scholarly journals 1003. Cytokine Levels in Sepsis and TNFα Association with Mortality but not Sepsis Severity or Infection Source: a Systematic Review and Meta-analysis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S592-S592
Author(s):  
Amal Gharamti ◽  
Omar Samara ◽  
Anthony Monzon ◽  
Lilian Vargas Barahona ◽  
Sias Scherger ◽  
...  

Abstract Background Sepsis is a global health problem associated with significant morbidity and mortality and is attributed to a “cytokine storm.”. However, anti-cytokine therapies have failed to lower sepsis mortality in clinical trials. Linking cytokine excess to sepsis pathogenesis requires quantification of cytokine levels in sepsis. This systematic review and meta-analysis characterizes levels of key cytokines in the circulation of sepsis patients and relates TNFα levels to mortality and patient characteristics. Methods Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched from 1946 to May 2020 for studies in English disclosing cytokine levels in sepsis. Keywords included sepsis, septic shock, purpura fulminans, and tumor necrosis factor (TNF)α. We related cytokine amounts to 28-day mortality. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). This systematic review is registered in PROSPERO under number CRD42020179800. Results A total of 3656 records were identified. After exclusions, 103 studies were included. Among these studies, 72 disclosed TNFα levels, 25 showed interleukin (IL)-1β levels, and 6 presented interferon (IFN)γ levels. The pooled estimate mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% CI, 39.8-85.8 pg.ml; I2 = 99.4%). Pooled estimate means for IL-1α and IFNγ in sepsis patients were 21.8 pg/ml (95% CI, 12.6-37.8 pg.ml; I2 =99.8%) and 63.3 pg/ml (95% CI, 19.4-206.6 pg/ml; I2 = 99.7%), respectively. Elevated TNFα concentrations were associated with increased 28-day mortality (P=0.001). In a subgroup analysis, TNFα levels did not relate to sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score (figure 1). In a metaregression, TNFα associated with age, percentage of females and mortality at 28 days. Figure 1: A: TNFa levels according to sepsis source. B: TNFa levels according to measurement technique. C: TNFa levels according to presence or absence of cardiovascular disease. D: TNFa levels according to presence or absence of malignancy. E: TNFa levels according to sepsis severity. F: TNFa levels in fungal compared to other causes of sepsis (Yes=fungal sepsis; No= Other types of sepsis). G: TNFa levels according to SOFA score. H: TNFa levels and mortality at 28 days. Conclusion We presented levels of TNFα, IL-1β, and IFNγ in human sepsis and showed that TNFα elevations are associated with sepsis mortality. TNFα concentrations did not correlate with sepsis severity. We believe the concept that elevated cytokines cause sepsis should be revisited in the context of these data. Disclosures All Authors: No reported disclosures

2021 ◽  
Author(s):  
Amal Gharamti ◽  
Omar Samara ◽  
Anthony Monzon ◽  
Gabrielle Montalbano ◽  
Sias Scherger ◽  
...  

Background: Sepsis is a global health problem associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to a "cytokine storm." However, anti-cytokine therapies have failed to lower sepsis mortality. We aim to characterize levels of key cytokines in sepsis patients and healthy controls and relate TNFα levels to patient characteristics and outcomes. Methods: We performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched from 1985 to May 2020 for studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy persons. Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800). Findings: We identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8-85.8 pg/ml) and 5.5 pg/ml (95% CI 3.8-8.0 pg/ml) in healthy controls. Pooled estimate means for IL-1β and IFNγ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p=0.001). In subgroup analyses, TNFα levels did not relate to sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score. Interpretation: TNFα concentration in sepsis is increased approximately 10-fold compared to healthy persons, and TNFα associated with sepsis mortality but not with sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jean-Baptiste Bouillon-Minois ◽  
Carolyne Croizier ◽  
Julien S. Baker ◽  
Bruno Pereira ◽  
Farès Moustafa ◽  
...  

AbstractNon-traumatic intracranial bleeding (NTIB), comprising subarachnoid hemorrhage (SAH) and intra-cranial bleeding (ICH) is a significant public health concern. Tranexamic acid (TXA) is a promising treatment with benefits yet to be fully demonstrated. We conducted a systematic review and meta-analysis on the impact of TXA on mortality in NTIB. We searched the PubMed, Cochrane Library, Google Scholar and ScienceDirect databases for studies reporting mortality data following the use of TXA in NTIB for comparisons with a control group. We computed random-effect meta-analysis on estimates of risk and sensitivity analyses. We computed meta-regression to examine the putative effects of the severity of NTIB, sociodemographic data (age, sex), and publication date. Among potentially 10,008 articles, we included 15 studies representing a total of 4883 patients: 2455 receiving TXA and 2428 controls; 1110 died (23%) during the follow-up. The meta-analysis demonstrated a potential of 22% decrease in mortality for patients treated by TXA (RR = 0.78, 95%CI 0.58–0.98, p = 0.002). Meta-regression did not demonstrate any influence of the severity of NTIB, age, sex, length of treatment or date of publication. Sensitivity analyses confirmed benefits of TXA on mortality. TXA appears to be a therapeutic option to reduce non-traumatic intracranial bleeding mortality, particularly in patients with SAH.


BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e048476
Author(s):  
Amal Gharamti ◽  
Omar Samara ◽  
Anthony Monzon ◽  
Sias Scherger ◽  
Kristen DeSanto ◽  
...  

IntroductionIt is widely assumed that sepsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1β and interferon γ are poorly characterised during sepsis. We believe this project will produce a ‘gold-standard’ document to which other reports on cytokine levels will be compared. The objective of this systematic review will be to identify key cytokine circulating levels in patients with sepsis and assess the association between these levels and morbidity and mortality outcomes related to sepsis.Methods and analysisWe would include reports of any design except for case reports. Sepsis patients will comprise those with a diagnosis of sepsis, severe sepsis or septic shock. The primary exposure is levels of three proinflammatory cytokines. The primary outcome is mortality at 28 or 30 days. Study subjects can be of any age, sex or ethnicity. Studies will be restricted to the English language. Medline, Embase, Cochrane Library and Web of Science Core Collection will be searched for eligible studies. A database search will include studies from 1985 to May 2020. Two reviewers will independently screen and select studies, assess methodological quality and extract data. A meta-analysis will be performed, if possible, and the Grading of Recommendations Assessment Development and Evaluation Summary of Findings presented.Ethics and disseminationFormal ethical approval is not required as data will be extracted from existing literature. This systematic review will be disseminated through a peer-reviewed publication and at conference meetings.PROSPERO registration numberCRD42020179800.


2020 ◽  
Vol 25 (6) ◽  
pp. 2177-2192 ◽  
Author(s):  
Ilky Pollansky Silva e Farias ◽  
Simone Alves de Sousa ◽  
Leopoldina de Fátima Dantas de Almeida ◽  
Bianca Marques Santiago ◽  
Antonio Carlos Pereira ◽  
...  

Abstract This systematic review compared the oral health status between institutionalized and non-institutionalized elders. The following electronic databases were searched: PubMed (Medline), Scopus, Web of Science, Lilacs and Cochrane Library, in a comprehensive and unrestricted manner. Electronic searches retrieved 1687 articles, which were analyzed with regards to respective eligibility criteria. After reading titles and abstracts, five studies were included and analyzed with respect their methodological quality. Oral status of institutionalized and non-institutionalized elderly was compared through meta-analysis. Included articles involved a cross-sectional design, which investigated 1936 individuals aged 60 years and over, being 999 Institutionalized and 937 non-institutionalized elders. Studies have investigated the prevalence of edentulous individuals, the dental caries experience and the periodontal status. Meta-analysis revealed that institutionalized elderly have greater prevalence of edentulous (OR = 2.28, 95%CI = 1.68-3.07) and higher number of decayed teeth (MD = 0.88, 95%CI = 0.71-1.05) and missed teeth (MD = 4.58, 95%CI = 1.89-7.27). Poor periodontal status did not differ significantly between groups. Compared to non-institutionalized, institutionalized elders have worse dental caries experience.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hyune June Lee ◽  
Sung Min Kim ◽  
Ji Yean Kwon

Abstract Background Peripartum depression is a common disorder with very high potential hazards for both the patients and their babies. The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression. Methods We performed a systematic review that followed the PRISMA guidelines. We searched for studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference, and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method. Results The therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.944–1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.689–1.459), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346 (95% CI: 0.214–0.506), a meaningful result. There were no severe side effects to the mothers or fetuses. Conclusions From various perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 401-401
Author(s):  
Yue-Heng Yin ◽  
Liu Yat Justina

Abstract Obesity has been shown to intensify the decline of physical function and lead to frailty. Nutrition is an important method in managing obesity and frailty, while seldom reviews have ever explored the effects of nutritional education interventions. We conducted a systematic review (PROSPERO: CRD42019142403) to explore the effectiveness of nutritional education interventions in managing body composition and physio-psychosocial parameters related to frailty. Randomized controlled trials and quasi-experimental studies were searched in CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, PubMed and Scopus from 2001 to 2019. Hand search for the reference lists of included papers was conducted as well. We assessed the quality of included studies by Cochrane risk of bias tool. Meta-analyses and narrative synthesis were used to analyse the data. Two studies with low risk of bias were screened from 180 articles, which involved 177 older people with an average age of 69.69±4.08 years old. The results showed that nutritional education was significantly effective in reducing body weight and fat mass than exercises, and it was beneficial to enhancing physical function and psychosocial well-being. But the effects of nutritional education in increasing muscle strength were not better than exercises. The combined effects of nutritional education and exercises were superior than either exercises or nutritional education interventions solely in preventing the loss of lean mass and bone marrow density, and in improving physical function. Due to limited numbers of relevant studies, the strong evidence of effectiveness of nutritional education interventions on reversing frailty is still lacking.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.


2021 ◽  
pp. 174749302110042
Author(s):  
Grace Mary Turner ◽  
Christel McMullan ◽  
Olalekan Lee Aiyegbusi ◽  
Danai Bem ◽  
Tom Marshall ◽  
...  

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.


Author(s):  
Yoonyoung Lee ◽  
Kisook Kim

Patients who undergo abdominal surgery under general anesthesia develop hypothermia in 80–90% of the cases within an hour after induction of anesthesia. Side effects include shivering, bleeding, and infection at the surgical site. However, the surgical team applies forced air warming to prevent peri-operative hypothermia, but these methods are insufficient. This study aimed to confirm the optimal application method of forced air warming (FAW) intervention for the prevention of peri-operative hypothermia during abdominal surgery. A systematic review and meta-analysis were conducted to provide a synthesized and critical appraisal of the studies included. We used PubMed, EMBASE, CINAHL, and Cochrane Library CENTRAL to systematically search for randomized controlled trials published through March 2020. Twelve studies were systematically reviewed for FAW intervention. FAW intervention effectively prevented peri-operative hypothermia among patients undergoing both open abdominal and laparoscopic surgery. Statistically significant effect size could not be confirmed in cases of only pre- or peri-operative application. The upper body was the primary application area, rather than the lower or full body. These findings could contribute detailed standards and criteria that can be effectively applied in the clinical field performing abdominal surgery.


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