We present a rare case of duodenal metastasis of hepatocellular carcinoma (HCC) following multimodal therapy, in which the patient died shortly after the palliative surgical intervention. An 80-year-old man with HCC associated with chronic hepatitis B was admitted to our emergency department owing to complaints of anorexia and vomiting. He had undergone conversion surgery following systemic therapy that included a multikinase inhibitor and immune checkpoint inhibitors. Three months prior, transcatheter arterial chemoembolization and radiofrequency ablation had been performed for two intrahepatic recurrences. Contrast-enhanced abdominal computed tomography and upper gastrointestinal endoscopy revealed multiple intrahepatic recurrences, pulmonary metastases, and duodenal metastasis of HCC. Following the resolution of obstructive jaundice, the patient underwent palliative gastrojejunostomy. His postoperative course was complicated by progressive renal dysfunction and coagulopathy, and he died on postoperative day 15. In the literature review, including this case, 61 patients with duodenal involvement of HCC were identified. Although a small subset of patients achieved long-term survival after curative-intent surgery performed under highly selective conditions, the overall life expectancy for most patients remained poor. Even with palliative intent, surgical intervention for unresectable duodenal involvement caused by HCC should be pursued with careful consideration of the patient’s prognosis and systemic condition.
The optimization of antifungal therapy based on pharmacokinetics/pharmacodynamics (PK/PD) principles is crucial for improving outcomes in invasive fungal infections; however, its clinical application faces considerable hurdles. This review presents a comprehensive overview of current knowledge and aims to bridge basic research and clinical practice. We outline the fundamental concepts of PK/PD and the characteristics of the major antifungal drug classes (polyenes, echinocandins, flucytosines, and azoles), along with preclinical evidence defining the main PK/PD indices (maximum concentration to minimum inhibitory concentration ratio, 24-h area under the concentration-time curve to the minimum inhibitory concentration ratio, and percentage of time the concentration remains above the minimum inhibitory concentration). Key challenges hindering translation are critically analyzed, including substantial knowledge gaps-particularly for filamentous fungi; high inter-patient pharmacokinetic variability complicating standard dosing; limitations of therapeutic drug monitoring (TDM); the narrow therapeutic window requiring careful balance between efficacy and toxicity; and the role of suboptimal exposure in antifungal resistance. Current strategies, including antifungal stewardship, are discussed, and future directions highlighted. Prioritizing research on understudied pathogens, improving TDM, developing novel agents, and strengthening collaboration between basic research and clinical practice are essential. A deeper understanding and effective application of PK/PD principles are vital to advance personalized antifungal therapies and improve patient outcomes.
Background:Parkinson's disease (PD) patients under medical treatment experience motor complications (MCs), namely, ON/OFF fluctuations (ON/OFF) and dyskinesias. Methods:We assessed 120 newly diagnosed PD patients after the initiation of medical treatment who were followed up for at least 24 months. We reviewed the latency of ON/OFF or dyskinesias by months and calculated the levodopa dose (LD), levodopa dose divided by daily intake (LDdiv), and levodopa equivalent dose (LED). We estimated cumulative incidence and median latency by Kaplan-Meier survival analysis. We classified patients with MCs into four groups and patients with ON/OFF or dyskinesias into three groups, according to latency. Results:Seventy-six patients experienced MCs with a median latency of 28 months. Fifty-seven patients experienced ON/OFF and 19 experienced dyskinesias with a median latency of 28 and 50 months, respectively. The medication dose at which each patient experienced ON/OFF or dyskinesias varied widely. The median LD, LDdiv, and LED was 300 (237.5-350), 100 (79-111), and 300 (250-450) mg at the onset of MCs; 300 (200-300), 100 (83-125), and 300 (249-400) mg at the onset of ON/OFF; and 400 (375-500), 125 (105-133), and 600 (466-722.75) mg at the onset of dyskinesias, respectively. Consistently, the shortest latency group had the lowest medication dose, while the longest latency group had the highest. Five patients experienced dyskinesias before ON/OFF, with similar medication doses at the onset of ON/OFF and dyskinesias. Some patients experienced ON/OFF but have not yet developed dyskinesias under a comparable medication dose as patients who experienced dyskinesias; the latter had a significantly younger age at onset. Conclusions:The pathophysiological backgrounds and changes causing ON/OFF or dyskinesias are not the same for all patients. The presence of ON/OFF and higher medication doses does not always cause dyskinesias. A younger age at onset may be associated with the occurrence of dyskinesias.
OBJECTIVES:To clarify the relationship between acute kidney injury (AKI) and vancomycin use in patients with renal impairment and to establish a risk score for AKI. METHODS:In this retrospective, multicentre, observational cohort study, trough and peak blood samples were collected from patients who initiated vancomycin therapy. The cumulative incidence of AKI within 14 days was compared among three groups classified according to renal function (estimated glomerular filtration rate ≥ 60, 30-59 and <30 mL/min/1.73 m2). The risk score and predicted probability of AKI incidence were calculated. AKI was defined in accordance with the Kidney Disease Improving Global Outcomes criteria. RESULTS:The incidence of AKI was 11.7% (99/847). No statistically significant difference was detected in the cumulative incidence of AKI among the three groups (P = 0.103). Cox proportional hazard analysis showed that the use of tazobactam/piperacillin [HR: 3.3, 95% CI (2.18-4.99), 2 points], vasopressors/inotropes [HR: 3.0, 95% CI (2.02-4.51), 2 points] and area under the concentration-time curve (AUC) on Day 2 [500-600 µg·h/mL: HR, 2.4, 95% CI (1.50-3.89), 1 point; >600 µg·h/mL: HR, 4.4, 95% CI (2.62-7.37), 3 points] were significantly related to the development of AKI. The predicted probabilities of AKI incidence were <5% (low-risk), 5% to <20% (moderate-risk), 20% to <40% (high-risk) and 40% to 67% (very high-risk), with total points of 0, 1-2, 3-4 and ≥5, respectively. CONCLUSIONS:A risk prediction model was developed for AKI based on AUC exposure and concomitant medications, and no difference in AKI risk was observed across renal function categories.
