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The American Journal of Emergency... Jun 2024Heatstroke (HS), associated with the early activation of the coagulation system and frequently presenting with thrombocytopenia, poses a significant healthcare...
BACKGROUND
Heatstroke (HS), associated with the early activation of the coagulation system and frequently presenting with thrombocytopenia, poses a significant healthcare challenge. Understanding the relationship of nadir platelet count (PLT) within 24 h for adverse outcomes in HS patients is crucial for optimizing management strategies.
METHODS
This retrospective cohort study, conducted in six tertiary care hospitals, involved patients diagnosed with HS and admitted to the emergency departments. The primary and secondary outcomes included in-hospital mortality and various acute complications, respectively, with logistic regression models utilized for assessing associations between nadir PLT and outcomes. The PLT count change curve was described using a generalized additive mixed model (GAMM), with additional analyses involving body temperature (BT) at 2 h also conducted.
RESULTS
Of the 152 patients included, 19 (12.5%) died in-hospital. The median nadir PLT within 24 h was 99.5 (58.8-145.0)*10^9/L. Notably, as a continuous variable (10*10^9/L), nadir PLT was significantly associated with in-hospital mortality (OR 0.76; 95% CI 0.64-0.91; P = 0.003) and other adverse outcomes like acute kidney and liver injury, even after adjustment for confounders. GAMM revealed a more rapid and significant PLT decline in the non-survival group over 24 h, with differential PLT dynamics also observed based on BT at 2 h.
CONCLUSIONS
Nadir PLT within 24 h were tied to in-hospital mortality and various adverse outcomes in HS patients. Early effective cooling measures demonstrated a positive impact on these associations, underscoring their importance in patient management.
PubMed: 38944919
DOI: 10.1016/j.ajem.2024.06.035 -
Neoplasia (New York, N.Y.) Jun 2024Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the...
Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.
PubMed: 38944914
DOI: 10.1016/j.neo.2024.101023 -
Neoplasia (New York, N.Y.) Jun 2024Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family,...
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.
PubMed: 38944913
DOI: 10.1016/j.neo.2024.101015 -
Heart & Lung : the Journal of Critical... Jun 2024Factors associated with cardiovascular complications of COVID-19 remain understudied.
Cardiovascular complications in the course of COVID-19 - lessons learned and implications for the future care of patients with viral respiratory diseases: Data from a single center retrospective observational study.
BACKGROUND
Factors associated with cardiovascular complications of COVID-19 remain understudied.
OBJECTIVES
Here we investigate the occurrence and risk factors of arrythmias, myocardial infarction and/or stroke, and thromboembolism in the course of COVID-19.
METHODS
We have performed an observational study with prospectively designed data collection. Data of patients diagnosed with COVID-19 who were admitted from March 6th 2020 to November 30th 2021 in our Hospital were analyzed. Logistic regression was used to identify variables associated with the odds of early hospital death due to COVID-19.
RESULTS
Fourteen-point three percent of 1964 patients had cardiovascular complications, 6.36 % arrhythmias, 5.5 % thromboembolic events and 2.39 % myocardial infarction and/or stroke. Factors independently increasing the odds of arrhythmia were older age (OR=1.49 [95 % CI: 1.17-1.92], p = 0.02), longer time between admission and the first onset of symptoms (1.02 [0.99-1.05], p = 0.049), concomitant atrial fibrillation/flutter (2.84 [1.37-5.70], p = 0.004), nicotinism (2.49 [1.37-4.49], p = 0.002), and eGFR<60 ml/min/1.73m (2.44 [1.08-5.59], p = 0.033). Factors independently increasing the odds of myocardial infarction and/or stroke were dementia (4.55 [0.97-19.3], p = 0.044), hemiplegia (12.67 [3.12-46.1], p < 0.001), nicotinism (3.36 [1.30-10.4], p = 0.013) and higher C-reactive protein concentration (1.01 [1.00-1.01], p = 0.040). Factors independently increasing the odds of thromboembolic events were longer hospitalization (1.08 [1.05-1.10], p < 0.001) and higher d-dimers (1.04 [1.02-1.05], <0.001).
CONCLUSIONS
The risk of cardiovascular complications was especially pronounced in patients with older age, pre-existing cardiovascular disease and more sever pneumonia at presentation to care. This underlines the importance of close and careful clinical follow-up in the course of COVID-19 for specific patients' populations, including a pro-active approach in diagnosis.
PubMed: 38944910
DOI: 10.1016/j.hrtlng.2024.06.009 -
European Journal of Radiology Jun 2024To develop and validate an open-source deep learning model for automatically quantifying scapular and glenoid morphology using CT images of normal subjects and patients...
OBJECTIVES
To develop and validate an open-source deep learning model for automatically quantifying scapular and glenoid morphology using CT images of normal subjects and patients with glenohumeral osteoarthritis.
MATERIALS AND METHODS
First, we used deep learning to segment the scapula from CT images and then to identify the location of 13 landmarks on the scapula, 9 of them to establish a coordinate system unaffected by osteoarthritis-related changes, and the remaining 4 landmarks on the glenoid cavity to determine the glenoid size and orientation in this scapular coordinate system. The glenoid version, glenoid inclination, critical shoulder angle, glenopolar angle, glenoid height, and glenoid width were subsequently measured in this coordinate system. A 5-fold cross-validation was performed to evaluate the performance of this approach on 60 normal/non-osteoarthritic and 56 pathological/osteoarthritic scapulae.
RESULTS
The Dice similarity coefficient between manual and automatic scapular segmentations exceeded 0.97 in both normal and pathological cases. The average error in automatic scapular and glenoid landmark positioning ranged between 1 and 2.5 mm and was comparable between the automatic method and human raters. The automatic method provided acceptable estimates of glenoid version (R = 0.95), glenoid inclination (R = 0.93), critical shoulder angle (R = 0.95), glenopolar angle (R = 0.90), glenoid height (R = 0.88) and width (R = 0.94). However, a significant difference was found for glenoid inclination between manual and automatic measurements (p < 0.001).
CONCLUSIONS
This open-source deep learning model enables the automatic quantification of scapular and glenoid morphology from CT scans of patients with glenohumeral osteoarthritis, with sufficient accuracy for clinical use.
PubMed: 38944907
DOI: 10.1016/j.ejrad.2024.111588 -
Immunobiology Jun 2024The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor...
The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs' biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.
PubMed: 38944891
DOI: 10.1016/j.imbio.2024.152831 -
Journal of Gastrointestinal and Liver... Jun 2024Endoscopy simulators are primarily designed to provide training in interventions performed during procedures. Peri-interventional tasks such as checking patient data,...
BACKGROUND AND AIMS
Endoscopy simulators are primarily designed to provide training in interventions performed during procedures. Peri-interventional tasks such as checking patient data, filling out forms for team time-out, patient monitoring, and performing sedation are often not covered. This study assesses the face, content, and construct validity of the ViGaTu (Virtual Gastro Tutor) immersive virtual reality (VR) simulator in teaching these skills.
METHODS
71 nurses and physicians were invited to take part in VR training. The participants experienced an immersive VR simulation of an endoscopy procedure, including setting up the endoscopic devices, checking sign-in and team time-out forms, placing monitoring devices, and performing sedation. The actions performed by the participants and their timing were continuously recorded. Face and content validity, as well as the System Usability Scale (SUS), were then assessed.
RESULTS
43 physicians and 28 nurses from 43 centers took a mean of 27.8 min (standard deviation ± 14.42 min) to complete the simulation. Seventy-five percent of the items for assessing face validity were rated as realistic, and 60% of items assessing content validity and usefulness of the simulation for different learning goals were rated as useful by the participants (four out of five on a Likert scale). The SUS score was 70, demonstrating a high degree of usability. With regard to construct validity, experienced endoscopy staff were significantly faster in setting up the endoscope tower and instruments than beginners.
CONCLUSIONS
This multicenter study presents a new type of interdisciplinary endoscopy training system featuring peri-interventional tasks and sedation in an immersive VR environment.
Topics: Humans; Virtual Reality; Clinical Competence; Simulation Training; Reproducibility of Results; Female; Adult; Male; Endoscopy, Gastrointestinal; Nurses; Middle Aged; Physicians
PubMed: 38944875
DOI: 10.15403/jgld-5440 -
Journal of Gastrointestinal and Liver... Jun 2024During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19...
BACKGROUND AND AIMS
During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication.
METHODS
17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes.
RESULTS
258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation.
CONCLUSIONS
COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.
Topics: Humans; COVID-19; Male; Female; Cholangitis, Sclerosing; Middle Aged; Retrospective Studies; Cholangiopancreatography, Endoscopic Retrograde; Tertiary Care Centers; Aged; SARS-CoV-2; Adult; Treatment Outcome; Risk Factors; Liver Transplantation
PubMed: 38944874
DOI: 10.15403/jgld-5476 -
Journal of Gastrointestinal and Liver... Jun 2024Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis...
BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy.
METHODS
Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020.
RESULTS
A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%).
CONCLUSIONS
A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Romania; Male; Neoplasm Staging; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Databases, Factual; Retrospective Studies
PubMed: 38944873
DOI: 10.15403/jgld-5414 -
Journal of Gastrointestinal and Liver... Jun 2024Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral...
BACKGROUND AND AIMS
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
MATERIALS
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Topics: Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Lipase; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Middle Aged; 17-Hydroxysteroid Dehydrogenases; Genetic Predisposition to Disease; Case-Control Studies; Hepatitis B, Chronic; Prognosis; Adult; Turkey; Risk Factors; Prospective Studies; Phenotype; Genetic Association Studies; Acyltransferases; Phospholipases A2, Calcium-Independent
PubMed: 38944871
DOI: 10.15403/jgld-5474