Poisoning Research Articles

Acute toxicity of salicylic acid and its derivatives on the diatom Phaeodactylum tricornutum: Physico-Biochemical and transcriptomic insights

Salicylate pollutants (SAs) poses a serious threat to marine ecosystems as emerging contaminants. However, the toxic effects of SAs on marine phytoplankton, as well as the potential mechanisms and their ecological risks linked with them, are remain largely unknown. In this study, we aimed to evaluate the toxic effects of salicylic acid (SA) and its 5-substituted derivatives (5-sSA) on the marine diatom Phaeodactylum tricornutum, as well as the potential molecular mechanism involved in the toxicity. Physiological assays conducted on P. tricornutum revealed significant changes in photosynthetic pigments, chlorophyll fluorescence parameters, and antioxidant enzyme activities. The results showed that exposure of P. tricornutum to SAs caused a significant decline in chlorophyll contents and damage to the photosystem II (PSII) core resulting in the decline of photosynthesis. Although the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were enhanced, oxidative damage occurred. Transcriptome analysis showed that a large number of differentially expresses genes (DEGs) were significantly enriched in metabolic pathways such as porphyrin metabolism, terpenoid backbone biosynthesis, and carbon fixation in photosynthetic organisms after SA and 5-BrSA treatments. In addition, key genes in transcriptomic metabolic pathways were further analyzed and validated using weighted correlation network analysis (WGCNA) and real-time fluorescence quantitative PCR (qPCR). Considering the above results, SAs mainly inhibit the processes of photosynthesis by repressing the expression of genes involved in secondary metabolite synthesis and photosynthetic carbon sequestration pathways, thus exerting toxic effects on algal cells. The results of the study will provide key data for understanding the ecological risk and toxicity mechanisms of SA pollutants.

Cardiovascular effects and clinical outcomes in acute opioid toxicity: A case-control study from Port Said and Damietta Governorates Egypt

Substance abuse, particularly opioid intoxication, presents a significant public health challenge, leading to severe cardiovascular complications. This case-control study assessed the cardiac profile and clinical outcomes of 51 patients with confirmed acute opioid toxicity, compared to 51 control participants, in general hospitals across Port Said and Damietta governorates, Egypt. The study revealed that opioid-intoxicated patients exhibited significant cardiovascular abnormalities, including hypotension (39.2 %) and electrocardiogram (ECG) changes (72.5 %), with sinus bradycardia (51 %) being the most common. Additionally, echocardiographic abnormalities were found in 40 % of cases, with abnormal regional wall motion and valvular defects observed in several patients. Elevated levels of cardiac enzymes, such as Troponin-I and CK-MB, were significantly correlated with increased ICU stay length and higher mortality rates. The most common morbidities included coma (64.7 %) and shock (39.2 %). The study underscores the critical need for early cardiac assessment in opioid-intoxicated patients to predict clinical outcomes and guide therapeutic interventions.

Determination of acute sertraline intoxication by high-performance thin-layer chromatography

Determination of acute sertraline intoxication by high-performance thin-layer chromatography

Risk assessment of Arsenic in surface water of China water systems based on a time-dependent species sensitivity distribution (SSD) method

Arsenic (As) is a naturally occurring metalloid element widespread in the environment. Assessing the ecological risk of As in surface water, especially the acute risk caused by emergent pollution incidents, is of great significance. However, acute toxicity data including median lethal concentration (LC50) and median effective concentration (EC50) of As derived by toxicology experiment may vary according to the exposure time, which is referred as time dependence effect. Time dependence not only affects toxicity data but also influences the characterization of acute risk in the ecosystem. However, previous research on the time dependence effect of As, especially the quantitative influence on the risk assessment is still limited. In this research, acute toxicity data of As(III) and As(V) was collected. Time dependence of toxicology data of inorganic As was studied. Time-dependent species sensitivity distributions of freshwater species were established. The hazardous concentration for 5% of species (HC5) values in different exposure time were further derived. Finally, the dynamic ecological risk of As in major Chinese water basins was evaluated. The results suggested that the toxicity data of inorganic As had a significant linear relationship (p < 0.01) with time. The HC5 values of As (III) and As (V) at an exposure time of four days were reduced by 15.5% and 77.5%, respectively, as compared to the HC5 value of one day. According to the ecological risk characterized by the probability density overlapping area method, the ecological risk of As(III) and As(V) increases with the exposure duration. The Yangtze River had the highest risk, with risk values ranging from 19.9% to 22.6%. According to the results, the time dependence of toxicity data should be fully considered in the formulation of water quality criteria or ecological risk assessment so as to provide better protection for the water ecosystem security.

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. Theexisting study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90days were also observed. In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Acute and sub-chronic oral GLP toxicity of Withania somnifera root extract in Sprague Dawley rats.

Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. Theexisting study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90days, respectively under OECD-423 and -408 guidelines as well as GLP compliance. In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90days were also observed. In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes. The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Optimization and pharmacological evaluation of phytochemical-rich Cuscuta reflexa seed extract for its efficacy against chlorpyrifos-induced hepatotoxicity in murine models

The popular organophosphorus (OP) compound chlorpyrifos (CP) has recently gained significant attention due to its health risks, particularly among farmers exposed to OP pesticides. This study aimed to evaluate the acute toxicity of Cuscuta reflexa seed extract (CRSE) and its efficacy of mitigating the adverse effects of CP in albino male mice. For acute toxicity analysis, the first group was served as the control group, while the second group was received CRSE (200 mg/kg/bw) on the first day of the 14-day experiment. For hepatotoxicity analysis, the first group was the control group, the second group (vehicle control) received corn oil (CO) (2 mL/kg/bw), the third group was given CP (20 mg/kg/bw) dissolved in corn oil and the fourth group was given CP (20 mg/kg/bw) along-with CRSE (200 mg/kg/bw) orally via gavage once daily for 21 days. The acute toxicity examination revealed no statistically significant differences between the CRSE-treated and control groups in serum biochemical indicators and histopathological analyses of various organs, suggesting that CRSE as safe at a dosage of 200 mg/kg/bw, with an oral LD50 in mice higher than 200 mg/kg. The hepatotoxicity study demonstrated that the CP administration resulted in liver damage and oxidative stress, while CRSE acted as an antioxidant and attenuated the signs of oxidative stress in liver damage. Hence, a promising therapeutic approach for lowering CP hepatotoxicity is co-treatment with CRSE.

Acute and Sub-Acute Toxicity Studies of Soursop Starch in Swiss Mice and Wistar Rats

Acute and Sub-Acute Toxicity Studies of Soursop Starch in Swiss Mice and Wistar Rats

Pinonic Acid Derivatives Containing Thiourea Motif: Promising Antifungal Lead Compound Targeting Cellular Barrier of Colletotrichum fructicola.

In order to explore novel antifungal lead compounds from plant essential oil, thirty-two pinonic acid derivatives containing thiourea groups were designed and synthesized using α-pinene as a raw material. One of these pinonic acid derivatives compound 3a exhibited noteworthy in vitro antifungal activity against Colletotrichum fructicola (EC50 = 9.22 mg/L), which was comparable to that of the positive control kresoxim-methyl (EC50 = 9.69 mg/L). Structure-activity relationship (SAR) studies demonstrated that the introduction of thiourea groups, F atoms, and Cl atoms into the structure of pinonic acid derivatives significantly improved their antifungal activity. The in vivo antifungal test revealed that compound 3a could effectively control pear anthracnose. It also proved that compound 3a showed low acute oral toxicity to honeybees (LD50 > 100 μg/bee) and low or no cytotoxicity to LO2 and HEK293 cell lines. The preliminary mechanism of action studies revealed that compound 3a caused mycelium deformity, increased cell membrane permeability, blocked the normal process of phospholipase C on the cell membrane, and reduced mycelium protein content. The results of molecular docking studies demonstrated the stable binding of compound 3a to phospholipase C and chitin synthetase. This study suggested that compound 3a could be used as a promising lead compound for the development of novel antifungal agents targeting the cellular barrier of C. fructicola.

A novel pectin-like polysaccharide from Crocus sativus targets Galectin-3 to inhibit hepatic stellate cells activation and liver fibrosis

Liver fibrosis may lead to cirrhosis and even cancer without effective clinical medicine available. Previous studies demonstrated that galactan-containing pectins or pectin-like polysaccharides might target Galectin-3 (Gal-3) to impede fibrosis. This research aims to discover novel pectin-like galactan to interfere with fibrosis for potential new drug development. Thus, we purify a novel homogeneous Rhamnogalacturonan-I like polysaccharide with galactan input, XHH2, from the Crocus sativus flower. XHH2 (MW: 35.7 kDa) consists of rhamnose, galacturonic acid, galactose, and arabinose in ratios of 6.6: 6.1: 25.2: 12.1. The backbone of XHH2 comprises 1, 3, 6-Gal and 1, 3, 4-GalA, with branches at O-3 of 1, 3, 6-Gal and O-4 of 1, 3, 4-GalA. O-3 branches include 1, 3-Gal, 1, 4-Gal, 1, 6-Gal, T-Gal, and T-Glc, while O-4 branches consist of 1, 2, 4-Rha, 1, 4-GalA, 1, 5-Ara, T-Ara, T-Gal, and T-α-HexA. Surface plasmon resonance measurement shows that XHH2 binds to both Gal-3 and integrin β1 to block Gal-3/integrin β1 interaction. Mechanism studies further suggest that XHH2 inactivates hepatic stellate cells (HSCs) via disturbing the Gal-3/Integrin-β1/FAK pathway to alleviate liver injury and fibrosis in vitro &in vivo. XHH2 shows a favorable drug safety in the acute toxicity test of oral administration of XHH2 in mice. Overall, XHH2 is an active ingredient against liver fibrosis by targeting the interaction between Gal-3 and Integrin-β1.

Safety assessment of novel oxadiazole derivatives in acute and sub-acute toxicity studies.

1,3,4-Oxadiazole is a fascinating heterocyclic compound with a unique five-membered ring structure containing nitrogen and oxygen atoms. It has garnered significant attention for its interactions and activities within biological systems. This versatility has led to the production of several ligands using this compound as a pharmacophore. This study evaluates the acute toxicity of three oxadiazole derivatives (1,3,4-Bromo, Chloro, and Iodo) followed by a 28days sub-acute study involving four different doses of each derivative. The study followed the guideline, the Organization for Economic Cooperation and Development (OECD) outlined, specifically OECD Guidelines 425 for the acute toxicity study and OECD Guidelines 407 for the sub-acute study. In the acute toxicity study, a high dose of 2000 mg/kg was administered to male and female rats to establish lethal dose 50 (LD50) values, and the rats were closely monitored for 14 days. The subsequent sub-acute study involved the administration of four different doses (1.25, 2.5, 5, and 10 mg/kg) of each derivative to male and female rats for 28 days. Throughout both studies, careful monitoring for signs of toxicity and comprehensive hematological, biochemical, and histological analysis were carried out thoroughly. The results of the acute toxicity study indicated that all three derivatives had LD50 values exceeding 2000 mg/kg, and the rats did not display significant signs of toxicity. Similarly, no organ or systemic toxicity was observed in the repeated dose sub-acute study for any of the three derivatives. In conclusion, based on the findings of these studies, it was determined that the derivatives are safe for further investigation of their pharmacological activity.

Preparation and Evaluation of Stability and Acute Oral Toxicity of a Drug Delivery System Combining MIL‐100(Fe) with Chloroquine Phosphate

AbstractMetal‐organic framework materials (MOFs) are highly porous and are the subject of growing interest among scientists globally for their utilization in drug delivery. In this work, iron‐based metal‐organic frameworks (MOFs) MIL‐100(Fe) were synthesized by ultrasonic method and studied for the loading of the chloroquine phosphate (CQP). The CQP‐release behavior of the material was investigated in water media with various pH solutions of 1.2, 2, 4.5, and phosphate‐buffered saline (PBS) at temperatures of 25 °C to 45 °C. MIL‐100(Fe) material had a high surface area of up to 1080 m2/g and could completely release the CQP at a pH of 1.2 after 25 hours. At other pH conditions, the drug exhibited an initial rapid release, followed by a gradual slowdown, ultimately achieving complete release after 96 hours. The maximal loading capacity for the CQP by the MIL‐100(Fe) was determined to be approximately 30 % at the pH solution of 2 (stomach environment). The findings from the activity assessment against the K1 malaria parasite strain (P. falciparum) indicated that the concentration at which the active ingredient, when carried by the material, exhibited inhibition was 193 nM/L. The evaluation outcomes for acute toxicity of the drug carrier material revealed an LD50 value exceeding 5000 mg/kg (equivalent to 1500 mg of CQP base). In contrast, when using the active substance alone, acute toxicity resulted in an LD50 value of 675 mg/kg.

Acute oral toxicity and genotoxicity assessment of the essential oil from Croton pulegiodorus Baill (Euphorbiaceae) leaves in mice

Essential oils obtained from Croton pulegiodorus leaf are renowned for their biological activities; however, data on their toxicity are limited. Therefore, this study aimed to evaluate the acute oral toxicity and genotoxicity of a C. pulegiodorus leaf essential oil (CPLEO). Chemical characterization of CPLEO was conducted by gas chromatography coupled to mass spectrometry (GC-MS). In vitro assay was performed to verify the hemolytic capacity of the oil in mice erythrocytes. Next, an acute oral toxicity study was conducted on female mice at CPLEO doses of 2000, 1000, 500, 250, 100, and 50 mg/kg. Hematological, biochemical, and histopathological markers were assessed in mice from groups were no death occurred. Relative consumption of water and food and the weight of animals and their organs were also recorded. Finally, a genotoxicity analysis was performed using the micronucleus and comet assays. The extraction yield of CPLEO was 1.149% and its major compounds were ascaridole (23.18%), eucalyptol (17.20%), camphor (14.20%), p-cymene (7.91%), α-terpineol (4.69%), and isobornyl acetate (4.57%). CPLEO showed a hemolytic effect only at high concentrations (185.5–1000 mg/mL). It showed acute oral toxicity in mice with a LD50 of 460.42 mg/kg. CPLEO (50–250 mg/kg) caused some significant changes in hematological and biochemical parameters. Histopathological evaluation indicated alterations in liver and kidneys but transaminases, urea and creatinine levels remained like the negative control. CPLEO administration impaired weight gain and reduced water and food consumption. Finally, it was not genotoxic by both comet and micronucleus tests. The results highlight the need for attention when choosing doses to evaluate the bioactivities of CPLEO.

Characterization of food color additives and evaluation of their acute toxicity in Wistar albino rats

Background and Aim: The use of food dyes can cause certain diseases, such as anemia and indigestion, along with other disorders, tumors, and even cancer. Therefore, this study aimed to determine the chemical nature and toxicity of some commercial dyes locally used in processed foods compared with standard food dyes. Materials and Methods: Three types of standard and commercial food color additives (Sunset Yellow, Tartrazine, and Carmoisine) were extensively examined. The chemical structures and functional groups of the dyes were evaluated by Fourier-transform infrared (FTIR) spectroscopy. The melting temperatures of the dyes were also determined by chemical thermal analysis. The acute toxicity test to evaluate the standard and commercial food color safety was estimated by a range-finding study using 150 Wistar albino rats. Sub-groups were administered one of the three colors under study at doses of 2, 3, 4, and 5 g/kg body weight (BW) orally for 7 days. When no mortality was observed, an additional 15 g/kg BW was administered. Concerning the median lethal dose 50 (LD50), 38 rats were exploited using the up-and-down method. Results: Commercial dyes had lower melting points than standard colors. Regarding the range-finding study, rats receiving different doses of the dyes exhibited no signs of toxicity, no deaths, and no clinical or gross pathological signs throughout the 7 days of the experiment. However, the animals that were dosed with 15 g/kg BW of each dye showed signs of loss of appetite, tachycardia, drowsiness, and eventual death. The LD50 values of the commercial food dyes, particularly Sunset Yellow and Carmoisine, were lower than those of the standard dyes. Conclusion: Commercial food colors were more toxic to rats than standard food colors. Differences were observed between the purity of the standard and commercial dyes, and the latter ones contained different percentages of salt, indicating the occurrence of fraud in commercial markets. Keywords: acute toxicity, food colors, Fourier-transform infrared spectroscopy, lethal dose 50, range-finding study.

Chemical Characterization, Evaluation of Acute Oral Toxicity, and Anti-Diabetic Activity of Aloe sabaea Flowers Extract on Alloxan-Induced Diabetic Rats.

The study aimed to conduct chemical profiling, acute in-vivo toxicity evaluation, and the potential anti-diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan-induced diabetic rats. The chemical composition was analyzed using GC-MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti-diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti-diabetic mechanism. GC-MS analysis displayed the existence of 18 compounds; mostof the compoundswere fatty acids and theiresters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in-vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD50 value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.

Effect of inulin on preventing drunkenness and relieving acute alcoholic intoxication of mice and preparation of its hangover beverage

AbstractThe aim of this study was to evaluate the effects of different types of inulin on acute alcoholic intoxication (AAI) in mice and prepare its hangover beverage. Basic physical and chemical properties of different types of inulin (short‐chain inulin, long‐chain inulin, and phosphorylated long‐chain inulin) were analyzed and given by gavage at a dose of 400 mg kg−1 day−1 for a continuous period of 7 days through animal behavior experiments, and the inebriation percentage, mortality rate, duration of inebriation, and sobering time were recorded with the righting reflex as the judgment criterion. The results showed that, compared with the control group, the drunkenness and mortality rates of short‐chain inulin decreased by 12% and 100%, respectively, and the sober time decreased by 18%, while alcohol tolerance was also improved. The best formula for a short‐chain inulin hangover drink was determined to be: 0.4% granulated sugar, 0.5% citric acid, and 0.5% pectin. These suggest that short‐chain inulin may have potential in preventing AAI.

Self-Nanoemulsifying Drug Delivery System of Morin: A New Approach for Combating Acute Alcohol Intoxication.

Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR's effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR's solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism. The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms. After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC0-t) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects. MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI.

Dihydrokoumine, a dual-target analgesic with reduced side effects isolated from a traditional Chinese medicine

IntroductionOpioids are the most common antinociceptive drugs, but long-term administration causes serious adverse side effects. Gelsemium elegans Benth. is traditionally used as an analgesic agent and mainly contains indole alkaloids with structures different from those in common opioids, indicating distinct pharmacological properties. This work aims to find a new analgesic from Gelsemium elegans Benth. and evaluate it in vitro and in vivo. MethodsDihydrokoumine was purified from Gelsemium elegans Benth. Binding to mu opioid receptor (MOR), M3 receptor (M3R) and other 15 G protein-coupled receptors were evaluated in vitro combined with molecular docking analysis. Analgesic efficacy and side effects were measured in vivo using hot-plate, formalin paw, and rotarod tests in mice. Cytotoxicity, acute toxicity in mice and pharmacokinetics were assessed. ResultsA MOR agonist, dihydrokoumine, was first identified from Gelsemium elegans Benth. Further investigations showed that dihydrokoumine exhibited selective partial agonist action on the MOR and antagonist action on the M3R among other 15 GPCRs. In in vivo mouse models, dihydrokoumine could relieve acute pain and chronic inflammatory pain without drug tolerance and sedative side effects. Additionally, we observed a good safety profile and favorable pharmacokinetic properties. ConclusionA MOR partial agonist/M3R antagonist analgesic with reduced side effects was isolated from a traditional Chinese medicine. This study bestows dihydrokoumine as a new dual-target analgesic and as a potential lead compound in pain management.

Impact of Sarcopenia on Treatment Outcomes and Toxicity in Locally Advanced Rectal Cancer

Background and Objectives: Sarcopenia, a condition characterized by muscle mass loss, is prevalent in up to 68% of rectal cancer patients and has been described as a negative prognostic factor, impacting overall survival and tumor response. While there are extensive data on rectal cancer globally, only a handful of studies have evaluated the role of sarcopenia in locally advanced rectal cancer (LARC). Our study aimed to investigate the relationship between sarcopenia, overall response rate, and toxicity in patients who underwent total neoadjuvant treatment (TNT) for LARC. Materials and Methods: We performed a retrospective study of patients with rectal cancer treated with TNT and surgery with curative intent between 2021 and 2023 at Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj-Napoca. Sarcopenia was assessed on MRI images by measuring the psoas muscle area (PMA) at the level of the L4 vertebra before and after neoadjuvant therapy. The primary endpoints were the overall complete response rate (oCR) and acute toxicity. Results: This study included 50 patients with LARC. The oCR rate was 18% and was significantly associated with post-treatment sarcopenia (OR 0.08, p = 0.043). Patients who did not achieve a clinical or pathologic complete response had, on average, an 8% muscle loss during neoadjuvant therapy (p = 0.022). Cystitis and thrombocytopenia were significantly associated with post-treatment sarcopenia (p = 0.05 and p = 0.049). Conclusions: Sarcopenia and loss of psoas muscle during neoadjuvant therapy were negatively associated with tumor response in locally advanced rectal cancer. Thrombocytopenia and cystitis are more frequent in sarcopenic than non-sarcopenic patients undergoing neoadjuvant chemoradiation for rectal cancer.

High dose rate brachytherapy for lip cancer with interstitial, surface, or a combination of interstitial and surface mold technique

High-dose-rate brachytherapy (HDR-BT) is now becoming more common than low-dose-rate and pulsed-dose-rate BT in the treatment of lip cancer. However, due to the limited history of HDR-BT, relatively few studies have been published. Two institutions (in Ukraine and the USA) reviewed their clinical outcomes of lip cancer patients treated with HDR-BT as monotherapy or in combination with external beam radiotherapy (EBRT). An interstitial (IS), surface custom mold (SC), or a combination of IS and SC (IS+SC) was used for treatments based on the depth of tumor invasion. Prescription doses were 24 Gy in 6 BID fractions when combined with 46-50 Gy of EBRT, 45-55 Gy in 9-10 BID fractions for IS and IS+SC monotherapy or 3 Gy × 16 daily fractions for SC monotherapy. A total of 33 cases of lip cancer were treated from 2015 to 2021. By using TNM staging classification, there were 14 stage I (42.4%), 15 stage II (45.5%), and 4 stage III (12.1%) lip cancers. Thirty-one patients (93.9%) had a complete response to the treatment. Only 2 patients (6.1%) displayed local recurrence. Grade 1, 2, and 3 acute toxicities were observed in 30.3%, 51.5%, and 18.2% of patients, respectively. Grade 1, 2, and 3 late toxicities were observed in 39.4%, 21.2%, and 0.0% of cases. Cosmetic results were excellent in 21.2%, good in 54.5%, fair in 18.2%, and poor in 6.1% of patients. HDR-BT is an effective and safe treatment for lip carcinomas with excellent local control, functional, and cosmetic outcomes and should be considered as a standard treatment.