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.
Introduction: Cervicobrachial symptoms are common causes of disability worldwide, yet the cost-effectiveness of combination therapy versus monotherapy remains unclear. In this nationwide multicenter study, we aimed to compare the economic value of multiple-drug therapy with that of monotherapy for cervicobrachial symptoms. Methods: This prospective observational study, conducted through the Japanese Society for Spine Surgery and Related Research, included 261 adults with cervicobrachial symptoms across 28 institutions (July 2020 to July 2022). Patients received monotherapy (n=112) or multiple-drug therapy (n=149) using five pre-specified agents: loxoprofen, celecoxib, acetaminophen, tramadol-acetaminophen, and pregabalin. The primary outcome was quality-adjusted life years (QALYs), calculated from monthly EuroQol 5-Dimension 5-Level assessments over six months. The secondary outcomes were drug costs and incremental cost-effectiveness ratios (ICERs), evaluated against Japan's reference threshold of 5,000,000 JPY per QALY. Results: Mean QALY gains were similar between the monotherapy (0.00267±0.00544) and multiple-drug therapy (0.00284±0.00774) groups, with no statistically significant difference (p>0.05). However, total drug costs were substantially higher with multiple-drug therapy (19,243 JPY vs. 8,275 JPY). ICERs were more favorable for monotherapy (3,093,957 JPY/QALY) than for multiple-drug therapy (6,781,101 JPY/QALY). Among agents used as monotherapy, loxoprofen (744,409 JPY/QALY) and acetaminophen (781,293 JPY/QALY) showed the most favorable cost-effectiveness profiles, whereas tramadol-acetaminophen (6,370,451 JPY/QALY) and pregabalin (10,995,651 JPY/QALY) had the least favorable cost-effectiveness. Most QALY gains occurred during the first three months in both groups. Conclusions: Multiple-drug therapy approximately doubled pharmaceutical costs without providing additional QALY gains over six months. Monotherapy, particularly with non-steroidal anti-inflammatory drugs or acetaminophen, offers superior cost-effectiveness and should be prioritized as first-line treatment. These findings underscore the need for restraint in polypharmacy and provide real-world evidence to guide clinical decision-making and national healthcare policy.
