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1.
Factors Disrupting Melatonin Secretion Rhythms During Critical Illness.
Maas, MB, Lizza, BD, Abbott, SM, Liotta, EM, Gendy, M, Eed, J, Naidech, AM, Reid, KJ, Zee, PC
Critical care medicine. 2020;(6):854-861
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Abstract
OBJECTIVES The circadian system modulates many important physiologic processes, synchronizing tissue-specific functions throughout the body. We sought to characterize acute alterations of circadian rhythms in critically ill patients and to evaluate associations between brain dysfunction, systemic multiple organ dysfunction, environmental stimuli that entrain the circadian rhythm (zeitgebers), rest-activity rhythms, and the central circadian rhythm-controlled melatonin secretion profile. DESIGN Prospective study observing a cohort for 24-48 hours beginning within the first day of ICU admission. SETTING Multiple specialized ICUs within an academic medical center. PATIENTS Patients presenting from the community with acute onset of either intracerebral hemorrhage as a representative neurologic critical illness or sepsis as a representative systemic critical illness. Healthy control patients were studied in using modified constant routine in a clinical research unit. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Light, feeding, activity, medications, and other treatment exposures were evaluated along with validated measures of encephalopathy (Glasgow Coma Scale), multiple organ system function (Sequential Organ Failure Assessment score), and circadian rhythms (profiles of serum melatonin and its urinary metabolite 6-sulphatoxymelatonin). We studied 112 critically ill patients, including 53 with sepsis and 59 with intracerebral hemorrhage. Environmental exposures were abnormal, including light (dim), nutritional intake (reduced or absent and mistimed), and arousal stimuli (increased and mistimed). Melatonin amplitude and acrophase timing were generally preserved in awake patients but dampened and delayed with increasing encephalopathy severity. Melatonin hypersecretion was observed in patients exposed to catecholamine vasopressor infusions, but unaffected by sedatives. Change in vasopressor exposure was the only factor associated with changes in melatonin rhythms between days 1 and 2. CONCLUSIONS Encephalopathy severity and adrenergic agonist medication exposure were the primary factors contributing to abnormal melatonin rhythms. Improvements in encephalopathy and medical stabilization did not rapidly normalize rhythms. Urinary 6-sulphatoxymelatonin is not a reliable measure of the central circadian rhythm in critically ill patients.
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Integrated diagnostics: the future of laboratory medicine?
Lippi, G, Plebani, M
Biochemia medica. 2020;(1):010501
Abstract
The current scenario of in vitro and in vivo diagnostics can be summarized using the "silo metaphor", where laboratory medicine, pathology and radiology are three conceptually separated diagnostic disciplines, which will increasingly share many comparable features. The substantial progresses in our understanding of biochemical-biological interplays that characterize many human diseases, coupled with extraordinary technical advances, are now generating important multidisciplinary convergences, leading the way to a new frontier, called integrated diagnostics. This new discipline, which is currently defined as convergence of imaging, pathology and laboratory tests with advanced information technology, has an enormous potential for revolutionizing diagnosis and therapeutic management of human diseases, including those causing the largest number of worldwide deaths (i.e. cardiovascular disease, cancer and infectious diseases). However, some important drawbacks should be overcome, mostly represented by insufficient information technology infrastructures, costs and enormous volume of different information that will be integrated and delivered. To overcome these hurdles, some specific strategies should be defined and implemented, such as planning major integration of exiting information systems or developing innovative ones, combining bioinformatics and imaging informatics, using health technology assessment for assessing cost and benefits, providing interpretative comments in integrated reports, developing and using expert systems and neural networks, overcoming cultural and political boundaries for generating multidisciplinary teams and integrated diagnostic algorithms.
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Oropharyngeal Administration of Mother's Milk Prior to Gavage Feeding in Preterm Infants: A Pilot Randomized Control Trial.
Abd-Elgawad, M, Eldegla, H, Khashaba, M, Nasef, N
JPEN. Journal of parenteral and enteral nutrition. 2020;(1):92-104
Abstract
BACKGROUND Oropharyngeal administration of mother's colostrum in early days has an immunoprotective effect in preterm infants. OBJECTIVES Our aim was to study the effect of oropharyngeal administration of mother's milk (OPAMM) on decreasing the incidence of nosocomial sepsis. METHODS In a pilot prospective randomized study on preterm (<32 weeks gestation and 1500 g weight) infants, we compared OPAMM practice (applying 0.2 mL of mother's colostrum or milk prior to gavage feeding until full oral feeding is reached) with regular gavage feeding. The primary outcome was incidence of culture-proven nosocomial sepsis. Secondary outcomes included bacterial colonization of the gastrointestinal tract, feeding intolerance, time to reach full feeding, incidence of necrotizing enterocolitis, ventilator-associated pneumonia, duration of respiratory support, incidence of bronchopulmonary dysplasia (BPD), length of hospital stay, and neonatal mortality. RESULTS The outcomes of 200 neonates (100 in each group) were analyzed. OPAMM practice did not significantly reduce the incidence of culture proven nosocomial sepsis (8% vs 13%, P = 0.35). Infants in the OPAMM group had a significantly lower growth of Klebsiella species in the oropharyngeal pouch, borderline lower incidence of ventilator-associated pneumonia, shorter duration of oxygen therapy, less episodes of feeding intolerance, reached full feeding earlier, and had a shorter length of hospital stay. OPAMM practice did not affect the incidence of necrotizing enterocolitis, BPD, or neonatal mortality. CONCLUSION OPAMM prior to gavage feeding does not reduce the incidence of nosocomial sepsis but had beneficial effects on early achievement of feeding, and early hospital discharge in preterm very low-birth-weight infants.
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Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study with a clinical phenotype approach.
Caballero-Islas, AE, Hoyo-Ulloa, I, García-Castro, A, Hinojosa-Azaola, A
Rheumatology international. 2020;(10):1657-1666
Abstract
Severe infections are common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to describe the characteristics of patients with AAV and severe infections according to clinical phenotype. Retrospective cohort study including patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Baseline characteristics were compared between patients with and without at least one severe infection. Demographics, comorbidities, clinical characteristics, laboratory and treatment were retrieved at diagnosis and at every infectious event. One hundred and eight patients were included (57 with and 51 without infections). Patients with an infection had received more frequently methylprednisolone boluses at AAV diagnosis than patients without infections (OR 2.6, 95% CI 1.1-5.9, p = 0.01). There were a total of 108 severe infections in 57 patients (median follow-up 18 months). Thirty-two patients (56%) had an infectious complication within the first year of AAV diagnosis, 43 (75%) had pulmonary involvement during the first infection. The most frequent type of infection was pneumonia. Phenotypes were: Non-severe AAV (n = 11), severe PR3-AAV (n = 30), severe MPO-AAV (n = 9); the number of infectious events in each group was 11, 69, 18, respectively. Patients with severe MPO phenotype were older and required more frequently ICU stay compared to other phenotypes. Positive correlation was found between total of infections and pulmonary infiltrates due to vasculitis (ρ = 0.40, p = 0.003), endobronchial involvement (ρ = 0.40, p = 0.003), and alveolar hemorrhage (ρ = 0.34, p = 0.015). Severe infections, most commonly pneumonia, were frequent in this cohort, especially during the first year after diagnosis, in patients with pulmonary involvement and severe PR3 phenotype who received methylprednisolone boluses.
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5.
Iron Homeostasis and Ferritin in Sepsis-Associated Kidney Injury.
McCullough, K, Bolisetty, S
Nephron. 2020;(12):616-620
Abstract
Sepsis associated acute kidney injury (SA-AKI) is a common clinical syndrome that occurs among hospitalized patients and significantly impacts mortality. Furthermore, survival after sepsis is intricately dependent on recovery of kidney function. In this review, we discuss the role of iron imbalance in mediating the pathogenic events during sepsis. Intracellular ferritin serves as a repository for iron and prevents iron-mediated injury and may limit the availability of iron to pathogens. Circulating levels of ferritin also increase during sepsis and often correlate with severity of sepsis. Herein, we examine preclinical and clinical data and discuss recent findings that suggest immunomodulatory roles for ferritin. We also discuss the possible mechanistic roles for ferritin in mitigating the pathogenic sequelae of sepsis and highlight current gaps in knowledge.
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Serum trace element and heavy metal levels in patients with sepsis.
Akkaş, İ, Ince, N, Sungur, MA
The aging male : the official journal of the International Society for the Study of the Aging Male. 2020;(3):222-226
Abstract
Background and objectives: Sepsis is defined as a life-threatening organ dysfunction syndrome, which occurs when the body's immune response to infection is impaired. The aim of the present study was to investigate serum Iron, Copper, Zinco, Cobalt, Chromium, Selenium, Vanadium, Nickel, Cadmium, and Aliminium levels in patients with sepsis.Materials and methods: This prospective and observational study was conducted at a tertiary care university hospital of Turkey from 2015 to 2016, and comprised patients with sepsis. Serum concentrations of 10 elements were analyzed using inductively coupled plasma mass spectrometry. Analyses were performed at the laboratory of Düzce University Scientific and Technological Research Application and Research Center. A total of 87 participants (52 men, 35 women; average age, 74.11 ± 14.26) were enrolled.Results: When evaluated in terms of trace elements, a significant difference was noted between the sepsis and control groups in terms of the levels of the five elements. Chromium, Iron, Nickel, Copper, and Cadmium levels were significantly higher in the sepsis group.Conclusion: Our study indicated in particular, Iron, Copper, Chromium, Nickel, and Cadmium levels were elevated in patients with sepsis.
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Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants.
Pammi, M, Suresh, G
The Cochrane database of systematic reviews. 2020;(3):CD007137
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Abstract
BACKGROUND Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. OBJECTIVES To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA In our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates. DATA COLLECTION AND ANALYSIS We used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence. MAIN RESULTS Meta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical RR 0.82, 95% CI 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06, -0.02; NNTB 25, 95% CI 17 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38, 95% CI, -4.67, -0.09; 3 studies, 1079 participants, low-certainty evidence). Sensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis with enteral lactoferrin supplementation (typical RR 0.87, 95% CI, 0.78, 0.97; typical RD -0.03, 95% CI, -0.05, -0.0; 9 studies, 4702 participants, low-certainty evidence). There were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86, 1.41; typical RD -0.00, 95% CI, -0.02, 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69, 1.17; typical RD -0.00, 95% CI, -0.01, 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence). Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence). Lactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies. AUTHORS' CONCLUSIONS We found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.
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Stool Short-Chain Fatty Acids in Critically Ill Patients with Sepsis.
Valdés-Duque, BE, Giraldo-Giraldo, NA, Jaillier-Ramírez, AM, Giraldo-Villa, A, Acevedo-Castaño, I, Yepes-Molina, MA, Barbosa-Barbosa, J, Barrera-Causil, CJ, Agudelo-Ochoa, GM
Journal of the American College of Nutrition. 2020;(8):706-712
Abstract
Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group.Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs.Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups (p > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight (p = 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group (p = 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria (p < 0.05).Conclusions: The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.
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[Diagnostic and prognostic value of peripheral lymphocyte subtyping for invasive candidiasis infection in critically ill patients with non-neutropenic sepsis].
Han, W, Wang, H, Cui, N, Zhang, JH, Bai, GX, Chen, JW, Long, Y
Zhonghua nei ke za zhi. 2020;(12):968-975
Abstract
Objective: To assess the diagnostic and prognostic value of lymphocyte subtyping for invasive candidiasis infection (ICI) in critically ill patients with non-neutropenic sepsis. Methods: A prospective observational cohort study was performed at Peking Union Medical College Hospital (PUMCH), 377 patients with non-neutropenic sepsis admitted to Department of Critical Care Medicine from January 2017 to November 2019 were enrolled. There were 9.0% (34/377) patients diagnosed as ICI. Vital signs, supportive care therapy and microbiological specimens were collected. Peripheral blood lymphocyte subtypes, serum globulin, complements, inflammatory factors such as interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor were detected within 24 hours after sepsis was diagnosed. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value and prognostic significance of immunological indicators for ICI. Multiple logistic regression was used to analyze the independent risk factors for ICI. Kaplan-Meier analysis was used to analyze survival. Results: The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 17.0 (13.0, 21.0) in all 377 patients. The sequential organ failure score (SOFA) was 11.0 (8.0, 13.0), and the 28-day mortality rate was 27.6% (104/377). Peripheral blood CD8+absolute T lymphocyte count≤177 cells/μl, CD28+CD8+T-cell count≤81 cells/μl and 1, 3-β-D-glucan (BDG) ≥88.20 ng/L were closely correlated with the diagnosis of ICI (AUC=0.793,95%CI 0.749-0.833,P<0.000 1;AUC=0.892,95%CI 0.856-0.921, P<0.000 1;AUC=0.761, 95%CI 0.715-0.803,P<0.000 1, respectively), with sensitivity of diagnosis 94.12%, 100.00%, and 88.24%; the specificity of diagnosis 81.34%, 62.39%, 63.56% respectively. Multivariate logistic regression analysis identified CD8+T-cell count≤139 cells/μl (OR=7.463, 95%CI 1.300-42.831, P=0.024) and CD28+CD8+T-cell counts≤52 cells/μl (OR=57.494, 95%CI 3.986-829.359, P=0.003) as independent risk factors for higher mortality. Kaplan-Meier survival analysis suggested that CD8+T-cell count ≤139 cells/μl (P=0.0159) and CD28+CD8+T-cell count≤52 cells/μl (P=0.000 1) were associated with higher mortality within 28 days (68.8%, 91.7%). Conclusions: Low CD28+CD8+T cell count in peripheral blood is closely related to the development and clinical outcome of ICI in sepsis patients, which could be used as an effective indicator for the diagnosis and prognosis prediction of ICI.
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[Transcutaneous electrical acupoint stimulation for early enteral nutrition tolerance in patients with sepsis of gastrointestinal dysfunction: a multi-center randomized controlled trial].
Liu, H, Zhu, J, Ni, HB, Hu, XX
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2020;(3):229-33
Abstract
OBJECTIVE To compare the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) combined with conventional western medicine and western medicine alone on early enteral nutrition tolerance in patients with sepsis. METHODS Forty-nine patients with sepsis were randomly divided into an observation group (24 cases) and a control group (25 cases). The control group was treated with conventional western medicine, including limited fluid resuscitation, anti-infection and maintenance of hemodynamics, and enteral nutrition was provided when the hemodynamics became stable and the dosage of vasoactive drugs was reduced. The observation group, on the basis of the treatment of the control group, was treated with TEAS at Tianshu (ST 25), Shangjuxu (ST 37), Jiexi (ST 41), Diji (SP 8), Zusanli (ST 36), Zhongwan (CV 12) and Daheng (SP 15) when the enteral nutrition was provided (dilatational wave, 2 Hz/10 Hz, twice a day, 30 min each time), and the TEAS stopped when enteral nutrition was normal. The antral motility index (MI) was evaluated by ultrasonography on the first, third and fifth day into treatment in the two groups, and the duration from providing enteral nutrition to normal enteral nutrition was recorded. The acute gastrointestinal injury (AGI) classification, admission time of intensive care unit (ICU) and hospitalization time were compared. RESULTS The antral MI on the third and fifth day into treatment in the observation group was significantly higher than that in the control group (P<0.05). The duration from providing enteral nutrition to normal enteral nutrition was (5.08±0.65) days in the observation group, which was shorter than (5.56±0.65) days in the control group (P<0.05). The improvement of AGI classification after treatment in the observation group was significantly superior to the control group (P<0.05). The hospitalization time in the observation group was shorter than that in the control group (P<0.05). CONCLUSION TEAS combined with conventional western medicine treatment could significantly promote gastrointestinal peristalsis, improve the early intestinal nutrition tolerance in patients with sepsis, so as to shorten the time of reaching the standard of enteral nutrition and hospitalization time, which is better than conventional western medicine treatment alone.