Voriconazole (VRCZ) exhibits highly variable pharmacokinetics. Although CYP2C19 poor metabolizers are common in Japan, routine genetic testing is rarely performed in daily clinical practice. Consequently, existing population pharmacokinetic (Pop-PK) models that lack genetic data require external validation in Japanese clinical settings. This study aimed to identify the most accurate nongenetic Pop-PK model for this population and elucidate the factors influencing prediction errors. We retrospectively analyzed 174 adult inpatients who received VRCZ within the first 14 d of therapy. Eight Pop-PK models were evaluated using prediction error metrics and specific clinical criteria. For the best-performing model, normalized prediction distribution error (NPDE) analysis was conducted. Subsequently, a classification and regression tree (CART) analysis with leave-one-out cross-validation (LOOCV) was performed to identify factors associated with prediction accuracy. Model H, incorporating the albumin-bilirubin (ALBI) score, performed best (relative root mean square error 2.97, criteria 33.91%, median prediction error (MDPE) -29.06%). However, NPDE analysis (mean 0.774, variance 2.394) revealed residual systematic underprediction and substantial unmodeled variability. CART analysis identified C-reactive protein (CRP) as the primary determinant of accuracy. While the best model (age, platelet count, serum creatinine, and CRP) achieved a training accuracy of 69.5%, internal validation via LOOCV yielded an accuracy of 56.9% and a multi-class area under the receiver operating characteristic curve of 0.568. While the ALBI-score-based Model H is the most accurate, predictions remain limited in high-inflammation states due to inherent stochastic variability. Stratifying patients by baseline CRP level is crucial for optimizing the initial VRCZ dosing.
BACKGROUND Tyrosine kinase inhibitors (TKIs) are effective for chronic myeloid leukemia (CML), but they may cause pulmonary toxicity, including pleural effusion. In severe cases, respiratory failure requiring mechanical ventilation can occur, and weaning from the ventilator may be difficult. Although multidisciplinary rehabilitation strategy may be necessary for favorable outcomes and physical function in such situations, it has not been well described. CASE REPORT A 73-year-old woman with CML was responding well to TKI treatment, but prolonged pleural effusion as an adverse effect led to home oxygen therapy 9 years after diagnosis. She was admitted with acute type II respiratory failure (pH: 7.076, PaO2: 181.1 mmHg, and PaCO2: 213.3 mmHg) triggered by pneumonia and required intubation and mechanical ventilation. Rehabilitation began the day after admission and advanced progressively. Extubation was considered impossible due to persistent hypercapnia, so a tracheostomy was performed on day 11. A structured multidisciplinary rehabilitation program was continued throughout the acute and recovery phases. Her physical function gradually improved, although without complete ventilator weaning. She regained independent ambulation and achieved a Barthel index score of 100. Daytime ventilator support was discontinued, while nocturnal ventilation was maintained. After caregiver training and coordinated discharge planning, she was discharged home on hospital day 105 with nighttime mechanical ventilation. CONCLUSIONS Early and coordinated multidisciplinary rehabilitation can facilitate functional independence and home discharge, even when complete ventilator weaning is impossible, in patients with cancer treatment-related pulmonary toxicity. Collaboration across specialties may be essential in managing complex cases of prolonged respiratory failure.
This study aimed to investigate the impact of sepsis on red blood cell (RBC) velocity, diameter, and categories of skeletal muscle capillaries 3–4 h after sepsis onset. Male Wistar rats (9–11 weeks old, n = 14) were randomly classified into sham and cecal ligation and perforation (CLP) groups, respectively. In vivo imaging of capillaries in the spinotrapezius muscle was performed using stain-free videocapillaroscopy. RBC velocity and capillary diameter were analyzed. Capillaries were classified into three groups: (1) continuously flowing capillaries defined as maintaining continuous flow for >30 s; (2) intermittently flowing, showing brief stagnation lasting <10 s; (3) stopped-flow, showing no flow for >10 s during 30 s of observation periods. The number of capillaries in each category is compared between the groups. The RBC velocity of the CLP group was significantly lower than that of the sham group (p = 0.01), but the capillary diameter was not different between the groups. The CLP group showed a trend of a weak negative correlation between capillary diameter and RBC velocity (r2 = 0.16, p = 0.08), but the sham group did not. No significant difference was observed between the groups in each capillary category. These results suggest that sepsis decreases RBC velocity in resting skeletal muscle capillaries but has no effect on capillary category or diameter.
BACKGROUND:Malnutrition is common in older patients with heart failure and predicts poor outcomes. However, the prognostic value of assessing muscle function and fat stores alongside GLIM remains unclear. We therefore tested whether assessing handgrip strength and fat mass index alongside GLIM improves risk stratification for mortality. METHODS:We conducted a post hoc analysis of patients ≥65 years in the multicenter observational FRAGILE-HF cohort. Malnutrition was evaluated using GLIM criteria at hospital discharge. Handgrip strength and fat mass index were also measured at discharge; low handgrip strength was defined as <28 kg in men and <18 kg in women, and low fat mass index as <4.62 kg/m2 in men and <5.86 kg/m2 in women. Patients were classified into four groups by GLIM-defined malnutrition and low handgrip strength and, separately, by GLIM-defined malnutrition and low fat mass index. Associations with 2-year all-cause mortality were examined using Cox proportional hazards regression. RESULTS:Of 1332 patients, 834 were analyzed (median age, 81 years; 57.6% men). In four-group analyses, GLIM-defined malnutrition with low handgrip strength (HR, 2.06; 95% CI, 1.14-3.73; P = 0.02) and GLIM-defined malnutrition with low fat mass index (HR, 1.87; 95% CI, 1.25-2.80; P = 0.01) had higher mortality than the corresponding reference groups (absence of malnutrition with normal handgrip strength and absence of malnutrition with normal fat mass index). CONCLUSION:Assessing handgrip strength or fat mass index alongside GLIM identified subgroups at higher risk of 2-year mortality.
[Purpose] This cross-sectional study investigated the association between shoulder external rotation strength and real-world arm use in patients with mild post-stroke hemiparesis. [Participants and Methods] Seventeen participants with ≥Brunnstrom stage IV and active shoulder flexion ≥110 degrees were assessed. External rotation strength was measured using a hand-held dynamometer. Real-world arm use was evaluated using the Motor Activity Log. [Results] External rotation strength was associated with Motor Activity Log scores and grip strength. Participants with movement-induced shoulder pain demonstrated lower external rotation strength compared with those without pain. [Conclusion] Reduced shoulder external rotation strength may contribute to decreased real-world arm use in mild hemiparesis.
