Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio.

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 µM and 100 µM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Monitoring of the Surfactants in Surface Waters in Slovakia and the Possible Impact of COVID-19 Pandemic on Their Presence

In order to keep the home and occupational environment clean and non-infectious, the consumption of cleaners and disinfectants, including cosmetics, is increasing. Excessive use of these products results in their accumulation in the aquatic environment. Conventional wastewater treatment plants are unable to effectively remove the emergent pollutants, including personal care products. This article is focused on the monitoring of the presence of personal care products in surface waters in two river basins in the Slovak Republic, in terms of the surfactant content. Ecotoxicological evaluation of the selected samples from the monitored river basins was performed by an acute toxicity test using the test organism Daphnia magna. The monitoring results indicate the presence of personal care products in the aquatic environment which poses an ecological and environmental risk. Monitoring in the Hron and Nitra river basins confirmed contamination with the surfactants, to which the measures related to the COVID-19 pandemic contributed. The content of the surfactants in personal care products is significant, and their impact on the aquatic environment is not sufficiently monitored.

A review on quality control, toxicity and clinical application of Amomum tsao-ko Crevost & Lemarie

The dried fruit of Amomum tsao-ko Crevost & Lemarie, a perennial herb of Cardamom in Zingiberaceae, has been widely used in food and as a folk medicine. It is used not only as an important food additive and spice for removing peculiar smell and improving taste, but also as a traditional Chinese medicine with significant efficacy in treating many kinds of disorders. Based on the high edible and medicinal value, large amounts of investigation have been reported for A. tsaoko in the past several years. This review specifically summarises its quality control, toxicology and clinical application, about which no literature had systematically reviewed, based on our best acknowledge. The current quality control of A. tsaoko is based on the content of volatile oil, which should be no less than 1.4% according to the Pharmacopoeia of the People's Republic of China (2020 edition), while a more possible Q-Markers should be developed to focus on either a specific bioactive ingredient or a component correlated with a certain clinical efficacy. Toxicity research suggests that A. tsaoko actually belongs to the non-toxic substance, although citral and 1,8-cineole, two main components of A. tsaoko, is hepatotoxic for the former and displays low acute toxicity and sub-chronic oral toxicity for the latter, but no obviously accumulative toxicity has so far been discovered for A. tsaoko. In clinical practice, A. tsaoko is often used in treatment of dampness/cold resistance, malaria, vomiting, fullness and epigastric distension across additional disorders, such as SARS, COVID-19 and hepatitis.Copyright © 2022 The Author(s)

Sub-Acute Toxicity Study of Pegagan Embun (Hydrocotyle Sibthorpioides Lam.) Extract on the Sgpt and Sgot Level of Wistar White Male Rats

Objective: Pegagan embun (Hydrocotyle sibthorpioides Lam.) is one of the herbs used in ethnomedicines as an immunostimulant during the COVID-19 pandemic. This present study aims to discover the potential toxicity effect of pegagan embun extract through sub-acute administration on the SGPT and SGOT levels of Wistar white male rats. Method(s): Thirty-six test animals were divided into four groups: the control group was given Na CMC 0.5%, and the treatment groups were treated with ethanol extract of pegagan embun at doses of 7, 35, and 150 mg/kgBW. All groups were treated orally for 7, 14, and 21 d once daily. On the 8th, 15th, and 22nd day, the SGPT and SGOT of the test animal level were measured. The data were analyzed by two-way ANOVA followed by Duncan's multiple range test (p<0.05). Result(s): The study revealed that administration of pegagan embun extract did not cause any harmful effect on the liver but significantly decreased the level of SGPT and SGOT influenced by the variety of doses and duration of administration (p<0.05). Significant reductions in SGPT and SGOT levels are seen after extract administration at dosages of 7 mg/kgBW for 21 d. Conclusion(s): This study showed that pegagan embun (Hydrocotyle sibthorpioides Lam.) extract sub-acute administration at doses of 7, 35, and 150 mg/kgBW is relatively non-toxic and safe to be used as an immunostimulant. There was no sign of damage showed in the liver of treated rats based on the levels of SGOT and SGPT.Copyright © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

The Impact of COVID-19 on Intoxication Pattern by Drugs of Abuse in Egypt

Background: Drug abuse is considered a global and growing problem worldwide. Emergency medical care is required for acute intoxication, which adds to the threat of COVID-19. This study aims to evaluate the effect of the COVID-19 pandemic on the pattern of acute toxicity in drug abuse patients admitted to National Environmental and Clinical Toxicology and Research Center (NECTR), Cairo University. Method(s): This comparative study included 978 cases admitted to NECTR during 12 months before the COVID-19 pandemic (2018-2019) and 12 months during the pandemic (2020-2021). Result(s): The number of cases during the pandemic was lower than before;adults and men predominate in both periods. During the pandemic, cannabis, heroin, opium, and alcohol showed a mild increase, while the new synthetic drugs, tramadol, and pregabalin, showed a mild decrease. A significant increase in discharges and a decrease in intensive care unit (ICU) admissions were observed during the pandemic. Besides, more oxygen (O2) therapy was required, and more cases died on mechanical ventilation. The worst outcome was associated with old age, male gender, heroin and opium toxicity, and the highest score of poisoning severity. Conclusion(s): The COVID-19 pandemic had a definite reforming effect on the pattern of intoxication by drugs of abuse in NECTR, Egypt.Copyright © 2023 Authors. All rights reserved.

Ultrahypofractionated breast radiotherapy during SARS-CoV-2 virus pandemic, beyond fast-forward trial: a local experience

Background: During the SARS-CoV-2 virus pandemic, University Hospital Birmingham NHS Trust Oncology Department incorporated the ultrahypofractionated regime of 26Gy/5 fractions alongside the moderate hypofractionated regime of 40Gy/15 fractions as part of local adjuvant breast radiotherapy treatment (RT) for eligible patients. We conducted a local study to assess the real-life experience of patients undergoing ultrahypofractionated schedule to compare feasibility and toxicity to the fast-forward trial during the COVID - 19 pandemic. Methods: A single institution, retrospective, qualitative study. Patients included had early-stage breast cancer and received adjuvant radiotherapy between 23 March 2020 and 31 May 2020, a total of 211 patients. Inclusion was irrespective of any other neoadjuvant/adjuvant treatments. Data were collected retrospectively for treatment dose, boost dose and toxicity. Results: Of the total 211 patients, 85 were treated with 26Gy in 5# and 19 patients received a boost as per the fast-forward protocol. Of these 85 patients, 15.9% did not report any skin toxicity post-treatment. 63.5% of patients reported RTOG Grade 1, 15.9% had RTOG Grade 2, and 1.6% reported RTOG Grade 3 skin toxicity. 3.2% of the patients could not be contacted for follow-up. Of the 19 patients who received a breast boost, 10.53% reported no skin changes. 78.9% reported Grade 1 skin toxicity. Both Grades 2a and 2b skin toxicity were reported by 5.26% each. The patient demographics and tumour characteristics in our study cohort were comparable to those within the fast-forward trial. In terms of post-RT skin toxicity, fewer patients reported any toxicity in the UHB patient cohort versus those in the trial, and the number of Grade 2/3 toxicities reported was also low. A delay in toxicity reporting from 2 weeks for 40Gy/15 to 3 weeks for 26Gy/5 was observed. Conclusion: Our study concluded that offering ultrahypofractionation was convenient for patients;reducing the number of hospital visits during the SARS-CoV-2 virus pandemic appeared safe in terms of acute post-RT-related skin toxicity. The reduced hospital visits limited exposure of patients and staff to the SARS-CoV-2 virus while also ensuring efficient use of Radiotherapy Department resources. Local follow-up protocols have been amended to ensure review at 3 weeks for the 26Gy/5 schedule to acknowledge the delay in acute toxicity development. To date, there is only 5-year toxicity and relapse data available from the fast-forward trial;therefore, hypofractionation schedules should be offered to patients as long as they fulfil the criteria and understand the limitations of the study as well as accelerated peer review processes in the face of the pandemic. © 2022 The Author(s).

Implementation of 26 Gy in five fractions over 1 week adjuvant radiotherapy for breast cancer: Prospective report of acute skin toxicity and consideration of resource implications.

PURPOSE: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. MATERIALS AND METHODS: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar-Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. RESULTS: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. CONCLUSION: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

Reduced Duration Intracavitary Brachytherapy in Cervix Malignancies: A Comparative Analysis from Single Institute

Purpose: The on-going pandemic has impacted the use of anesthesia and the operating room frequency thereby affecting the brachytherapy treatment in various institutions due to the COVID-19 protocols. This has led to single applications of Intracavitary brachytherapy (ICRT) being used to deliver entire treatment boost in cervix cancer. We present our dosimetric and early clinical outcomes comparing traditional weekly three-fractions ICRT with single application/ two-applications ICRT Material(s) and Method(s): In this retrospective analysis conducted in our department, a total of 39 cases, treated between January 2021 to January 2022 were evaluated for the study. Of these, 15 cases were treated with the traditional once a week applicator insertion for 3 fractions and 24 cases underwent lesser application - 20 cases underwent 2 insertions and 4 cases single insertion (all receiving total 3 fractions of 7Gy each). The dosimetric parameters were compared including CTV D90 and D95 along with rectum, sigmoid and bladder D2cc, 1cc and 0.1cc respectively. The acute toxicity assessment was done using the RTOG scale. The follow-up was undertaken as per the institutional protocol and Mann-Whitney U-test were applied to compare the cohorts. Result(s): With a median follow-up of 6 months, the median CTV was D90%: 81.2 vs. 80.9 Gy and the median CTV volume was 44.3 vs 42.9 cc respectively. The 0.1 cm3 and 2 cm3 to bladder, rectum, and sigmoid were 105.6 vs 104.2 Gy and 85.5 vs 85.9Gy, 89.4Gy vs 88.7Gy and 69.1 vs 67.8Gy, and 84.7 vs 84.1Gy and 71.7 vs 69.9Gy, respectively suggesting no significant difference in the dosimetric outcomes with the two forms of applications. The less than three applications had a shorter overall treatment time with median OTT of 43 days vs. 55 days (p = 0.02). On completion of treatment and 6 months follow-up, local control was achieved in all patients. There was no significant difference in the acute toxicities in terms of cystitis and proctitis in both forms of the application. Conclusion(s): The single application/ twice application ICRT procedure showed similar outcomes as the traditional three-week duration treatment in terms of dosimetric outcomes and acute toxicities and ultimately leading to shortened overall treatment time. It also helped reduce the anesthesia burden and various resources associated with the procedure. Copyright © 2022

Hypofractionated radiotherapy for pancreatic cancer

Category: Outcomes of treatment (including chemotherapy, chemo-RT and RT) Purpose: Hypofractionated (5#) radiotherapy for non-metastatic pancreatic cancer was introduced during the COVID-19 pandemic as an alternative to conventional treatment pathways. This study was performed to evaluate clinical outcomes and acute toxicity of 5# radiotherapy. Methods and materials: We retrospectively identified pancreatic cancer patients treated with 5# radiotherapy at Addenbrookes Hospital from March 2020 to September 2021. Patient characteristics, response on follow-up computed tomography (CT) scans, dosimetry and toxicity data were analysed using Excel and SPSS. Result(s): 40 patients were treated with 5# radiotherapy, 60% (n=24) had locally advanced pancreatic cancer, 30% (n=12) operable disease, 7.5% (n=3) postoperative recurrences and 2.5% (n=1) borderline resectable disease. 45% of patients (n=19) had induction chemotherapy. Radiotherapy was delivered as 35 Gy (67.5%, n= 27) and 30 Gy (32.5%, n=13) in 5# in 1.5 weeks using volumetric-modulated arc therapy (VMAT) technique. Median overall survival (mOS) for all patients was 14.2 months (95% CI 10.3-15.6 months). For induction chemotherapy + radiotherapy versus radiotherapy alone, mOS was 14.2 months (95% CI 8.2-17.7 months) versus 13.9 months (95% CI 10.3-15.7 months), p=0.97. Median progression-free survival (mPFS) for all patients was 10.2 months (95% CI 8.0-11.9 months). For induction chemotherapy + radiotherapy versus radiotherapy alone, mPFS was 10.5 months (95% CI 9.5-12.4 months) versus 10.1 months (95% CI 5.5-10.4 months), p=0.99. There were no grade 3 acute toxicities. When compared to 28# radiotherapy, the 5# regimen reduced patient hospital visits by 82%. Conclusion(s): The observed mOS is comparable with mOS of conventional 28# radiotherapy (14.2 versus 15.2 months (SCALOP trial)), 5# radiotherapy for non-metastatic pancreatic cancer is a safe alternative treatment pathway. Copyright © 2022

Antioxidant, Dermal and Acute Toxicological Effects of Eucalyptus camaldulensis (Dehn-Blakely) Essential Oil on Male Wistar Rats

During the era of the COVID-19 lockdown, many Nigerians resorted to home remedies like herbal mixtures for therapy because they could not have access to orthodox medicine. Eucalyptus camaldulensis (E. camaldulensis) essential oil was one of such remedies as many believed it had the potential to treat colds, flu, sore throats, bronchitis and even prevent SARS-CoV-2 infection. The objective of the study is to check the antioxidant, dermal and acute toxicological effects of the E. camaldulensis essential oil. Rats were grouped into 8 of 5 each. Normal and corn oil (2ml/kg body weight) control groups. E. camaldulensis essential oil from Jos, Niger, Nasarawa, Kogi, Kwara, and Benue zones were given at 2ml/kg body weight for 14 days as well as applied on the shaved skin of the rats. No mortality was recorded in the sub-acute toxicity study at low and high doses (10mg/kg and 5000mg/kg). The levels of AST, ALT, TNF-alpha and IL-6 did not significantly differ from normal control rats. Lungs Investigation recorded a significant increase in the TNF-alpha. Antioxidant enzyme assays showed a significant increase in catalase, superoxide dismutase and glutathione-s-transferase. Histological examination showed focal inflammation with moderate cytoplasmic clearing in the liver and focal mild epidermal sclerosis of the skin. Dermal application of the oil shows no significant toxic effect except some mild inflammation (skin irritation). Oral administrations were relatively safe with mild adverse effect observed in the lung inflammatory markers. Copyright © 2007 The authors.

Screening and Identification of candidate therapeutic drugs from plants for the management of patients infected Bacterial Infection Associated with SARS COV-2

The emergence of COVID-19 (SARS-COV-2) has resulted in millions of deaths worldwide. Nigeria has recorded over 2000 deaths due to the disease. Development of alternative medicine from plants against SARS-COV-2 can be a potential therapy for treatment of secondary complications. To investigate plants with potential to manage respiratory tract infections. The plants were extracted and screened for phytochemical constituents;their acute and subacute toxicity profile was evaluated. The plant extracts were tested against clinical microbial isolates associated with respiratory tract infection. All the plants extract were found to have acute toxicity dose above 5000 mg per kg body weight. Among the four tested medicinal plants Guiera senegalensis was found to have significant zone of inhibition against Klebsiella pneumonia and Moraxella catarrhalis more than the standard drug (Gentamicin). Guiera senegalensis has been used in traditional medicine to treat bacterial infections without any report of toxicity. The preclinical study indicated that Guiera senegalensis can be used in the management of respiratory infections associated with symptoms of COVID 19. Guiera senegalensis can therefore be used as a potential medicinal plant for management of secondary bacterial infections in Covid19 patients. Copyright © 2007 The authors.

Ultrahypofractionated breast radiotherapy during SARS-CoV-2 virus pandemic, beyond fast-forward trial: a local experience

Background:During the SARS-CoV-2 virus pandemic, University Hospital Birmingham NHS Trust Oncology Department incorporated the ultrahypofractionated regime of 26Gy/5 fractions alongside the moderate hypofractionated regime of 40Gy/15 fractions as part of local adjuvant breast radiotherapy treatment (RT) for eligible patients. We conducted a local study to assess the real-life experience of patients undergoing ultrahypofractionated schedule to compare feasibility and toxicity to the fast-forward trial during the COVID − 19 pandemic.Methods:A single institution, retrospective, qualitative study. Patients included had early-stage breast cancer and received adjuvant radiotherapy between 23 March 2020 and 31 May 2020, a total of 211 patients. Inclusion was irrespective of any other neoadjuvant/adjuvant treatments. Data were collected retrospectively for treatment dose, boost dose and toxicity.Results:Of the total 211 patients, 85 were treated with 26Gy in 5# and 19 patients received a boost as per the fast-forward protocol. Of these 85 patients, 15·9% did not report any skin toxicity post-treatment. 63·5% of patients reported RTOG Grade 1, 15·9% had RTOG Grade 2, and 1·6% reported RTOG Grade 3 skin toxicity. 3·2% of the patients could not be contacted for follow-up. Of the 19 patients who received a breast boost, 10·53% reported no skin changes. 78·9% reported Grade 1 skin toxicity. Both Grades 2a and 2b skin toxicity were reported by 5·26% each. The patient demographics and tumour characteristics in our study cohort were comparable to those within the fast-forward trial. In terms of post-RT skin toxicity, fewer patients reported any toxicity in the UHB patient cohort versus those in the trial, and the number of Grade 2/3 toxicities reported was also low. A delay in toxicity reporting from 2 weeks for 40Gy/15 to 3 weeks for 26Gy/5 was observed.Conclusion:Our study concluded that offering ultrahypofractionation was convenient for patients;reducing the number of hospital visits during the SARS-CoV-2 virus pandemic appeared safe in terms of acute post-RT-related skin toxicity. The reduced hospital visits limited exposure of patients and staff to the SARS-CoV-2 virus while also ensuring efficient use of Radiotherapy Department resources. Local follow-up protocols have been amended to ensure review at 3 weeks for the 26Gy/5 schedule to acknowledge the delay in acute toxicity development. To date, there is only 5-year toxicity and relapse data available from the fast-forward trial;therefore, hypofractionation schedules should be offered to patients as long as they fulfil the criteria and understand the limitations of the study as well as accelerated peer review processes in the face of the pandemic.

Comparison between Two Hypofractionated Treatment Schedules in Prostate Cancer: Preliminary Results on Acute Toxicity

Aim: This study compares the efficacy and toxicity of the hypofractionated schedule (70 Gy) used at our center to the hypofractionated schedule of the conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer protocol (CHHiP) (60 Gy), with the aim of reducing the waiting list and the number of accesses of patients, in the COVID-19 era. Patients and Methods: From June 2021 to December 2021, 20 consecutive patients were enrolled in 2 arms (mean age 65 years, range: 60-81, ECOG 0-1), affected by prostate cancer (cT1-cT3a, cN0, cM0 - GS <8, PSA level between 6 and 28 ng/ml), grouped according to National Comprehensive Cancer Network (NCCN) risk classes (2021) and consequently sent to short- or long-term androgen deprivation therapy (ADT). The different NCCN risk categories were equally represented in the 2 arms. Ten patients of 1st arm received a total dose of 70 Gy in 28 fractions and 10 patients of 2nd arm received a total dose of 60 Gy in 20 fractions. All patients were treated with Intensity-modulated radiotherapy-simultaneous boost integrated (IMRT-SIB) with 6 MV photons. During radiotherapy treatment, all patients were examined at least once a week. Acute genitourinary (GU) and gastrointestinal (GI) toxicity was assessed according to the CTCAE scale v.5.0 Median follow-up was 7 months (range: 6-9). Result(s): There was no significant difference in GU and GI toxicity between the two schedules. Acute GU and GI toxicity >grade 2 (G2) was not detected in either arm. In the 1st arm, 9/10 and 8/10 patients presented G0-1 GU and GI toxicities, respectively. In the 2nd arm, 8/10 patients had G0-1 GU toxicities and 8/10 had G0-1 GI. Only 1 patient (10%) of Group 1 had GU toxicity G1, at month 4 after the end of the treatment. Discussion and Conclusion(s): Acute toxicity was comparable between the two arms. These results encourage us to continue the study by enrolling more patients. Further data will be needed to evaluate late toxicities and equal treatment efficacy, to definitively adopt the CHHiP schedule..

Acute and Sub-Acute Toxicity Studies of the Siddha Preparation Mv Kashayamin Wistar Rats

The acute and sub-acute toxicity analysis of Siddha preparation MV kashayam was carried out with Wistar rats as per the guidelines 423 and 407of the Organization for Economic Co-operation and Development (OECD), respectively. In the acute toxicity study, a single dose of MV kashayam (1000 and 2000 mg/kg body weight) was administered orally to the rats and monitored for 14 days. In the sub-acute toxicity study, rats were orally administered with MV kashayam daily for 28 days at doses of 100 and 200 mg/kg body weight. In both the toxicity study, no rats have exhibited clinical signs of toxicity or mortality, and the doses were well tolerated by rats and no significant change in their mean body weight, food and water intake, haematological, biochemical parameters and his to pathological examinations as compared to that of control group rats. The findings suggest that MV kashayam has a wide margin of safety and a negligible amount of toxicity to ensure the safety and potency of the kashayam, which can be recommended to use as a novel prophylactic and therapeutic agent for COVID 19 based on the clinical study. All Copyright © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research.

ANTIVIRAL POTENTIAL OF DESMODIUM GANGETICUM (L.) DC. EXTRACT: DEVELOPMENT OF ANTIVIRAL PHYTOMEDICINE (GANJHUVIRR) FOR THE TREATMENT OF DENGUE FEVER ASSOCIATED WITH THROMBOCYTOPENIA

Natural products can be the alternative of synthetic medicine and antiviral drugs can be potential from natural products. An attempt was made to evaluate the antiviral activity from the extract of Desmodium gangeticum (L.) DC. as a phytomedicine (GanjhuVirR) for the treatment of dengue fever associated with thrombocytopenia. The present study was evaluated acute and subacute toxicity in rat as well as clinical trial in treated and without treated patients who admitted in hospital due to dengue fever associated with thrombocytopenia. The rats were grouped into group 1 (control) and 2, 3 and 4 (treated) for toxicity test while 51 patients were included in the clinical trial and 25 were treated and 26 provided only standard management as control. The parameters viz. platelet count, fever profile, average hospitalization period, clinical profiles and viral load reduction were tested for both the group. All the data related to morbidity, mortality and behavioural features were observed similar between exposed and control group. The haematological and biochemicals findings were comparable between the group. The platelet counts were significantly (P<0.001) increased and body temperature and hospital stay were significantly (P<0.001) decreased in the treated group than control group. Moreover, GanjhuVirR is a phytomedicine extracted from studied plant and capable to treat viral activity especially for Dengue virus. This is non-toxic as per animal study and is safe without any adverse events and normalize the clinical findings among patients. Future research is suggested to know the efficacy of mild to moderate Covid-19 Patients.

THE BIG IMPACT OF SMALL CHANGES IN NARROW THERAPEUTIC INDEX DRUGS

CASE: An 84-year-old woman with atrial fibrillation on Digoxin presented with acute onset of confusion associated with a week history of abdominal pain, vomiting, and poor fluid intake. A few days prior, Amiodarone was added to her drug regimen which included Lasix. Additionally, she received the COVID-19 booster vaccine which led to a viral-like syndrome resulting in dehydration. The patient was afebrile, normotensive, but bradycardic. EKG showed a prolonged PR interval and scooped ST segments. Labs showed hyperkalemia, pre-renal acute kidney injury (AKI), and a Digoxin level of 4.3 ng/mL (therapeutic range: 0.8-2.0 ng/mL). Digoxin and Lasix were held and Digoxin antidote, Digibind, was administered with normalizing heart rate, potassium, and clinical improvement. IMPACT/DISCUSSION: Digoxin is used to slow conduction in atrial fibrillation and increase cardiac contractility in heart failure. It inhibits the membrane sodium-potassium-adenosine triphosphatase pump (Na/K ATPase), resulting in increased cytosolic calcium and subsequent cardiac contractility and automaticity. In turn, this can also cause premature ventricular contractions and tachycardia. In the carotid sinus, increased baroreceptor firing and subsequent increased vagal tone occurs which can cause bradycardia, atrioventricular blocks, hypotension, and GI symptoms. In skeletal muscle, hyperkalemia can result due to the abundance of Na/K ATPase pumps. Digoxin has a narrow therapeutic index with serum levels easily affected by many commonly prescribed drugs by way of decreasing renal clearance, inhibiting P-glycoprotein, and inducing secondary electrolyte disturbances. That said, drug dosing should be individualized with close monitoring to avoid potentially life-threatening effects that may result with even mildly increased digoxin levels. Acute toxicity manifests as non-specific GI, and neurologic symptoms (confusion, lethargy, visual changes), hyperkalemia, and brady or tachy-arrhythmias. Treatment is with digoxin specific fragment antigen binding (Fab) antibody, Digibind, which binds digoxin, inactivating it within 6-8 hours. Postadministration, digoxin serum testing cannot distinguish free verse bound drug;therefore, drug levels remain elevated for days to weeks until the FabDigoxin complex is excreted. In the case above, the viral-like-syndrome after the booster vaccine with subsequent AKI secondary to dehydration likely precipitated Digoxin toxicity. Accompanying drug interactions of diuretics causing dehydration and hypokalemia, P-glycoprotein inhibitors (Amiodarone, Verapamil, Diltiazem, Quinidine), and ACE inhibitors can further worsen renal clearance and culminate in Digoxin toxicity. CONCLUSION: Given Digoxin's narrow therapeutic index, small clinical changes such as post COVID-19 vaccine flu-like symptoms, dehydration, and medication changes can manifest drug toxicity. Therefore, attentive monitoring of accompanying comorbidities and drug interactions is imperative at preventing catastrophic toxic effects.

Predictive toxicity markers in elderly patients underwent RT and managed by an oncogeriatric model

Purpose or Objective A growing number of elderly patients every year is treated with radiation therapy (RT), but little is known about side effects and outcome of irradiation in this potentially frail population. The identification of predictive factors of toxicity and frailty could offer a personalized treatment approach, thanks also to a multidisciplinary management of patients with increased risk of adverse outcomes. In this study we investigated the correlation of patient parameters with acute toxicities in elderly aged > 75 years treated with curative RT. Materials and Methods A prospective observational study was designed in our Center for patients with > 75years, candidate for curative RT. To these patients the radiation oncologist submitted the Geriatric 8 questionnaire (G8q) before and at the end of RT. Patients with G8 score < 14 were then evaluated by a multidimensional geriatric assessment, investigating cognitive (MMSE, GDS), functional (ADL, IADL, Tinetti) and nutritional (MNA short) domains, to define the frailty phenotype. In this setting, we retrospectively analyzed parameters like body mass index (BMI), number of comorbidities, total blood count, neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and basal G8 score, and correlated these parameters to acute toxicity. Results G8q was administered to 150 patients from December 2019 to April 2021. In this study we included 98 patients who started and completed RT in our Unit in this period. Of them, 38 (38.8%) had a baseline G8 score < 14 (range 4-14) and 23 agreed to underwent a multidimensional assessment, while 15 could not be evaluated due to COVID-19 dispositions or their refusal. Eleven patients resulted fit, while 12 patients were classified as vulnerable. Acute toxicity grade was < grade 2 in 67 patients (68.4%) (Table 1). We evaluated associations between BMI, number of comorbidities, total blood count, NLR, PLR, G8 score and acute toxicity (Table 2). Total blood count, NLR, PLR and G8 score resulted not significantly correlated to toxicity. Instead, a higher BMI was associated with worse acute toxicity (p=0.031): considering the 31 patients reporting toxicity > grade 2, 17 patients were over-weighted (54.8%), 1 patient was under-weighted (3.2%). Overall, the 63.3% of population (62 patients) was over-weighted, with a median BMI of 26.3. (Table Presented) (Table Presented) Conclusion Although G8q considers under-weight as a possible responsible of frailty, our study suggested that attention should be paid to over-weight too, due to its prevalence in elderly patients. Furthermore our results suggested that in elderly patients > 75years the BMI correlates with worse acute toxicity, according to literature data. The 38.8% of patients needed a multidimensional evaluation;this approach resulted useful in order to obtain compliance to the treatment without increased toxicity. The study is still ongoing and further analysis will be done.

Moderate hypofractionated radiotherapy after prostatectomy in the context of the COVID19

Purpose or Objective We designed a hypofractionated radiotherapy protocol for adjuvant or salvage treatment after radical prostatectomy. In this first report we present the implementation of this protocol in the context of a COVID-19 pandemic. Materials and Methods Patients meeting the inclusion criteria (high-risk features on histopathology or biochemical recurrence) received radiotherapy to the prostate bed 51 Gy in 17 fractions, elective treatment of the pelvis at a dose of 36 Gy in 12 fractions was permited. Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events versión 4.03. The disease-related quality of life, urinary, gastrointestinal, sexual and hormonal function were evaluated with the Expanded Prostate Cancer Index Composite (EPIC), QLQc30 and PR25 questionnaires at baseline before the start of radiotherapy and at one month after radiotherapy, then every six monts for two years. In addition, the incidence of COVID-19 cases was reported in the patients recruited in the trial and in those who underwent standard fractionation treatment (1.8-2.0 Gy per fraction), and in health personnel involved in the treatment of patients in study period. Results From August 2020 to March 2021, 22 patients have been registered. Fourteen patients have completed treatment and are included in this report. The median age was 64 years and most had a Gleason 3 + 4 (50%), with a pT3a (35.7%) and negative surgical margins (71.4%). Three patients (21.4%) were staged as pN1. Most patients were treated for salvage (57.1%), with an median PSA prior to the start of RT of 0,29 ng/ml. Most patients report minimal or low acute radiation effects in terms of GI and GU toxicity, with an acute toxicity grade 2 GI and GU of 50% and 14.3%, respectively. Without Grade 3 or higher GI / GU toxicity. Of the 14 patients who received the trial protocol, none had a clinical of COVID-19 infection, while one patient who received treatment with conventional fractionation development a COVID-19 infection. Conclusion We present the implementation of an protocol of hypofractionated schedule of postoperative prostate radiotherapy in an academic center in a developing country in the context of a COVID-19 pandemic. Preliminary results show the absence of COVID infection in the included patients, and low GU and GI toxicity.

Ultra-hypofractionated whole breast radiotherapy as adyuvant treatment for early breast cancer

Radiotherapy is an essential treatment in the local control of breast cancer. Standard treatment is currently carried out in 15 daily sessions. At present, following the results of the phase III Fast-Foward trial and in view of the situation triggered by COVID-19, the number of sessions has been reduced to 5. We present the data of our series to evaluate the results of the extreme hypofractionation scheme as a radiotherapy treatment for breast cancer at the Multihospital Clinical Unit of Radiation Oncology of Aragón (UCMORA). Materials and Methods After implantation, 115 patients were treated with 3D conformal radiotherapy between April 2020 and May 2021 at UCMORA using the extreme hypofractionation scheme (26 Gy at 5.2 Gy per fraction in 5 fractions). Demographic, tumor, dosimetric and toxicity characteristics were analyzed. Results The mean age was 63.5 years. 53 patients were treated at the Lozano Blesa Clinical Universitary Hospital and 62 at the Miguel Servet Universitary Hospital, in total 59 right and 56 left breasts. The predominant histology was infiltrating ductal carcinoma (84.3%), followed by infiltrating lobular carcinoma (10.4%), ductal carcinoma in situ (4.3%) and mucinous (0.9%). 51.7% were luminal A, 39.1% luminal B, 1.8% Her2 positive and 7.8% triple negative. In relation to staging, we found 4pTis, 8pT1a, 45pT1b, 58pT1c, 2Nx, 8N0, 1Nmi and 13N1a. Only 45% had acute toxicity at one month after the end of treatment, predominantly G1 radiodermatitis (86.6%), followed by G2 (11.2%) and G3 (2.2%). When analyzing the dose-volume histograms, values were obtained for ipsilateral lung V8 between 1.32 and 21.2%, for the heart, in case of left breast a median for V1.5 of 8.2% and 1.05% for V7;in case of right breast the median Dmed for the heart was 0.5Gy (Figure Presented) Conclusion Ultra-hypofractionated whole breast radiotherapy as a radiation treatment for breast cancer is well tolerated, reduces costs and number of sessions, while increasing comfort for patients.

Evaluation of Antiviral Effects and Toxicity of Herbal Medicine Vipdervir Capsules

Background: Antiviral vaccine is not effective, synthetic antiviral drugs are highly toxic, leading to increased interest in herbal medicines as promising antiviral drugs. Recently, Vipdervir has been developed from medicinal herbs with the aim to support and treat diseases caused by viruses such as H5N1 and SARSCoV- 2. In the present study, we assessed Vipdervir's antiviral activity against H5N1 and SARS-CoV-2. In addition, we also evaluated the acute toxicity and repeated dose toxicity of Vipdervir in mice and rabbits, respectively. Methods: H5N1 inhibitory effect of Vipdervir was assessed using hemagglutination inhibition assay. Vipdervir's SARS-CoV-2 inhibitory effect was evaluated by Plaque Reduction Neutralization assay. Acute and repeated dose oral toxicities of Vipdervir were determined according to OECD 423 and OECD 407 guidelines, respectively. Results: Data show that Vipdervir is effective against both H5N1 and SARSCoV- 2. At concentrations of 3 mg/mL and 5 mg/mL Vipdervir completely inhibits H5N1. At a concentration of 50 μg/mL Vipdervir showed an inhibitory effect on SARS-CoV-2. Acute toxicity data revealed that the LD50 of Vipdervir is greater than 35200 mg/kg, b.wt. in mice. Repeated toxicity data indicated that Vipdervir did not induce significant differences in body weight gain, hematology and clinical biochemistry in compared to the control group. The No Observed Adverse Effect Level of Vipdervir is greater than 613.8 mg/kg b.wt./day in rabbits. No delayed toxicity effects of Vipdervir were observed. Conclusion: Vipdervir capsules were found to be antiviral effective and relatively safe in the tested doses and experimental conditions.