated fatty acids. One of the most well-characterized oxylipins produced by plants is the hormone jasmonic acid (JA); however, the function of the vast majority of oxylipins remains a mystery. One of the lesser-studied groups of oxylipins is comprised of ketols produced by the sequential action of LOX, allene oxide synthase (AOS), followed by non-enzymatic hydrolysis. For decades, ketols were mostly considered mere by-products of JA biosynthesis. Recent accumulating evidence suggests that ketols exhibit hormone-like signaling activities in the regulation of diverse physiological processes, including flowering, germination, plant–symbiont interactions, and defense against biotic and abiotic stresses. To complement multiple reviews on jasmonate and overall oxylipin biology, this review focuses specifically on advancing our understanding of ketol biosynthesis, occurrence, and proposed functions in diverse physiological processes.

BackgroundWidespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking.ObjectiveComparison of the epidemiology and clinical characteristics of COVID-19 patients during the pandemic with those of influenza patients in previous influenza seasons at the same hospitalDesignAdmission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020, were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014.SettingLarge tertiary care teaching hospital in Boston, MAParticipantsLaboratory-confirmed COVID-19 and influenza inpatientsMeasurementsPatient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, and hospital and intensive care admissions.ResultsData was abstracted from medical records of 1052 influenza patients and 582 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 582 COVID-19 admissions over 2 months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%) and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Pneumonia/ARDS secondary to the virus was the predominant cause of mechanical ventilation in COVID-19 patients (94%) as opposed to influenza (56%).LimitationThis is a single-center study which could limit generalization.ConclusionCOVID-19 resulted in more weekly hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital.