Aspecific binding of anti-NK1.1 antibodies on myeloid cells in an experimental model for malaria-associated acute respiratory distress syndrome.

BACKGROUND: Conventional natural killer (cNK) cells play an important role in the innate immune response by directly killing infected and malignant cells and by producing pro- and anti-inflammatory cytokines. Studies on their role in malaria and its complications have resulted in conflicting results. METHODS: Using the commonly used anti-NK1.1 depletion antibodies (PK136) in an in-house optimized experimental model for malaria-associated acute respiratory distress syndrome (MA-ARDS), the role of cNK cells was investigated. Moreover, flow cytometry was performed to characterize different NK cell populations. RESULTS: While cNK cells were found to be dispensable in the development of MA-ARDS, the appearance of a NK1.1+ cell population was observed in the lungs upon infection despite depletion with anti-NK1.1. Detailed characterization of the unknown population revealed that this population consisted of a mixture of monocytes and macrophages that bind the anti-NK1.1 antibody in an aspecific way. This aspecific binding may occur via Fcγ receptors, such as FcγR4. In contrast, in vivo depletion using anti-NK1.1 antibodies was proved to be specific for cNK cells. CONCLUSION: cNK cells are dispensable in the development of experimental MA-ARDS. Moreover, careful flow cytometric analysis, with a critical mindset in relation to potential aspecific binding despite the use of commercially available Fc blocking reagents, is critical to avoid misinterpretation of the results.

A Comprehensive Evaluation of Dioxins and Furans Occurrence in River Sediments from a Secondary Steel Recycling Craft Village in Northern Vietnam.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

Performance measures of 8,169,869 examinations in the National Breast Cancer Screening Program in Taiwan, 2004-2020.

BACKGROUND: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods. METHODS: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. RESULTS: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period. CONCLUSIONS: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

NSAID: Current limits to prescription.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to alleviate pain and inflammation in conditions like arthritis, migraines, and post-operative recovery. Their mechanism involves inhibiting prostaglandins that contribute to inflammation. NSAIDs are categorized based on their structure, selectivity for COX-1 and COX-2 enzymes, and plasma half-life. They are effective in treating osteoarthritis, spondyloarthritis, and rheumatoid arthritis but might carry an elevated risk of adverse events. Despite their effectiveness, NSAIDs have limitations and risks that warrant cautious consideration. Extensive research has investigated their side effects, and this review aims to examine the current limitations of oral NSAID therapy, including safety profiles, specific scenarios where their use may not be appropriate, and gaps in knowledge. By critically evaluating these aspects, healthcare practitioners can make informed decisions about prescribing NSAIDs, optimizing patient outcomes while minimizing potential risks. This narrative review summarizes existing knowledge and underscores the importance of risk-benefit assessments in NSAID prescribing. Ultimately, the goal is to enhance the rational use of NSAIDs, maximizing benefits while mitigating adverse effects.

Lymphocyte radiosensitivity: An extension to the linear-quadratic model?

BACKGROUND AND PURPOSE: The linear-quadratic (LQ) model has been pivotal for evaluating the effects of radiation on cells, but it is primarily characterized by linear responses, which has exhibited limitations when applied to lymphocyte data. The present research aims to address these limitations and to explore an alternative model extended from the conventional LQ model. MATERIALS AND METHODS: Literature providing lymphocyte counts from assays investigating apoptosis and survival after in vitro irradiation was selected. To address the nonlinearity in lymphocyte responses to radiation, we developed a saturation model characterized by a negative exponential relationship between radiation dose and cellular response. We compared the performance of this saturation model against that of conventional models, including the LQ model and its variants (linear model LM and linear-quadratic-cubic model LQC), as well as the repair-misrepair (RMR) model. The models were evaluated based on prediction-residual plots, residual standard errors, and the Akaike information criterion (AIC). We applied the saturation model to two additional datasets: (1) a dataset from the existing literature that assessed stimulated and unstimulated human lymphocytes exposed to gamma irradiation in vitro and (2) a novel dataset involving T lymphocytes from rodent spleens after exposure to various radiation types (X-rays and protons). RESULTS: The literature (n = 15 out of 2342) showed that lymphocyte apoptosis varies with dose, time and experimental conditions. The saturation model had a lower AIC of 718 compared to the LM, LQ, LQC and RMR models (AIC of 728, 720, 720 and 734, respectively). The saturation model had a lower residual error and more consistent error distribution. Integrating time as a covariate, the saturation model also had a better AIC for demonstrating time-dependent variations in lymphocyte responses after irradiation. For datasets involving unstimulated lymphocytes before irradiation, the saturation model provided a more accurate fit than did the LM, LQ, and RMR models. In these cases, the fit of the saturation model was comparable to that of the LQC model but offered an advantage when extrapolating to higher doses, where the LQC model might underestimate survival. For stimulated lymphocytes, which are radioresistant, all the models approximated the LM. Both the LQ and saturation models indicated greater radiosensitivity to protons in vitro. CONCLUSION: The new "saturation model" performed better than the LQ model in quantifying lymphocyte apoptosis and survival, estimating time dependency and assessing the role of radiation modalities or lymphocyte stimulation. Further experiments are warranted to experimentally explore the validity of the saturation model as a promising alternative in the clinical setting.

Effect of Indentation Depth on Friction Coefficient in Adhesive Contacts: Experiment and Simulation.

The quasi-static regime of friction between a rigid steel indenter and a soft elastomer with high adhesion is studied experimentally. An analysis of the formally calculated dependencies of a friction coefficient on an external load (normal force) shows that the friction coefficient monotonically decreases with an increase in the load, following a power law relationship. Over the entire range of contact loads, a friction mode is realized in which constant shear stresses are maintained in the tangential contact, which corresponds to the "adhesive" friction mode. In this mode, Amonton's law is inapplicable, and the friction coefficient loses its original meaning. Some classical works, which show the existence of a transition between "adhesive" and "normal" friction, were analyzed. It is shown that, in fact, there is no such transition. A computer simulation of the indentation process was carried out within the framework of the boundary element method, which confirmed the experimental results.

Gender balance in Australian pharmacy organisations: Are we there yet?

Introduction: In the dynamic landscape of healthcare, pharmacists play a critical role in ensuring the well-being of communities, and having solid professional organisations to support pharmacists is essential in crucial activities, including continuing education, advocacy and establishing service standards. Eight pharmacy organisations play vital roles in representing pharmacists in various sectors and collectively contribute to developing, regulating, and promoting the pharmacy profession in Australia. However, a notable lack of female representation in these organisations' leadership roles has led to an increased focus on gender balance and equity. Objective: To determine if the gender distribution in pharmacy leadership aligns with the pharmacy workforce in Australia (64% women) and how it has changed in the five years since our last study on the issue. Setting: Australia. Method: Eight key Australian pharmacy organisations were identified. The website for each organisation was accessed, and data were recorded for their 2023 boards/committees/councils based on annual reports. Data recorded include name, number of males, number of females, and the gender of the president/chair of each board/committee/council. Results: Data were obtained for 340 separate professional committee members from the eight organisations (including state/territory branches) in 2023. Gender balance in pharmacy organisations has increased significantly since 2018, with women's representation in leadership positions now at 58% (47% 2018). Conclusion: Gender equity within Australian pharmacy professional organisations has significantly progressed.

Revealing the effect of X-ray or proton brain irradiation on systemic inflammation and leukocyte subpopulation interplay in rodents.

The absolute lymphocyte count (ALC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR) offer convenient means to assess systemic inflammation post-cancer treatment, which influences treatment outcomes. Understanding these biomarker variations and leukocyte subpopulation interplay is crucial for optimizing radiotherapy. Herein, leukocyte subpopulations (T-CD4+, T-CD8+, B-cells, NK-cells, neutrophils, monocytes) during and after brain irradiation (using X-rays or Protons) in tumor-free mice were used to compute ALC, LMR, and NLR, on which radiation parameter influence was assessed by principal component analysis (PCA). NLR kinetics were further examined using modeling. Leukocyte subpopulations interplays and their response to radiation parameters were examined using PCA and correlation analysis. Under X-rays, ALC and LMR decreased, with ALC recovered to baseline after irradiation, but not LMR. Both X-rays and protons increased the NLR during irradiation, recovering in protons but not X-rays. Both irradiation volume and dose rate had a pronounced effect on the NLR. Leukocyte subpopulation interplay was observed under X-rays and protons, normalizing in the proton group by day 28. Lymphopenia was observed in all lymphocyte subpopulations under X-ray irradiation but not protons. The recovery patterns varied among the subpopulations. Neutrophil counts increased during irradiation, with the recovery of protons, but not X-rays, by day 28. Interplays between NK-cells and myeloid subpopulations were evident under X-rays but not protons. Importantly, no interplay was detected between myeloid cells and T/B-cells, indicating that LMR and NLR variations were primarily due to independent responses to brain irradiation. A tumor-free experimental mouse model was used to study the effects of brain radiotherapy on systemic immunity. When administering fractionated irradiation with a total dose of 20 Gy using a vertical beam to either the whole brain or hemi-brain, proton irradiation had fewer adverse impacts on the immune system compared to X-rays in tumor-free rodents.

Altered Sex Ratio at Birth with Maternal Exposure to Dioxins in Vietnamese Infants.

Excess female births (lower sex ratio at birth) associated with paternal exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) have been reported in Italy. However, no significant effects of maternal TCDD exposure on the sex ratio were reported. We investigated the effects of maternal TCDD exposure and the toxic equivalent quantity of polychlorinated dibenzo-p-dioxins/dibenzofurans (TEQ-PCDD/Fs) on the sex ratio at birth in 576 Vietnamese infants from three birth cohorts. TCDD and TEQ-PCDD/Fs in breast milk were stratified (low, mild, moderate, and high) as maternal exposure markers. Logistic regression analysis was used to investigate associations between female birth and dioxin exposure groups after adjusting for confounders. In sprayed and unsprayed areas, adjusted odds ratios (ORs) of female birth (reference: low-TCDD group) were 2.11 in the moderate-TCDD group and 2.77 in the high-TCDD group, which were significantly associated with increased TCDD exposure. In sprayed areas, a significantly increased OR in the high-TCDD group was observed. No significant associations, however, were found between having a girl and TEQ-PCDD/F levels. These results suggest that maternal TCDD exposure may alter the sex ratio at birth among Vietnamese residents of areas with high dioxin contamination.

Early effects of different brain radiotherapy modalities on circulating leucocyte subpopulations in rodents.

PURPOSES: Lymphopenia is extensively studied, but not circulating leucocyte subpopulations, which however have distinct roles in tumor tolerance. Proton therapy has been shown to have a lesser impact on the immune system than conventional X-ray radiotherapy through lower dose exposure to healthy tissues. We explored the differential effects of brain X-ray and proton irradiation on circulating leucocyte subpopulations. MATERIALS AND METHODS: Leucocyte subpopulation counts from tumor-free mice were obtained 12 hours after 4 fractions of 2.5 Gy. The relationships between irradiation type (X-rays or protons), irradiated volume (whole-brain/hemi-brain) and dose rate (1 or 2 Gy/min) with circulating leucocyte subpopulations (T-CD4+, T-CD8+, B, and NK-cells, neutrophils, and monocytes) were investigated using linear regression and tree-based modeling approaches. Relationships between dose maps (brain, vessels, lymph nodes (LNs)) and leucocyte subpopulations were analyzed and applied to construct the blood dose model, assessing the hypothesis of a direct lymphocyte-killing effect in radiation-induced lymphopenia. RESULTS: Radiation-induced lymphopenia occurred after X-ray but not proton brain irradiation in lymphoid subpopulations (T-CD4+, T-CD8+, B, and NK-cells). There was an increase in neutrophil counts following protons but not X-rays. Monocytes remained unchanged under both X-rays and protons. Besides irradiation type, irradiated volume and dose rate had a significant impact on NK-cell, neutrophil and monocyte levels but not T-CD4+, T-CD8+, and B-cells. The dose to the blood had a heterogeneous impact on leucocyte subpopulations: neutrophil counts remained stable with increasing dose to the blood, while lymphocyte counts decreased with increasing dose (T-CD8+-cells > T-CD4+-cells > B-cells > NK-cells). Direct cell-killing effect of the dose to the blood mildly contributed to radiation-induced lymphopenia. LN exposure significantly contributed to lymphopenia and partially explained the distinct impact of irradiation type on circulating lymphocytes. CONCLUSIONS: Leucocyte subpopulations reacted differently to X-ray or proton brain irradiation. This difference could be partly explained by LN exposure to radiation dose. Further researches and analyses on other biological processes and interactions between leucocyte subpopulations are ongoing. The various mechanisms underlying leucocyte subpopulation changes under different irradiation modalities may have implications for the choice of radiotherapy modalities and their combination with immunotherapy in brain cancer treatment.

Mitral valve repair with resection and non-resection techniques in Barlow's disease: A multi-center study.

BACKGROUND: Various mitral valve (MV) repair techniques are nowadays in use. Non-resection techniques, that rely exclusively on Gore-Tex® neochords and annuloplasty, have been popularized; however, their efficacy in Barlow's disease, characterized by large myxomatous leaflets, is yet unclear. METHODS: Consecutive patients undergoing MV repair for Barlow's disease between 2011 and 2019 were selected on the basis of being eligible for resection and non-resection techniques. Study endpoints included overall survival, freedom from MV reintervention and recurrent regurgitation. RESULTS: Of 209 patients meeting the inclusion criteria, 135 (65%) underwent MV repair with and 74 (35%) without resection. There was one early reoperation due to residual regurgitation (resection group). Mean clinical follow-up duration was 6.1 (IQR 3.9-8.5) years. At 6 years after surgery, there was no difference in overall survival or freedom from MV reintervention. Mean echocardiographic follow-up (95% complete) duration was 3.5 (IQR 2.3-5.8) years. At 6 years, there was no difference in freedom from recurrent regurgitation rate (86.1%, 95% CI 78.5-93.7% vs. 83.0%, 95% CI 71.6-94.4%, P = 0.20) between the groups. Inverse probability-of-treatment weighting adjusted analysis demonstrated no significant difference between groups (HR 0.535, 95% CI 0.212-1.349, P = 0.20). Uni- and multivariable Cox proportional regression analysis did not demonstrate an effect of valve repair technique on the occurrence of recurrent regurgitation. CONCLUSIONS: At mid-term, the clinical and echocardiographic results of valve repair for Barlow's disease were very good and MV reintervention was rarely needed. At this time point, the results of non-resection techniques were comparable to the "gold standard" resection techniques.

Trametinib potentiates anti-PD-1 efficacy in tumors established from chemotherapy-primed pancreatic cancer cells.

Despite advances in immune checkpoint inhibitors (ICIs), chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX (5-fluorouracil (5FU), irinotecan, and oxaliplatin) regimen, and ICIs have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in PDAC patients. In this study, we report that neoadjuvant FOLFRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of 5FU (F), irinotecan (I), and oxaliplatin (O) (FIO). In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with 6-8 cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a pro-inflammatory immune profile similar to human PDAC tumors following neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor Trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining Trametinib and anti-PD-1 antibodies in PDAC patients following neoadjuvant or short-term FOLFIRINOX treatment to achieve effective anti-tumor responses.

Triplex glycan quantification by metabolic labeling with isotopically labeled glucose in yeast.

Mass spectrometry-based approaches encompass a powerful collection of tools for the analysis biological molecules, including glycans and glycoconjugates. Unlike most traditional bioanalytical methods focusing on these molecules, mass spectrometry is especially suited for multiplexing, by utilizing stable-isotope labeling. Indeed, stable isotope-based multiplexing can be regarded as the gold-standard approach in reducing noise and uncertainty in quantitative mass spectrometry and quantitative analyses generally. The increasing sophistication and depth of biological questions being asked continue to challenge the practitioners of mass spectrometry method development. To understand the biological relevance of glycans, many stable isotope labeling-based mass spectrometry methods have been developed. Based on the duplex MILPIG (metabolic isotope labeling of polysaccharides with isotopic glucose), we establish here a novel triplex isotope labeling method using baker's yeast as the model system. Two differentially isotope-labeled glucoses (medium: 1-13C1 and heavy: 1,2-13C2), in addition to natural abundance glucose (light), were successfully used to label each monosaccharide ring in N-linked glycans in three different cell culture conditions, that, after sample mixing, resulted in a predictable triplet spectrum amenable for relative quantitation. We demonstrate excellent accuracy and precision of relative quantitation for a 1:1:1 mixture of glycans labeled in such a fashion. In addition, we applied triplex MILPIG to interrogate differential N-glycan profiles in tunicamycin-treated and control yeast cells and show that different N-glycans respond differently to tunicamycin.

BET inhibition rescues acinar-ductal-metaplasia and ciliogenesis and ameliorates chronic pancreatitis-driven changes in mice with loss of the polarity protein Par3.

BACKGROUND AND AIMS: The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas injury and regeneration are poorly understood. METHODS: Cerulein-induced pancreatitis was induced in mice with conditional deletion of the polarity protein Par3 in the pancreas. The impact of Par3 loss on pancreas injury and regeneration was assessed by histological analyses and transcriptional profiling by RNA sequencing. Mice were pretreated with the bromodomain and extraterminal domain (BET) inhibitor JQ1 before co-treatment with cerulein to determine the effect of BET inhibition on pancreas injury and regeneration. RESULTS: Initially, we show that Par3 is increased in acinar-ductal metaplasia (ADM) lesions present in human and mouse chronic pancreatitis specimens. While Par3 loss disrupts tight junctions, Par3 is dispensable for pancreatogenesis. However, with aging, Par3 loss results in low-grade inflammation, acinar degeneration, and pancreatic lipomatosis. Par3 loss exacerbates acute pancreatitis-induced injury and chronic pancreatitis-induced acinar cell loss, promotes pancreatic lipomatosis, and prevents regeneration. Par3 loss also results in suppression of chronic pancreatitis-induced ADM and primary ciliogenesis. Notably, targeting BET proteins attenuates chronic pancreatitis-induced loss of primary cilia and promotes ADM in mice lacking pancreatic Par3. Targeting BET proteins also attenuates cerulein-induced acinar cell loss and enhances recovery of acinar cell mass and body weight of mice lacking pancreatic Par3. CONCLUSIONS: Combined, this study demonstrates how Par3 restrains chronic pancreatitis-induced changes in the pancreas and identifies a potential role for BET inhibitors to attenuate pancreas injury and facilitate regeneration.

Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer.

MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance the efficacy of MRTX1133 to further promote cell death and tumor regression. In this study, we demonstrated that MRTX1133 increased the levels of the pro-apoptotic protein BIM in PDAC cells and conferred sensitivity to the FDA-approved BCL2 inhibitor venetoclax. Combined treatment with MRTX1133 and venetoclax resulted in cell death and growth suppression in 3D cultures. BIM was required for apoptosis induced by the combination treatment. Consistently, BIM was induced in tumors treated with MRTX1133, and venetoclax enhanced the efficacy of MRTX1133 in vivo. Venetoclax could also re-sensitize MRTX1133-resistant PDAC cells to MRTX1133 in 3D cultures, and tumors established from resistant cells responded to the combination of MRTX1133 and venetoclax. These results provide a rationale for the clinical testing of MRTX1133 and venetoclax in PDAC patients.

Cannula-Associated Deep Vein Thrombosis Following Extracorporeal Membrane Oxygenation Decannulation: Incidence and Risk Factors.

Thrombotic complications during and after extracorporeal membrane oxygenation (ECMO) are commonly observed clinically. The incidences of cannula-associated deep vein thrombosis (CaDVT) post-ECMO support have predominantly focused on Caucasian demographics. This study aims to determine the incidence and risk factors for CaDVT in Vietnamese patients following ECMO decannulation. The retrospective study from January 2019 to February 2020 observed ECMO weaning patients and screened for CaDVT using Doppler ultrasonography. Data were collected on patient demographics, ECMO parameters, and transfusion and coagulation profiles during ECMO support. Of the 82 patients successfully weaned ECMO, 89% were assessed for CaDVT. We observed a CaDVT incidence of 24.7%, and only one patient (5.6%) had a pulmonary embolism in the CaDVT group. Noteworthy is that the anticoagulation goals, transfusion during ECMO, and hospital mortality showed no significant difference between the CaDVT and non-CaDVT groups. The findings showed that the duration of ECMO support is a risk factor for CaDVT. The incidence of CaDVT following ECMO decannulation was 24.7%, and the diagnosis of CaDVT can be underestimated. Therefore, we suggest routine screening for CaDVT after cannula removal.

DeepARV: ensemble deep learning to predict drug-drug interaction of clinical relevance with antiretroviral therapy.

Drug-drug interaction (DDI) may result in clinical toxicity or treatment failure of antiretroviral therapy (ARV) or comedications. Despite the high number of possible drug combinations, only a limited number of clinical DDI studies are conducted. Computational prediction of DDIs could provide key evidence for the rational management of complex therapies. Our study aimed to assess the potential of deep learning approaches to predict DDIs of clinical relevance between ARVs and comedications. DDI severity grading between 30,142 drug pairs was extracted from the Liverpool HIV Drug Interaction database. Two feature construction techniques were employed: 1) drug similarity profiles by comparing Morgan fingerprints, and 2) embeddings from SMILES of each drug via ChemBERTa, a transformer-based model. We developed DeepARV-Sim and DeepARV-ChemBERTa to predict four categories of DDI: i) Red: drugs should not be co-administered, ii) Amber: interaction of potential clinical relevance manageable by monitoring/dose adjustment, iii) Yellow: interaction of weak relevance and iv) Green: no expected interaction. The imbalance in the distribution of DDI severity grades was addressed by undersampling and applying ensemble learning. DeepARV-Sim and DeepARV-ChemBERTa predicted clinically relevant DDI between ARVs and comedications with a weighted mean balanced accuracy of 0.729 ± 0.012 and 0.776 ± 0.011, respectively. DeepARV-Sim and DeepARV-ChemBERTa have the potential to leverage molecular structures associated with DDI risks and reduce DDI class imbalance, effectively increasing the predictive ability on clinically relevant DDIs. This approach could be developed for identifying high-risk pairing of drugs, enhancing the screening process, and targeting DDIs to study in clinical drug development.

Thoracic Endovascular Aortic Repair for an Aortoesophageal Fistula Caused by Esophageal Cancer: A Case Report and Literature Review.

Aortoesophageal fistula (AEF) is an uncommon complication of esophageal cancer and can be extremely fatal if left untreated. Compared to open repair, thoracic endovascular aortic repair (TEVAR), a less invasive technique, is the initial recommended treatment in cases of hemorrhagic shock secondary to AEF, as this procedure showed a favorable outcome in controlling the overt bleeding. Here, we present a case of a patient with a history of stage IV esophageal cancer being treated with chemotherapy and an esophageal stent due to a previous tracheoesophageal fistula who presented to the emergency room due to severe gastroesophageal bleeding and hemorrhagic shock. A CT angiography of the chest revealed an AEF. The patient was subsequently resuscitated and treated with TEVAR. After the procedure, the hemorrhage was managed, and the patient was discharged with palliative radiation therapy. However, after one month, the patient had a major gastrointestinal hemorrhage, which caused her death. This example indicates the necessity of early detection and surgical intervention in AEF patients with unstable hemodynamics who have underlying unresectable esophageal cancer and chemotherapy. TEVAR should be conducted as soon as possible before the open surgery to achieve the best outcome for patients.

Challenges in Diagnosing and Managing Severe Hypernatremia in Patients With Major Depressive Disorder: A Case Report.

Hypernatremia, characterized by a plasma sodium concentration above 145 mmol/L, is frequently observed in critically ill patients, often due to factors such as gastrointestinal losses, dehydration, and diabetes insipidus. Psychiatric patients, particularly those with major depressive disorder, are also at risk of developing hypernatremia due to abnormalities in thirst sensation, mineralocorticoid excess, or medication side effects. Severe hypernatremia in psychiatric patients is associated with a high mortality rate, presenting challenges in diagnosis and management. The treatment of chronic hypernatremia (>48 hours) typically involves administering isotonic saline to hypovolemic patients until normalization of vital signs, followed by dextrose 5% in water (D5W) based on water deficit and losses. The goal is to decrease plasma sodium by 8-10 mmol/day. Acute hypernatremia (<48 hours) is corrected with a plasma sodium reduction of 1 mmol/L/hour in the first six to eight hours. While there are no clear guidelines for sodium correction in severe hypernatremia, the literature suggests a safe correction rate of 8-10 mmol/day for chronic hypernatremia and 1 mmol/L/hour for acute cases. In a specific case, a 51-year-old female with severe depression and reduced oral intake was admitted. She exhibited signs of dehydration and was found to have severe hypernatremia (191 mmol/L) with acute kidney injury. Treatment involved D5W, followed by D5W/half-normal saline at 150 mL/hr. Within 24 hours, her plasma sodium decreased to 178 mmol/L and gradually normalized to 143 mmol/L without neurological complications. This case highlights the challenges and underscores the importance of early recognition and management of severe hypernatremia in psychiatric patients. The primary treatment approach addresses water deficits and losses and administers D5W. Recent findings suggest that rapid correction of the condition is acceptable.

Genetic diversity of G9, G3, G8 and G1 rotavirus group A strains circulating among children with acute gastroenteritis in Vietnam from 2016 to 2021.

Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and mortality caused by RVA. From 2016 to 2021, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 2020. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 2021 were mapped using next-generation sequencing. From 2016 to 2021, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P[8], G3P[8] and G8P[8]. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019-2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2-99.9% and 99.1-99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.