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World Journal of Clinical Cases May 2021Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus...
BACKGROUND
Several reports with clinical, histological and imaging data have observed the involvement of lung vascular function to explain the severe hypoxemia in coronavirus disease 2019 (COVID-19) patients. It has been hypothesized that an increased pulmonary blood flow associated with an impairment of hypoxic pulmonary vasoconstriction is responsible for an intrapulmonary shunt. COVID-19 may lead to refractory hypoxemia (PaO/FiO ratio below 100 mmHg) despite mechanical ventilation and prone positioning. We hypothesized that the use of a pulmonary vasoconstrictor may help decrease the shunt and thus enhance oxygenation.
CASE SUMMARY
We report our experience with three patients with refractory hypoxemia treated with almitrine to enhance oxygenation. Low dose almitrine (Vectarion; Servier, Suresnes, France) was started at an infusion rate of 4 μg × kg/min on a central line. The PaO/FiO ratio and total respiratory system compliance during almitrine infusion were measured. For the three patients, the PaO/FiO ratio time-course showed a dramatic increase whereas total respiratory system compliance was unchanged. The three patients were discharged from the intensive care unit. The intensive care unit length of stay for patient 1, patient 2 and patient 3 was 30 d, 32 d and 31 d, respectively. Weaning from mechanical ventilation was performed 13 d, 18 d and 15 d after almitrine infusion for patient 1, 2 and 3, respectively. We found no deleterious effects on the right ventricular function, which was similar to previous studies on almitrine safety.
CONCLUSION
Almitrine may be effective and safe to enhance oxygenation in coronavirus disease 2019 patients. Further controlled studies are required.
PubMed: 34002149
DOI: 10.12998/wjcc.v9.i14.3385 -
Molecular Genetics and Genomics : MGG Sep 2020Identifying the cause-and-effect mechanism behind the drug-disease associations is a challenging task. Recent studies indicate that microRNAs (miRNAs) play critical...
Identifying the cause-and-effect mechanism behind the drug-disease associations is a challenging task. Recent studies indicate that microRNAs (miRNAs) play critical roles in human diseases. Targeting specific miRNAs with drugs to treat diseases provides a new aspect for drug repositioning. Drug repositioning provides a way to identify new clinical applications for approved drugs. Drug discovery is expensive and complicated. Therefore, computational methods are necessary for predicting the potential associations between drugs and diseases based on the target miRNAs. Our approach bilateral-inductive matrix completion (BIMC) performed two rounds of inductive matrix completion algorithm, one on the drug-miRNA and another on the miRNA-disease, association matrices, and integrated the results for predicting the drug-disease relationships through the target miRNAs. The fundamental idea of inductive matrix completion (IMC) is to fill the unknown entries of the association matrices by utilizing existing associations and side information. In our study, the integrated similarities of drugs, miRNAs, and diseases were utilized as side information. Our method predicts drug-miRNA and miRNA-disease associations, as intermediate results. To estimate the performance of our approach, we conducted leave-one-out cross-validation (LOOCV) experiments. The method could achieve AUC scores of 0.792, 0.759, and 0.791 in drug-disease, drug-miRNA, and miRNA-diseases association predictions. The results and case studies indicate the prediction ability of our method, and it is superior to previous models with high robustness. The proposed approach predicts new drug-disease relationships and the causal miRNAs. The top predicted relationships are the promising candidates, and they are released for further biological tests.
Topics: Algorithms; Almitrine; Aminolevulinic Acid; Computational Biology; Drug Repositioning; Humans; MicroRNAs; Molecular Targeted Therapy
PubMed: 32583015
DOI: 10.1007/s00438-020-01702-9 -
Pharmaceuticals (Basel, Switzerland) Feb 2024Leishmaniasis, a neglected tropical disease, poses a significant global health challenge, necessitating the urgent development of innovative therapies. In this study, we...
Leishmaniasis, a neglected tropical disease, poses a significant global health challenge, necessitating the urgent development of innovative therapies. In this study, we aimed to identify compounds from the COVID Box with potential efficacy against two species, laying the foundation for future chemical development. Four promising molecules were discovered, demonstrating notable inhibitory effects against and . Our study revealed that bortezomib, almitrine, and terconazole induced a significant decrease in mitochondrial membrane potential, while the above compounds and ABT239 induced plasma permeability alterations, chromatin condensation, and reactive oxygen species accumulation, indicating early apoptosis in promastigotes, preventing inflammatory responses and tissue damage, thereby improving patient outcomes. Furthermore, ADME predictions revealed favorable pharmacokinetic profiles for all compounds, with bortezomib and ABT239 standing out as potential candidates. These compounds exhibited intestinal absorption, blood-brain barrier penetration (excluding bortezomib), and good drug-likeness for bortezomib and ABT239. Toxicity predictions for CYP-inhibition enzymes favored bortezomib as the safest candidate. In conclusion, our study identifies bortezomib as a promising aspirant for leishmaniasis treatment, demonstrating potent antiparasitic activity, favorable pharmacokinetics, and low toxicity. These findings emphasize the potential repurposing of existing drugs for neglected diseases and highlight the importance of the COVID Box in drug discovery against tropical diseases.
PubMed: 38543052
DOI: 10.3390/ph17030266 -
Anaesthesia, Critical Care & Pain... Aug 2020
Topics: Almitrine; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Nitric Oxide; Oxygen Consumption; Pandemics; Pneumonia, Viral; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; SARS-CoV-2; Vasoconstrictor Agents
PubMed: 32505755
DOI: 10.1016/j.accpm.2020.05.014 -
The Journal of Trauma and Acute Care... Aug 2020According to the Joint Theater Trauma Registry, 26% to 33% of war casualties develop acute respiratory distress syndrome (ARDS), with high mortality. Here, we aimed to... (Observational Study)
Observational Study
BACKGROUND
According to the Joint Theater Trauma Registry, 26% to 33% of war casualties develop acute respiratory distress syndrome (ARDS), with high mortality. Here, we aimed to describe ARDS incidence and severity among patients evacuated from war zones and admitted to French intensive care units (ICUs).
METHODS
We performed an observational retrospective multicentric review of all patients evacuated from war zones and admitted to French ICUs between 2003 and 2018. Our analysis included all medical and trauma patients developing ARDS according to the Berlin definition. We evaluated ARDS incidence, and determined ARDS severity from arterial blood gas analysis. Analyzed parameters included invasive ventilation duration, ARDS treatments, ICU stay length, and 30-day and 90-day mortalities.
RESULTS
Among 141 included patients (84% military; median age, 30 years), 57 (42%) developed ARDS. Acute respiratory distress syndrome was mild in 13 (22%) patients, moderate in 24 (42%) patients, and severe in 20 (36%) patients. Evacuation occurred in less than 26 hours for 32 war casualties, 17 non-war-related trauma patients, and 8 medical patients. Among severe trauma patients, median Injury Severity Score was 34, and Abbreviated Injury Scale thorax was 3. Upon French ICU admission, median partial pressure of oxygen in arterial blood/inspirated fraction of oxygen ratio was 241 [144-296]. Administered ARDS treatments included intubation (98%, n = 56), protective ventilation (87%, n = 49), neuromuscular blockade (76%, n = 43), prone position (16%, n = 9), inhaled nitric oxide (10%, n = 6), almitrine (7%, n = 7), and extracorporeal life support (4%, n = 2). Median duration of invasive ventilation was 13 days, ICU stay was 18 days, 30-day mortality was 14%, and 90-day mortality was 21%.
CONCLUSION
Acute respiratory distress syndrome was frequent and severe among French patients evacuated from war theaters. Improved treatment capacities are needed in the forward environment-for example, a specialized US team can provide extracorporeal life support for highly hypoxemic war casualties.
LEVEL OF EVIDENCE
Prognostic and epidemiological study, level III.
Topics: Adult; Blood Gas Analysis; Extracorporeal Membrane Oxygenation; Female; France; Humans; Incidence; Injury Severity Score; Intensive Care Units; Length of Stay; Male; Military Personnel; Patient Acuity; Respiratory Distress Syndrome; Retrospective Studies; War-Related Injuries
PubMed: 32102034
DOI: 10.1097/TA.0000000000002633 -
Anaesthesia, Critical Care & Pain... Aug 2020
Topics: Aged; Almitrine; Betacoronavirus; COVID-19; Case-Control Studies; Coronavirus Infections; Female; Humans; Hypoxia; Injections, Intravenous; Male; Middle Aged; Oxygen; Pandemics; Partial Pressure; Patient Positioning; Pneumonia, Viral; Prone Position; Respiratory Distress Syndrome; Respiratory System Agents; SARS-CoV-2
PubMed: 32505756
DOI: 10.1016/j.accpm.2020.05.013 -
Anaesthesia, Critical Care & Pain... Jun 2020
Topics: Almitrine; Betacoronavirus; COVID-19; Capillary Leak Syndrome; Coronavirus Infections; Humans; Hypoxia; Lung; Lung Compliance; Pandemics; Patient Positioning; Pneumonia, Viral; Positive-Pressure Respiration; Pulmonary Circulation; Pulmonary Edema; Respiratory Mechanics; SARS-CoV-2; Switzerland; Tomography, X-Ray Computed; Vasoconstriction; Vasoconstrictor Agents
PubMed: 32305591
DOI: 10.1016/j.accpm.2020.04.003 -
Anesthesia and Analgesia Aug 2019This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal... (Observational Study)
Observational Study
This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.
Topics: Adult; Almitrine; Extracorporeal Membrane Oxygenation; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Recovery of Function; Respiration; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 29337729
DOI: 10.1213/ANE.0000000000002786 -
Saudi Journal of Anaesthesia 2021
PubMed: 33824652
DOI: 10.4103/sja.SJA_782_20 -
Chest Nov 2020
Topics: Aged; Almitrine; Betacoronavirus; Blood Gas Analysis; COVID-19; Coronavirus Infections; Extracorporeal Membrane Oxygenation; Female; Humans; Hypoxia; Male; Middle Aged; Oxygen; Oxygen Inhalation Therapy; Pandemics; Partial Pressure; Patient Positioning; Pneumonia, Viral; Positive-Pressure Respiration; Prone Position; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; SARS-CoV-2; Treatment Outcome
PubMed: 32512007
DOI: 10.1016/j.chest.2020.05.573