Cefiderocol (CFDC) is a novel siderophore cephalosporin with a unique cell entry feature and a high stability against a wide range of β-lactamases. We conducted antimicrobial susceptibility testing on 89 clinical isolates of carbapenem-non-susceptible gram-negative bacilli (CNS-GNB) strains detected at our hospital, evaluating the efficacy of novel antibiotics including CFDC, ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/cilastatin/relebactam. The strains included were as follows, 21 carbapenemase-producing Enterobacterales (CPE), 40 carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 28 Stenotrophomonas maltophilia. Carbapenemase production were detected using NG-Test® CARBA 5. Carbapenemase genes were analyzed by PCR-sequencing and extended-spectrum β-lactamase (ESBL) genes were detected by PCR. CPE isolates produced 17 IMP-, 3 NDM-, and one KPC-type carbapenemases, and 12 out of 21 CPE isolates produced ESBLs. All 40 CRPA did not produce carbapenemases. All 21 CPE isolates and 95% of CRPA were susceptible to CFDC. Colistin were intermediate against all CPE and 92.5% of CRPA isolates. In S. maltophilia isolates, susceptibility to CFDC and trimethoprim-sulfamethoxazole were 100% and 89.3 %. Although non-susceptibility to CFDC appeared in 2 CRPA isolates, MIC90 of CFDC was within susceptible range against all three groups of clinical isolates. CFDC showed significant promise as a treatment option for infections caused by CNS-GNB.
Background/Objectives: Nivolumab plus ipilimumab (IO-IO) provides durable clinical benefit in metastatic renal cell carcinoma (mRCC), yet long-term real-world data focusing on progression-free and treatment-free (PF-TF) survival remain limited. This study aimed to evaluate the long-term outcomes of IO-IO with a particular focus on the frequency and clinical characteristics of PF-TF. Methods: We retrospectively analyzed 63 patients with mRCC treated with first-line IO-IO across eight institutions with a minimum potential follow-up of five years. Progression-free survival (PFS), PFS2, and overall survival (OS) were assessed. PF-TF was defined as absence of disease progression and any cancer-directed therapy at the five-year landmark. Clinical and treatment-related factors were compared between patients with and without PF-TF. Results: The median PFS, PFS2, and OS were 7.5 (95% confidence interval [CI], 5.1-13.3), 26.2 (95% CI, 13.6-46.6), and 47.4 months (95% CI, 29.3-not reached), respectively. At 5 years, 11 patients (17%) achieved PF-TF. Baseline characteristics, IMDC risk classification, and peripheral blood biomarkers were not predictive of PF-TF. PF-TF was associated with the absence of bone metastases, presence of lymph node metastases, and occurrence of immune-related adverse events (irAEs), as well as the delayed onset of irAEs. No PF-TF patients required corticosteroid pulse therapy, and durable PF-TF was observed even after early treatment discontinuation due to adverse events. Conclusions: IO-IO demonstrated sustained long-term efficacy in real-world practice, with a subset achieving durable PF-TF. These findings highlight IO-IO as a strategy capable of providing long-term disease control with reduced treatment burden in selected patients with mRCC.
ABSTRACT Enfortumab vedotin (EV) is a crucial treatment for patients with metastatic urothelial carcinoma (mUC). However, a significant proportion of patients experience adverse events (AEs). The identification of biomarkers for AEs is imperative for the detection and treatment of AEs at an early stage. In this exploratory study, we aimed to identify biomarkers of AEs in patients with mUC treated with EV. We retrospectively examined 10 factors identified from the data of 116 patients with mUC treated with EV to identify biomarkers (age, body mass index, C‐reactive protein level, Eastern Cooperative Oncology Group performance status, eosinophil proportion, history of diabetes, lymphocyte proportion, neutrophil proportion, neutrophil‐to‐lymphocyte ratio, and platelet count) associated with the occurrence of AEs of any grade. The candidate biomarkers were measured at the start of EV treatment. The least absolute shrinkage and selection operator method was used to select the most useful parameters for predicting AE occurrence. Among the 10 factors, eosinophil proportion was identified as the only potential biomarker. The optimal cutoff value for eosinophil proportion against the occurrence of AEs of any grade was 2.5% (area under the curve = 0.625). Univariable logistic regression analyses showed that an eosinophil proportion of ≥ 2.5% was a risk factor for AE development (odds ratio = 4.35, 95% confidence interval = 1.35–14.0). Therefore, the results of this exploratory study indicated that an eosinophil proportion of ≥ 2.5% at the start of EV treatment may be a candidate biomarker for the occurrence of AEs of any grade.
Abstract Study design A retrospective case control study Objective To predict proximal junctional kyphosis (PJK) risk by normalizing individual vertebral bone strength using the ratio of vertebral Hounsfield unit (HU) values around the upper instrumented vertebrae (UIV). Summary of background data PJK poses a significant challenge in treating patients after adult spinal deformity (ASD) surgery. While the vertebral body HU value is associated with PJK risk, the optimal threshold remains unclear, and a relative assessment of HU values within individuals has not been conducted. Methods Data on patients who underwent corrective fusion of the middle to lower thoracic region of the pelvis for ASD were assessed. The 126 patients were categorized into PJK and non-PJK groups. We compared the patients’ backgrounds, vertebral body HU, and junctional HU ratio, defined as the HU value of UIV+1 divided by the HU value of UIV (HU UIV+1 /HU UIV ). The UIV+2/UIV+1 HU ratio was calculated similarly. Results The PJK and non-PJK groups included 30 and 96 patients, respectively. After propensity score matching, 28 patients from each group were analyzed. HU values at UIV+2 and UIV+1 (117.0 ± 46.6 vs 145.1 ± 45.9, p=0.018, and 105.5 ± 36.2 vs 147.3 ± 44.9, p<0.001, respectively) were lower in the PJK group. Junctional HU ratio was significantly lower in the PJK group (0.88 ± 0.18 vs 1.13 ± 0.25, p<0.001), and receiver operating characteristic analysis showed that the junctional HU ratio had the highest discriminative ability (area under the curve 0.812). At the optimal cutoff value (HU ratio of 0.905), the sensitivity and specificity for PJK were 64.3% and 89.3%, respectively. Conclusions A low junctional HU ratio was strongly associated with PJK after ASD surgery. This parameter reflects the bone strength mismatch at the proximal junction and may help improve preoperative risk assessment and UIV selection.
STUDY DESIGN:Cross-sectional reliability study. OBJECTIVE:To propose and validate a novel biomechanical classification for high-grade spondylolisthesis (HGS) that incorporates compensatory mechanisms into the assessment of sagittal alignment patterns. BACKGROUND:Existing classifications of HGS are primarily descriptive, rely on parameters often distorted by sacral endplate dysplasia, offer limited guidance for surgical decision-making and do not completely capture the spectrum of compensation in sagittal alignment. The new classification system defines four alignment types: type 1: proportioned sagittal alignment (SVA ≤50 mm, LSA ≥90°, IP ≤T11, LL Apex ≤L3). Type 2: compensated lower lumbar hypolordosis, with cranialization of IP and/or LL Apex. Type 3: compensated lumbosacral kyphosis (LSA <90° despite SVA ≤50 mm). Type 4: sagittal malalignment with exhausted compensation (SVA >50 mm). METHODS:Fourteen spine surgeons from 12 countries evaluated 29 anonymized cases of HGS using the new classification. Each case was presented with full-spine and lumbosacral anteroposterior and lateral standing radiographs. Classifications were repeated in two separate rounds. Interobserver reliability was assessed with Fleiss' Kappa, while intraobserver reliability was evaluated with Cohen Kappa and simple percentage agreement. RESULTS:Interobserver reliability was almost perfect (Fleiss' Kappa=0.916; 95% CI: 0.888-0.945; overall concordance 82.8%). Intraobserver reliability was equally high (mean Cohen Kappa=0.958; 95% CI: 0.926-0.991; mean agreement 97.0%). CONCLUSION:This novel biomechanical classification provides a reproducible framework to describe HGS without reliance on approximated parameters. By integrating SVA, LSA, IP, and LL Apex, it captures compensated and decompensated states of malalignment with direct therapeutic implications. The system demonstrated excellent reliability and may serve as a foundation for future surgical guidelines.
