Nephroprotective and diuretic effect of Alternanthera brasiliana (L.) Kuntze leaf extract; acute and sub-acute toxicity assessment.
Alternanthera brasiliana (L.) Kuntze of the family Amaranthaceae has been extensively used in traditional medicinal practices in Brazil and India for its reputed efficacy in promoting diuresis, as well as treating wounds, inflammation, postnatal symptoms, diarrhea, and cough. Its selection for this study was driven not only by its ethnomedicinal significance but also by its rich phytochemical composition, including bioactive compounds such as flavonoids, saponins, and alkaloids, which are known to exhibit nephroprotective and diuretic effects. Additionally, while many species from the Amaranthaceae family have demonstrated similar therapeutic properties, A. brasiliana remains underexplored in this context. Therefore, this research aimed to scientifically evaluate its potential nephroprotective and diuretic activities, providing a pharmacological basis for its traditional uses.
This experiment was designed to determine nephroprotective effect against cisplatin-induced kidney injury and diuretic effect of Alternanthera brasiliana (L.) in rats. This study also aimed to evaluate the toxicity of plant's extract by performing acute and sub-acute toxicity trials.
In current study, the nephroprotective effect of aqueous-ethanol extract of A. brasiliana was evaluated after induction of kidney injury with cisplatin. Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A diuretic activity was also performed by comparing results with control and standard (furosemide). Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A 14 day trial for acute toxicity assessment was performed at doses 2000 mg/kg and 3000 mg/kg, whereas a 28 day trial for sub-acute toxicity assessment was performed at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. The biological active ingredients were identified and determined using HPLC technique.
The aqueous-ethanol extract of A. brasiliana (ABAE) safeguarded the rats from toxic effects of cisplatin. This extract also enhanced urine output. The protective effect of ABAE increased with increasing dose and produced maximum nephroprotective effect and diuresis at a dose 300 mg/kg. The outcomes from acute toxicity trials suggested that LD50 lied beyond 3000 mg/kg, and no antagonizing effects occurred in sub-acute toxicity trials at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. ABAE posed no toxicities on kidney, liver, and heart tissues as evident from histopathological, hematological, and serum biochemical analysis. HPLC-DAD analysis of ABAE indicated the presence of betanin, kaempherol, gallic acid, p-coumaric acid and oxalic acid.
These results demonstrate an abundant supply of bioactive chemicals found in A. brasiliana (L.) extracts, which should be taken into account to improve renal functions with fewer negative effects.
Bilal MH
，Bibi I
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RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.
French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.
Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). Concerns have been raised regarding this article, the substance of which relate to the articles' adherence to Elsevier's publishing ethics policies and the appropriate conduct of research involving human participants, as well as concerns raised by three of the authors themselves regarding the article's methodology and conclusions. Elsevier's Research Integrity and Publishing Ethics Team, in collaboration with the journal's co-owner, the International Society of Antimicrobial Chemotherapy (ISAC), and with guidance from an impartial field expert acting in the role of an independent Publishing Ethics Advisor, Dr. Jim Gray, Consultant Microbiologist at the Birmingham Children's and Women's Hospitals, U.K., conducted an investigation and determined that the below points constituted cause for retraction: • The journal has been unable to confirm whether any of the patients for this study were accrued before ethical approval had been obtained. The ethical approval dates for this article are stated as being 5th and 6th of March 2020 (ANSM and CPP respectively), while the article states that recruitment began in “early March”. The 17th author, Prof. Philippe Brouqui, has confirmed that the start date for patient accrual was 6th March 2020. The journal has not been able to establish whether all patients could have entered into the study in time for the data to have been analysed and included in the manuscript prior to its submission on the 20th March 2020, nor whether all patients were enrolled in the study upon admission as opposed to having been hospitalised for some time before starting the treatment described in the article. Additionally, the journal has not been able to establish whether there was equipoise between the study patients and the control patients. • The journal has not been able to establish whether the subjects in this study should have provided informed consent to receive azithromycin as part of the study. The journal has concluded that that there is reasonable cause to conclude that azithromycin was not considered standard care at the time of the study. The 17th author, Prof. Philippe Brouqui has attested that azithromycin treatment was not, at the time of the study, an experimental treatment but a possible treatment for, or preventative measure against, bacterial superinfections of viral pneumonia as described in section 2.4 of the article, and as such the treatment should be categorised as standard care that would not require informed consent. This does not fully address the journal's concerns around the use of azithromycin in the study. In section 3.1 of the article, it is stated that six patients received azithromycin to prevent (rather than treat) bacterial superinfection. All of these were amongst the patients who also received hydroxychloroquine (HCQ). None of the control patients are reported to have received azithromycin. This would indicate that only patients in the HCQ arm received azithromycin, all of whom were in one center. The recommendations for use of macrolides in France at the time the study was conducted indicate that azithromycin would not have been a logical agent to use as first-line prophylaxis against pneumonia due to the frequency of macrolide resistance amongst bacteria such as pneumococci. These two points suggest that azithromycin would not have been standard practice across southern France at the time the study was conducted and would have required informed consent. • Three of the authors of this article, Dr. Johan Courjon, Prof. Valérie Giordanengo, and Dr. Stéphane Honoré have contacted the journal to assert their opinion that they have concerns regarding the presentation and interpretation of results in this article and have stated they no longer wish to see their names associated with the article. • Author Prof. Valérie Giordanengo informed the journal that while the PCR tests administered in Nice were interpreted according to the recommendations of the national reference center, it is believed that those carried out in Marseille were not conducted using the same technique or not interpreted according to the same recommendations, which in her opinion would have resulted in a bias in the analysis of the data. This raises concerns as to whether the study was partially conducted counter to national guidelines at that time. The 17th author, Prof. Philippe Brouqui has attested that the PCR methodology was explained in reference 17 of the article. However, the article referred to by reference 17 describes several diagnostic approaches that were used (one PCR targeting the envelope protein only; another targeting the spike protein; and three commercially produced systems by QuantiNova, Biofire, and FTD). This reference does not clarify how the results were interpreted. It has also been noted during investigation of these concerns that only 76% (19/25) of patients were viral culture positive, resulting in uncertainty in the interpretation of PCR reports as has been raised by Prof. Giordanengo. As part of the investigation, the corresponding author was contacted and asked to provide an explanation for the above concerns. No response has been received within the deadline provided by the journal. Responses were received by the 3rd and 17th authors, Prof. Philippe Parola and Prof. Philippe Brouqui, respectively, and were reviewed as part of the investigation. These two authors, in addition to 1st author Dr. Philippe Gautret, 13th author Prof. Philippe Colson, and 15th author Prof. Bernard La Scola, disagreed with the retraction and dispute the grounds for it. Having followed due process and concluded the aforementioned investigation and based on the recommendation of Dr. Jim Gray acting in his capacity as independent Publishing Ethics Advisor, the co-owners of the journal (Elsevier and ISAC) have therefore taken the decision to retract the article.
Gautret P
，Lagier JC
，Parola P
，Hoang VT
，Meddeb L
，Mailhe M
，Doudier B
，Courjon J
，Giordanengo V
，Vieira VE
，Tissot Dupont H
，Honoré S
，Colson P
，Chabrière E
，La Scola B
，Rolain JM
，Brouqui P
，Raoult D
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Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.
The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction.
We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data.
A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m 2 [IQR 20 to 25 kg/m 2 ] versus 22 kg/m 2 [IQR 20 to 25 kg/m 2 ]), higher platelet count (240 × 10 3 /µL [IQR 173 to 327 × 10 3 /µL] versus 227 × 10 3 /µL [IQR 165 to 302 × 10 3 /µL], higher lymphocyte count (15 × 10 3 /µL [IQR 9 to 21× 10 3 /µL] versus 14 × 10 3 /µL [IQR 8 to 21 × 10 3 /µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times.
Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application ( https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/ ) that allows the use of SORG-MLA with up to three missing items.
The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made.
The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.
Huang CC
，Peng KP
，Hsieh HC
，Groot OQ
，Yen HK
，Tsai CC
，Karhade AV
，Lin YP
，Kao YT
，Yang JJ
，Dai SH
，Huang CC
，Chen CW
，Yen MH
，Xiao FR
，Lin WH
，Verlaan JJ
，Schwab JH
，Hsu FM
，Wong T
，Yang RS
，Yang SH
，Hu MH
... -
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ResearchGate
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钛学术
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