Tumor-derived mitochondrial formyl peptides suppress tumor immunity through modification of the tumor microenvironment.

Mitochondrial N-formylpeptides are released from damaged or dead cells to the extracellular spaces and cause inflammatory responses. The role of mitochondrial N-formylpeptides in aseptic systemic inflammatory response syndromes induced by trauma or cardiac surgery has been well investigated. However, there are no reports regarding the role of mitochondrial N-formylpeptides in cancer. In this study, we investigated the role of tumor cell-derived mitochondrial N-formylpeptides in anti-tumor immunity using knockout murine tumor cells of mitochondrial methionyl-tRNA formyltransferase (MTFMT), which catalyze N-formylation of mitochondrial DNA-encoded proteins. There was no apparent difference among the wild-type and MTFMT-knockout clones of E.G7-OVA cells with respect to morphology, mitochondrial dynamics, glycolysis and oxidative phosphorylation, oxygen consumption rate, or in vitro cell growth. In contrast, in vivo tumor growth of MTFMT-knockout cells was slower than that of wild-type cells. A reduced number of myeloid-derived suppressor cells and an increase of cytotoxic T-lymphocytes in the tumor tissues were observed in the MTFMT-knockout tumors. These results suggested that tumor cell-derived mitochondrial N-formylpeptides had a negative role in the host anti-tumor immunity through modification of the tumor microenvironment.

Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm.

PURPOSE: Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). METHODS: We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. RESULTS: Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. CONCLUSION: The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.

Validating a New Surgical Gouge for Autogenous Ear Reconstruction During Simulated Microtia Workshops.

Autologous ear reconstruction remains a gold standard surgical technique for the treatment of external ear deformities. This highly technical procedure requires experience, an understanding of aesthetic principles, and a surgical approach that can consistently produce optimal results. As an experienced microtia surgeon having trained under Dr Satoru Nagata, the senior author has emphasized the importance of appropriate surgical tools during this procedure. Here, we present results of a novel surgical handle and gouge meant to optimize complex cartilage carving. The senior author regularly holds microtia workshops to help train individuals around the United States. During 2 of such workshops held in 2022, participants were given access to both the standard, commercially available surgical gouge as well as a prototype of a novel surgical gouge developed by the authors. Participants were then given a Likert-scale survey to assess their subjective feedback for both tools. Twenty-seven total participants completed the postworkshop survey. Cumulatively, the results demonstrated that participants rated the custom gouge significantly higher than its counterpart (4.2 versus 3.2, P<0.001). They also had a significantly higher likelihood of using the custom gouge again (4.1 versus 3.2, P=0.023). The custom gouge designed by the senior author demonstrated higher subjective ratings when compared with what is currently available on the market. This serves as a primary validation study that demonstrates feasibility for further assessment in a true operative setting.

Assessing the Current State of Microtia Reconstruction in the United States.

OBJECTIVE: Microtia is a congenital ear deformity with variability in surgical techniques and tools across surgeons pursuing an autologous reconstruction. Different techniques have emerged over time, and surgeons opt for various tools to aid in creating the complex three-dimensional cartilaginous ear framework. The purpose of this study was to understand the current state of microtia reconstruction in the United States. METHODS: Microtia surgeons affiliated with the nonprofit, Ear Community, were invited to complete a 20-item survey. Data were collected on demographic information regarding surgeons, considerations when approaching microtia repair in patients, and techniques and comfort levels. Additional data were collected on materials, tools, flaps, and skin grafts used for reconstruction. RESULTS: Twenty-two surgeons responded to the survey reporting 3 different techniques learned and utilized in practice including the Brent, Nagata, and Firmin techniques. About two-thirds of surgeons were "extremely comfortable" with their techniques and one-third were "extremely uncomfortable" or "somewhat uncomfortable." Most respondents reported using a tunneled temporoparietal fascial flap or a posterior fascial flap along with a full-thickness skin graft for the second stage (ear elevation). Most surgeons utilized a combination of scalpels and gouges when carving the ear framework along with sutures or wire. CONCLUSIONS: This study highlights the current state of autogenous microtia reconstruction underscoring the variability in approaches and preferences. These data may guide future directions that aim to improve patient outcomes. Surgeons may gain insight into different practices and choose to adopt different aspects to enhance their surgical approach.

Recent trends in AI applications for pelvic MRI: a comprehensive review.

Magnetic resonance imaging (MRI) is an essential tool for evaluating pelvic disorders affecting the prostate, bladder, uterus, ovaries, and/or rectum. Since the diagnostic pathway of pelvic MRI can involve various complex procedures depending on the affected organ, the Reporting and Data System (RADS) is used to standardize image acquisition and interpretation. Artificial intelligence (AI), which encompasses machine learning and deep learning algorithms, has been integrated into both pelvic MRI and the RADS, particularly for prostate MRI. This review outlines recent developments in the use of AI in various stages of the pelvic MRI diagnostic pathway, including image acquisition, image reconstruction, organ and lesion segmentation, lesion detection and classification, and risk stratification, with special emphasis on recent trends in multi-center studies, which can help to improve the generalizability of AI.

Long-term prognostic value of changes in left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has emerged as a more sensitive index than LV ejection fraction (LVEF) for detecting subclinical LV dysfunction. We examined whether changes in GLS values are associated with the long-term prognosis of patients with a preserved LVEF and acute decompensated heart failure (HF). METHODS: We studied 100 consecutive patients (mean age: 71 years) who were hospitalized for HF with preserved ejection fraction (HFpEF) and had a preserved LVEF (≥ 50%) in both the acute and stable phases. We performed two-dimensional speckle-tracking echocardiography in the acute (GLS-acute) and stable (GLS-stable) phases at a median of 2 and 347 days after admission, respectively, and calculated the rate of change of the absolute value of GLS-stable with respect to that of GLS-acute. An improved GLS was defined as a rate of change in GLS ≥ 16%, and a non-improved GLS was a rate of change < 16%. The primary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: During a mean follow-up period of 1218 days, MACE occurred in 26 patients, including 8 all-cause deaths and 18 readmissions for HF. The rate of change in GLS for patients with MACE was lower than compared to those without MACE (10.6% vs 26.0%, p < 0.001). Multivariate Cox regression analyses indicated the rate of change in GLS was an independent predictor of MACE (p < 0.001). A non-improved GLS was correlated with a high risk of MACE. CONCLUSION: Changes in GLS values could be useful for the long-term risk stratification of patients hospitalized for HFpEF and persistently preserved LVEF.

Resting echocardiographic parameters can exclude significant coronary artery disease: A comparison with coronary computed tomography angiography.

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.

Possible Mechanisms of Stiffness Changes Induced by Stiffeners and Softeners in Catch Connective Tissue of Echinoderms.

The catch connective, or mutable collagenous, tissue of echinoderms changes its mechanical properties in response to stimulation. The body wall dermis of sea cucumbers is a typical catch connective tissue. The dermis assumes three mechanical states: soft, standard, and stiff. Proteins that change the mechanical properties have been purified from the dermis. Tensilin and the novel stiffening factor are involved in the soft to standard and standard to stiff transitions, respectively. Softenin softens the dermis in the standard state. Tensilin and softenin work directly on the extracellular matrix (ECM). This review summarizes the current knowledge regarding such stiffeners and softeners. Attention is also given to the genes of tensilin and its related proteins in echinoderms. In addition, we provide information on the morphological changes of the ECM associated with the stiffness change of the dermis. Ultrastructural study suggests that tensilin induces an increase in the cohesive forces with the lateral fusion of collagen subfibrils in the soft to standard transition, that crossbridge formation between fibrils occurs in both the soft to standard and standard to stiff transitions, and that the bond which accompanies water exudation produces the stiff dermis from the standard state.

Management of a Gluteal Noninvoluting Hemangioma With Glue Embolization and Excision.

Noninvoluting congenital hemangiomas (NICHs) persist in a high-flow state into childhood and often require surgical excision. The inherent vascular nature of these tumors make effective surgical treatment challenging. Here we report on a patient that underwent intraoperative glue embolization and complete excision of a large gluteal NICH. Concurrent glue embolization followed by complete excision allows for decreased intraoperative blood loss and easier discrimination between the tumor and surrounding structures. Treating difficult vascular tumors with a multidisciplinary approach and subsequent intraoperative glue embolization with surgical excision allows for an effective, single-stage approach to NICHs.

Diagnosis and Treatment of a Nonhealing Wound Secondary to a Reepithelialized Hair Tourniquet With Ultrasound.

A 9-month-old girl presented with a chronic wound on the dorsal surface of her toe that failed 6 months of medical management. Due to the prolonged clinical course, there was a concern for a foreign body. Intraoperative ultrasound was utilized to identify linear echogenic structures, which were excised and consistent with reepithelialized hairs secondary to hair-thread tourniquet syndrome. There were also erosive changes to the underlying phalanx. Intraoperative ultrasound was also used to guide the incision size and confirm the complete removal of the hairs.

Revisiting the U-Shaped Elevator for Zygomaticomaxillary Fracture: Study and Comparison of Elevators for Zygomaticomaxillary Fracture Reduction.

The authors present the case of a 15-year-old male who sustained a unilateral zygomaticomaxillary complex fracture and underwent open reduction and rigid internal fixation, for which a U-shaped elevator was utilized. The authors discuss techniques in reduction and fixation of zygomaticomaxillary complex fractures, focusing on the use of various elevators during reduction, including straight-type and curved elevators. The U-shaped elevator is a handheld tool with bilateral symmetrically curved ends that is seldom used, despite its specific benefits including nonslip serrated tips, symmetrical nature that allows for direct loading needed for accurate reduction, visualization of the fracture site, and avoidance of tissue compression during elevation.

Clinical applications of artificial intelligence in liver imaging.

This review outlines the current status and challenges of the clinical applications of artificial intelligence in liver imaging using computed tomography or magnetic resonance imaging based on a topic analysis of PubMed search results using latent Dirichlet allocation. LDA revealed that "segmentation," "hepatocellular carcinoma and radiomics," "metastasis," "fibrosis," and "reconstruction" were current main topic keywords. Automatic liver segmentation technology using deep learning is beginning to assume new clinical significance as part of whole-body composition analysis. It has also been applied to the screening of large populations and the acquisition of training data for machine learning models and has resulted in the development of imaging biomarkers that have a significant impact on important clinical issues, such as the estimation of liver fibrosis, recurrence, and prognosis of malignant tumors. Deep learning reconstruction is expanding as a new technological clinical application of artificial intelligence and has shown results in reducing contrast and radiation doses. However, there is much missing evidence, such as external validation of machine learning models and the evaluation of the diagnostic performance of specific diseases using deep learning reconstruction, suggesting that the clinical application of these technologies is still in development.

New trend in artificial intelligence-based assistive technology for thoracic imaging.

Although there is no solid agreement for artificial intelligence (AI), it refers to a computer system with intelligence similar to that of humans. Deep learning appeared in 2006, and more than 10 years have passed since the third AI boom was triggered by improvements in computing power, algorithm development, and the use of big data. In recent years, the application and development of AI technology in the medical field have intensified internationally. There is no doubt that AI will be used in clinical practice to assist in diagnostic imaging in the future. In qualitative diagnosis, it is desirable to develop an explainable AI that at least represents the basis of the diagnostic process. However, it must be kept in mind that AI is a physician-assistant system, and the final decision should be made by the physician while understanding the limitations of AI. The aim of this article is to review the application of AI technology in diagnostic imaging from PubMed database while particularly focusing on diagnostic imaging in thorax such as lesion detection and qualitative diagnosis in order to help radiologists and clinicians to become more familiar with AI in thorax.

Suppression of high mobility group box 1 in B16F10 tumor does not inhibit the induction of neoantigen-specific T cells.

Accumulated clinical data of immune checkpoint blockades have suggested the importance of neoantigens in cancer immunity. Tumor antigens are released from dead cancer cells together with cellular components, such as damage-associated molecular patterns (DAMPs), into the tumor microenvironment. We recently reported that high mobility group box 1 (HMGB1), a representative DAMP molecule, showed a negative impact on anti-tumor immunity. However, a positive role of HMGB1 in the initiation of innate and subsequent adaptive immunity has also been demonstrated; thus, the effects of HMGB1 on anti-tumor immunity have not been well understood. In this study, we identified nine immunogenic neoantigen epitopes of B16F10 murine melanoma cells and subsequently investigated the effects of suppression of HMGB1 on the induction of neoantigen-specific immunity using HMGB1-knockout tumors. Neoantigen-reactive T cells were expanded in B16F10 tumor-bearing mice, and T cell receptor repertoire analysis suggested that neoantigen-reactive T cells were oligo-clonally increased in B16F10 tumor bearers. An increase of neoantigen-reactive T cells and oligoclonal expansion of the T cells were similarly detected in HMGB1-knockout tumor-bearing mice. The induction of neoantigen-specific immunity under the suppression of HMGB1 in the tumor microenvironment shown in this study supports further development of combination therapy of HMGB1 suppression with neoantigen-targeted cancer immunotherapies, including immune checkpoint blockade therapy.

Physical and chemical aspects at the interface and in the bulk of CuInSe2-based thin-film photovoltaics.

Chalcopyrite CuInSe2 (CISe)-based thin-film photovoltaic solar cells have been attracting attention since the 1970s. The technologies of CISe-based thin-film growth and device fabrication processes have already been put into practical applications and today commercial products are available. Nevertheless, there are numerous poorly understood areas in the physical and chemical aspects of the underlying materials science and interfacial and bulk defect physics in CISe-based thin-films and devices for further developments. In this paper, current issues in physical and chemical studies of CISe-based materials and devices are reviewed. Correlations between Cu-deficient phases and the effects of alkali-metals, applications to lightweight and flexible solar minimodules, single-crystalline epitaxial Cu(In,Ga)Se2 films and devices, differences between Cu(In,Ga)Se2 and Ag(In,Ga)Se2 materials, wide-gap CuGaSe2 films and devices, all-dry processed CISe-based solar cells with high photovoltaic efficiencies, and also fundamental studies on open circuit voltage loss analysis and the energy band structure at the interface are among the main areas of discussion in this review.

Association of resting left ventricular global longitudinal strain with myocardial perfusion abnormalities evaluated by 13 N-ammonia positron emission tomography in patients with stable angina pectoris and normal left ventricular ejection fraction.

AIMS: Little is known about whether resting left ventricular global longitudinal strain (GLS) impairment is associated with myocardial perfusion abnormalities evaluated using 13 N-ammonia positron emission tomography (13 N-NH3 -PET)-myocardial perfusion imaging (MPI). This study aimed to investigate the correlation between resting GLS and myocardial perfusion parameters in patients with a normal left ventricular ejection fraction (LVEF). We evaluated whether resting GLS can predict myocardial perfusion abnormalities in these patients. METHODS AND RESULTS: We selected 157 patients with suspected stable angina pectoris who underwent both ATP-stress NH3 -PET-MPI and 2-dimentional speckle tracing echocardiography. All subjects had a preserved LVEF and no known history of myocardial infarction. Patients were stratified into Group N (normal perfusion; summed stress score [SSS], 0-3; n = 101), Group M (mildly to moderately abnormal perfusion; SSS, 4-11; n = 41), or Group S (severely abnormal perfusion; SSS, 12+; n = 15). GLS was more impaired as myocardial perfusion abnormality severity increased (-17.9 ± 2.9% for Group N, -16.8 ± 3.1% for Group M, and -14.2 ± 3.5% for Group S; p < .001). GLS was weakly but significantly correlated with SSS (R = .32, p < .001), summed difference score (R = .32, p < .001), and myocardial blood flow during stress (R = -0.27, p < .001). Multivariate logistic regression analysis showed that male sex, diabetes mellitus, systolic blood pressure, and GLS were independent predictors of myocardial perfusion abnormality defined as Groups M and S. Additionally, the area under the curve for GLS for detecting myocardial perfusion abnormality was .65, and the optimal cutoff value for GLS was -16.5%, with sensitivity and specificity of 59% and 66%, respectively. CONCLUSION: In patients with suspected angina pectoris, resting GLS impairment despite a normal LVEF might aid the detection of hemodynamically significant coronary artery disease.

Cardiac perturbations after high-intensity exercise are attenuated in middle-aged compared with young endurance athletes: diminished stress or depleted stimuli?

Strenuous exercise elicits transient functional and biochemical cardiac imbalances. Yet, the extent to which these responses are altered owing to aging is unclear. Accordingly, echocardiograph-derived left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) and high-sensitivity cardiac troponin I (hs-cTnI) were assessed before (pre) and after (post) a 60-min high-intensity cycling race intervention (CRIT60) in 11 young (18-30 yr) and 11 middle-aged (40-65 yr) highly trained male cyclists, matched for cardiorespiratory fitness. LV and RV GLS were measured at rest and during a semirecumbent exercise challenge performed at the same intensity (young: 93 ± 10; middle-aged: 85 ± 11 W, P = 0.60) pre- and post-CRIT60. Augmentation (change from rest-to-exercise challenge) of LV GLS (pre: -2.97 ± 0.65; post: -0.82 ± 0.48%, P = 0.02) and RV GLS (pre: -2.08 ± 1.28; post: 3.08 ± 2.02%, P = 0.01) was attenuated and completely abolished, in the young following CRIT60, while augmentation of LV GLS (pre: -3.21 ± 0.41; post: -3.99 ± 0.55%, P = 0.22) and RV GLS (pre: -3.47 ± 1.44; post: -1.26 ± 1.00%, P = 0.27) was preserved in middle-aged following CRIT60. While serum hs-cTnI concentration increased followingCRIT60 in the young (pre: 7.3 ± 1.6; post: 17.7 ± 1.6 ng/L, P < 0.01) and middle-aged (pre: 4.5 ± 0.6; post: 10.7 ± 2.0 ng/L, P < 0.01), serum hs-cTnI concentration increased to a greater extent in the young than in the middle-aged following CRIT60 (P < 0.01). These findings suggest that functional and biochemical cardiac perturbations induced by high-intensity exercise are attenuated in middle-aged relative to young individuals. Further study is warranted to determine whether acute exercise-induced cardiac perturbations alter the adaptive myocardial remodeling response.NEW & NOTEWORTHY High-intensity endurance exercise elicits acute cardiac imbalances that may be an important stimulus for adaptive cardiac remodeling. This study highlights that following a bout of high-intensity exercise that is typical of routine day-to-day cycling training, exercise-induced autonomic, biochemical, and functional cardiac imbalances are attenuated in middle-aged relative to young well-trained cyclists. These findings suggest that aging may alter exercise-induced stress stimulus response that initiates cardiac remodeling in athlete's heart.

Ultrastructural Features of the Aortic Wall in a Patient with Kommerell Diverticulum.

We report on the ultrastructural features of the aortic wall in a patient with Kommerell diverticulum. A 70-year-old woman with a right aortic arch, aberrant left subclavian artery, and Kommerell diverticulum underwent a successful total arch replacement plus the frozen elephant trunk procedure with anatomical left subclavian artery reconstruction. Small pieces of the ascending aorta, distal arch, right common carotid artery, and left subclavian artery were investigated ultrastructurally. In the ascending aortic wall, multiple cystic cavities were observed in the subintimal region of the media by scanning electron microscopy. Changes in organelles, including mild dilation of rough-surfaced endoplasmic reticulum and mitochondrial swelling and degrading, were also observed in all specimens by transmission electron microscopy. These ultrastructural features may indicate the fragility or stress of the aortic wall and are useful when considering the early surgical intervention of a patient with Kommerell diverticulum.

The peritumoral hypointense rim around hepatocellular carcinoma on T2*-weighted magnetic resonance imaging: radiologic-pathologic correlation.

BACKGROUND: A peritumoral hypointense rim (PTHR) is sometimes observed around hepatocellular carcinoma (HCC) on T2*-weighted images (T2*WIs). We aimed to investigate the association between the PTHR and histopathologic findings on T2*WIs. METHODS: We assessed the presence of a PTHR on T2*WIs in 39 pathologically proven HCCs from April 2012 to December 2013. Prussian blue staining was performed, and iron deposition was evaluated by semiquantitative and quantitative methods. Optical density was used in the quantitative methods. The associations between a PTHR on T2*WI and histopathologic peritumoral or background liver iron deposition were analyzed. RESULTS: A PTHR on T2*WI was observed in 23 of 39 (59%) HCCs. There was no significant difference in the histopathologic fibrous capsule findings (P = 0.394). In the semiquantitative methods, both peritumoral and background liver iron deposition grade were significantly higher in HCCs with a PTHR compared with HCCs without a PTHR (P < 0.001). The mean optical density in HCCs with a PTHR was significantly higher compared with HCCs without a PTHR, in the quantitative peritumoral (42,244.1 ± 20,854.9 vs. 18,739.1 ± 12,258.7, respectively; P < 0.001) and background liver iron deposition analyses (35,554.7 ± 19,854.8 vs. 17,292.4 ± 11,605.8, respectively; P < 0.001). Tumor size (P = 0.005), etiology (P = 0.001), and degree of fibrosis (P = 0.042) were significantly associated with the presence of a PTHR. CONCLUSIONS: A PTHR in HCCs on T2*WIs was strongly associated with peritumoral iron deposition in the iron-deposited background liver but not with the fibrous capsule.

Integrity of circulating cell-free DNA as a prognostic biomarker for vaccine therapy in patients with nonsmall cell lung cancer.

BACKGROUND: Many clinical trials of immune checkpoint blockade-based combination therapies are under way. Vaccine therapy is a promising partner of combination therapies. We have developed a personalized peptide vaccination and conducted clinical trials of it in patients with various cancers. At the present time, we have only a limited number of biomarkers related to the prognosis of vaccine-treated patients. Thus, new biomarkers are urgently needed. METHODS: In this study, we investigated the plasma cell-free DNA (cfDNA) integrity-a ratio of the necrotic tumor cell-derived long cfDNA fragments to the total dead cell-derived short cfDNA fragments from genomic Alu elements-in patients with advanced nonsmall cell lung cancer during treatment with the personalized peptide vaccination. RESULTS: We found that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the patients with high prevaccination cfDNA integrity survived longer than those with low prevaccination integrity (median survival time (MST): 17.9 versus 9.0 months, respectively; hazard ratio (HR): 0.58, p = .0049). A similar tendency was observed in postvaccination cfDNA integrity (MST: 16.4 vs 9.4 months; HR: 0.65, p = .024). CONCLUSIONS: These results suggest that cfDNA integrity is a possible prognostic biomarker in patients treated with the personalized peptide vaccine.