Objective The study objective was to examine the incidence, risk factors, and mortality rate of acute exacerbation of interstitial lung diseases in patients with lung cancer undergoing pulmonary ...resection in a large-scale multi-institutional cohort. Methods We retrospectively analyzed 1763 patients with non–small cell lung cancer who had undergone pulmonary resection and presented with a clinical diagnosis of interstitial lung diseases between January 2000 and December 2009 at 61 hospitals in Japan. The incidence and outcomes of acute exacerbation within 30 days from the operation were investigated. Univariate and multivariate logistic regression analyses were used to identify independent risk factors of acute exacerbation. Results Acute exacerbation occurred in 164 patients (9.3%; 95% confidence interval, 8.0-10.8), with a mortality rate of 43.9%, and was the top cause of 30-day mortality (71.7%). The following 7 independent risk factors of acute exacerbation were identified: surgical procedures, male sex, history of exacerbation, preoperative steroid use, serum sialylated carbohydrate antigen KL-6 levels, usual interstitial pneumonia appearance on computed tomography scan, and reduced percent predicted vital capacity. Surgical procedures showed the strongest association with acute exacerbation (using wedge resection as the reference, lobectomy or segmentectomy: odds ratio, 3.83; 95% confidence interval, 1.94-7.57; bi-lobectomy or pneumonectomy: odds ratio, 5.70; 95% confidence interval, 2.38-13.7; P < .001). The effect of perioperative prophylactics, such as steroids and sivelestat, was not confirmed in this study. Conclusions Pulmonary resection for patients with lung cancer with interstitial lung diseases may provoke acute exacerbation at a substantially high rate and has high associated mortality. Surgical procedures that proved to be a risk factor for acute exacerbation should be chosen cautiously for these high-risk patients.
Acute kidney injury (AKI) is relatively common after cardiothoracic surgery for type A acute aortic dissection (TA-AAD) and increases mortality. We investigated the incidence and risk factors for AKI ...in patients with TA-AAD and its impact on their outcomes. The records of 375 consecutive patients who underwent surgical treatment for TA-AAD from October 2007 to March 2013 were analyzed retrospectively. We defined AKI using the Kidney Disease Improving Global Outcomes criteria, which are based on serum creatinine concentration or glomerular filtration rate. We used Kaplan-Meier methods and multivariate Cox proportional hazards regression to assess the impact of AKI on both mortality and major adverse cardiovascular and cerebrovascular events. We also examined the association between risk factors and AKI using logistic regression modeling. Postoperative AKI was observed in 165 patients (44.0%). The overall 30-day and mid- to long-term mortality was 1.6% and 8.8%, respectively. Mortality and major adverse cardiovascular and cerebrovascular events correlated significantly with the severity of AKI, and multivariate analysis showed that AKI stage 3 (the most sever stage) was an independent risk factor for mortality (hazard ratio 6.83, 95% confidence interval 2.52 to 18.52) after adjustment for important confounding factors. Extracorporeal circulation time, body mass index, perioperative peak serum C-reactive protein concentration, renal malperfusion, and perioperative sepsis were found to be risk factors for AKI. In conclusion, AKI was common in patients who underwent surgery for type A acute aortic dissection. The severity of AKI strongly influences patient outcomes, so it should be recognized promptly and treated aggressively when possible.
Objectives Patients with interstitial lung diseases have a poor prognosis and are at increased risk of developing lung cancer. We evaluated the survival and predictors of survival after surgical ...resection in lung cancers in patients with interstitial lung diseases. Methods We retrospectively analyzed data from 1763 patients with non–small cell lung cancer with a clinical diagnosis of interstitial lung disease who underwent pulmonary resection between 2000 and 2009 at 61 Japanese institutions. Results Male patients (90.4%) and smokers (93.8%) were in the majority. The overall 5-year survival was 40%. The 5-year survivals were 59%, 42%, 43%, 29%, 25%, 17%, and 16% for patients with stage Ia, Ib, IIa, IIb, IIIa, IIIb, and IV, respectively. Patients with stage IA had a 5-year survival of 33.2%, 61.0%, and 68.4% in the wedge resection, segmentectomy, and lobectomy groups, respectively (log-rank test, P = .0038). The leading cause of death was cancer recurrence (50.2%), followed by respiratory failure (26.8%). Wedge resection reduced mortality due to respiratory failure when compared with that of lobectomy ( P = .022). Multivariable analysis revealed that the type of surgical procedure, predicted percent vital capacity, and tumor locations were independent predictors for survival. The 5-year survival was 20% for patients with stage Ia with a predicted percent vital capacity of 80% or less, and 64.3% for patients with a predicted percent vital capacity greater than 80% (log-rank test, P < .0001). Conclusions In these patients, there are competing risks of death. Wedge resection reduced death caused by respiratory failure but resulted in poorer long-term prognosis than lobectomy. For patients with poor predictors of survival, such as predicted percent vital capacity of 80% or less, surgical resection should be limited.
Background The clarification of cutaneous dendritic cell subset and the role of thymic stromal lymphopoietin (TSLP) signaling in epicutaneous sensitization with protein antigens, as in the ...development of atopic dermatitis, is a crucial issue. Objectives Because TSLP is highly expressed in the vicinity of Langerhans cells (LCs), we sought to clarify our hypothesis that LCs play an essential role in epicutaneous sensitization with protein antigens through TSLP signaling. Methods By using Langerin-diphtheria toxin receptor knock-in mice and human Langerin-diphtheria toxin A transgenic mice, we prepared mice deficient in LCs. We also prepared mice deficient in TSLP receptors in LCs by using TSLP receptor–deficient mice with bone marrow chimeric technique. We applied these mice to an ovalbumin (OVA)-induced epicutaneous sensitization model. Results Upon the epicutaneous application of OVA, conditional LC depletion attenuated the development of clinical manifestations as well as serum OVA-specific IgE increase, OVA-specific T-cell proliferation, and IL-4 mRNA expression in the draining lymph nodes. Consistently, even in the steady state, permanent LC depletion resulted in decreased serum IgE levels, suggesting that LCs mediate the TH 2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. Conclusion LCs initiate epicutaneous sensitization with protein antigens and induce TH 2-type immune responses via TSLP signaling.
Background Nonsense mutations in filaggrin (FLG) represent a significant genetic factor in the cause of atopic dermatitis (AD). Objective It is of great importance to find drug candidates that ...upregulate FLG expression and to determine whether increased FLG expression controls the development of AD. Methods We screened a library of bioactives by using an FLG reporter assay to find candidates that promoted FLG mRNA expression using a human immortalized keratinocyte cell line (HaCaT). We studied the effect of the compound on keratinocytes using the human skin equivalent model. We examined the effect of the compound on AD-like skin inflammation in NC/Nga mice. Results JTC801 promoted FLG mRNA and protein expression in both HaCaT and normal human epidermal keratinocytes. Intriguingly, JTC801 promoted the mRNA and protein expression levels of FLG but not the mRNA levels of other makers for keratinocyte differentiation, including loricrin, keratin 10, and transglutaminase 1, in a human skin equivalent model. In addition, oral administration of JTC801 promoted the protein level of Flg and suppressed the development of AD-like skin inflammation in NC/Nga mice. Conclusion This is the first observation that the compound, which increased FLG expression in human and murine keratinocytes, attenuated the development of AD-like skin inflammation in mice. Our findings provide evidence that modulation of FLG expression can be a novel therapeutic target for AD.
Objectives This study sought to assess the influence of chronic kidney disease (CKD) classification on clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). ...Background The prognostic value of impaired renal function according to CKD classification has not been thoroughly investigated in very elderly TAVI cohorts. Methods Data from 642 consecutive patients who underwent TAVI were prospectively collected. Clinical outcomes were compared in enrolled patients, divided into CKD stage 1+2, CKD stage 3a, CKD stage 3b, and CKD stage 4 on the basis of estimated glomerular filtration rate ≥60, 45 to 59, 30 to 44, and 15 to 29 ml/min/1.73 m2 , respectively. Results Among the study patients (mean age: 83.5 ± 6.5 years, logistic European System for Cardiac Operative Risk Evaluation score 20.0% range: 13.6% to 28.8%), 34% were categorized as CKD stage 1+2 (n = 218), 28.3% as CKD stage 3a (n = 182), 28.2% as CKD stage 3b (n = 181), and 9.5% as CKD stage 4 (n = 61). Thirty-day and cumulative 1-year mortality rates increased significantly across the 4 groups (6.9% vs. 8.8% vs. 13.3% vs. 26.2%, p = 0.002, and 17.2% vs. 23.4% vs. 29.2% vs. 47.8%, p < 0.001, respectively). After adjustment for considerable influential confounders in a Cox multivariate regression model, CKD stage 4 was associated with increased risk for 30-day mortality (hazard ratio: 3.04; 95% confidence interval CI: 1.43 to 6.49; p = 0.004), and CKD stages 3b and 4 were related to increased cumulative 1-year mortality (hazard ratios: 1.71 and 2.91; 95% CI: 1.09 to 2.68 and 1.73 to 4.90; p = 0.020 and p < 0.001, respectively) compared with CKD stage 1+2 as the referent. Conclusions Classification of CKD stages before TAVI allows risk stratification for early and midterm clinical outcomes. TAVI for patients with CKD stage 4 is still considered challenging because of high mortality rates after the procedure.
The aim of this study was to examine whether left atrial (LA) strain and synchrony can be assessed using three-dimensional (3D) speckle-tracking echocardiography (STE) and how 3D STE parameters are ...modified by atrial fibrillation (AF).
LA peak ventricular systolic longitudinal strain (LSs), circumferential strain (CSs), and area strain (ASs) and LA peak pre-atrial contraction longitudinal strain, circumferential strain (CSa), and area strain were determined using 3D STE, and SDs of times to peaks of regional LA strain were calculated as indices of LA dyssynchrony. Three-dimensional speckle-tracking was able to measure LA strain in 75 of the 77 healthy subjects and in all 47 patients with AF (31 with paroxysmal AF PAF and 16 with permanent AF).
The mean time for analysis with 3D STE was 18% shorter than with two-dimensional (2D) STE (P < .05). On 3D STE, values of interobserver and intraobserver variability of LA strain were <10% and <12%, respectively. LSs, CSs, ASs, and 2D STE LSs were reduced in patients with PAF compared with controls, and further reductions of these parameters were observed in patients with permanent AF. SDs of LSs, CSs, and ASs were similarly larger in patients with PAF and in those with permanent AF compared with controls. Patients with PAF showed smaller LA peak pre-atrial contraction longitudinal strain, CSa, and LA peak pre-atrial contraction area strain and larger SDs of CSa and LA peak pre-atrial contraction area strain compared with controls. In multivariate analysis, 2D STE LSs (P = .044), LSs (P = .040), ASs (P = .007), and CSa (P = .020) were independent predictors of PAF.
Three-dimensional speckle-tracking enables the measurement of both LA strain and synchrony with excellent reproducibility. Three-dimensional LA strain appears to be beneficial compared with 2D LA strain for identifying patients with PAF.
Objective We aimed to investigate risk factors associated with more rapid growth of abdominal aortic aneurysms (AAA) <50 mm (small AAAs) in Japan. Methods We retrospectively investigated the clinical ...data of 374 patients with small AAAs (maximum diameter, ≤50 mm) who were referred to The University of Tokyo Hospital, Tokyo Medical University Hospital, or Saitama Medical Center, between 1995 and 2008. Results A total of 374 patients (321 men and 53 women) were followed up for a median of 66 months. The median diameter on initial examination was 40 mm, and the median growth rate of the AAAs was 2.1 mm/y. The growth rate of AAAs with an initial diameter ≥45 mm was significantly greater than those with an initial diameter <45 mm (3.3 mm/y vs 2.0 mm/y, respectively; P = .007). The growth rate of AAAs was significantly greater in patients with hypertension than in those without (2.3 mm/y vs 1.7 mm/y, respectively; P = .006) and in patients with a family history of aortic aneurysm than in those without (4.2 mm/y vs 2.0 mm/y, respectively; P = .009). Logistic regression analysis revealed that a large initial diameter and family history of aortic aneurysm were independent predictors of accelerated growth rate of small AAAs in Japan. Conclusions In the present study, a large initial diameter and family history of aortic aneurysm were independent risk factors for more rapid growth of small AAAs. Although few studies have reported similar findings thus far, family history of aortic aneurysm should be carefully considered during follow-up of patients with small AAAs.
Docetaxel plus ramucirumab could be a promising treatment for chemo-naive elderly patients with NSCLC, but high incidence of febrile neutropenia (FN) is a critical concern. We thus adopted a routine ...primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF) to reduce FN and maximize the efficacy of docetaxel plus ramucirumab in elderly patients.
This is a single arm phase 2 trial for chemo-naive elderly patients (aged ≥75 y) with advanced NSCLC. Docetaxel (60 mg/m2, d 1) plus ramucirumab (10 mg/kg, d 1) with PEG-G-CSF (3.6 mg, d 2) was administered every 3 weeks until progression. The primary end point was overall response rate (ORR) (expected ORR: 35%).
Between February 2018 and January 2021, 54 patients were enrolled. Median age was 78 (range: 75–86). A total of 21 (38.9%) partial response, 22 (40.7%) stable disease, nine (16.7%) progressive disease, and two (3.7%) not assessable were confirmed, resulting in ORR of 38.9% (90% confidence interval CI: 27.7%–51.0%) and disease control rate of 79.6%. Median progression-free survival and overall survival were 5.2 (95% CI: 4.2–6.9) and 12.7 (95% CI: 10.2–18.9) months, respectively. There were one (1.9%) FN, two (3.7%) bleeding grade greater than or equal to 3, and one (1.9%) treatment-related death (pneumonitis). Pneumonitis occurred in five patients (9.3%). Main adverse events grade greater than or equal to 3 were observed: four (7%) thrombocytopenia; three (5.6%) neutropenia; six (11.1%) hyposodium; five (9.3%) infection; five (9.3%) hypertension; four (7.4%) anorexia; and three (5.6%) oral mucositis.
Docetaxel plus ramucirumab with PEG-G-CSF revealed efficacy and safety for chemo-naive elderly patients with NSCLC. Primary prophylactic PEG-G-CSF highly prevented FN.
Abstract Background The majority of patients who undergo coronary arteriography are discharged from the hospital on the day of the procedure or on the following day. The aim of this study is to ...investigate whether the change in serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) on the day following cardiac catheterization can predict the development of contrast-induced nephropathy (CIN). Methods This is a multicenter prospective observational study, which consists of 860 patients who underwent cardiac catheterization. We measured SCr and eGFR before cardiac catheterization, on the following day, and 48–72 h post-procedure. Definition of CIN is changes in SCr ≥0.5 mg/dL or ≥25% from baseline 48–72 h after contrast exposure. Results CIN occurred in 40 patients. SCr levels significantly increased from a baseline of 1.55 ± 1.08 mg/dL to 1.79 ± 1.26 mg/dL on the following day in patients with CIN ( p < 0.0001), but significantly decreased from a baseline of 1.21 ± 0.65 mg/dL to 1.18 ± 0.61 mg/dL on the following day in those without CIN ( p < 0.0001). eGFR significantly decreased from a baseline of 47.3 ± 28.3 mL/min/1.73 m2 to 40.6 ± 26.7 mL/min/1.73 m2 on the following day in patients with CIN ( p < 0.0001), but significantly increased from a baseline of 53.1 ± 22.0 mg/dL to 53.6 ± 21.2 mg/dL on the following day in those without CIN ( p = 0.0236). Receiver operating characteristic curve analysis indicated that SCr change ≥0.1 mg/dL area under the curve (AUC) = 0.852, sensitivity 72.5%, specificity 86.1% and eGFR change ≤−1.1 mL/min/1.73 m2 (AUC = 0.789, sensitivity 85.0%, specificity 64.9%) were the best cut-off values for predicting CIN. Multivariate logistic regression showed that a change in SCr ≥0.1 mg/dL odds ratio (OR), 29.3; 95% confidence interval (CI), 10.8–96.2 and change in eGFR ≤−1.1 mL/min/1.73 m2 (OR, 69.7; 95% CI, 13.3–952) were powerful independent predictors of CIN. Conclusions Changes in SCr and eGFR on the day following cardiac catheterization predict the development of CIN.
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