St. Luke's International Hospital

Targeted temperature management (TTM) for patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) has not been fully studied. This study aimed to investigate the association between blood glucose levels during TTM and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing ECPR.

This was a secondary analysis of the SAVE-J II study, a retrospective, multicenter study of OHCA patients treated with ECPR in Japan. The average inpatient blood glucose levels for days 2-4 was divided into four categories (Category 1: 80-140 mg/dL, Category 2: 140-180 mg/dL, Category 3: 180-300 mg/dL, and Category 4: 300 mg/dL or more). The primary outcome was a favorable neurological status.

Multivariable analyses were performed for 891 enrolled patients. There were 153, 278, 142, and 18 patients in categories 1, 2, 3, and 4, respectively. Category 3 blood glucose levels were significantly more associated with unfavorable outcomes than Category 2 (adjusted OR, 0.45; 95 % CI, 0.24-0.81; p = 0.01). Although not statistically significant, Category 1 blood glucose levels may indicate a potential trend toward favorable neurological outcomes compared to Category 2. [adjusted OR, 1.41; 95 % CI, 0.96-2.08; p = 0.079].

During TTM, blood glucose levels of 180 mg/dL or more were significantly more associated with unfavorable outcomes than those of 140-180 mg/dL, in patients on ECPR. Further studies to evaluate more intensive glucose control than the current target of 140-180 mg/dL are required.

Rationale: Equivocal interstitial lung abnormality (ILA) involves less than 5% of any lung zone or presents unilaterally without satisfying the diagnostic criteria for ILA. However, the prevalence and prognosis of equivocal ILA are unknown. Objectives: We sought to investigate the prevalence and long-term prognosis of equivocal ILA. Methods: This retrospective cohort study included individuals who underwent chest computed tomography as part of a health check-up program in 2010 at St. Luke's International Hospital in Tokyo, Japan. ILA and equivocal ILA were diagnosed using the Fleischner Society criteria. The primary outcome was the annual rate of forced vital capacity (FVC) decline in the groups with ILA, equivocal ILA, and no ILA, evaluated using a mixed-effects model. Radiological progression was also evaluated. Results: Among the 20,896 individuals included in the study, ILA and equivocal ILA were present in 2.0% (95% confidence interval = 1.8-2.2) and 0.4% (95% confidence interval = 0.4-0.5) of individuals, respectively. Follow-up pulmonary function tests were available for 18,101 (87%) individuals, with a median follow-up time of 8.3 years (interquartile range = 4.0-9.0). Individuals with equivocal ILA showed a significantly greater rate of FVC decline than those without ILA (-36.7 vs. -27.7 ml/yr; P = 0.008). Of the 86 individuals with equivocal ILA, 20 (23%) exhibited progression during the follow-up period; of these, 19 progressed to definite ILA. Conclusions: Individuals with equivocal ILA showed a significant tendency for FVC decline compared with those without ILA. A considerable number of cases progressed to definite ILA, warranting careful attention. Clinicians should be aware that even mild interstitial changes that do not meet the current criteria for ILA may deteriorate.

In the randomized phase III TASUKI-52 trial, nivolumab with carboplatin, paclitaxel, and bevacizumab significantly prolonged the progression-free survival (PFS) of treatment-naive patients with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC). Here, we report the long-term outcomes of patients treated with nivolumab plus carboplatin, paclitaxel, and bevacizumab with 3 years of follow-up.

Patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 mutations were randomized (1:1) to receive either nivolumab or placebo, in addition to carboplatin, paclitaxel, and bevacizumab, every 3 weeks. Treatment was continued for a maximum of six cycles. The endpoints included PFS, overall survival (OS), and safety. Exploratory analyses included efficacy and safety in subgroups.

A total of 550 patients were randomized to the nivolumab arm (n = 275) and placebo arm (n = 275). At the minimum follow-up of 36.1 months, PFS was consistently longer in the nivolumab arm than in the placebo arm (median, 10.6 vs. 8.2 months; hazard ratio [HR], 0.59; 95 % confidence interval [CI], 0.47-0.73; P < 0.0001), with PFS rates of 20.2 % vs. 4.9 %. The median OS was 31.6 months (95 % CI, 26.8-36.5) in the nivolumab arm and 24.7 months (95 % CI, 21.1-28.0) in the placebo arm (HR, 0.71; 95 % CI, 0.57-0.88), with OS rates of 44.2 % and 32.3 %, respectively. Of note, PFS and OS favored the nivolumab arm across patients with different PD-L1 expression levels, and regardless of baseline brain metastasis status. Grade 3-4 treatment-related adverse events occurred in 76.2 % and 74.9 % of the patients in the nivolumab and placebo arms, respectively, while no new safety concerns were identified.

Nivolumab, in addition to carboplatin, paclitaxel, and bevacizumab, remained to demonstrate significantly longer PFS and long-term OS benefit compared with placebo in the first-line treatment of patients with nonsquamous NSCLC. The extended follow-up identified no new safety signals.