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Medicine May 2024Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric... (Review)
Review
RATIONALE
Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation.
PATIENTS CONCERNS
A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced.
DIAGNOSIS
Based on the course of the illness and imaging findings, the patient was diagnosed with AFE.
INTERVENTIONS
By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications.
OUTCOMES
By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae.
LESSONS
VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.
Topics: Humans; Female; Embolism, Amniotic Fluid; Extracorporeal Membrane Oxygenation; Adult; Pregnancy; Cesarean Section; Blood Transfusion; Tranexamic Acid; Disseminated Intravascular Coagulation; Anticoagulants
PubMed: 38758915
DOI: 10.1097/MD.0000000000038176 -
Frontiers in Nutrition 2024The French maritime pine bark extract Pycnogenol is a proprietary product from Aiton. It complies with the quality specifications in the monograph "Pine extract" in... (Review)
Review
The French maritime pine bark extract Pycnogenol is a proprietary product from Aiton. It complies with the quality specifications in the monograph "Pine extract" in the section of dietary supplements. Pycnogenol is standardized to contain 65-75% procyanidins which are a variety of biopolymers consisting of catechin and epicatechin monomeric units. The effects of Pycnogenol have been researched in a multitude of human studies. The basis for any activity is the bioavailability of constituents and metabolites of the extract. General principles of compound absorption, distribution, metabolism and elimination as well as specific data from studies with Pycnogenol are summarized and discussed in this review. Based on plasma concentration profiles it can be concluded that low molecular weight constituents of the extract, such as catechin, caffeic and ferulic acid, taxifolin are readily absorbed from the small intestine into systemic circulation. Procyanidin oligomers and polymers are subjected to gut microbial degradation in the large intestine yielding small bioavailable metabolites such as 5-(3',4'-dihydroxyphenyl)-γ-valerolactone. After intake of Pycnogenol, constituents and metabolites have been also detected in blood cells, synovial fluid and saliva indicating a substantial distribution in compartments other than serum. In studies simultaneously investigating concentrations in different specimen, a preferential distribution of individual compounds has been observed, e.g., of ferulic acid and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone into synovial fluid compared to serum. The main route of elimination of constituents and metabolites of the French pine bark extract is the renal excretion. The broad knowledge accumulated regarding the pharmacokinetics of compounds and metabolites of Pycnogenol constitute a rational basis for effects characterized on a cellular level and observed in human clinical studies.
PubMed: 38757126
DOI: 10.3389/fnut.2024.1389422 -
Brain & Spine 2024Both intracranial pressure (ICP) and cerebral arterial blood volume (CBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP...
INTRODUCTION
Both intracranial pressure (ICP) and cerebral arterial blood volume (CBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear.
RESEARCH QUESTION
Does ICP pulse waveform become similar to non-invasively estimated CBV pulse during ICP plateau waves.
MATERIAL AND METHODS
A total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CBV waveforms, representing the area between the pulses.
RESULTS
ICP increased (19.4 mm Hg [Q1-Q3: 18.2-23.4 mm Hg] vs. 42.7 mm Hg [Q1-Q3: 36.5-45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1-Q3: 34.8-69.5 cm/s] vs. 32.9 cm/s [Q1-Q3: 24.7-68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1-Q3: 15.74-23.0]) compared to the baselines (26.3 [Q1-Q3: 24.2-34.7], p < 0.001).
DISCUSSION AND CONCLUSION
The area between corresponding ICP and CBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.
PubMed: 38756859
DOI: 10.1016/j.bas.2024.102832 -
Frontiers in Neurology 2024Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing...
BACKGROUND AND PURPOSE
Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption.
METHODS
We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction.
RESULTS
A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05).
CONCLUSION
Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.
PubMed: 38756220
DOI: 10.3389/fneur.2024.1349369 -
Communications Medicine May 2024Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics...
BACKGROUND
Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics are not known.
METHODS
A typical von Hippel-Lindau tumor suppressor (VHL)-PROTAC C-A947 (BRM degrader)-was synthesized and its tissue distribution kinetics was studied by quantitative whole-body autoradiography (QWBA) and tissue excision in rats following IV dosing. Bile duct-cannulated (BDC) rats allowed the elucidation of in vivo clearance pathways. Distribution kinetics was evaluated in the tissues and tumors of mice to support PK-PD correlation. In vitro studies enabled the evaluation of cell uptake mechanisms and cell retention properties.
RESULTS
Here, we show that A947 quickly distributes into rat tissues after IV dosing, where it accumulates and is retained in tissues such as the lung and liver although it undergoes fast clearance from circulation. Similar uptake/retention kinetics enable tumor growth inhibition over 2-3 weeks in a lung cancer model. A947 quickly excretes in the bile of rats. Solute carrier (SLC) transporters are involved in hepatocyte uptake of PROTACs. Sustained BRM protein degradation is seen after extensive washout that supports prolonged cell retention of A947 in NCI-H1944 cells. A947 tissue exposure and pharmacodynamics are inversely correlated in tumors.
CONCLUSIONS
Plasma sampling for VHL-PROTAC does not represent the tissue concentrations necessary for efficacy. Understanding of tissue uptake and retention could enable less frequent IV administration to be used for therapeutic dosing.
PubMed: 38755248
DOI: 10.1038/s43856-024-00505-y -
Scientific Reports May 2024The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is...
The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or "knobs" on the iRBC surface. These knobs and the proteins that are concentrated within them allow the parasites to escape the immune response and host spleen clearance by mediating cytoadherence of the iRBC to the endothelial wall, but this also slows down blood circulation, leading in some cases to severe cerebral and placental complications. In this work, we have applied genetic and biochemical tools to identify proteins that interact with P. falciparum KAHRP using enhanced ascorbate peroxidase 2 (APEX2) proximity-dependent biotinylation and label-free shotgun proteomics. A total of 30 potential KAHRP-interacting candidates were identified, based on the assigned fragmented biotinylated ions. Several identified proteins have been previously reported to be part of the Maurer's clefts and knobs, where KAHRP resides. This study may contribute to a broader understanding of P. falciparum protein trafficking and knob architecture and shows for the first time the feasibility of using APEX2-proximity labelling in iRBCs.
Topics: Erythrocytes; Plasmodium falciparum; Protozoan Proteins; Humans; Proteomics; Malaria, Falciparum; DNA-(Apurinic or Apyrimidinic Site) Lyase; Ascorbate Peroxidases; Protein Binding; Biotinylation; Endonucleases; Peptides; Proteins; Multifunctional Enzymes
PubMed: 38755230
DOI: 10.1038/s41598-024-61295-w -
Scientific Reports May 2024This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research...
This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018-2019) and pandemic (2020-2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1-13.1%, p = .020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1-65.8%, 22.3-13.0%, respectively; both p < .001), while bystander-initiated automated external defibrillator (AED) use increased (3.7-4.9%, p = .029). Multivariate logistic regression analyses identified factors associated with reduced pre-hospital ROSC during the pandemic. Post-pandemic, there was no noticeable change in the one-month survival rate. The lack of significant change in survival may be attributed to the negative effects of reduced chest compressions and ventilation being offset by the positive impact of widespread AED availability in Japan. These findings underscore the importance of innovative tools and systems for safe bystander cardiopulmonary resuscitation during a pandemic, providing insights to optimize pediatric OHCA care.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Japan; COVID-19; Female; Child; Male; Cardiopulmonary Resuscitation; Child, Preschool; Infant; Adolescent; Registries; Pandemics; Defibrillators; SARS-CoV-2; Emergency Medical Services; Infant, Newborn; Return of Spontaneous Circulation; Survival Rate
PubMed: 38755175
DOI: 10.1038/s41598-024-61650-x -
Frontiers in Neurology 2024Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding...
Blood glucose to predict symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke with large infarct core: a prospective observational study.
INTRODUCTION
Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage.
METHODS
Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT.
RESULTS
The study recruited a total of 490 patients, of whom 13.3% ( = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; < 0.001). The overall mortality was 41.8% ( = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, < 0.001, confidence interval (CI) 1.076-1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616-0.754).
DISCUSSION
The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk.
PubMed: 38751885
DOI: 10.3389/fneur.2024.1367177 -
Frontiers in Pediatrics 2024Massive tricuspid regurgitation (TR) is the most common feature of pulmonary atresia with intact ventricular septum (PA/IVS), and mild or absent TR is observed in severe...
BACKGROUND
Massive tricuspid regurgitation (TR) is the most common feature of pulmonary atresia with intact ventricular septum (PA/IVS), and mild or absent TR is observed in severe right ventricular (RV) dysplasia or RV-to-coronary fistulous connections, resulting in non-biventricular (BV) outcomes postnatally.
CASE SUMMARY
We report a case of fetal severe pulmonary stenosis with IVS diagnosed at 26 weeks of gestation. The severity of RV hypoplasia did not worsen or reach indications for intrauterine intervention, while the jet velocity of TR decreased significantly during pregnancy. The fetus was definitely diagnosed with PA/IVS with mild RV dysplasia after birth. Unusually, the fetus did not experience severe TR and myocardial sinusoids, the TR jet velocity was maintained at 2.0 m/s, and the coronary artery was almost normal. The incapable RV cannot pump blood into pulmonary circulation after RV decompression from valvular perforation and balloon dilation. It may be an extraordinary finding of subsystemic RV.
CONCLUSION
PA/IVS is a heterogeneous disease with various degrees of RV dysplasia. Mild or no baseline TR is a reliable indicator with non-BV outcomes for fetal PA/IVS, even with acceptable dysplasia RV structures.
PubMed: 38751746
DOI: 10.3389/fped.2024.1251274 -
TORCHLIGHT trial, brightening the life of more patients with advanced triple-negative breast cancer.Translational Breast Cancer Research :... 2024Toripalimab (JS001) is a monoclonal antibody against programmed cell death-1 (PD-1), independently developed by Shanghai Junshi Biosciences Co., LTD, which is the first... (Review)
Review
Toripalimab (JS001) is a monoclonal antibody against programmed cell death-1 (PD-1), independently developed by Shanghai Junshi Biosciences Co., LTD, which is the first domestic original PD-1 inhibitor approved in China. TORCHLIGHT is the first phase III trial of PD-1 inhibitor combined chemotherapy in advanced triple-negative breast cancer (TNBC) in China, evaluating the efficacy and safety of toripalimab plus nab-paclitaxel as first- or second-line therapy. Nab-paclitaxel has significant advantages over other chemotherapy drugs, as paclitaxel nanoparticles combine with natural albumin to increase drug delivery and bioavailability of paclitaxel. Firstly, nab-paclitaxel has a higher therapy response; Secondly, albumin carries paclitaxel out of the blood circulation faster, reducing the damage to normal tissues, ensuring the survival of more normal immune cells and exerting immune efficacy. Finally, nab-paclitaxel does not cause allergic reactions caused by organic solvents and does not require glucocorticoid pretreatment, avoiding immune suppression and ensuring the maximum efficacy of immune checkpoint inhibitors (ICIs). In TORCHLIGHT trial, 95% of subjects were on the first line treatment, with only 5% being on the second line, and 56% patients were programmed death-ligand 1 (PD-L1) positive in total population. It achieved the survival benefits of progression-free survival (PFS) and overall survival (OS) dual efficacy end points, which stood out among numerous ICIs in advanced TNBC. TORCHLIGHT trial, as the name of it, like a torch to more patients with advanced TNBC, lighting up their lives. We described the design background of TORCHLIGHT trial and reviewed primary trials of PD-1 or PD-L1 inhibitor in advanced TNBC both domestically and internationally.
PubMed: 38751675
DOI: 10.21037/tbcr-23-33