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Objective Previous studies have described several prognostic factors for heart failure (HF); however, these results were derived from registries consisting of conventional age groups, which might not represent the increasingly aging society. The present study explored the prognostic factors for all-cause death in hospitalized patients with HF across different age categories using an acute HF registry that included relatively old patients. Methods From a total of 1,971 consecutive patients with HF, 1,136 patients were enrolled. We divided the patients into 4 groups (≤65, 66-75, 76-85, and >85 years old) to evaluate all-cause death and prognostic factors of all-cause death. Results During the mean follow-up period of 1,038 days, 445 patients (39.2%) had all-cause death. A Kaplan-Meier analysis demonstrated significantly higher incidence of all-cause death in the elderly groups than in the younger groups (log-rank p85 years old group. Conclusions Atrial fibrillation was a notable predictor of HF in young patients, whereas frailty and low-grade albuminemia were essential predictive factors of HF in elderly patients. With the increasing number of elderly patients with HF, comprehensive multidisciplinary treatment will be necessary.

Background Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. Methods We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. Results In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors’ prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, "CTC-chip," for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM-chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression-free survival (P = .037) and cancer-specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression-free survival was worse in CTC-positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM-chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.

Background Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055. Conclusions The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

Background: Because the effectiveness of strengthening guideline-based therapy (GBT) to prevent heart failure (HF) rehospitalization of chronic HF patients remains unclear, this study investigated the characteristics of HF patients in the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) acute cohort. Methods and Results: We studied 254 rehospitalized HF patients from the KUNIUMI Registry. Optimized GBT was defined as a Class I or IIa recommendation for chronic HF based on the guidelines of the Japanese Circulation Society. The primary endpoint was all-cause death or first HF rehospitalization after discharge. Outcomes tended to be more favorable for patients who had rather than had not received optimized GBT (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.57-1.19; P=0.27). Similarly, among New York Heart Association (NYHA) Class IV patients, outcomes tended to be more favorable for those who had rather than had not undergone optimized GBT (HR 0.73; 95% CI 0.47-1.12; P=0.15). Importantly, outcomes were significantly more favorable among NYHA Class IV patients aged

Background: The effect of intraindividual variability in lipid levels on the onset of acute coronary syndrome (ACS) remains uncertain. We evaluated the relationship between intraindividual variability in lipid levels and culprit lesion morphologies by optical coherence tomography (OCT). Methods and Results: Seventy-four consecutive patients with ACS whose cholesterol levels were assessed ≥3 times during outpatient visits before the onset of ACS were enrolled in the study; 222 patients without significant stenotic lesions were used as a control group. Based on OCT findings of culprit lesions, ACS patients were categorized into a plaque rupture ACS (PR-ACS) group (n=44) or a non-plaque rupture ACS (NPR-ACS) group (erosion or calcified nodule; n=30). Visit-to-visit variability in lipid levels was evaluated using the corrected variability independent of the mean (cVIM). Patients with ACS had significantly higher low-density lipoprotein cholesterol (LDL-C) levels and cVIM in LDL-C than the control group. The PR-ACS group had significantly higher mean LDL-C levels and greater cVIM in LDL-C than the control group. The PR-ACS group had a significantly higher cVIM than the NPR-ACS group, despite similar mean LDL-C levels. Multivariate analysis revealed that higher cVIM of LDL-C was an independent predictor of PR-ACS (odds ratio 1.06; P=0.018). Conclusions: In addition to the LDL-C level, greater visit-to-visit variability in LDL-C levels may be associated with the onset of ACS induced by plaque rupture.

Kounis syndrome is a rare disease in which coronary spasm or acute coronary syndrome is induced by type I allergy. Concurrence of allergic reaction and chest pain are important clues to establish diagnosis. We report a rare case of Kounis syndrome without obvious signs of allergy. A 52-year-old woman experienced abdominal pain followed by ventricular fibrillation (VF) storm. Ten months earlier, the patient underwent subcutaneous implantable cardioverter-defibrillator implantation based on the previous diagnosis of idiopathic VF. In both episodes, the patient was given dental treatment and administered loxoprofen before VF onset. After we performed loxoprofen provocation test, electrocardiogram revealed ST-segment elevation in leads II, III, and aVF. Moreover, the patient developed VF again. An emergency coronary angiography after recovery showed no significant findings. However, myocardial scintigraphy presented a perfusion-metabolism mismatch in the inferior wall. Furthermore, laboratory test results after provocation revealed increased histamine level. Based on these findings, we diagnosed the patient with Kounis syndrome. Kounis syndrome without typical allergic symptoms is challenging to diagnose. Therefore, suspecting the possibility of allergic reactions and detailed history taking are important, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest. LEARNING OBJECTIVE: Kounis syndrome is a rare coronary disease with vasospasm or plaque rupture, induced by type I allergy. Since Kounis syndrome without typical allergic symptoms is challenging to diagnose, a high index of suspicion is necessary. Detailed history taking can provide important clues to establish diagnosis, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest.

Aims Increased left atrial pressure leads to pulmonary congestion. Although the B-lines in lung ultrasound (LUS) are useful in detecting pulmonary congestion, data regarding the association between B-lines and invasive haemodynamics are inconsistent. This study aimed to explore the correlation of the B-line count by LUS with pulmonary capillary wedge pressure (PCWP) stratified for preserved and reduced ejection fraction (EF) in acute heart failure patients. Methods and results We performed a prospective observational study on 116 hospitalized patients with acute heart failure (mean age, 75.2 ± 10.3 years), who underwent right heart catheterization before discharge. LUS was performed in eight zones within 4 h of right heart catheterization and compared with PCWP separately in each EF group. Cardiac events were recorded 1 year after discharge. PCWP revealed a clear pivot point at which the B-lines began to increase in the overall cohort and each EF. Specific thresholds of the increase in B-lines were identified at 19 and 25 mmHg for preserved and reduced EF, respectively. Residual congestion at discharge was defined as the presence of ≥6 B-lines. Patients with residual congestion had a higher risk for cardiac events than those without residual congestion (hazard ratio, 12.6; 95% confidence interval, 4.71–33.7; log-rank, P < 0.0001). Conclusion A clear pivot point was associated with increased B-lines count in PCWP at 19 and 25 mmHg for preserved and reduced EF, respectively. Moreover, the increased B-line count above the defined cut-off used to quantify residual congestion was associated with significantly worse outcomes.

Recent reports have revealed that patients who experienced early rehospitalization for heart failure (HF) had worse prognoses in terms of all-cause and cardiovascular deaths as compared to those who did not. However, precipitating factors for early rehospitalization for HF remain unknown. In this study, we assessed the precipitating factors for early rehospitalization and their impact in patients with HF.We consecutively included 242 patients (mean age: 80.4 years, females: 46.3%) with a history of rehospitalization for HF. They were divided into 2 groups: the early rehospitalization group (71 patients who were readmitted within 3 months of discharge) and the late rehospitalization group (171 patients who were readmitted after more than 3 months following discharge). During the mean follow-up period of 1,144 days (range: 857-1,417 days), 121 patients (50.0%) died. Kaplan-Meier analysis revealed that patients in the early rehospitalization group had worse prognosis (all-cause death and cardiovascular death) than those in the late rehospitalization group (log-rank p0.001). As the major precipitating factor for rehospitalization, poor compliance with the doctor's instructions on fluid and physical activity restrictions (determined by the patients or their families admittance of non-compliance with the instructions given at the time of discharge) was higher in the early rehospitalization group than in the late rehospitalization group [poor compliance with fluid restriction: 19.7% vs. 7.6% (p = 0.006), poor compliance with physical activity restriction: 21.1% vs. 9.4% (p = 0.013)].We concluded that early hospital readmission in patients with HF was associated with higher mortality rates. Compared to late rehospitalization, precipitating factors for early rehospitalization were more strongly dependent on the self-care behaviors of the patients. A more effective approach, such as multidisciplinary intervention, is essential to prevent early hospital readmission and subsequent poor prognosis.

A 73-year-old woman was diagnosed by bronchoscopic examination with primary left lung cancer (Adenocarcinoma, cT3N0M0, stage IIB), which was closely adjacent to the descending aorta in contrast enhanced computed tomography (CT). This CT did not reveal any invasion of a tumor into the descending aorta, and a dynamic fourth dimension CT (4D-CT) indicated that there was no invasion of the aorta by this tumor, so we decided to perform surgery. The operative procedure was a left lower lobectomy and lymph node dissection with the use of a thoracoscope. An intraoperative finding was that the tumor had not invaded the aorta. There are few reports about the evaluation of vascular invasion using the dynamic 4D-CT. We consider that the dynamic 4D-CT gave very useful information about vascular invasion.

CD155 serves an important role in tumor progression by promoting cell proliferation and migration. CD155 is also involved in the immune evasion of tumor cells, which may cause the development and progression of tumors. Accordingly, CD155 has emerged as a novel target in cancer immunotherapy; however, its expression in lung cancer remains unclear. To assess CD155 expression and its prognostic significance, 96 patients with completely resected pathologic stage I adenocarcinoma of the lung were retrospectively reviewed. Immunohistochemical staining was performed to evaluate CD155 expression on tumor cells. Expression levels of programmed death-ligand 1 (PD-L1), another molecule participating in immune evasion, were also evaluated immunohistochemically. CD155 expression was positive in 37 patients (38.5%). CD155-positivity was associated with aggressive tumor behavior, such as pleural invasion and vascular invasion. In addition, CD155-positivity was a significant factor to predict a poor prognosis (5-year overall survival (OS) rate, 63.3% for CD155-positive patients vs. 93.1% for CD155-negative patients; P0.001). Patients harboring tumors with positive CD155 and PD-L1 expression showed the poorest prognosis (5-year OS rate, 44.4% for both-positive patients vs. 85.4% for the other patients; P0.001). The positive expression status of both CD155 and PD-L1 was a significant and independent unfavorable prognostic factor (hazard ratio, 3.86; 95% confidence interval, 1.51-9.89; P=0.004; in a multivariate analysis). In conclusion, CD155-positivity was associated with aggressive tumor behavior, and was a factor to predict a poor prognosis. Its prognostic impact was enhanced when combined with PD-L1 expression status. These results should be validated in a large-scale study.

There is little evidence to demonstrate the impact of heparin bridging (HB) in major surgery. This study aimed to evaluate the benefits and risks of HB in lung cancer surgery by comparing HB and non-HB (NHB) groups. We extracted patients who were taking an anticoagulant, were diagnosed with lung cancer, and underwent lung resection between April 2014 and March 2018 from a nationwide database in Japan. We compared the HB and NHB groups to determine the benefits and risks of HB. The proportion of postoperative thromboembolism and bleeding events between the HB and NHB groups was the primary outcome. We performed propensity score matching to remove any HB assignment bias. We selected 2416 patients, and among these, 1068 patients had HB and 1348 did not. Propensity score matching extracted 1500 patients: 750 with HB and 750 without HB. After matching, a Chi-square test showed no significant difference in the incidence of postoperative thromboembolism (1.5% vs 0.9%, p value = 0.343) and bleeding events (5.9% vs 4.0%, p value = 0.124) between the two groups. There was no significant difference in the incidence of postoperative thromboembolism and bleeding in the patients with and those without HB.

A sigmoid septum is a state of angulation between the basal interventricular septum and the ascending aorta. Although considered to have no clinical importance, it may cause left ventricular outflow tract obstruction (LVOTO) in a hypercontractile state. Percutaneous transluminal septal myocardial ablation (PTSMA) is a catheter-based therapy aimed at improving drug-refractory symptoms in patients with hypertrophic obstructive cardiomyopathy. Few studies have reported the use of PTSMA for patients with LVOTO caused by sigmoid septum. We present a successful case of a 71-year-old female patient who presented with a long history of exertional dyspnea. The presence of a sigmoid septum was revealed on echocardiography. At rest, the left ventricular outflow tract pressure gradient was low and there were no signs of systolic anterior motion (SAM) of the mitral valve; however, during Valsalva maneuver, the gradient increased significantly, and SAM could be seen. We successfully performed PTSMA, resulting in a significant lowering of the pressure gradient and disappearance of SAM. The patient’s symptoms dramatically improved by the following day.

Background: In-stent neoatherosclerosis (NA) is a risk for future cardiovascular events through atherosclerotic progression in non-stented lesions. Using optical coherence tomography, this study assessed the efficacy of intensive therapy with 10 mg/day rosuvastatin plus 1,800 mg/day eicosapentaenoic acid (EPA) vs. standard 2.5 mg/day rosuvastatin therapy on native coronary plaques in patients with NA. Methods and Results: This was a subgroup analysis of the randomized LINK-IT trial, which was designed to compare changes in the lipid index in NA between intensive and standard therapy for 12 months. In all, 42 patients with native coronary plaques and NA were assessed. Compared with standard therapy, intensive therapy resulted in greater decreases in serum low-density lipoprotein cholesterol concentrations and greater increases in serum 18-hydroxyeicosapentaenoic acid concentrations, with significantly greater decreases in the lipid index and macrophage grade in both NA (-24 vs. 217 [P

Background: The clinical frailty scale (CFS) predicts late mortality in patients undergoing transcatheter aortic valve replacement. We evaluated the CFS and other parameters associated with 1-year mortality after balloon aortic valvuloplasty (BAV). Methods and Results: Between January 2013 and May 2018, 148 patients with severe aortic stenosis (AS) who underwent BAV at the present hospital were enrolled. We recorded pre-procedural CFS grade, baseline characteristics, echocardiographic, and hemodynamic parameters. To investigate the potential risk to patients before BAV, we evaluated the Society of Thoracic Surgeons (STS) score. After patients who underwent surgical aortic valve replacement, transcatheter aortic valve replacement or repeat BAV were excluded, we investigated 1-year survival. Of 127 patients, 41 (32.3%) died ≤1 year after BAV, 8 of whom (19.5% of all-cause deaths) had cardiac deaths. Higher grade of CFS and STS score significantly correlated with 1-year mortality. Severe frailty and the high operative risk group (CFS ≥7 and STS score ≥8.7%) had an extremely poor prognosis (1-year mortality, 81.2%). Conclusions: In this BAV cohort, severe frailty was a predictor of 1-year mortality in elderly patients with severe AS.

Background: Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as "cholesterol uptake capacity (CUC)". Objective: To clarify the cross-sectional relationship between CUC and coronary plaque properties. Methods: We enrolled 135 patients to measure CUC and assess the morphological features of angiographic stenosis by optical coherence tomography (OCT). We estimated the extent of the lipid-rich plaque by multiplying the mean lipid arc by lipid length (lipid index). The extent of the OCT-detected macrophage accumulation in the target plaque was semi-quantitatively estimated using a grading system. Results: Lipid-rich plaque lesions were identified in 125 patients (92.6%). CUC was inversely associated with the lipid index (R = -0.348, P < 0.0001). In addition, CUC was also inversely associated with macrophage score (R = - 0.327, P < 0.0001). Conversely, neither circulating levels of HDL cholesterol nor apoA1 showed a similar relationship. Conclusions: We demonstrated that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation, suggesting that CUC could be useful for cardiovascular risk stratification.

The prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression. There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 53.0% in PD-L1-positive patients versus 70.1% in PD-L1-negative patients; P = 0.117). Among NLR-low (P = 0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact (P = 0.680). When NLR status and tumoral PD-L1 status were combined, “NLR-low and PD-L1-negative” was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P = 0.007) and OS (hazard ratio, 0.260 [0.091 to 0.745]; P = 0.012). These results suggest the prognostic impact of tumoral PD-L1 expression might be influenced by the status of NLR.

The impact of perioperative heparin bridging (HB) for lung surgery in patients on anti-clotting drugs remains unclear. We performed a retrospective study to assess its effect on surgical safety by comparing HB and non-HB groups. This study included 274 consecutive patients on anti-clotting drugs who underwent surgery for lung cancer. Of these, 77 received HB and 197 did not. Propensity score matching extracted 124 patients, consisting of 62 patients with HB and 62 patients without HB. Endpoints were surgical safety. There was no statistically significant difference in the outcomes of surgical safety outcomes between the HB and non-HB group after propensity-score matching, operative time (172 vs. 203 min, p = 0.131), volume of blood loss (60 vs. 70 ml, p = 0.335), need for intraoperative RBC transfusion (3.2 vs. 6.5%, p = 0.680), chest tube drainage volume on the 1st postoperative day (200 vs. 200 ml, p = 0.796), and chest tube placement duration (3 vs. 3 days, p = 0.606). The influence of perioperative HB on postoperative thromboembolic or bleeding events in lung cancer surgery is not obvious, but its surgical safety appears to be acceptable.

Background Although patients with a cancer history have a 2 to 3 times higher risk for acute coronary syndrome (ACS), the morphological characteristics of ACS culprit plaque in those patients and their relations with clinical outcomes remain unknown. Methods and Results This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent optical coherence tomography‐guided emergent percutaneous coronary intervention. Patients were categorized into those without a cancer history, those with a cancer history, and those currently receiving cancer treatment. ACS culprit lesions were classified as plaque rupture, plaque erosion, or calcified nodule using optical coherence tomography. Plaque erosion frequency was significantly higher in culprit lesions of patients with current cancer and patients with cancer history than in those of patients without cancer history (56.3% versus 61.7% versus 36.5%). Calcified nodule incidence was significantly higher in patients without cancer history than in patients with current cancer and patients without cancer history (patients with current cancer: 12.4% versus patients without cancer history: 25.5% versus patients without cancer history: 12.6%, P P P =0.002). Nonplaque rupture in ACS culprit lesions was independently associated with major adverse cardiovascular events (HR, 1.60; P =0.011). Conclusions Patients with a cancer history had significantly worse clinical outcomes after ACS than those without a cancer history. Those with a cancer history had significantly higher plaque erosion and calcified nodule incidences in the ACS culprit lesions, which might partly explain their worse clinical outcomes. Registration URL: www.umin.ac.jp/ctr/index.htm . Unique Identifier: UMIN000038442.

Both extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are used for the surgical treatment of malignant pleural mesothelioma (MPM). This study aimed to compare the operative and clinical outcomes and survival between EPP and P/D.We performed a retrospective analysis of the surgical and clinical data of 40 patients who underwent either EPP (n = 18) or P/D (n = 22) for MPM at our institution between January 2000 and December 2018.In comparison to EPP, P/D was associated with a higher intraoperative bleeding volume (1175 vs 1805 ml, p = 0.0020) and greater duration of postoperative thoracic drainage (3 vs 16 days, p 0.0001). Adjuvant chemotherapy was more common after P/D (81.8%) than after EPP (33.3%; p = 0.0024). For epithelioid-type MPM, overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients who underwent P/D in comparison to those who underwent EPP (p = 0.040 and p = 0.015, respectively), with no difference for the biphasic and sarcomatoid types of MPM. A Cox proportional hazards regression model identified P/D as a significant favorable prognostic factor for OS [hazard ratio (HR), 0.391; 95% confidence interval (CI), 0.175-0.871; p = 0.022] and RFS (HR, 0.418; 95% CI, 0.190-0.920; p = 0.030).Based on our findings, P/D may be superior to EPP for improving the prognosis of patients with resectable epithelioid-type MPM.

We report the case of a 70-year-old man who developed a splenic infarction due to a thrombus in the pulmonary vein (PV) stump after left upper lobectomy (LUL). Preoperative imaging showed a mass measuring > 5 cm in the upper lobe of the left lung, and sputum cytology revealed squamous cell carcinoma. Therefore, video-assisted thoracoscopic LUL was performed. The postoperative course was uneventful but biochemical blood tests showed an increased inflammatory response. Contrast-enhanced computed tomography revealed splenic infarction and a thrombus in the left superior PV stump. Prompt treatment with anticoagulants was administered, and the patient was discharged with mild recovery. However, the patient developed cerebral infarction after discharge and died 33 days after the surgery. Splenic infarction is a rare postoperative complication, with only three reported cases, including this report. However, this condition should be considered along with PV thrombus when evaluating an increased inflammatory response after LUL.

In our previous study, a microfluidic system was developed based on podoplanin detection for capturing circulating tumor cells (CTCs), derived from malignant pleural mesothelioma (MPM). However, non-epithelioid MPM shows low podoplanin protein expression compared with that in epithelioid MPM; thus, some CTC populations may be missed. To overcome this limitation, a new CTC-detection chip was developed by combining the conventional podoplanin antibody (clone: NZ-1.2) with an epidermal growth factor receptor (EGFR)-targeted antibody (cetuximab). The cell-capture efficiency of the Cocktail-chip reached 100% in all the histological MPM cell lines. The median CTC-counts from 19 patients with MPM (epithelioid/non-epithelioid: 10/9) with the NZ-1.2- and Cocktail-chips were 1 and 3 (P=0.311) in 1 ml peripheral blood, 1.5 and 2 (P=0.332) in epithelioid MPM, and 1 and 3 (P=0.106) in non-epithelioid MPM, respectively. Overall, the Cocktail-chip showed an improved ability to detect more CTCs in patients with non-epithelioid MPM compared with that in the conventional NZ-1.2-chip, showing non-significant, but higher CTC detection. Furthermore, CTC-counts, determined using the Cocktail-chip were significantly correlated with the clinical stage of non-epithelioid MPM. In epithelioid MPM, the Cocktail-chip achieved a CTC-detection efficiency equivalent to that in the conventional NZ-1.2-chip. The Cocktail-chip enabled sensitive CTC detection of all histological MPM, including the non-epithelioid subtype, which may provide a foundation for the diagnosis, treatment, and prognosis of MPM progression.

A 58-year-old woman with pallor on her left hand due to chronic hemodialysis presented with a recent intractable skin ulcer on her left 3rd finger; the skin perfusion pressure (SPP) was 19 mmHg. Preoperative angiography revealed an occluded proximal left radial artery, no communication between the ulnar and superficial palmar arteries, several collaterals from the left ulnar to the radial artery, and no visualization of the finger arteries. Successful endovascular therapy to the occluded radial artery increased flow to the arteriovenous fistula (AVF), but not to the fingertips. Slightly compressing the AVF augmented the flow and wound blush at the wound sites on the 3rd fingertip, leading to a diagnosis of hemodialysis access-induced distal ischemia (HAIDI). Surgical AVF banding with intra-operative SPP monitoring improved the SPP to 34 mmHg, leading to complete wound healing over 1 month with a preserved AVF. We performed a bilateral temporal artery biopsy and diagnosed giant cell arteritis. As the angiographic wound blush at wound sites is reportedly an important factor for wound healing, angiography with AVF manual compression is essential to diagnose HAIDI and evaluate the blood flow for wound healing.