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Sepsis remains a major cause of death despite advances in medical care. Metabolic deregulation is an important component of the survival process. Metabolomic analysis allows profiling of critical metabolic functions with the potential to classify patient outcome. Our prospective longitudinal characterization of 33 septic and non-septic critically ill patients showed that deviations, independent of direction, in plasma levels of lipid metabolites were associated with sepsis mortality. We identified a coupling of metabolic signatures between liver and plasma of a rat sepsis model that allowed us to apply a human kinetic model of mitochondrial beta-oxidation to reveal differing enzyme concentrations for medium/short-chain hydroxyacyl-CoA dehydrogenase (elevated in survivors) and crotonase (elevated in non-survivors). These data suggest a need to monitor cellular energy metabolism beyond the available biomarkers. A loss of metabolic adaptation appears to be reflected by an inability to maintain cellular (fatty acid) metabolism within a "corridor of safety".
Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS.
The objective of this study is to report EEG findings in both COVID-19 survivors and non-survivors who underwent EEG either due to seizure or encephalopathy. Out of total 1468 COVID-19-positive patients, 19 patients underwent EEG. Eight out of 19 patients had a history of seizure disorder and in the remaining 11 with no prior history of seizures, four had a clinical seizure during their hospital stay. Only one had new-onset complex focal status epilepticus on EEG. Amongst the survivors (13/19), the most common EEG findings were normal followed by mild diffuse slowing. Amongst the non-survivors (6/19), the most common EEG finding was moderate to severe slowing in 50% of the patients. It can be deduced that COVID-19 infection does not increase the propensity of epileptiform discharges on EEG. There is perhaps a trend towards increased risk of new-onset status epilepticus in patients with encephalopathy and focal lesions.
Tobacco cessation among those recently diagnosed with cancer is important to improve their prognosis, yet, many cancer survivors continue to smoke. The epidemiology of tobacco use differs by race and ethnicity, and limited cessation research has been conducted in African American (AA) populations. Here, we assess demographic and clinical variables associated with continued smoking in AAs after a cancer diagnosis. The Detroit Research on Cancer Survivors study is a cohort comprised of AA cancer survivors with breast, prostate, lung, and colorectal cancers. Detroit Research on Cancer Survivors data were utilized from survivors who completed their baseline survey within 18 months of cancer diagnosis (n = 1145); 18% (n = 356) reported smoking at the time of cancer diagnosis, and 57% of these (n = 203) continued to smoke after their diagnosis. Logistic regression models were used to assess factors associated with continued smoking. Living with a smoker (odds ratio [OR] = 2.78, 95% confidence interval [CI]: 1.64, 4.70), higher cumulative years of smoking (OR = 1.03, 95% CI: 1.01, 1.05, for each year), and a prostate cancer diagnosis (OR = 7.35, 95% CI: 3.89, 13.89) were all associated with increased odds of continued smoking. Survivors with higher social well-being scores (measured by the Functional Assessment of Cancer Therapy, a quality of life assessment) were more likely to quit smoking after diagnosis (OR = 0.96, 95% CI: 0.93, 1.00). These findings highlight the continued need for personalized cessation strategies to be incorporated into treatment plans for cancer survivors.
Maximal oxygen uptake (VO2max) has been used to assess risk for all-cause mortality and cardiovascular disease (CVD), and low VO2max has recently been associated with increased mortality from breast cancer. The purpose of this study was to determine the proportion of breast cancer survivors with 2 or more risk factors for CVD exhibiting a low VO2max and to determine whether sub-maximal endpoints which could be applied more readily to intervention research would correlate with the maximal treadmill test. We performed a single VO2max test on a treadmill with 30 breast cancer survivors age 30-60 (mean age 50.5 ± 5.6 years) who had 2 or more cardiac risk factors for CVD not related to treatment and who had received systemic therapy and or left chest radiation. Submaximal VO2 endpoints were assessed during the VO2max treadmill test and on an Arc trainer. Resting left ventricular ejection fraction (LVEF) was also assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA). A majority (23/30) of women had a VO2max below the 20th percentile based on their predicted normal values. The group mean resting LVEF was 60.5 ± 5.0%. Submaximal VO2 measures were strongly correlated with the maximal test including; 1) 85% age predicted maximum heart rate VO2 on treadmill, (r = .89; p < 0.001), 2) treadmill VO2 at anaerobic threshold (AT), (r = .83; p < 0.001), and 3) Arc VO2 at AT, (r = .80; p < 0.001). Breast cancer survivors with 2 or more CVD risk factors but normal LVEF had a low cardiorespiratory fitness level compared to normative values in the healthy population placing them at increased risk for breast cancer and cardiovascular mortality. Submaximal VO2 exercise testing endpoints showed a strong correlation with the VO2max test in breast cancer survivors and is a good candidate for testing interventions to improve cardiorespiratory fitness.
Estimation of the risk of cancer and other health effects following exposure to the atomic bombing of Hiroshima and Nagasaki remains largely empirical, and the models used to adduce risk incorporate few, if any, of the advances in molecular biology of the past decade or so. These facts compromise the estimation of risk where the epidemiologic data are weakest, namely, at low doses and dose rates. Although the risk estimates may be sufficient for regulatory purposes, without a better understanding of the molecular and cellular events ionizing radiation initiates or promotes, it seems unlikely that the estimates will be as intellectually satisfying as they might be. Nor will the situation improve further without attention to the identification and estimation of the effects of those host and environmental factors that enhance or diminish risk of cancer or the effects on the developing brain.
Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic.
Severe fever with thrombocytopenia syndrome (SFTS), a newly emerging tick-borne viral disease, has been detected in Asia since 2009, and person-to-person transmission is possible. SFTS is characterized by atypical signs, including mild to severe febrile illness similar to that associated with hemorrhagic fever, with 16.2 to 30% mortality. We found that the titers of neutralizing antibodies, play an important role in protective immunity, to SFTS virus (SFTSV) in survivors and healthy residents who lived in endemic areas and who were positive for SFTSV IgG, were higher than those in non-survivor patients. Moreover, the titers were maintained in surviving patients and healthy residents but not in non-surviving patients in South Korea.
Since the emergence of the coronavirus disease 19 (COVID-19), a number of studies have reported the presence of cardiovascular diseases in affected patients and linked them with a higher risk of mortality. We conducted an online search in Medline/PubMed to identify original cohorts comparing data between survivors and non-survivors from COVID-19. The presence of cardiovascular events and related biomarkers were compared between the 2 groups. Data on 1,845 hospitalized patients with COVID-19 were pooled from 12 comparative studies. The overall mortality rate in relation to COVID-19 was 17.6%. Men aged > 50 years old were more likely to die from COVID-19. Significant co-morbidities contributing to mortality were hypertension, diabetes mellitus, smoking, a previous history of cardiovascular disease including chronic heart failure, and cerebrovascular accidents. A significant relationship was observed between mortality and patient presentation with dyspnea, fatigue, tachycardia, and hypoxemia. Cardiovascular disease-related laboratory biomarkers related to mortality were elevated serum level of lactate dehydrogenase, creatine kinase, brain natriuretic peptide, and cardiac troponin I. Adverse cardiovascular disease-related clinical events preceding death were shock, arrhythmias, and acute myocardial injury. In conclusion, severe clinical presentation and elevated biomarkers in COVID-19 patients with established risk factors can predict mortality from cardiovascular causes.
Survivors of sepsis often suffer from prolonged post-critical illness syndrome secondary to the immune system's reprogramming. It is unclear if this process is static and pervasive due to methodological difficulties studying long-term outcomes of sepsis. The purpose of this study is to evaluate transcriptional profiles longitudinally in Drosophila melanogaster in the aftermath of sepsis to provide preliminary data for targets playing a role in post-sepsis immunostasis. Adult Drosophila melanogaster were infected with E. coli, and survivors were euthanized at 7, 14, and 21 days. Control flies were subjected to sham stress. Gene profiling was done with RNA-seq, and potential miRNA factors were computed. Profiling identified 55 unique genes at seven days, 61 unique genes at 14 days, and 78 genes at 21 days in sepsis survivors vs. sham control. Each post-sepsis timepoint had a distinctive transcriptional pattern with a signature related to oxidative stress at seven days, neuronal signal transduction at 14 days, and metabolism at 21 days. Several potential miRNA patterns were computed as potentially affecting several of the genes expressed in sepsis survivors. Our study demonstrated that post-sepsis changes in the transcriptome profile are dynamic and extend well into the Drosophila melanogaster natural life span.
Internationally, there are growing numbers of cancer survivors. Survivors report a range of persistent symptoms and unmet needs, which are quite consistent, internationally. Current models of post-treatment survivorship care are suboptimal, and unsustainable given the number of survivors, and limited health workforce. The most appropriate model of care for an individual will depend on a range of patient, disease and treatment factors. Alternatives to traditional follow up have been evaluated including nurse led follow up, follow up led by a primary care physician and formalized models of shared care. There should be greater focus on implementation of proven models.
Although exercise is widely recommended for survivors of cancer, readily implementable approaches for evaluating exercise tolerance enabling exercise prescriptions at appropriate levels of cardiovascular exertion are not always available. We evaluated the utility of modified Harvard Step tests within the context of a standard physical examination for fitness evaluation and exercise prescription for survivors of cancer across a range of age, BMI and exercise history. While 52% of presenting individuals with a past cancer diagnosis were able to complete a 3-min test at pace with a reduced 9-in. step, adoption of self-determined pacing, test duration and completion on a flat surface enabled relative fitness rating and appropriate exercise prescription for the remaining survivors. Younger age and more vigorous exercise histories correlated with completion of the standard 3-min test at pace, but all 9-in. formats led to exercise prescriptions more vigorous than current activity. The physical examination setting expedited inclusion of core and specific muscle group strength testing. The approach is adaptable to a range of health care settings, providers, and patients, providing a shared opportunity for providers and patients to evaluate exercise tolerance. It can be used to further expand incorporation of exercise testing and prescription into routine care.
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