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Platelets Dec 2024Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity,...
Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 10/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, = .003) and 28-ventilator-free (median value, 0 vs. 19 days, = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 10/L had a higher 28-day mortality rate (63.6% vs. 45%, = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia ( value from the log-rank test, = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.
Topics: Humans; Thrombocytopenia; Shock, Septic; Male; Female; Prognosis; Retrospective Studies; Child; Child, Preschool; Infant; Platelet Count
PubMed: 38860550
DOI: 10.1080/09537104.2024.2363242 -
European Journal of Medical Genetics Jun 2024CCP110 (centriolar coiled coil protein 110, also known as CP110) is one of the essential proteins localized in the centrosome that plays critical roles in the regulation...
CCP110 (centriolar coiled coil protein 110, also known as CP110) is one of the essential proteins localized in the centrosome that plays critical roles in the regulation of the cell cycle and also in the initiation of ciliogenesis. So far, no human congenital disorders have been identified to be associated with pathogenic variants of CCP110. Mice with biallelic loss-of-function variants of Ccp110 (Ccp110) are known to manifest multiple organ defects, including a small body size, polydactyly, omphalocele, congenital heart defects, cleft palate, short ribs, and a small thoracic cage, a pattern of abnormalities closely resembling that in "ciliopathies" in humans. Herein, we report a 7-month-old male infant who presented with growth failure and skeletal abnormalities, including a narrow thorax and severe brachydactyly. Trio exome analysis of the genomic DNA of the patient and his parents showed that the patient was a compound heterozygote for truncating variants of CCP110, including a frameshift variant NM_001323572.2:c.856_857del, p.(Val286Leufs*5) inherited from the father, and a nonsense variant NM_001323572.2:c.1129C>T, p.(Arg377*) inherited from the mother. The strikingly similar pattern of malformations between Ccp110 mice and the 7-month-old male infant reported herein carrying unequivocal truncating CCP110 variants strongly supports the contention that CCP110 is a novel disease-causative gene.
PubMed: 38857829
DOI: 10.1016/j.ejmg.2024.104955 -
World Journal of Critical Care Medicine Jun 2024Extracorporeal organ support (ECOS) has made remarkable progress over the last few years. Renal replacement therapy, introduced a few decades ago, was the first...
Extracorporeal organ support (ECOS) has made remarkable progress over the last few years. Renal replacement therapy, introduced a few decades ago, was the first available application of ECOS. The subsequent evolution of ECOS enabled the enhanced support to many other organs, including the heart [veno-arterial extracorporeal membrane oxygenation (ECMO), slow continuous ultrafiltration], the lungs (veno-venous ECMO, extracorporeal carbon dioxide removal), and the liver (blood purification techniques for the detoxification of liver toxins). Moreover, additional indications of these methods, including the suppression of excessive inflammatory response occurring in severe disorders such as sepsis, coronavirus disease 2019, pancreatitis, and trauma (blood purification techniques for the removal of exotoxins, endotoxins, or cytokines), have arisen. Multiple organ support therapy is crucial since a vast majority of critically ill patients present not with a single but with multiple organ failure (MOF), whereas, traditional therapeutic approaches (mechanical ventilation for acute respiratory failure, antibiotics for sepsis, and inotropes for cardiac dysfunction) have reached the maximum efficacy and cannot be improved further. However, several issues remain to be clarified, such as the complexity and cost of ECOS systems, standardization of indications, therapeutic protocols and initiation time, choice of the patients who will benefit most from these interventions, while evidence from randomized controlled trials supporting their use is still limited. Nevertheless, these methods are currently a part of routine clinical practice in intensive care units. This editorial presents the past, present, and future considerations, as well as perspectives regarding these therapies. Our better understanding of these methods, the pathophysiology of MOF, the crosstalk between native organs resulting in MOF, and the crosstalk between native organs and artificial organ support systems when applied sequentially or simultaneously, will lead to the multiplication of their effects and the minimization of complications arising from their use.
PubMed: 38855267
DOI: 10.5492/wjccm.v13.i2.92458 -
Journal of Acute Medicine Jun 2024Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported....
BACKGROUND
Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported. We study the association of organ systems involved with in-hospital mortality and hospital length of stay (LOS) in COVID-19.
METHODS
Retrospective study of 808 consecutive patients with confirmed-laboratory diagnosis of COVID-19 in a New York hospital from March 1-May 15, 2020.
RESULTS
Increased number of organs systems involved was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.11-1.66, < 0.01) and increased LOS (B = 0.02, SE = 0.01, < 0.05). Increased platelet count was associated with decreased odds for mortality (OR: 0.996, 95% CI: 0.994-0.998, < 0.001). Increased white blood cell count was associated with increased odds for mortality (OR: 14.00, 95% CI: 3.41-57.38, < 0.001). Increased creatinine and glucose were each associated with increased LOS (B = 0.11, SE = 0.04, < 0.01, and B = 0.12, SE = 0.05, < 0.05, respectively). Increased odds for mortality were also found in high FiO2 oxygen requirement (OR: 11.63, 95% CI: 3.90-34.75, < 0.001) and invasive mechanical ventilation (OR: 109.93, 95% CI: 29.44-410.45, < 0.001).
CONCLUSION
Multiple organ systems involvement in COVID-19 is associated with worse prognosis. Clinical/laboratory values corresponding to each organ system may be used as prognostic tools in clinical settings to tailor treatments for COVID-19 patients.
PubMed: 38855050
DOI: 10.6705/j.jacme.202406_14(2).0002 -
International Journal of Surgery Case... Jul 2024Aortoenteric fistulas are rare and life-threatening pathology characterized by an abnormal connection between the aorta and the gastrointestinal tract.
BACKGROUND
Aortoenteric fistulas are rare and life-threatening pathology characterized by an abnormal connection between the aorta and the gastrointestinal tract.
CASE PRESENTATION
The patient is a 61-year-old male who initially presented with hypogastric pain, hematemesis, and melena. Computed tomography angiography (CTA) revealed an abdominal aorta aneurysm but not a fistula. Imaging modalities were inconclusive in the diagnosis. The patient became unstable hemodynamically and was transferred to the operation room. The definitive diagnosis of aortoenteric fistula was confirmed during surgical exploration. Urgent surgery was performed; however, the patient experienced a cascade of complications, including rebleeding, intestinal leakage, and hemodynamic instability due to aortic bleeding. Despite rigorous interventions, the patient expired due to multiple organ failure 53 days after the first repair surgery.
CLINICAL DISCUSSION
There is no definite imaging method due to the lack of guidelines, and the absence of exact findings has led to intraoperative diagnosis in up to 50 % of cases. This is one of the modalities of choice to examine suspected aortoenteric fistulas. Many authors prefer Computed tomography (CT) with intravenous contrast for suspected AEF despite its limitations in clarity. Others recommend CT angiography as the preferred modality. It is worth noting that, as reported in a comprehensive retrospective review, the mortality rate is approximately 46 % within 60 days after AEF repair surgery.
CONCLUSION
This report adds to the limited data about primary aortojejunal fistulas, an extremely rare type of aortoenteric fistulas which has been reported in only a few cases. Understanding the importance of promptly suspecting, diagnosing, and intervening is crucial, emphasizing the importance of sharing such cases for medical guidance and better patient outcomes.
PubMed: 38851068
DOI: 10.1016/j.ijscr.2024.109842 -
Fa Yi Xue Za Zhi Apr 2024
Topics: Humans; Middle Aged; Female; Sepsis; Drugs, Chinese Herbal; Bacteremia; Multiple Organ Failure; Fatal Outcome; Procalcitonin
PubMed: 38847042
DOI: 10.12116/j.issn.1004-5619.2023.430407 -
Mucosal Immunology Jun 2024The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the... (Review)
Review
The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the clearance of debris. A deficiency in key activators/amplifiers of the cascade results in recurrent infection, whereas a deficiency in regulating the cascade predisposes to accelerated organ failure, as observed in colitis and transplant rejection. Given that there are over 60 proteins in this system, it has become an attractive target for immunotherapeutics, many of which are United States Food and Drug Administration-approved or in multiple phase 2/3 clinical trials. Moreover, there have been key advances in the last few years in the understanding of how the complement system operates locally in tissues, independent of its activities in circulation. In this review, we will put into perspective the abovementioned discoveries to optimally modulate the spatiotemporal nature of complement activation and regulation at mucosal surfaces.
PubMed: 38838816
DOI: 10.1016/j.mucimm.2024.05.006 -
Scientific Reports Jun 2024Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis,...
Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12-48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.
Topics: Humans; Adrenomedullin; Male; Female; Respiratory Distress Syndrome; Middle Aged; Aged; Postoperative Complications; Retrospective Studies; Aortic Aneurysm, Thoracic; Biomarkers; Sepsis; Multiple Organ Failure; Postoperative Period
PubMed: 38834580
DOI: 10.1038/s41598-024-63412-1 -
Cardiology Journal Jun 2024The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired...
IMTRODUCTION
The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired prognosis have been identified. However, with machine learning (ML) approaches, certain phenotypes may be confined to classify the affected population and to predict outcome. This study aimed to phenotype patients using unsupervised ML technique within the International Postgraduate Course Heart Failure Registry for patients hospitalized with COVID-19 and Cardiovascular disease and/or RF (PCHF-COVICAV).
MATERIAL AND METHODS
Patients from the eight centres with follow-up data available from the PCHF-COVICAV registry were included in this ML analysis (K-medoids algorithm).
RESULTS
Out of 617 patients included into the prospective part of the registry, 458 [median age: 76 (IQR:65-84) years, 55% male] were analyzed and 46 baseline variables, including demographics, clinical status, comorbidities and biochemical characteristics were incorporated into the ML. Three clusters were extracted by this ML method. Cluster 1 (n = 181) represents mainly women with the least number of overall comorbidities and cardiovascular RF. Cluster 2 (n = 227) is characterized mainly by men with non-CV conditions and less severe symptoms of infection. Cluster 3 (n=50) mainly represents men with the highest prevalence of cardiac comorbidities and RF, more extensive inflammation and organ dysfunction with the highest 6-month all-cause mortality risk.
CONCLUSIONS
The ML process has identified three important clinical clusters from hospitalized COVID-19 CV and/or RF patients. The cluster of males with severe CV disease, particularly HF, and multiple RF presenting with increased inflammation had a particularly poor outcome.
PubMed: 38832553
DOI: 10.5603/cj.98489 -
World Journal of Gastroenterology May 2024Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients.
BACKGROUND
Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients.
AIM
To improve overall understanding of this disease's diagnosis and prognosis.
METHODS
We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria.
RESULTS
Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively.
CONCLUSION
Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.
Topics: Humans; Female; Male; Retrospective Studies; Adult; Middle Aged; Prognosis; Biopsy; Glucocorticoids; Polyendocrinopathies, Autoimmune; Ileum; Duodenum; Diarrhea; Intestinal Mucosa; Immunosuppressive Agents; Aged; Young Adult; Endoscopy, Gastrointestinal
PubMed: 38817655
DOI: 10.3748/wjg.v30.i19.2523