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International Journal of Applied &... 2020Sparse literature is available regarding autopsy findings of coronavirus disease 2019 (COVID-19) despite high mortality due to its highly contagious nature and lack of... (Review)
Review
Sparse literature is available regarding autopsy findings of coronavirus disease 2019 (COVID-19) despite high mortality due to its highly contagious nature and lack of robust infrastructure for appropriate handling of the infected cases. Based on clinical findings and various diagnostic tests, it is evident that it holds the potential to affect multiple organ systems of the body preferably lungs and immune and coagulation systems. Cytokine storm-induced thrombotic complication such as disseminated intravascular coagulation is a significant feature in severe cases of COVID-19. This review captures the current information on lung histopathology in COVID-19 infection and severe respiratory failure. In COVID-19, lungs are affected bilaterally, become edematous and red/tan mottled to maroon in color with firm consistency. Distinct parenchymal changes, firm thrombi in the peripheral pulmonary vessels along with diffuse alveolar damage, have been the most consistent feature of COVID-19-related lung pathology. Electron microscopy has also been used to demonstrate viral particles.
PubMed: 33376694
DOI: 10.4103/ijabmr.IJABMR_381_20 -
Medicina (Kaunas, Lithuania) Jun 2021Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a... (Review)
Review
Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. : A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. : To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. : Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.
Topics: Adult; Child; Enterocolitis, Neutropenic; Humans; Lymphoma; Neoplasms; Prognosis; Sepsis
PubMed: 34203105
DOI: 10.3390/medicina57060638 -
The Journal of Emergency Medicine Dec 2020The concept of sepsis has recently been redefined by an International Task Force. The task force recommended the use of the quick Sequential Organ Failure Assessment... (Review)
Review
BACKGROUND
The concept of sepsis has recently been redefined by an International Task Force. The task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of Systemic Inflammatory Response Syndrome (SIRS) criteria to identify patients at high risk of mortality from sepsis outside of the intensive care unit, including in emergency departments (EDs). However, the primary outcome for qSOFA is prediction of risk for mortality, which is not the principal outcome measure considered in the ED. From the ED perspective, the priorities are the identification (diagnosis) of the septic patient and then the initiation of time-sensitive, life-saving interventions.
METHOD
We performed a structured review of PubMed from January 2012 to December 2018, limited to reports involving human subjects and written in English language and containing relevant keywords. The highest-quality studies were then reviewed in a structured format. We utilized these studies to estimate the sensitivity and specificity of SIRS and qSOFA for diagnosis of sepsis.
RESULTS
Thirteen unique articles were identified for further review, and the 11 highest-grade articles (C and D) were determined to be appropriate for inclusion in this review, and the two low-grade articles were excluded (E).
CONCLUSIONS
Based on multiple retrospective and few prospective studies, it appears that qSOFA performs poorly in comparison with SIRS as a diagnostic tool for ED patients who may have sepsis or septic shock. However, qSOFA does have a strong prognostic accuracy for mortality in those ED patients already diagnosed with sepsis or septic shock.
Topics: Emergency Service, Hospital; Hospital Mortality; Humans; Organ Dysfunction Scores; Prognosis; Prospective Studies; Retrospective Studies; Sepsis
PubMed: 32829969
DOI: 10.1016/j.jemermed.2020.06.043 -
Journal of Intensive Care Medicine Jul 2023To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis.
DATA COLLECTION
A systematic search was performed using the following databases: Medline, EMBASE, CINAHL, and Cochrane from January 1990 till December 2022. Comparative studies of TPE in severe sepsis were selected. Adult and pediatric data were analyzed separately.
DATA SYNTHESIS
Eight randomized control trials and 6 observational studies (n = 50,142 patients) were included. Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1173/1306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio, : 0.64 [95% confidence interval, : 0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (: 2.23, 95% : 1.93, 2.57). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome.
CONCLUSION
Current evidence indicates that TPE is a potential adjunct therapy in adults with severe sepsis but not in children.
Topics: Adult; Humans; Child; Shock, Septic; Plasma Exchange; Sepsis; Multiple Organ Failure; Plasma
PubMed: 37097910
DOI: 10.1177/08850666231170775 -
European Journal of Trauma and... Jun 2023The effect of systemic hemostatic agents initiated during pre-hospital care of severely injured patients with ongoing bleeding or traumatic brain injury (TBI) remains... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The effect of systemic hemostatic agents initiated during pre-hospital care of severely injured patients with ongoing bleeding or traumatic brain injury (TBI) remains controversial. A systematic review and meta-analysis was therefore conducted to assess the effectiveness and safety of systemic hemostatic agents as an adjunctive therapy in people with major trauma and hemorrhage or TBI in the context of developing the Italian National Institute of Health guidelines on major trauma integrated management.
METHODS
PubMed, Embase, and Cochrane Library databases were searched up to October 2021 for studies that investigated pre-hospital initiated treatment with systemic hemostatic agents. The certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach, and the quality of each study was determined with the Cochrane risk-of-bias tool. The primary outcome was overall mortality, and secondary outcomes included cause-specific mortality, health-related quality of life, any adverse effects and blood product use, hemorrhage expansion, and patient-reported outcomes.
RESULTS
Five trials of tranexamic acid (TXA) met the inclusion criteria for this meta-analysis. With a high certainty of evidence, when compared to placebo TXA reduced mortality at 24 h (relative risk = 0.83, 95% confidence interval = 0.73-0.94) and at 1 month among trauma patients (0.91, 0.85-0.97). These results depend on the subgroup of patients with significant hemorrhage because in the subgroup of TBI there are no difference between TXA and placebo. TXA also reduced bleeding death and multiple organ failure whereas no difference in health-related quality of life.
CONCLUSION
Balancing benefits and harms, TXA initiated in the pre-hospital setting can be used for patients experiencing major trauma with significant hemorrhage since it reduces the risk of mortality at 24 h and one month with no difference in terms of adverse effects when compared to placebo. Considering the subgroup of severe TBI, no difference in mortality rate was found at 24 h and one month. These results highlight the need to conduct future studies to investigate the role of other systemic hemostatic agents in the pre-hospital settings.
Topics: Humans; Antifibrinolytic Agents; Quality of Life; Hemorrhage; Tranexamic Acid; Hemostatics; Brain Injuries, Traumatic
PubMed: 36526811
DOI: 10.1007/s00068-022-02185-6 -
European Journal of Clinical... Jan 2021The coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine storm, contributing to ARDS, multiple-organ failure and, in the most severe cases, death. We aimed to quantify the differences in the circulating levels of major inflammatory and immunological markers between severe and nonsevere COVID-19 patients.
METHODS
Relevant studies were identified from PubMed, EMBASE, Web of Science, SCOPUS and preprint servers. Risk of bias was assessed for each study, using appropriate checklists. All studies were described qualitatively and a subset was included in the meta-analysis, using forest plots.
RESULTS
Based on 23 studies, mean cytokine levels were significantly higher (IL-6: MD, 19.55 pg/mL; CI, 14.80, 24.30; IL-8: MD, 19.18 pg/mL; CI, 2.94, 35.43; IL-10: MD, 3.66 pg/mL; CI, 2.41, 4.92; IL-2R: MD, 521.36 U/mL; CI, 87.15, 955.57; and TNF-alpha: MD, 1.11 pg/mL; CI, 0.07, 2.15) and T-lymphocyte levels were significantly lower (CD4+ T cells: MD, -165.28 cells/µL; CI, -207.58, -122.97; CD8+ T cells: MD, -106.51 cells/µL; CI, -128.59, -84.43) among severe cases as compared to nonsevere ones. There was heterogeneity across studies due to small sample sizes and nonuniformity in outcome assessment and varied definitions of disease severity. The overall quality of studies was sub-optimal.
CONCLUSION
Severe COVID-19 is characterized by significantly increased levels of pro-inflammatory cytokines and reduced T lymphocytes. Well-designed and adequately powered prospective studies are needed to amplify the current evidence and provide definitive answers to dilemmas regarding timing and type of anti-COVID-19 therapy particularly in severe patients.
Topics: CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19; Cytokine Release Syndrome; Cytokines; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lymphocyte Count; Receptors, Interleukin-2; SARS-CoV-2; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 33058143
DOI: 10.1111/eci.13429 -
Journal of Clinical Medicine Oct 2021Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure.... (Review)
Review
Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.
PubMed: 34682792
DOI: 10.3390/jcm10204667 -
Stem Cell Research & Therapy May 2022Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments.
METHODS
We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu's score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3.
RESULTS
It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu's score (- 1.96, 95% CI - 2.72 to - 1.19, P < 0.00001), less intestinal inflammation (IL-6 (- 2.73, 95% CI - 4.19 to - 1.27, P = 0.0002), TNF-α (- 3.00, 95% CI - 4.74 to - 1.26, P = 0.0007)) and oxidative stress (MDA (- 2.18, 95% CI - 3.17 to - 1.19, P < 0.0001)), and decreased serum levels of DAO (- 1.39, 95% CI - 2.07 to - 0.72, P < 0.0001), D-Lactate (- 1.54, 95% CI - 2.18 to - 0.90, P < 0.00001) and TNF-α (- 2.42, 95% CI - 3.45 to - 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells.
CONCLUSIONS
Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.
Topics: Animals; Inflammation; Interleukin-6; Lactates; Mesenchymal Stem Cells; Reperfusion Injury; Tumor Necrosis Factor-alpha
PubMed: 35619154
DOI: 10.1186/s13287-022-02896-y -
Pediatrics Jan 2022Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome....
CONTEXT
Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome. However, existing systems do not reflect current practice and are not consistently evidence based.
OBJECTIVE
We aimed to review the literature to identify the components of respiratory failure associated with outcomes in children, with the purpose of developing an operational and evidence-based definition of respiratory dysfunction.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from 1992 to January 2020 by using a combination of medical subject heading terms and text words to define respiratory dysfunction, critical illness, and outcomes.
STUDY SELECTION
We included studies of critically ill children with respiratory dysfunction that evaluated the performance of metrics of respiratory dysfunction and their association with patient-centered outcomes. Studies in adults, studies in premature infants (≤36 weeks' gestational age), animal studies, reviews and commentaries, case series with sample sizes ≤10, and studies not published in English in which we were unable to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted into a standard data extraction form.
RESULTS
We provided binary (no or yes) and graded (no, nonsevere, or severe) definitions of respiratory dysfunction, prioritizing oxygenation and respiratory support. The proposed criteria were approved by 82% of members in the first round, with a score of 8 of 9 (interquartile range 7-8).
LIMITATIONS
Exclusion of non-English publications, heterogeneity across the pediatric age range, small sample sizes, and incomplete handling of confounders are limitations.
CONCLUSIONS
We propose definitions for respiratory dysfunction in critically ill children after an exhaustive literature review.
Topics: Critical Illness; Humans; Multiple Organ Failure; Noninvasive Ventilation; Organ Dysfunction Scores; Respiratory Insufficiency
PubMed: 34970679
DOI: 10.1542/peds.2021-052888G -
Transplantation and Cellular Therapy Apr 2023Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication of the transplantation process that has been...
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication of the transplantation process that has been consistently associated with substantially greater morbidity and mortality compared with HSCT recipients who do not develop TMA. This study aimed to systematically review published signs and symptoms of HSCT-TMA and compare patients with HSCT-TMA and HSCT recipients who do not develop TMA. Publications were identified using multiple search term variations for stem cell transplantation that were entered into the PubMed, Embase, and CINAHL databases. Two reviewers screened references at the abstract level before reviewing full texts against inclusion and exclusion criteria using a PICOS-T framework. Complication proportions were grouped by organ class and then by complication type. Meta-analyses were conducted using a random-effects model in RevMan 5.4. After 2338 references were screened, a total of 30 studies were included in our analyses. The majority of studies (n = 23; 14 adult, 5 pediatric, 4 both) examined allogeneic transplantations only. Four studies examined autologous transplantation only (all pediatric), and 3 studies included both transplantation types (all pediatric). HSCT-TMA was associated with renal dysfunction (odds ratio [OR], 11.04 for adult, allogeneic and 7.35 for pediatric, all transplantations), renal failure (OR, 2.41 for adult and pediatric, allogeneic), renal replacement therapy (OR, 6.99 for pediatric, all transplantations and 60.85 for adult, allogeneic), and hypertension (OR, 5.44 for adult, allogeneic). HSCT-TMA was associated with respiratory failure (OR, 8.00 for adult and pediatric, allogeneic), pulmonary hypertension (OR, 9.86 for adult and pediatric, allogeneic), need for pleurocentesis (OR, 5.45 for pediatric, all transplantations), noninvasive ventilation (OR, 6.15 for pediatric, all transplantations), and invasive mechanical ventilation (OR, 5.18 for pediatric, all transplantations). Additionally, HSCT-TMA was associated with neurologic symptoms (OR, 2.28 for adult and pediatric, allogeneic), pericardial effusion (OR, 2.56 for adult and pediatric, allogeneic and 8.76 for pediatric, all transplantations), liver injury (OR, 3.87 for adult, allogeneic), infection (OR, 9.25 for adult, allogeneic; 2.06 for pediatric, all transplantations), gastrointestinal (GI) bleeding (OR, 7.78 for adult and pediatric, allogeneic), and acute graft-versus-host disease grade III-IV (OR, 3.29 for adult and pediatric, allogeneic). This study represents the first systematic review of HSCT-TMA signs and symptoms. Current diagnostic criteria systems involve laboratory markers for multiorgan dysfunction, including renal dysfunction, liver injury, and general tissue damage. Diagnostic criteria include neurologic symptoms, increased need for transfusions, and hypertension. This study identified additional associations with HSCT-TMA, including increased pulmonary hypertension, respiratory failure, fever, GI bleeding, and pericardial effusion. These symptoms might be included for evaluation in future diagnostic criteria and current practice.
Topics: Adult; Child; Humans; Hematopoietic Stem Cell Transplantation; Hypertension; Hypertension, Pulmonary; Pericardial Effusion; Thrombotic Microangiopathies
PubMed: 36592719
DOI: 10.1016/j.jtct.2022.12.023