Knowledge, attitude, and practice toward total neoadjuvant therapy for rectal cancer among oncologists in China: A survey study.

This cross-sectional survey study aimed to explore the knowledge, attitude, and practice (KAP) toward total neoadjuvant therapy (TNT) for rectal cancer (RC) among specialists in Hainan Province, China. RC specialists working in Hainan Province (China) were enrolled in this cross-sectional study between March and June 2023. A self-designed questionnaire was used to collect the participants' characteristics and KAP toward TNT for RC. A total of 279 valid questionnaires were collected. The KAP scores were 15.91 ± 6.02 (possible range: 0-24), 34.16 ± 5.11 (possible range: 10-50), and 12.42 ± 1.83 (possible range: 3-15), respectively. The KAP scores of specialists who had applied TNT in clinical practice or research and had evaluated RC patients treated with TNT were significantly higher than those who had not (all P < 0.05). The structural equation model showed that knowledge of TNT directly affected attitude (ß = 0.292, P = 0.007) and practice (ß = 0.912, P = 0.007), and attitude toward TNT also had a direct effect on practice (ß = 1.047, P = 0.008). In conclusion, RC specialists in Hainan (China) had inadequate knowledge, negative attitudes, and sufficient practice toward TNT in Hainan Province, China. It is necessary to enhance education for RC specialists to improve their knowledge and attitude toward TNT.

A case report of Extra-neurologic metastasis of ventricular meningioma with literature review.

Ventricular meningiomas are neoplastic cells originating from the ependymal lining of the central canal of the spinal cord and the ventricles of the brain. These tumorigenic cells predominantly manifest in the fourth ventricle, followed by the spinal cord. Most intraparenchymal ventricular meningiomas are located within the brain tissue, exhibiting a higher degree of malignancy compared to their intracerebroventricular counterparts. While intracranial dissemination and metastasis to the spinal cord can occur, extra-neurologic metastasis is an exceedingly rare phenomenon that lacks a clear elucidation regarding its underlying mechanism. The authors presented a case of supratentorial brain parenchymal type ventricular meningioma surgical treatment in a young female patient, occurring two years after the development of multiple metastases in both lungs, pleura, and mediastinum. This may be attributed to the high malignancy degree and strong invasiveness of this lesion, as well as its proximity to the dura mater and venous sinus. The craniotomy provided an opportunity for tumor cells to invade the adjacent venous sinus, leading to dissemination through the blood system. Additionally, postoperative radiation and chemotherapy were administered to inhibit tumor angiogenesis; however, these treatments also increased the likelihood of tumor cell invasion into neighboring brain tissues and distant metastasis.

SARS-CoV-2 Antiviral Prescribing Gaps Among Nonhospitalized High-Risk Adults.

Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers.

Factors Influencing the Progression of Patellofemoral Articular Cartilage Damage After Anterior Cruciate Ligament Reconstruction.

Background: Although anterior cruciate ligament reconstruction (ACLR) can restore the stability and function of the knee joint, patellofemoral joint cartilage damage still progresses. Currently, the clinically important factors that lead to the progression of patellofemoral articular cartilage damage are not fully understood. Purpose: To investigate the factors that affect the progression of patellofemoral articular cartilage damage after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: Among 160 patients who underwent ACLR between January 2015 and December 2019, the authors evaluated 129 patients for at least 1 year after surgery. Within 1 week before ACLR and at the last follow-up, patients underwent subjective functional assessment and magnetic resonance imaging evaluations of articular cartilage damage (modified Outerbridge assessment). At the last follow-up, the side-to-side difference on KT-2000 arthrometer and bilateral quadriceps muscle strength were measured. Univariate and multivariate logistic regression analyses were performed. Results: The mean follow-up was 24.69 ± 10.74 months. Progression of patellar cartilage damage from preoperatively to final follow-up was seen in 45 patients (P < .001). Logistic regression analysis revealed that the follow-up period (P = .047; odds radio (OR) = 0.953) (improvement of patellar cartilage damage with longer follow-up), partial lateral meniscal resection (P = .004; OR = 6.929), partial medial meniscal resection (P = .004; OR = 6.032), and quadriceps muscle strength <80% of the contralateral side (P = .001; OR = 4.745) were risk factors for the progression of patellar cartilage damage. Conclusion: Cartilage damage at the patellofemoral joint, especially the patellar cartilage, still progresses after ACLR. At a mean follow-up of 24.69 months after ACLR, partial meniscal resection and quadriceps femoris muscle strength were found to be the main risk factors for the progression of patellofemoral articular cartilage damage after ACLR.

Early Stage Markers of Late Delayed Neurocognitive Decline Using Diffusion Kurtosis Imaging of Temporal Lobe in Nasopharyngeal Carcinoma Patients.

Purpose: To determine whether the early assessment of temporal lobe microstructural changes using diffusion kurtosis imaging (DKI) can predict late delayed neurocognitive decline after radiotherapy in nasopharyngeal carcinoma (NPC) patients. Methods and Materials: Fifty-four NPC patients undergoing intensity-modulated radiotherapy (IMRT) participated in a prospective DKI magnetic resonance (MR) imaging study. MR imaging was acquired prior to IMRT (-0), 1 month (-1), and 3 (-3) months after IMRT. Kurtosis (Kmean, Kax, Krad) and Diffusivity (Dmean, Dax, Drad) variables in the temporal lobe gray and white matter were computed. Neurocognitive function tests (MoCA) were administered pre-radiotherapy and at 2 years post-IMRT follow-up. All the patients were divided into neurocognitive function decline (NFD group) and neurocognitive function non-decline groups (NFND group) according to whether the MoCA score declined ≥3 2 years after IMRT. All the DKI metrics were compared between the two groups, and the best imaging marker was chosen for predicting a late delayed neurocognitive decline. Results: Kurtosis (Kmean-1, Kmean-3, Kax-1, Kax-3, Krad-1, and Krad-3) and Diffusivity (Dmean-1 and Dmean-3) of white matter were significantly different between the two groups (p<0.05). Axial Kurtosis (Kax-1, Kax-3) of gray matter was significantly different between the two groups (p<0.05). By receiver operating characteristic (ROC) curves, Kmean-1 of white matter performed best in predicting of MoCA scores delayed decline (p<0.05). The radiation dose was also significantly different between NFD and NFND group (p=0.031). Conclusions: Temporal lobe white matter is more vulnerable to microstructural changes and injury following IMRT in NPC. Metrics derived from DKI should be considered as imaging markers for predicting a late delayed neurocognitive decline. Both temporal lobe white and gray matter show microstructural changes detectable by DKI. The Kmean early after radiotherapy has the best prediction performance.

The impact of the interval between the induction of chemotherapy and radiotherapy on the survival of patients with nasopharyngeal carcinoma.

BACKGROUND: There have been no reliable scientific studies examining whether the interval between induction chemotherapy (IC) and initiating radiotherapy is associated with poor outcomes of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: In this retrospective study, we included a total of 239 local advanced NPC patients who underwent concurrent chemoradiotherapy and IC. Based on the interval between IC and intensity-modulated radiation therapy (IMRT), the patients were classified into three groups as follows: Group A (≤7 vs >7 days), Group B (≤14 vs >14 days), and Group C (≤ 21 vs >21 days). Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes. The differences between the two groups were compared by the log-rank test. RESULTS: The median IC-IMRT interval was 9 days (range, 1-76 days). The median follow-up time was 40 months (range, 4-58 months). The IC-IMRT interval including Group A, Group B, and Group C was not significantly associated with overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), or disease-free survival (DFS). Multivariate analysis showed that the tumor stage was the independent significant predictor for OS, DMFS, LRFS, and DFS. But it appears that there was a trend toward improvement in the outcome of ≤7 days group in OS from the Kaplan-Meier curves. CONCLUSION: It is also feasible to postpone radiotherapy for 1-3 weeks if patients were unable to receive treatment immediately due to chemotherapy complications such as bone marrow suppression. However, we suggest that patients should start IMRT as soon as possible after IC.

The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model.

BACKGROUND: Acetaminophen (N-acetyl-para-aminophenol) is the most widely used over-the-counter or prescription painkiller in the world. Acetaminophen is metabolized in the liver where a toxic byproduct is produced that can be removed by conjugation with glutathione. Acetaminophen overdoses, either accidental or intentional, are the leading cause of acute liver failure in the United States, accounting for 56,000 emergency room visits per year. The standard treatment for overdose is N-acetyl-cysteine (NAC), which is given to stimulate the production of glutathione. METHODS: We have created a mathematical model for acetaminophen transport and metabolism including the following compartments: gut, plasma, liver, tissue, urine. In the liver compartment the metabolism of acetaminophen includes sulfation, glucoronidation, conjugation with glutathione, production of the toxic metabolite, and liver damage, taking biochemical parameters from the literature whenever possible. This model is then connected to a previously constructed model of glutathione metabolism. RESULTS: We show that our model accurately reproduces published clinical and experimental data on the dose-dependent time course of acetaminophen in the plasma, the accumulation of acetaminophen and its metabolites in the urine, and the depletion of glutathione caused by conjugation with the toxic product. We use the model to study the extent of liver damage caused by overdoses or by chronic use of therapeutic doses, and the effects of polymorphisms in glucoronidation enzymes. We use the model to study the depletion of glutathione and the effect of the size and timing of N-acetyl-cysteine doses given as an antidote. Our model accurately predicts patient death or recovery depending on size of APAP overdose and time of treatment. CONCLUSIONS: The mathematical model provides a new tool for studying the effects of various doses of acetaminophen on the liver metabolism of acetaminophen and glutathione. It can be used to study how the metabolism of acetaminophen depends on the expression level of liver enzymes. Finally, it can be used to predict patient metabolic and physiological responses to APAP doses and different NAC dosing strategies.

Responses of wheat seedlings to cadmium, mercury and trichlorobenzene stresses.

The molecular response of wheat (Triticum aestivum L., cv. Yangmai 13) seedlings to heavy metal (Cd, Hg) and 1,2,4-trichlorobenzene (TCB) stresses were examined by two-dimensional gel electrophoresis, image analysis, and peptide mass fingerprinting. The results showed inhibitions of root and shoot growth by Cd, Hg, and TCB. These stresses led to water deficit and lipid phosphorylation in the seedling which also promoted protein phophorylation in the leaves. Hg stress inhibited protein synthesis while Cd and TCB stresses induced or up-regulated more proteins in the leaves. Most of these induced proteins played important roles in the biochemical reactions involved in tolerance of wheat to Cd and TCB stresses. The primary functions of Cd- and TCB-induced proteins included methionine metabolism, Rubisco modification, protein phosphorylation regulation, protein configuration protection, H+ transmembrane transportation and also the synthesis of ethylene, defense substances and cell wall compounds.