Aframomum melegueta seed powder (AMSP) is a phytogenic supplement with notable antioxidant and anti-inflammatory properties. This study assessed its potential to protect broiler chickens against aflatoxin B₁ (AFB₁)-induced toxicity. AMSP was screened for phytochemicals and antioxidant activity. A total of 320 Cobb 500 chicks were assigned to four diets using a completely randomized design: CTRL (control), ATB1 (0.4mg/kg AFB₁), A1AF (AFB₁ + 0.5g/kg AMSP), and A2AF (AFB₁ + 1.0g/kg AMSP) for six weeks. Exposure to AFB₁ by the birds in ATB1 markedly (P < 0.05) impaired growth performance, as evidenced by reduced final body weight (2,315.82g vs. 2,743.23g in CTRL), lower protein intake (813.45g vs. 837.24g), and increased feed conversion ratio (1.70 vs. 1.47). AMSP supplementation, particularly at 1.0g/kg in A2AF, restored growth performance to control levels, while supplementation at 0.5g/kg in A1AF achieved partial recovery. Compared with the CTRL group, AFB₁ exposure in the ATB1 birds reduced (P < 0.05) packed cell volume (29.37% vs. 35.05%) and haemoglobin concentration (9.79g/dL vs. 11.68g/dL), elevated (P < 0.05) ALT (24.04 vs. 16.77 IU/L), AST (70.62 vs. 57.59 IU/L), creatinine (74.85 vs. 52.43 µmol/L), TNF-α, IL-6, and corticosterone, and suppressed (P < 0.05) IL-10. These disruptions were largely normalised by AMSP, especially at 1.0g/kg, restoring ALT, AST, creatinine, IL-10, and corticosterone to CTRL values. Histopathological analysis further confirmed that periportal inflammation and hepatic architectural damage induced by AFB₁ in ATB1 were attenuated in A1AF and absent in A2AF. In conclusion, AMSP supplementation at 1.0g/kg effectively mitigated AFB₁-induced growth, biochemical, and hepatic impairments in broilers. These findings highlight AMSP as a promising natural feed additive for improving poultry health and ensuring feed safety, warranting further investigation into its application under commercial production conditions.

Factors Associated With 1-Year Home Health Admission Among Older Adults Initiating Long-Term Opioid Therapy.

IntroductionFor ovarian cancer patients undergoing preoperative Neoadjuvant Chemotherapy (NACT), the toxicity of chemotherapeutic agents may cause hepatic and renal function impairment, altered sensitivity of the central nervous system or abnormal pain perception thresholds. These changes can further affect the metabolism and efficacy of intraoperative anaesthetics. However, the optimal intraoperative opioid dosage regimen for this specific patient population remains unclear. Currently, nociceptive stimulation monitoring technology has achieved certain progress in guiding intraoperative opioid administration. Among this technology, the index of consciousness 2 (IOC2), as a representative monitoring indicator in this field, provides important references for optimising opioid dosage regimens. This trial will investigate the opioid requirements and patient outcomes in the anaesthetic management of ovarian cancer patients undergoing preoperative NACT guided by IOC2.Methods and analysisThis prospective, single-blind, single-centre randomised controlled trial will randomly recruit 90 patients undergoing open ovarian cancer cytoreductive surgery under general anaesthesia, with equal numbers assigned to the control and experimental groups. The experimental group will adjust the remifentanil plasma target concentration based on the IOC2 value, while the control group will adjust according to the patients’ mean arterial pressure. The primary outcome will be intraoperative opioid use (calculated in morphine equivalents per hour). Secondary outcomes include the average intraoperative propofol dose, post-anaesthesia care unit (PACU)-related metrics (including extubation time, time to spontaneous eye opening and morphine consumption in PACU), pain levels at 4, 24 and 48 hours postoperatively, as well as the use of analgesics and antiemetics. Postoperative recovery quality will also be assessed, including time to first flatus, time to ambulation, length of hospital stay and the 24-hour Quality of Recovery-15 (QoR-15) score.Ethics and disseminationThis study involves human participants and was approved by the Ethics Committee of the Jiangsu Cancer Hospital (ethics no: XJS-2024-017). Patients gave informed consent to participate in the study before taking part. The study results will be published in peer-reviewed journals and presented at relevant academic conferences.Trial registration numberChiCTR2400091897.

Ervogastat, a diacylglycerol-O-acyltransferase-2 inhibitor, and clesacostat, an acetyl-CoA carboxylase inhibitor, are in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Study 1 and Study 2 were open-label, Phase 1 trials that assessed the pharmacokinetics (PK) of a single dose of ervogastat (100 mg) and clesacostat (25 mg), respectively, in participants (n = 6/cohort) with mild, moderate, or severe hepatic impairment (HI) and compared to those without HI (reference). Plasma samples were analyzed for both total and unbound concentrations in Study 2 as clesacostat is highly protein bound. In Study 1, compared to participants without HI, ervogastat exposure (AUCinf) was 56%, 65%, and 52% higher in participants with mild, moderate, and severe HI, respectively. However, when excluding PK data from a participant with unexplained low exposures in reference group, ervogastat exposures were similar between those with/without HI. In Study 2, total clesacostat exposure was 36%, 24%, and 19% higher for mild, moderate, and severe HI, respectively, as compared to reference group. Unbound clesacostat exposures were 70%, 83%, and 166% higher for mild, moderate, and severe HI cohorts, respectively, with clesacostat plasma protein binding shown to decrease with increasing HI severity. Ervogastat and clesacostat were well tolerated with no clinically significant laboratory abnormalities or changes in vital signs and/or electrocardiograms observed. Observed exposures in HI studies were consistent with simulated exposures in MASH population. Taking into consideration the safety margins at the highest doses evaluated in Phase 2, no dose adjustment of ervogastat or clesacostat is currently warranted for patients with hepatic impairment.

Lemborexant, a dual orexin receptor antagonist, is suitable for the long-term treatment of insomnia. It is primarily metabolized in the liver. The aim was to develop physiologically based pharmacokinetic (PBPK) models of lemborexant to provide dosing regimens for populations with hepatic impairment. The PBPK models of lemborexant were developed and validated using PK-Sim for healthy populations and populations with mild, moderate hepatic impairment, respectively. Then, the effect of severe hepatic impairment on lemborexant pharmacokinetics was investigated to determine dosing regimens. The developed model successfully described the pharmacokinetics of lemborexant in healthy and hepatic impairment populations. Mean plasma concentrations of lemborexant were higher in populations with hepatic impairment compared to those with normal hepatic function. The area under the plasma concentration-time curve at steady state (AUCss,24h) values in populations with mild, moderate, and severe hepatic impairment were 1.54-, 2.18-, and 2.08-fold higher, respectively, compared to those with normal hepatic function. Based on the changes in exposure, it is recommended that the maximum dose for populations with severe hepatic impairment should be limited to 5 mg once daily, which is similar to moderate hepatic impairment. The PBPK model can be used as a tool for dose adjustments in populations with hepatic impairment.

Sotorasib is a small molecule KRASG12C inhibitor approved for the treatment of KRASG12C mutated locally advanced or metastatic non-small cell lung cancer in adult patients. The effect of hepatic impairment on the pharmacokinetics (PK) of sotorasib and major metabolites M10, M18, and M24, safety, and tolerability after a single oral dose of 960 mg was assessed in a phase 1, parallel-arm, multi-center (US), open-label study. Sotorasib AUCinf ratio for subjects with moderate (n = 7) or severe (n = 4) hepatic impairment relative to normal hepatic function (n = 7) was 0.746 (90% CI: 0.431-1.29) and 1.04 (0.545-1.97), respectively. Cmax ratio for moderate and sever hepatic impairment was 0.955 (0.512-1.78) and 1.43 (0.688-2.96), respectively. Mean t1/2 values for sotorasib were similar in subjects with normal hepatic function and subjects with moderate or severe hepatic impairment. Cmax and AUCinf of M10 and M24 increased, while M18 decreased with increasing severity of hepatic impairment. Treatment-emergent adverse events were mild in severity and no serious adverse events were reported. Overall, moderate or severe hepatic impairment did not considerably affect the exposure of sotorasib, M10, M18, and M24. This data supports that adjustments to sotorasib dosing are not indicated for moderate or severe hepatic impairment.

Hepatic impairment (HI) leads to pharmacokinetic and pharmacodynamic changes demanding adjustment of drug therapy. To increase medication safety, hospital pharmacists need to quickly identify patients at risk. Laboratory parameters and liver scores are often available only with timely delay. Alternatively, screening for typical drugs used in severe HI in electronic prescribing systems could be an option. To test a new approach for the timely identification of patients with hepatic impairment. Drugs typically used in severe HI and its complications were evaluated as screening tools in patients with documented liver disease to identify patients who probably require drug adjustment to liver function. Patients ≥ 18 years and hospitalized in the year 2022 with an ICD-10-GM coding for liver disease were identified retrospectively. ICD-10-GM classes of special interest, reflecting severe HI, were defined (K70 (alcoholic liver disease), K72 (hepatic failure) and K74 (liver fibrosis/cirrhosis)). Drugs typically used in severe hepatic impairment and its complications (index drugs) were defined as carvedilol, propranolol, lactulose, L-ornithin-L-aspartate, rifaximin, spironolactone and ursodeoxycholic acid. For all patients, use of index drugs according to the electronic prescribing system, laboratory liver parameters, MELD (Model of Endstage Liver Disease) and MELD 3.0 were documented. We analysed, how many patients and how many cases of hepatic ICD-10-GM-codes were identified by screening for index drugs. Of 2319 patients with a hepatic ICD-10-GM-code in 2022, 2012 had electronic charts available. For these, 2916 main class ICD-10-GM codes were documented (4505 including main and sub-classes; median 1; IQR 1-3). Of 2012 patients, 1005 (50%) were treated with index drugs. Of the 2916 main ICD-10-GM classes, 1754 (60%) had index drugs, more often in codes of special interest (K74 82.5%, K70 79.7%, K72 68.9%). Patients in these main classes of special interest had higher MELD (median 14.8-18.2) and MELD 3.0 (18-22.9) compared to the overall patient cohort (MELD 12; MELD 3.0 15.9) and frequently laboratory liver parameters out of normal range. Screening via index drugs typically used in hepatic impairment is a promising tool to identify patients at risk probably needing drug adjustment to hepatic function. Further studies need to determine the practical use of this tool to increase drug therapy safety.

Background: Doxazosin, an α1-adrenergic antagonist, is commonly used in the management of hypertension and benign prostatic hyperplasia (BPH). Pharmacokinetic (PK) variability across populations may affect drug exposure and clinical response. This systematic review and meta-analysis aimed to summarize PK differences and generate pooled estimates of key parameters, including area under the curve (AUC) and maximum plasma concentration (Cmax). Methods: A systematic search of Google Scholar, PubMed, ScienceDirect, and the Cochrane Library identified 25 eligible studies reporting doxazosin PK data. All extracted AUC and Cmax values were dose-normalized prior to synthesis to ensure comparability across different doses and formulations. A random-effects meta-analysis was performed using the metafor package in R to estimate pooled dose-normalized AUC and Cmax while accounting for between-study variability. Heterogeneity was assessed using the I2 statistic. Sensitivity analyses—including leave-one-out diagnostics and Baujat plots—were used to identify influential studies. Publication bias and small-study effects were evaluated through funnel plots, trim-and-fill procedures, and Egger’s regression test. Meta-regression analyses examined the influence of age and body weight on PK parameters. Results: The meta-analysis produced pooled dose-normalized estimates for AUC and Cmax, with high heterogeneity across studies (I2 ≈ 90%). Leave-one-out analyses demonstrated stable pooled estimates; for dose-normalized AUC, exclusion of three influential studies reduced heterogeneity to 82% with only a modest decrease in the pooled mean. Baujat plots identified a small number of studies as key contributors to heterogeneity, while most exerted minimal influence. Funnel plots showed notable asymmetry for both AUC and Cmax, and trim-and-fill analyses suggested possible small-study effects; however, adjusted pooled estimates remained consistent. Egger’s regression confirmed significant asymmetry for dose-normalized AUC (t = 4.41, p = 0.0003) and Cmax (t = 4.35, p = 0.0001). Meta-regression revealed that body weight significantly reduced Cmax, whereas age had no significant effect on either AUC or Cmax. Conclusions: This systematic review and meta-analysis provide a comprehensive evaluation of doxazosin PK across diverse populations. Despite normalization, substantial variability remained in AUC and Cmax, related in part to ethnicity, hepatic impairment, dosage formulation, and body weight. While pooled estimates offer valuable summary reference points, the high heterogeneity and evidence of small-study effects highlight the need for more standardized PK trials and patient-level analyses to better support individualized dosing strategies.

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that can occur after solid organ transplantation but remains underrecognized in this setting. The diagnosis is often delayed due to overlapping clinical manifestations with infection, rejection, or malignancy, and management becomes particularly challenging when accompanied by severe hepatic dysfunction. Here, we describe a pediatric patient who developed Epstein–Barr virus (EBV)–associated secondary HLH following liver re‐transplantation for biliary atresia. On postoperative Day 10, the patient presented with high fever, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and marked hyperferritinemia, accompanied by rapidly worsening liver injury. Bone marrow biopsy confirmed hemophagocytosis. Given the severe hepatic impairment and persistent inflammation, the patient received three doses of emapalumab (1 mg/kg), a monoclonal antibody blocking interferon‐γ, combined with corticosteroids, intravenous immunoglobulin, and antimicrobial prophylaxis. The treatment led to a rapid decline in ferritin levels, reversal of liver dysfunction, and complete clinical recovery without opportunistic infections. The patient has remained stable with normal liver function and negative EBV DNA for over 2 years of follow‐up. This case demonstrates that early interferon‐γ blockade can safely and effectively reverse HLH‐related liver injury after transplantation, offering a promising therapeutic strategy for the management of secondary HLH complicated by severe hepatic dysfunction.

This study evaluated the long-term safety and effectiveness of ruxolitinib in Japanese patients with polycythemia vera in clinical practice. This multicenter, single-arm, non-interventional, prospective, observational study assessed patients receiving ruxolitinib after approval. Of 550 patients (median age: 71 years, mean disease duration: 5.43 years, median treatment duration: 1091 days), 51.27% reported adverse drug reactions (ADRs) and 12.18% had serious ADRs, with anemia being the most common ADR. The highest incidence of ADRs (40%) was observed from treatment initiation to Day 182, with no tendency for increased incidence thereafter. ADRs of special interest included myelosuppression (27.64%), hepatic impairment (13.45%), infections (9.27%), hemorrhagic events (5.64%), cardiac failure (1.27%), malignancy (1.09%), interstitial lung disease (0.36%), and tuberculosis (0.18%). Baseline hepatic impairment did not increase the incidence of ADRs, but numerical incidence was higher in patients with baseline renal impairment, with similar events being observed in patients with or without renal impairment. At 36 months, spleen response and symptom improvement were observed in 31.43% and 61.14% of patients, respectively. Reductions in hematocrit, white blood cell count, and platelet count were observed throughout the treatment duration. Ruxolitinib demonstrated sustained effectiveness with no new safety concerns in the real-world setting.

Remimazolam is an ultra–short-acting benzodiazepine that positively modulates GABA_A receptors and is rapidly hydrolyzed by nonspecific tissue carboxylesterases to an inactive metabolite, yielding organ-independent clearance, rapid onset and offset, and generally stable hemodynamics; its effects are promptly reversible with flumazenil. Accruing evidence across “painless” endoscopy, perioperative general anesthesia, and ICU sedation shows non-inferior procedural success to propofol or midazolam—with fewer hypotensive and respiratory events and faster cognitive recovery in gastrointestinal endoscopy—and emerging feasibility in ambulatory gynecologic procedures and awake neurosurgery. Practical considerations include the absence of intrinsic analgesia (necessitating opioid co-administration), heightened pharmacodynamic sensitivity in older or frail patients, reduced clearance in severe hepatic impairment, and the potential for re-sedation after antagonism. Adverse events largely mirror class effects (hypoxemia, blood-pressure perturbations), while serious hypersensitivity and clinically meaningful effects on cardiac repolarization appear rare at therapeutic exposure. This review integrates mechanism, pharmacokinetics, dosing strategies, clinical efficacy, and safety to guide rational use of remimazolam in modern, comfort-oriented anesthesia, and highlights priorities for rigorous trials in organ dysfunction and critical illness where putative anti-inflammatory actions remain to be validated.

Hepatic ischemia-reperfusion injury (HIRI) is a common and inevitable complication of liver surgery that induces severe hepatic functional impairment and can trigger multiple organ dysfunction syndrome. From the rice culture of Paraconiothyrium sp. H-B collected from Hypericum wilsonii N. Robson, 11 novel bergamotane-type sesquiterpenoids, paramotanes A-K (1-11), along with three known congeners, were obtained by the guidance of the DeepSAT system (a neural network-based tool for HSQC spectrum analysis). The structures and configurations of these compounds were confirmed via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Notably, compound 1 is the first reported 10-nor-bergamotane sesquiterpenoid. The pharmacodynamics assays demonstrated that compound 12 exhibits hepatoprotective effects and can ameliorate liver function in HIRI mice, positioning it as a promising leading compound for developing novel hepatoprotective agents for the clinical management of HIRI.

Dordaviprone (ONC201) is a small molecule protease activator being developed for gliomas. The aim of this work was to evaluate the pharmacokinetics and safety of dordaviprone when administered to participants with moderate hepatic impairment compared to healthy matched participants. A non-randomized, open-label, single-dose study was conducted in eight participants with moderate hepatic impairment classified according to Child-Pugh criteria, and eight healthy participants matched based on age (+10 years), body mass index (BMI; +20%), and sex. Plasma concentrations of dordaviprone and the major inactive metabolite, ONC207, were determined by a validated liquid chromatography-tandem mass spectrometry method. Exposure following oral administration of 125 mg dordaviprone was increased in participants with moderate hepatic impairment relative to healthy matched participants, with the largest impact occurring on AUC. Ratios of geometric means and 90% confidence intervals (CIs) of dordaviprone exposure for Cmax, AUClast, and AUCinf in the moderate hepatic impairment cohort compared to the healthy matched cohort were 1.21 (0.88, 1.67), 1.50 (1.02, 2.20), and 1.55 (1.05, 2.29), respectively. Treatment-emergent adverse events were mild in nature and considered not related to dordaviprone administration. While administration of dordaviprone in participants with moderate hepatic impairment led to increased dordaviprone exposures, the anticipated increase after the recommended 625 mg dose is within exposures assessed in the thorough QT study. Therefore, no dose adjustment in patients with mild or moderate hepatic impairment is recommended.

A common challenge in conducting phase 1 studies that assess the impact of organ impairment on the pharmacokinetics of a drug is the recruitment of a demographically matched control group. The work presented here evaluated alternative approaches for generating control groups in these studies. Available phase 1 data from the upadacitinib and elagolix clinical programs were leveraged as case studies. A statistical matching approach and a population pharmacokinetic model-based approach were evaluated retrospectively for these programs' hepatic and renal impairment clinical studies. Geometric mean ratios of logarithmically transformed Cmax and AUCinf were used to compare exposure in organ impairment groups to respective matched or virtual control groups. In the statistical matching approach, the genetic matching algorithm using Mahalanobis distance showed that external control groups were adequately demographically balanced across all impairment groups of the study except for age. A 3:1 k-match approach minimized the prediction error between matched and reference in-study results for both case studies, resulting in differences in geometric mean ratios ranging from -19% to 3% and -27% to 40% for upadacitinib and elagolix, respectively, compared to in-study controls. Similarly, the population pharmacokinetic approach used models developed from phase 1 data in healthy participants and found that the results were generally comparable to the in-study results, with differences in geometric mean ratios ranging from -30% to 17% and -24% to 41% for upadacitinib and elagolix, respectively. These analyses demonstrate that both approaches may be viable alternatives to assess the impact of organ impairment on pharmacokinetics.

Atogepant is an oral calcitonin gene-related peptide receptor antagonist developed for the preventive treatment of migraine. This work aimed to develop a population pharmacokinetic (popPK) model to support dosage regimen selection during the clinical development of atogepant in patients with episodic migraine (EM) or chronic migraine (CM) and to guide the dosing recommendations for regulatory approval. Pharmacokinetic data collected from 12 phase 1 studies, 1 phase 2b/3 study, and 1 phase 3 study in healthy participants and patients with EM were used to develop a popPK model that was externally validated with data from a CM phase 3 study and a phase 3 study in patients with EM for whom two to four classes of conventional oral preventive treatments have failed. The model was built and evaluated using nonlinear mixed-effect modeling and diagnostic assessments. The final model featured three disposition compartments, with linear elimination from the central compartment and a sequential zero-/first-order lagged absorption process. Formulation, dose, food status, liver function, concomitant medication, and body weight were each found to have a statistically significant influence on atogepant's pharmacokinetics. Absorption was affected by dose and formulation, the apparent central volume of distribution (V1/F) increased with body weight, relative bioavailability (Frel) modestly increased with dose, and a high-fat meal lengthened absorption lag time. Severe hepatic impairment and coadministration of itraconazole, quinidine, or a single rifampin dose decreased apparent clearance (CL/F) by ~37% and ~66%, ~29%, and ~13%, respectively, while coadministration of multiple rifampin doses increased CL/F by 1.82-fold. Frel increased by 1.95 and 2.4 fold with coadministration of itraconazole and a single rifampin dose, respectively, and decreased by ~25% with multiple rifampin doses. Mild/moderate renal impairment, coadministration of breast cancer resistance protein (BCRP) inhibitors, BCRP substrates and statins, age, and sex had no clinically relevant effect on atogepant pharmacokinetics. No statistically significant differences were observed in atogepant's pharmacokinetics between healthy participants and patients with migraine. The pharmacokinetics of atogepant are similar in healthy participants and patients with CM or EM. Dose adjustments owing to intrinsic factors of age, sex, race, and body weight, or owing to concomitant medications consisting of P-glycoprotein (P-gp) inhibitors, BCRP inhibitors, oral contraceptive components (ethinyl estradiol and levonorgestrel), famotidine, esomeprazole, sumatriptan, acetaminophen, and naproxen are not necessary. Atogepant's popPK model provides a valuable tool for evaluating specific questions for patients, healthcare providers, and regulatory agencies. Integration into other modeling approaches has also aided in model-informed drug development decisions. NCT03855137 (EudraCT number: 2018-004337-32).

ObjectiveLow-dose methotrexate (LD-MTX), a treatment regimen involving weekly doses ≤20 mg, is widely used in rheumatoid arthritis. Methotrexate (MTX) is primarily excreted via the kidneys. However, the assessment protocol for the adverse reaction risk threshold of the LD-MTX dosing regimen in renal impairment remains inadequate. This study aims to use pharmacovigilance analysis and physiologically-based pharmacokinetic (PBPK) model to combine the analysis of the risk of adverse reactions of LD-MTX in patients with renal impairment.MethodsCollected and analyzed disproportionate signals from adverse reaction reports on MTX in patients with renal impairment from the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2024. The restricted cubic spline (RCS) model explored the nonlinear relationship between MTX maximum plasma concentration and dose to derive risk thresholds. The PBPK model was developed and validated using MTX data in healthy adults, and further extended to chronic kidney disease (CKD) populations to simulate dose risks.ResultsFAERS analysis revealed heightened risks of hematological disorders, hepatic impairment, and pulmonary adverse events (AEs) with MTX in renal impairment. The optimized threshold based on RCS and the PBPK model simulation results indicated that the risk of adverse reactions increased starting from CKD stage 2.ConclusionLD-MTX confers increased adverse reaction risks in renal impairment, notably from CKD stage 2 or higher, necessitating dose adjustments and vigilant monitoring.

Systemic chemotherapy is the cornerstone for treating patients with locally advanced non-small-cell lung cancer (NSCLC). Various adverse effects (AEs) are caused by anticancer therapy, limiting the efficacy of chemotherapy. The precise prediction and early detection of AEs could result in improved efficacy of chemotherapy and quality of life. In the present study, machine learning (ML) algorithms, including random forest (RF), multilayer perceptron and AdaBoost, were employed to develop prediction models for common AEs using dynamic treatment information. A total of 1,659 chemotherapeutic information data points for 403 patients with NSCLC who underwent chemotherapy were extracted from an electronic health record system. A five-fold cross-validation was performed, and the received operating characteristic (ROC) curve and calibration curve were used to evaluate the model performance. Patients with multi-AEs had worse therapeutic efficacy of neoadjuvant chemotherapy (P<0.001; Fisher's exact test) and worse prognosis (P<0.05; log-rank test) compared with patients without multi-AEs. The area under ROC curve values of the RF model were 0.75, 0.74 and 0.76 for predicting myelosuppression, low albumin and hepatic impairment, respectively, and its calibration curve was found linear in the calibration range with regression factor r2≥0.99. The RF model outperformed the other models. A marked performance improvement was observed when <10 selected features were used and feature importance was ranked by Shapley Additive Explanation values. In conclusion, the occurrence of multi-AEs limits the efficacy of chemotherapy and negatively affects the outcomes of patients with lung cancer. ML-based prediction models of chemotherapy-associated AEs may be a breakthrough for improving the prognosis of patients receiving lung cancer chemotherapy.

Characterization of sickle cell disease-associated organ dysfunction in aged Townes HbSS mice and effect of IMA001

Dual anti-HLH and antitumor efficacy of golidocitinib in relapsed/refractory PTCL-associated hemophagocytic lymphohistiocytosis: A retrospective safety and activity analysis

Early efficacy and safety of luspatercept in myelofibrosis-associated anemia: A clinical study with biomarker exploration