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Scientific Reports Jun 2024Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of...
Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.
Topics: Humans; Shock, Septic; Thromboplastin; Male; Female; Lipoproteins; Middle Aged; Aged; Multiple Organ Failure; Disseminated Intravascular Coagulation; Case-Control Studies; Adult; Biomarkers
PubMed: 38914630
DOI: 10.1038/s41598-024-65262-3 -
Heliyon Jun 2024A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have...
A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.
PubMed: 38912444
DOI: 10.1016/j.heliyon.2024.e32647 -
Heliyon Jun 2024Hyperammonemia syndrome has a high mortality rate in the immunosuppressed population due to its association with mental status changes. Recently studies have shown that...
Hyperammonemia syndrome has a high mortality rate in the immunosuppressed population due to its association with mental status changes. Recently studies have shown that organisms' infection can lead to hyperammonemia in post-transplant patients. Symptoms typically occur within 30 days postoperatively. However, the late-onset hyperammonemia caused by infection after kidney transplantation has never been reported. In this case study, a 64-year-old Chinese male presented with symptoms such as nausea, vomiting, trouble sleeping, and deteriorating mental status 81 days after kidney transplantation. His plasma ammonia level was significantly elevated, and there was no evidence of liver synthetic dysfunction. Although common methods for ammonia clearance, such as haemodialysis and oral lactulose were initiated, his serum ammonia levels remained high. Metagenomic sequencing of serum determined infection. Levofloxacin and minocycline were administered respectively, which resulted in a decrease in ammonia levels, but normalization was not achieved. The computed tomographic scan revealed the presence of cerebral edema. Unfortunately, the patient eventually became brain dead with multiple organ failure. This case highlights that can cause late-onset hyperammonemia in kidney transplant patients. Once the mental status changes are identified, immediate empiric treatments should be initiated without waiting for a confirmed diagnosis of spp. infection.
PubMed: 38912440
DOI: 10.1016/j.heliyon.2024.e32134 -
International Journal of Applied &... 2024Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which...
BACKGROUND AND OBJECTIVES
Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU).
METHODOLOGY
30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily.
RESULTS
D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases ( = 0.04). D-dimer in ICU patients was significantly elevated ( = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate ( = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure.
CONCLUSION
Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.
PubMed: 38912365
DOI: 10.4103/ijabmr.ijabmr_483_23 -
Journal of Neurology Jun 2024Hereditary transthyretin-related amyloidosis (ATTRv amyloidosis) is a rare and progressively debilitating disease characterized by the deposition of transthyretin (TTR)... (Review)
Review
Hereditary transthyretin-related amyloidosis (ATTRv amyloidosis) is a rare and progressively debilitating disease characterized by the deposition of transthyretin (TTR) amyloid fibrils in various organs and tissues, most commonly in the heart and peripheral nerves. This pathological deposition can lead to significant organ dysfunction and, ultimately, organ failure. ATTRv amyloidosis exhibits a broad range of clinical presentations, from purely neurological symptoms to purely cardiac manifestations, as well as mixed phenotypes which result from both neurological and cardiac implications. This wide phenotypical spectrum realistically challenges disease diagnosis and prognosis, especially in individuals without or with an unknown family history. Multiple factors are thought to contribute to this variability, including genetic, epigenetic, and even environmental influences. Understanding these factors is crucial, as they can significantly affect disease expression and progression. This review aims to summarize each of these contributing factors, to help elucidate the current knowledge on the phenotypical variability of ATTRv amyloidosis.
PubMed: 38907862
DOI: 10.1007/s00415-024-12509-8 -
Molecular Biology Reports Jun 2024Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms...
BACKGROUND
Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism.
METHODS
Rats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72 h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro.
RESULTS
MKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1α-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown.
CONCLUSION
MKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.
Topics: Animals; Male; Rats; Cell Line; Disease Models, Animal; Intestinal Mucosa; Intestines; MAP Kinase Kinase 3; Mitochondria; Mitophagy; Rats, Sprague-Dawley; Reactive Oxygen Species; Shock, Hemorrhagic; Shock, Traumatic
PubMed: 38904879
DOI: 10.1007/s11033-024-09691-3 -
Annals of Transplantation Jun 2024BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We...
BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.
Topics: Humans; Kidney Transplantation; Female; Male; Middle Aged; Retrospective Studies; Graft Survival; Adult; Reoperation; Graft Rejection; Aged; Survival Rate
PubMed: 38902916
DOI: 10.12659/AOT.943903 -
World Journal of Clinical Cases Jun 2024Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and...
Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and potentially fatal outcomes. Reports suggest that the mortality of DQ poisoning can be as high as 50%. DQ poisoning can be categorized as mild, moderate to severe or fulminant. In cases of fulminant poisoning, victims often succumb to multiple organ failure within 48 h. This presents a significant challenge in the clinical management. Scholars have discovered that oxidative stress, inflammatory injury, and cell apoptosis play crucial roles in the DQ poisoning. However, the underlying connection of the extensive organ damage remains unknown. The abnormal function and activity of endothelial cells (EC) should play a crucial role in tissue damage caused by DQ due to rich microcirculation and high sensitivity to perfusion in the vulnerable organs. However, reports on DQ-induced EC injury is rare. We made a preliminary discovery-the presence of severe vascular endothelial damage in the kidneys and lungs affected by DQ. Therefore, we hypothesize that DQ poisoning may be attributed to EC damage, ultimately resulting in multiple organ failure.
PubMed: 38898842
DOI: 10.12998/wjcc.v12.i17.2917 -
Journal of Visceral Surgery Jun 2024Treatment of ulcerative colitis (UC) has been revolutionized by the arrival of biotherapies and technical progress in interventional endoscopy and surgery. (Sub)total... (Review)
Review
Treatment of ulcerative colitis (UC) has been revolutionized by the arrival of biotherapies and technical progress in interventional endoscopy and surgery. (Sub)total emergency colectomy is required in the event of complicated severe acute colitis: colectasis, perforation, hemorrhage, organ failure. Corticosteroid therapy is the reference treatment for uncomplicated severe acute colitis, while infliximab and ciclosporin are 2nd-line treatments. At each step, before and after each line of treatment failure, surgery should be considered as an option. In cases refractory to medical treatment, the choice between surgery and change in medication must weigh the chronic symptoms associated with the disease against the risks of postoperative complications and functional sequelae inherent to surgery. Detection of dysplastic lesions necessitates chromoendoscopic imaging with multiple biopsies and anatomopathological verification. Endoscopic treatment of these lesions remains reserved for selected patients. These different indications call for multidisciplinary medical-surgical discussion. Total coloproctectomy with ileo-anal anastomosis (TCP-IAA) is the standard surgery, and it holds out hope for healing. Modalities depend on patient characteristics, previous emergency colectomy, and presence of dysplasia. It may be carried out in one, in two modified, or in three phases. The main complications are anastomotic fistula, short-term pouch-related fistula, ileo-anal pouch syndrome, pouchitis and long-term digestive and sexual disorders. For selected cases, an alternative can consist in total colectomy with ileo-rectal anastomosis or permanent terminal ileostomy. The objective of this update is to clarify the indications, modalities, and results of surgical treatment of ulcerative colitis in accordance with the most recent data in the literature.
Topics: Colitis, Ulcerative; Humans; Proctocolectomy, Restorative; Treatment Outcome; Colectomy; Postoperative Complications
PubMed: 38897710
DOI: 10.1016/j.jviscsurg.2024.05.004 -
International Journal of Molecular... May 2024The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1...
The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, < 0.001) and thrombocytopenia (<150/nL, = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.
Topics: Humans; Hepatitis A Virus Cellular Receptor 1; Sepsis; Male; Female; Middle Aged; Critical Illness; Aged; Acute Kidney Injury; Biomarkers; Severity of Illness Index; Multiple Organ Failure; Intensive Care Units; Adult
PubMed: 38892009
DOI: 10.3390/ijms25115819