Treatment Dose Research Articles

Administration patterns of magnesium sulphate for women with preeclampsia and immediate newborn outcomes in Kawempe National Referral Hospital-Uganda: a cohort study.

Preeclampsia is the second leading cause of maternal death in Uganda. WHO recommends using magnesium sulphate (MgSO4) to prevent and treat preeclampsia with severe features (PEC) and eclampsia. MgSO4 is used to prevent eclampsia and treat women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. We set out to assess MgSO4 administration patterns in women with PEC or eclampsia and the immediate newborn outcomes of neonates. This was an analyticalobservational cohort study at Kawempe National Referral Hospital in Uganda. Two hundred ten pregnant mothers with PEC or eclampsia were recruited in the study after receiving the loading dose of MgSO4 and then followed through labour and delivery to observe MgSO4 administration patterns and immediate newborn outcomes using Apgar and Thompson scores. SPSS version 23 was used to analyse data, and both bivariate and multivariate logistic regressions were used to determine factors associated with the low Apgar score at five minutes. Overall, majority of the patients received more than one dose with 33.3% received a sixth dose of MgSO4. The majority, 84.8%, of the mothers delivered live babies, 31.0% babies had complications, and were admitted to the neonatal intensive care unit (NICU). NICU admissions were mostly due to respiratory distress21.4%, preterm delivery21.0%, and 5.5% died within seven days. Majority 93.3% of the newborns had an Apgar score of seven and above at five minutes, of the newborns who were Thompson scored, 70.4% scored between 1 to 10 which is mild HIE. Initiation of MgSO4 treatment within one hour from prescription (AOR = 0.49, CI: 0.01-1.94), 4-hourly timing of the first maintenance dose (AOR = 0.22, CI: 0.06-0.79) and having complete doses of MgSO4 treatment (AOR = 0.89, CI: 0.03-3.05) decreased the likelihood of having low Apgar scores at five minutes. Timely administration of the first maintenance dose of MgSO4 decreases the likelihood of low Apgar score at 5min and NICU admission in newborns, and most NICU admissions were due to respiratory distress and preterm delivery.

Long-term changes on behavioral addictions symptoms among adults with attention deficithyperactivity disorder treated withmethylphenidate.

Attention deficit hyperactivity disorder (ADHD) and behavioral addictions (BAs) are highly comorbid but little is known about the effect of anti-ADHD medications on behavioral addiction symptoms. Thus, the aim of this naturalistic prospective study was to investigate the long-term changeson BAs symptoms among methylphenidate-treated adults with a primary diagnosis of ADHD. 37 consecutive adult ADHD outpatients completed a baseline and follow-up assessment of ADHD, mood and BAs symptoms (internet, shopping, food, sex addictions and gambling disorder) after one year of methylphenidate (flexible dose) treatment. Internet addiction test scores pre-treatment were significantly higher than post-treatment scores (p < 0.001). The same trend was seenfor the shopping addiction (p = 0.022), food addiction scores (p = 0.039) and sex addiction scores (p = 0.047). Gambling disorder scores did not differ pre and post treatment since none of the included patients reported significant gambling symptoms at baseline. The rate of ADHD patients with at least one comorbid BA was reduced after methylphenidate treatment (51.4% vs 35.1%). The correlation analyses showed a moderate positive correlation between the changes in sluggish cognitive tempo symptoms, cognitive impulsivity, mood and anxiety symptoms and changes in internet addiction symptoms. This is the first study showing that after one-year of treatment with methylphenidate,adult ADHD patients show a significant reduction on internet, food, shopping and sex addiction symptoms. Further controlled studies with larger samples should replicate these preliminaryresults and elucidate the role of methylphenidate and other moderator factors (such as concomitant psychological treatments or lifestyle habits changes) on BAs improvements.

Risk of Infertility in Reproductive-Age Patients With Thyroid Cancer Receiving or Not Receiving 131I Treatment

Background Fertility is the crucial concern for many survivors of cancer diagnosed as children, adolescents, and young adults. The objective of this study was to determine the risk of infertility in reproductive-age patients with thyroid cancer receiving or not receiving radioiodine treatment in Taiwan. Methods This nationwide population-based cohort study was conducted using data obtained from the Taiwan National Health Insurance Database from 2009 to 2019. A total of 20,259 thyroid cancer patients aged from 15 to 50 years (8037 did not receive 131I treatment, and 12,222 received 131I treatment) and 20,259 controls were enrolled. A Cox proportional hazards model was applied to estimate the risk of infertility in thyroid cancer patients receiving or not receiving 131I treatment in terms of hazard ratios and 95% confidence intervals. Results The incidence rates of infertility in thyroid cancer receiving 131I therapy, those not receiving 131I therapy, and controls were 5.55, 5.07, and 3.61 per 1000 person-years, respectively. Compared with thyroid cancer patients treated with a cumulative 131I dose of 4.44 GBq or less, the risk of infertility was not significantly increased in those treated with a cumulative 131I dose of more than 4.44 GBq (adjusted hazard ratio, 1.13; 95% confidence interval, 0.95–1.36). Conclusion The greatest increased risk of infertility in reproductive-age patients with thyroid cancer is associated with the fact that the patient has thyroid cancer regardless of 131I administration. 131I treatment or cumulative dose of 131I greater than 4.44 GBq did not further increase the risk of infertility.

Abstract 4136116: Metformin Therapy for Reperfusion Injury Consolidates Cardioprotection in the High-Risk Elderly Heart

Introduction: Metformin (MET), a first-line diabetes therapy, exhibits cardioprotective effects during acute ischemia and reperfusion (I/R). Cardiac injury is enhanced in the aging heart in murine and humans. Acute, high dose MET treatment at the onset of reperfusion (R) markedly reduced infarct size (MI) in the high risk aged heart via modulation of mitochondrial complex I. However, the effect of subsequent chronic, standard dose MET to consolidate and possibly enhance cardioprotection and survival following I/R in the aged heart remains unknown. Hypothesis: Administration of chronic standard dose of MET will ameliorate mortality and morbidity following MI through rescuing an impaired adaptive metabolic remodeling. Methods: Aged (22-24 month) C57BL6/J mice were subjected to sham operations or 45 min of ischemia by LAD ligation followed by R. All mice received acute, high dose MET (2 mM, i.v.) at the onset of R followed by randomization to chronic MET (300 mg/kg/day) in drinking water versus vehicle (VEH) administered for 14 days. Cardiac function was determined by echocardiography weekly. IonOptix Myocyte Calcium and Contractility System measured the contractile functions and transient calcium signaling of isolated cardiomyocytes. Results: The Kaplan-Meier survival analysis showed that chronic MET treatment following acute treatment at the onset of R significantly reduced mortality compared to VEH group. Although chronic MET treatment did not further reduce MI size, echo and histology showed that chronic MET preserved diastolic function, prevented left ventricular hypertrophy and reduced collagen deposition following I/R in aging. Moreover, isolated cardiomyocytes from MET treated hearts showed improvements in contractile function, transit calcium signaling, and the coupling between contractility and calcium levels as compared to the cardiomyocytes from VEH group hearts. Immunoblotting results showed that Sens2/AMPK metabolic signaling was significantly upregulated by chronic MET post-MI, indicating the metabolic homeostasis modulated by MET is a critical factor involved in the beneficial effects of chronic MET on limiting I/R-induced myocardial damage that leads to deleterious remodeling in aging. Conclusions: The mortality and morbidity of MI in the high risk aged heart is attenuated with acute, high dose of MET treatment followed by chronic standard dose MET treatment to consolidate protection via rescuing the impaired adaptive metabolic response in aging.

Dynamic distribution of systemically administered antibiotics in orthopeadically relevant target tissues andsettings.

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English-published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady-state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target.

A phase 4, multicenter, global clinical study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib.

Pexidartinib is effective in patients with tenosynovial giant cell tumor (TGCT) for whom surgery is not feasible. Durability of response after discontinuation of pexidartinib and the safety and efficacy of restarting pexidartinib have not been previously recorded. This phase 4 study was designed to mimic the real-world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug. This was a global, multicenter, phase 4 study that enrolled patients with TGCT who were experiencing clinical benefit from pexidartinib in one of four prior phase 1 or phase 3 studies investigating pexidartinib in the disease. Patients could choose to continue pexidartinib at the same dose (the treatment-continuation cohort) or discontinue treatment with the option to restart pexidartinib (the treatment-free/retreatment cohort). Tumor progression determined by Response Evaluation Criteriain Solid Tumors (RECIST) version 1.1, patient-reported outcomes (the Patient-Reported Outcomes Measurement Information System-Physical Function [PROMIS-PF] questionnaire and the EuroQol 5-dimension, 5-level [EQ-5D-5L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment-free/retreatment cohort who remained treatment-free at month 12 and 24; this did not depend on disease progression. Thirty-two patients were enrolled: 21 chose to enter the treatment-continuation cohort, and 11 entered the treatment-free/retreatment cohort. During the treatment-free period, six of 11 (54.5%) patients in the treatment-free/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment-continuation cohort had disease progression. Over the 24-month study, three of 11 (27.3%) patients in the treatment-free/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (n=1 each). The probability of remaining treatment-free in the treatment-free/retreatment cohort was 73% (95% confidence interval, 37%-90%). In the treatment-free/retreatment cohort, the median progression-free survival of the treatment-free period was 22.8 months (95% confidence interval, 1.6 months to not estimable). By 6 months of retreatment, all retreated patients achieved new disease stabilization with no new safety concerns; two patients had clinically significant improvements in PROMIS-PF and EQ-5D-5L visual analog scale scores. The mean PROMIS-PF and EQ-5D-5L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort. In this small phase 4 study designed to evaluate outcomes in patients who stopped and restarted pexidartinib, 54.5% of patients who discontinued pexidartinib showed PD, with a median progression-free survival of 22.8 months. Each of the three patients who restarted pexidartinib stopped progressing, and some reported a new gain in physical function. No PD was detected in patients who remained on treatment, and the safety profile did not indicate long-term hepatotoxicity or any new safety concerns. Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended. This study examined what happens when patients stop taking pexidartinib (after it has helped them) to see whether it is safe and effective to restart if needed. Thirty-two patients were followed for 2 years: 21 chose to continue pexidartinib and did not experience disease progression, while 11 chose to stop pexidartinib; 54.5% of them had disease progression within 2 years. Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened. Restarting pexidartinib was safe and effective in these patients.

RADT-05. VASCULAR OVERLAP PROVIDES PROTECTION FROM GAMMA-KNIFE-INDUCED RADIATION NECROSIS IN A METASTATIC BRAIN TUMOR COHORT

Abstract INTRODUCTION Radiation necrosis (RN) is a long-term complication of Gamma-Knife (GK) Radiosurgery, an established treatment for metastatic brain tumors. Few dosimetric parameters have shown to predict RN, including tumor target volume, treatment dose, and V12 Gy (volume of normal brain receiving 12 Gy). Vascularity has yet to be explored as an independent predictor of RN. OBJECTIVE To evaluate the role of vascular overlap in GK-induced RN. METHODS All metastatic brain tumor patients treated with GK between 2014-2019 were retrospectively screened for post-treatment radiographic RN. Vascular overlap, defined by the MCA-ACA and MCA-PCA border regions, was determined by two blinded neurosurgeons and one radiation oncologist. Multivariate logistic regression analysis was performed to determine factors predictive of RN using variables determined significant by univariate analysis and clinical relevance. Covariates included V12 as a binary variable (≥8 vs. &amp;lt;8 cm3), vascular overlap, supratentorial location, and eloquent location. RESULTS 6% (20/321) of all metastatic brain tumor patients developed RN and were included for analysis, with the final cohort being 60% (12/20) female with a mean age of 59 years, comprising 77 lesions. V12 (≥8 cm3) showed a significant increase in risk of developing RN [OR = 8.18; (coef, 95% CI: 2.10 (0.49, 3.72), p=0.011)]. Conversely, vascular overlap showed a protective effect against RN [OR = 0.23 (-1.49 (-2.79, -0.19), p=0.024)], with a lower rate of RN in areas of vascular overlap (10%) than non-vascular overlap (26%). Neither supratentorial location [OR = 3.31 (1.20 (-0.76, 3.16), p=0.231)] nor location within eloquent brain [OR = 0.96 (-0.04 (-1.48, 1.39), p=0.95)] showed significance. CONCLUSION For the first time, we show that patients with metastatic brain lesions in anatomical regions of vascular overlap treated with GK are less likely to develop RN. Future work should validate these findings with the goal of optimizing radiation dosing to mitigate RN incidence and recurrence rates.

Cost minimization analysis of treatments for metastatic HER2-positive breast cancer in Peru: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injections.

The main objective of this study is to determine whether the employment of fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC; and Phesgo as brand name) to treat metastatic HER2-positive breast cancer patients would minimize costs compared to the traditional treatment of separate intravenous doses of pertuzumab and trastuzumab in Peru. To achieve this, we used EsSalud (the social security health insurance) data and assessed it through a mixed strategy, which consisted of a quantitative and a qualitative approach. The first one aimed to calculate the direct (non-drug consumables, drugs, and healthcare professionals) and indirect costs of both treatments to develop a comparison, whilst the second aimed to validate information and internalize the procedure in an EsSalud context. Overall, we found that the usage of PH FDC SC would be cost saving in EsSalud's context. Specifically, we found three main advantages. Firstly, PH FDC SC generates a savings of 62% in non-drug consumables, which helps alleviate the healthcare system budget constraint. Secondly, its adoption frees up 61 hours of treatment and observation time for a single patient per year, which in turn increases the attention capacity of the healthcare system in terms of nursing hours and chemotherapy couches. Thirdly, the reduction of clinic time supposes an advantage for the patient in the form of increased productivity and well-being. Hence, the adoption of this drug would improve the quality of life of patients while reducing costs and pressure on the healthcare system. This is aligned with the strategy of prioritizing the appropriate breast cancer treatment within the National Cancer Care Plan. In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment.

CTNI-11. A PHASE 1 OPEN-LABEL STUDY OF BRAF INHIBITOR ABM-1310 IN PATIENTS (PTS) WITH RECURRENT BRAF V600-MUTATED PRIMARY CNS TUMORS

Abstract BACKGROUND ABM-1310 is a blood-brain barrier penetrant BRAF inhibitor. Here we report interim results from our phase 1 study of ABM-1310. METHODS This is a dose-escalation plus expansions trial for adult pts with BRAF V600-mutated primary CNS tumors. In the dose-escalation, ABM-1310 is given at 150 or 200 mg twice a day (bid). In the expansion, ABM-1310 150 mg bid is administered. Study objectives include patient safety, maximum tolerated dose (MTD), preliminary efficacy and pharmacokinetics (PK). Clinical trial information: NCT05892653. RESULTS By May 6, 2024, 15 pts (7 male; median age 39 years old) have been treated. In the dose escalation: 4 pts received ABM-1310 150 mg bid, and another 7-pts received ABM-1310 200 mg bid. In the expansion, all 4 pts were given ABM-1310 at 150 mg bid. Among 14 efficacy evaluable pts, 3 had partial response (PR) (including one each of glioblastoma, WHO grade 2 and 3 pleomorphic xanthoastrocytoma) and 9 pts had stable disease as their best responses. Two pts have PR response for &amp;gt; 8 months and continue study treatment. All pts experienced treatment-related AEs. Common AEs were asymptomatic QT prolongation (n=11) and rash (n=10). Seven pts had grade 3 QT prolongation. There was no drug-related SAE. There was no ABM-1310 related dose limiting toxicity although a few pts had study treatment interruption or dose reduction. One patient discontinued prematurely due to asymptomatic Grade 3 QT prolongation. There were no drug-related deaths. The MTD for ABM-1310 was 200 mg bid, the recommended dose was 150 mg bid. In PK assessment, ABM-1310 drug exposure vs. dosage showed a linear proportional relationship. This trial is ongoing. CONCLUSIONS ABM-1310 was generally safe and tolerated. There were no new safety signals. Preliminary efficacy data demonstrate favorable anti-cancer activity in patients with recurrent BRAF V600-mutated primary CNS tumors.

CTNI-73. ASSESSMENT OF MOLECULAR ALTERATIONS IN NEWLY DIAGNOSED GBM MGMT-UNMETHYLATED PATIENTS TREATED WITH VAL-083

Abstract Glioblastoma (GBM) commonly features molecular alterations in the TERT, EGFR, PTEN, and TP53 genes, which contributes to uncontrolled cell growth, evasion of apoptosis, and enhanced tumor cell survival. VAL-083 is a bi-functional DNA-targeting agent which rapidly induces inter-strand DNA cross-links at N7 and O6-guanine inducing double-strand breaks causing cell death independently of MGMT DNA repair and DNA mismatch repair deficiency. VAL-083 was evaluated in an open-label, biomarker-driven, phase 2 trial in MGMT-unmethylated, bevacizumab-naïve GBM patients. The molecular profile of tumors from a newly diagnosed GBM patient subgroup who received VAL-083 alone after chemo-radiation with concurrent TMZ, was determined in order to correlate with clinical outcomes. Thirty-four (34/36, 94.4%) patients who received 30 mg/m2 VAL-083 (days 1-3 of 21-day cycle) had available next-generation sequencing data on their primary tissue. Patient median age was 54.8 years (5-95pth: 29.8-66.0), median KPS was 90 (5-95pth: 80-100) and 58.8% were males. The median number of cycles of VAL-083 was 7.5 (5-95pth: 1-12). There were 5 dose reductions due to toxicity. The median time to progression (PFS) and overall survival (OS) were 9.2 mo (95%CI: 7.6-10.2) and 16.5 mo (95%CI: 13.3-19.0), respectively. The mean number of molecular alterations was 3.9 (5-95pth 1-8). Six (17.6%) patients had gene fusions. The most common molecular alterations were TERT promoter (91.2%), EGFR amplification (amp) (52.9%), PTEN (50.0%), EGFR (20.6%), and TP53 (20.6%). Additional alterations (in ≥2 patients; 6%) included EGFR-EGFR (EGFRvIII), BRCA2, CDKN2A/B, CDK4/6 amp, MDM2/4 amp, NF1, NOTCH1, PIK3R1 and RB1. While TP53 mutations showed a trend as predictors for time to progression (P 0.027), this was not observed with OS. None of the molecular alterations were predictors of number of treatment cycles or dose reductions. No specific molecular alterations were identified that predicted either improved or poorer patient outcome, during treatment with VAL-083. Clinicaltrials.gov identifier: NCT02717962.

The influence of daily imaging and target margin reduction on secondary cancer risk in image-guided and adaptive proton therapy

Objective. Image-guided and adaptive proton therapy rely on daily CBCT or CT imaging, which increases radiation dose and radiation-induced cancer risk. Online adaptation however also reduces setup uncertainty, and the additional risk might be compensated by reducing the setup robustness margin. This work developed a framework to investigate how much this robustness margin should be reduced to offset the secondary cancer risk from additional imaging dose and applied it to proton therapy for head-and-neck cancer.Approach. For five patients with head-and-neck cancer, voxel-wise CT and CBCT imaging doses were estimated with Monte Carlo radiation transport simulations, calibrated with air and PMMA phantom measurements. The total dose of several image-guided and adaptive treatments protocols was calculated by summing the planning CT dose, daily and weekly CBCT or CT dose, and therapy dose, robustly optimized with setup margins between 0 and 4 mm. These were compared to a reference protocol with 4 mm setup margin without daily imaging. All plans further used 3% range robustness. Organ-wise excess absolute risk (EAR) of cancer was calculated with three models to determine at which setup margin the total EAR of image-guided and adaptive treatment protocols was equal to the total EAR of the reference.Results. The difference between the simulated and measured CT and CBCT doses was within 10%. Using the Monte Carlo models, we found that a 1 mm setup margin reduction was sufficient for most patients, treatment protocols, and cancer risk models to compensate the additional risk imposed by daily and weekly imaging. For some protocols, even a smaller reduction sufficed, depending on the imaging frequency and type. The risk reduction by reducing the margin was mainly due to reducing the risk for carcinomas in the brain and, for some patients, the oral cavity.Significance. Our framework allows to compare an increased imaging dose with the reduced treatment dose from margin reductions in terms of radiation-induced cancer risk. It is extendable to different treatment sites, modalities, and imaging protocols, in clinic-specific or even patient-specific assessments.

RADT-48. ANALYSIS OF PROTON RADIATION THERAPY INDUCED CONTRAST ENHANCEMENT: A SINGLE INSTITUTION, RETROSPECTIVE STUDY

Abstract Proton radiotherapy (PRT) has superior physical dose distribution with a lesser integral off target radiation dose exposure compared with standard photon radiotherapy resulting in reduced toxicity of uninvolved normal tissues. However, there may be toxicity in areas targeted for high dose treatment as a result of uncertainty about the relative radiobiologic effect (RBE) of proton radiotherapy compared with photon radiotherapy and the potential for localized high doses at the end of the proton beam range (Bragg peak). This may result in radiation-induced contrast enhancement (RICE) reflecting transient toxicity or permanent injury, particularly when associated with concurrent chemotherapy. We analyzed 150 consecutive adult patients, with a histopathologic diagnosis of CNS malignancy, who underwent only PRT at Johns Hopkins Hospital between 2019 – 2023 with least 1 year of follow-up imaging. RICE was defined as a new post-treatment contrast enhancement on MRI within the radiation field. The determination of disease progression or RICE was confirmed with additional follow-up MRI or pathology. RICE was identified in 14 cases (9.3%). The median age was 48 y (range 19 – 72 years), sex 50% female. Diagnosis was 5 astrocytoma, 3 meningioma, 2 glioblastoma, 1 medulloblastoma, 2 oligodendroglioma, 1 tectal glioma. 4/5 astrocytoma patients were grade 2, 2/3 meningioma was grade 1, 1/3 was grade 2, 2/2 oligodendroglioma was grade 2. The median time since completing PRT to development of RICE was 3.5 months. The median radiation dose was 52.20 Gye (range 23.40 - 60.06). Dexamethasone was used in 11 patients (78 %) and in bevacizumab was used 2. Chemotherapy with temozolomide 7 (50%), PCV 1, and none in 5. 12 (85%) patients were still alive. PRT can also be associated with radiation injury in the target, and more information is needed about the incidence, natural history, and associations with localized dosimetry.

Corticosteroid Effect in Acute Spinal Cord Injury in the Rural Area

Spinal cord injuries (SCI) are devastating traumatic events in the lives of patients, often resulting in severe and/or permanent neurologic disabilities. Nearly half a million people are living permanently disabled in the United States due to traumatic SCI and 12,000–15,000 patients per year incur new injuries. A 78-year-old male patient came to the emergency room with a history of falling from a height with a pelvic position below exposed to trees 30 hours before admission, found weakness in the lower limbs, unable to urinate since yesterday. On radiologic examination, a burst fracture was found in the collumna of the 1st lumbar vertebra. The patient could not be examined for MRI due to limitations and unavailability of equipment at the hospital. The patient was given high dose of Methylprednisolone treatment for 3 days and there was no motoric improvement in the patient. Acute spinal cord injury is a very dangerous disease because it can cause patients both psychological and non psychological disorders. In areas that are left behind and do not have very good facilities and medical personnel to carry out this treatment. There is no treatment option other than using corticosteroids. However, the effect of corticosteroids still needs to be further developed and researched.

Longer-term safety and efficacy of baricitinib for atopic dermatitis in pediatric patients 2 to

Background Baricitinib, an oral selective Janus kinase inhibitor, improved clinical signs and symptoms of moderate-to-severe atopic dermatitis (AD) at week 16 in the phase 3 pediatric study BREEZE-AD-PEDS. Objective To assess longer-term efficacy and safety of baricitinib in pediatric patients aged 2 to <18 years. Methods In BREEZE-AD-PEDS long-term extension, responders and partial responders (validated Investigator Global Assessment-Atopic Dermatitis [vIGA-AD®] 0/1/2) at Week 16 remained on double-blind treatment to which they were randomized (placebo, baricitinib [1-mg equivalent, 2-mg equivalent, or 4-mg equivalent); non-responders (vIGA-AD 3 or 4) at Week 16 transitioned to open-label baricitinib 4-mg equivalent. Safety was summarized for all randomized patients who received ≥1 dose of study treatment. Results In total 467 patients received baricitinib for 750.7 patient-years. Proportion of responders/partial responders (at Week 16) who achieved vIGA-AD 0/1 at Week 52 was greater for baricitinib 4-mg equivalent (56.8%) versus all other treatment groups (42.2%, 47.7%, and 39.7% for 2-mg equivalent, 1-mg equivalent, and placebo, respectively). Most treatment-emergent adverse events were mild/moderate in severity. No deaths, pulmonary emboli, deep vein thromboses or arterial thrombotic events, major adverse cardiovascular events, malignancies, tuberculosis events, or gastrointestinal perforations were reported. Conclusions Baricitinib demonstrated sustained long-term efficacy. No new safety signals were identified. Trial Registration ClinicalTrials.gov Identifier: NCT03952559

Developing Guidelines for Azolla microphylla Production as Compost for Sustainable Agriculture

Azolla is a substitute compost that has the potential to enhance nutrient cycling in agricultural systems for sustainable development. In this study, four experiments were conducted to compare the Department of Agriculture (DOA, Thailand) ‘s methodology for determining the suitable type and rate of animal manure and the optimal light intensity for the growth and yield of Azolla (Azolla microphylla). The results revealed that applying 100% pig manure gave the highest yield of Azolla compared to the other manures. However, there was no discernible (p &gt; 0.05) difference in yield across the various doses (20.16, 30.16, and 40.16 gN m−2) of pig manure treatments, for which the minimal pig manure dosage of 20.16 gN m−2 was chosen. For further experimentation in the optimal light intensity, the 40% shading gave the highest yield of Azolla compared to no shading or 20 and 60% shading (p ≤ 0.01). When compared with the DOA Thailand methodology (1.27 kg m−2 of cow manure and covered with a size 32 mesh net), the findings indicated that the modified method (20.16 gN m−2 of pig manure + 40% shading) gave a 16% greater Azolla yield than that under the DOA Thailand methodology. The current finding method can produce a monthly fresh biomass of A. microphylla of 40.7 t ha−1 year−1 with higher contents of total N (4.92%) and lower C:N ratio (≤10:1) that could release minerals relatively rapidly. Its use can be encouraged by farmers to produce their own ecofriendly biofertilizer or soil amendment for sustainable agriculture.

A comprehensive and systematic review on Curcumin as a promising candidate for the inhibition of melanoma growth: From pre-clinical evidence to molecular mechanisms of action

BackgroundMelanoma, a highly malignant skin tumor, can develop systemic metastases during the early stage. Several studies of melanoma animal models indicate that curcumin, a natural plant extract, inhibits melanoma growth through various mechanisms. To evaluate the relationships among different experimental conditions, curcumin itself, its derivatives, and special formulations, it is necessary to conduct a systematic review and meta-analysis. PurposeThis meta-analysis aims to evaluate the potential of Curcumin as a drug for inhibiting the growth of melanoma and to determine the optimal dosage range and treatment duration for Curcumin administration. MethodsA systematic search of studies published from inception to December 2023 was conducted across six databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP). Methodological quality was assessed using SYRCLE's RoB tool. Study heterogeneity was assessed using Cochran's Q test and I2 statistics. Publication bias risk was evaluated using a funnel plot. All analyses were performed using R (version 4.3.3). Additionally, three-dimensional effect analysis and machine learning techniques were utilized to determine the optimal dosage range and treatment duration for Curcumin administration. ResultsForty studies involving 989 animals were included. The results demonstrated that, relative to the control group, administration of Curcumin resulted in a significant reduction in tumor volume. [SMD=−3.44; 95 % CI (−4.25, −2.63); P<0.01; I2 = 79 %] and tumor weight [SMD=−1.93; 95 % CI (−2.41, −1.45); P<0.01; I2 = 75 %]. Additionally, Curcumin demonstrated a significant capacity to decrease the number of lung tumor nodules and microangiogenesis, as well as to extend survival time, in animal models. The results from three-dimensional effect analysis and machine learning emphasize that the optimal dosage range for Curcumin is 25–50 mg/kg, with an intervention duration of 10–20 days. ConclusionCurcumin can inhibit the growth of melanoma, and the dose-response relationship is not linear. However, further large-scale animal and clinical studies are required to confirm these conclusions.

Danicopan (Voydeya)

Canada’s Drug Agency (CDA-AMC) recommends that Voydeya be reimbursed by public drug plans as an add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have residual hemolytic anemia due to extravascular hemolysis (EVH) if certain conditions are met. Voydeya should only be covered to treat adult patients with a diagnosis of PNH, who have met the public drug plan reimbursement criteria for initiating complement 5 inhibitor (C5i) treatments (ravulizumab or eculizumab) before receiving C5i treatment, and who have been on a stable dose of C5i treatment for 6 months or more, in addition, patients should also have persistent anemia caused by EVH, and an absolute reticulocyte count of 120 × 109/L or greater. Voydeya should only be reimbursed if prescribed by a hematologist with experience managing PNH. The cost of Voydeya should be negotiated so that Voydeya plus a C5i as a regimen does not exceed the drug program cost of treatment with pegcetacoplan for the treatment of adult patients with PNH who have residual hemolytic anemia due to EVH.

Olaparib-associated toxicity in cancer patients: a systematic review and meta-analysis.

To investigate the characteristics of olaparib-associated adverse events (AEs) in cancer patients. Databases were searched for phase II and III randomized controlled trials (RCTs) involving olaparib treatment up to March 2024. A systematic assessment was performed. Twenty-seven RCTs involving 9542 patients were included. This meta-analysis indicates that olaparib could significantly increase the risk of developing any all-grade (RR, 1.08; 95% CI, 1.03-1.13; p = 0.001) and high-grade (RR, 1.45; 95% CI, 1.19-1.77; p = 0.0003) AEs in cancer patients. Olaparib could increase the risk of dose reduction (RR, 3.00; 95% CI, 1.59-5.70; p = 0.0007) and treatment discontinuation (RR, 2.00; 95% CI, 1.28-3.14; p = 0.002). Hematologic toxicities and gastrointestinal toxicities commonly occur in patients receiving olaparib. Anemia, nausea, and fatigue were the most frequent AEs, with olaparib increasing the risk of both all-grade and high-grade occurrences of these events. Patients with longer treatment durations tend to have a higher risk of anemia. Patients with urinary system tumors tend to have a higher risk of nausea, while those with breast cancer tend to have a higher risk of fatigue. Olaparib maintenance therapy may be associated with a higher risk of fatigue. Olaparib could increase other AEs such as diarrhea, vomiting, decreased appetite, dyspepsia, dysgeusia, dizziness, headache, back pain, urinary tract infection, dyspnea, and cough. Olaparib-containing therapy could increase the occurrence of specific AEs in patients with cancer. Clinicians should be aware of these risks and conduct regular monitoring.

The Effects of Proton and Photon Radiation Therapy on the Development of Pediatric Dermatitis

Although radiation therapy is the leading option for effective cancer treatment, a prevalent side effect associated with it is dermatitis. Despite some available literature on this topic, there remain many gaps that need to be addressed. The goal of this study is to determine the incidence of radiation-induced dermatitis (RID) among children receiving proton and photon therapies; a retrospective chart review, at a single institution, was conducted on oncology patients who underwent proton or photon therapy radiation between 2018 and 2023. Significant differences were found between the Radiation Therapy Oncology Group (RTOG) score and the total radiation dose (p = 0.04). The median total dose of radiation received by those with an RTOG score of l was 5040.0 mGy and increased to 7600 mGy for those with a score of 3. A significant association was found between those who received chemotherapy and dermatitis (p = 0.04). No significance was found between the incidence of dermatitis in photon and proton therapy (p = 1.00). The study showed that multiple factors, including total radiation dose and chemotherapy, can affect RID. These relationships can be used to determine the modality, dose, and additional treatment options best suited to treat cancer patients in the pediatric population.

The effect of resveratrol on the viability of rat bone marrow mesenchymal stem cells

Background and aimResveratrol is a plant polyphenol that has antioxidant properties. In this research, in order to better understand the role of resveratrol on bone, the effect of different doses of resveratrol on the viability, proliferation, differentiation and biochemical factors of rat bone marrow mesenchyme stem cells (MSCs) was investigated. MethodsTo evaluate the ability of proliferation and differentiation, the MSCs were cultured up to three passages and were placed in culture media without osteogenic stimulation. At first to investigation the proliferation ability, the viability was evaluated by MTT test and trypan blue staining with 7.5, 15 and 30 mg/L treatment doses after 12, 24 and 36 hours. Then, to investigation the differentiation ability, the effect of 7.5, 15, and 30 mg/L treatment doses was assessed on the viability, electrolyte levels, and the activity of LDH, AST, ALP and ALT enzymes in differentiated cells after 5, 10, 15, and 21 days. To investigation the differentiation ability, the effect of 7.5, 15, and 30 mg/L treatment doses was assessed on the viability, electrolyte levels, and the activity of Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) enzymes in differentiated cells after 5, 10, 15, and 21 days. The data were analyzed by ANOVA and Tukey's test, and p<0.05 was considered as a significant level. ResultsThe obtained results showed that in mesenchyme cells, the level of viability does not change in low dose of resveratrol, however increase in the time followed by decrease in the activity of metabolic enzymes (ALP, ALT and AST P<0.5) and subsequently viability (p<0.05), and this trend was reversed with increasing resveratrol concentration (significant differences among 5 days and others). ConclusionThe effect of resveratrol depends on the type of cell and the treatment conditions, so it was shown in this study that the sensitivity of mesenchymal cells is higher than that of osteoblast cells. In addition, high doses of resveratrol had a positive effect on bone differentiation, so high doses of resveratrol can have a beneficial role on the health of mesenchymal cells and their differentiation into osteoblasts.