Is annual screening by fecal immunochemical test necessary after a recent colonoscopy?

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

Elevated blood bicarbonate levels and long-term adverse outcomes in patients with chronic heart failure.

AIMS: The bicarbonate (HCO3 -) buffer system is crucial for maintaining acid-base homeostasis and blood pH. Recent studies showed that elevated serum HCO3 - levels serve as an indicator of the beneficial effects of acetazolamide in improving decongestion in acute heart failure. In this study, we sought to clarify the clinical relevance and prognostic impact of HCO3 - in chronic heart failure (CHF). METHODS: This cohort study enrolled 694 hospitalized patients with CHF (mean age 68.6 ± 14.6, 62% male) who underwent arterial blood sampling and exhibited neutral pH ranging from 7.35 to 7.45. We characterized the patients based on HCO3 - levels and followed them to register cardiac events. RESULTS: Among the patients, 17.3% (120 patients) had HCO3 - levels exceeding 26 mmol/L. Patients presenting HCO3 - > 26 mmol/L were more likely to use loop diuretics and had higher serum sodium and lower potassium levels, but left ventricular ejection fraction did not differ compared with those with HCO3 - between 22 and 26 (379 patients) or those with HCO3 - < 22 mmol/L (195 patients). During a median follow-up period of 1950 days, Kaplan-Meier analysis revealed that patients with HCO3 - > 26 mmol/L had the lowest event-free survival rate from either cardiac deaths or heart failure-related rehospitalization (P < 0.01 and 0.03, respectively). In the multivariable Cox model, the presence of HCO3 - > 26 mmol/L independently predicted increased risks of each cardiac event with a hazard ratio of 2.31 and 1.69 (P < 0.01 and 0.02, respectively), while HCO3 - < 22 mmol/L was not associated with these events (hazard ratios, 0.99 and 1.19; P = 0.98 and 0.43, respectively). CONCLUSIONS: Elevated blood HCO3 - levels may signify enhanced proximal nephron activation and loop diuretic resistance, leading to long-term adverse outcomes in patients with CHF, even within a normal pH range.

Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.

BACKGROUND: The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. METHODS: We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. RESULTS: The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. CONCLUSIONS: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.

Fulminant Non-occlusive Mesenteric Ischemia After Head Trauma: Report of Two Cases.

There have been no case reports of non-occlusive mesenteric ischemia (NOMI) following head trauma. Our two patients with non-surgical traumatic intracerebral hemorrhage succumbed to NOMI one week after the injury. Both were women over age 80 years and were clinically improving before NOMI occurred. One patient had been eating since admission, while the other had not, which prompted the initiation of enteral nutrition on day 5. The patients shared many characteristics: 1) over age 80 years; 2) minor brain contusion; 3) constipation for a week; 4) minimal abdominal symptoms; 5) rapidly developing leukocytosis, hyperglycemia, hypernatremia, and elevated blood urea nitrogen; 6) massive diarrhea with a small amount of blood on the same day that laboratory data became abnormal; and 7) fever and shock developed shortly after diarrhea appeared. Because of the fulminant worsening of the condition, shock status, and old age, surgical intervention was considered high risk and not performed in either patient. In retrospect, if NOMI had been diagnosed earlier when the acute pancreatitis-like symptoms began, surgical intervention may have saved their lives. Clinicians should be aware that NOMI can occur after relatively minor head trauma, which can cause death if the diagnosis is delayed.

Case of Pulmonary Tumor Embolism due to Oropharyngeal Carcinoma Diagnosed by a Transbronchial Lung Biopsy.

Pulmonary tumor embolisms (PTEs) are primarily caused by adenocarcinoma. However, only a few cases of oropharyngeal carcinoma have been reported. We herein report a 47-year-old man who presented with a fever, cough, and dyspnea 6 months after treatment for stage II oropharyngeal carcinoma. Chest computed tomography revealed centrilobular granular and nodular shadows and subpleural consolidation. A transbronchial lung biopsy revealed a mass of squamous tumor cells forming emboli in the small vessels, resulting in the diagnosis of PTE due to oropharyngeal carcinoma. Therefore, PTE should be considered for patients with a history of hypoxia.

The significance of cerebrospinal fluid dynamics in adolescent idiopathic scoliosis using time-SLIP MRI.

Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = - 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p < 0.05). In Risser5 patients with Lenke type 5 showed a significant negative correlation between Cobb angle and TD (r = - 0.44). Lenke type 5 patients had significantly shorter CSF TD compared to type1, correlating with worsening Cobb angles. Further analysis and exploration are required to understand the mechanism of onset and progression.

Outcome of surgical parathyroidectomy for tertiary hyperparathyroidism in kidney transplant recipients: tertiary hyperparathyroidism should not be ignored, for the sake of precious allografts.

Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.

Secondary normal pressure hydrocephalus following pituitary apoplexy: A case report.

Background: Although secondary normal pressure hydrocephalus (sNPH) can occur in various central nervous system diseases, there are no reports of sNPH caused by pituitary lesions. Herein, we present a unique case of sNPH caused by pituitary apoplexy. Case Description: A 70-year-old man was transferred to our hospital because of a sudden onset of headache and loss of consciousness. The cerebrospinal fluid (CSF) test showed slightly elevated cell counts and protein levels but a negative CSF culture test. Magnetic resonance imaging showed a dumbbell-like cystic lesion with hemorrhagic change at the sella turcica. From the above, the patient was diagnosed with aseptic meningitis caused by pituitary apoplexy. Pituitary hormone replacement therapy was undertaken, and his symptoms fully improved. However, two months later, he complained of a gait disturbance and incontinence that had gradually appeared. Brain imaging with computed tomography showed no ventricular enlargement compared with initial images, although the lateral ventricles were slightly enlarged. As a CSF drainage test improved his symptoms temporarily, sNPH with possible longstanding overt ventriculomegaly in adults (LOVA) background was suspected. We performed a lumboperitoneal shunt (LPS) placement, which improved his symptoms. Conclusion: This case suggests that sNPH can develop even after a small subarachnoid hemorrhage caused by a pituitary apoplexy in LOVA patients. If the aqueduct of Sylvius is open, sNPH with a LOVA background can be successfully treated with LPS placement.

Negative impact of ratio of the microvascular area to tumor area on the response to EGFR-TKI in non-small cell lung cancer with an EGFR mutation.

Background: The clinical impact of tumor microvessels on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC) is unclear. Thus, the aim of this study was to investigate whether a tumor microenvironment, abundant in microvessels, affects EGFR-TKI efficacy in patients with NSCLC and EGFR mutations. Methods: We retrospectively studied the data of 40 post-operative patients with recurrent NSCLC and EGFR mutations who received EGFR-TKIs as a first-line treatment at Kumamoto University Hospital from January 2010 to February 2021. Tumor sections were retrieved from the tissue registry and analyzed for CD34-positive microvessels using immunohistochemical techniques. The ratio of microvascular area to tumor area (RMV), which is the CD34-positive microvascular area compared to the total tumor area, was measured using StrataQuest. The predictive value of RMV on treatment outcome, assessed via progression-free survival (PFS), was evaluated using a multivariate Cox proportional hazard model. Results: The median PFS in the high RMV group (≥0.058) was significantly shorter than that in the low RMV group [<0.058; 296 days, 95% confidence interval (CI): 217-374 vs. 918 days, 95% CI: 279-1,556, P=0.002]. Multivariate analysis revealed that high RMV was an independent negative predictor of PFS (hazard ratio, 3.21; 95% CI: 1.18-8.76, P=0.022). Conclusions: High RMV may critically affect EGFR-TKI resistance in patients with NSCLC and EGFR mutations.

[Case of a Patient with Cancer of Unknown Primary in the Poor Prognosis Group Who Had a Experienced a Beneficial Treatment Course].

A 47-year-old woman with general malaise and abdominal pain presented with multiple liver tumors and lymph node metastasis. She was diagnosed with small cell carcinoma on the basis of a lymph node biopsy; however, the primary lesion was not identified. Finally, we diagnosed her with cancer of unknown primary lesion and placed her in the poor prognosis group. Although her general condition was poor, she experienced a relatively good response to treatment for small cell carcinoma.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC. Methods: The study group included 49 patients with stage I-III LUSC. We collected resected tumor tissue, paired peritumoral tissue, distant normal tissue, and corresponding plasma samples. A bespoke lung cancer bisulfite sequencing panel was used to profile the methylation level. Another 48 healthy volunteers provided control plasma samples. Results: Peritumoral and distant normal tissues presented similar methylation signatures, distinct from those in tumor tissue samples. A comparison of methylation profiles led to the identification of 871 tumor-specific differentially methylated blocks, including 847 hypermethylated and 24 hypomethylated blocks (adjusted P value <0.05). All top-ranked blocks were tumor-related. Tissue samples were analyzed for field cancerization to identify progressively aggravating aberrant methylations during tumor initiation and development. The analysis revealed that 221 blocks presented a stepwise increase in methylation levels, while seven blocks presented a stepwise decrease in methylation pattern as the sampling drew nearer to the tumor. The malignant contaminated ratio (MCR) confirmed the presence of distinct methylation patterns between tumor and peritumoral tissue samples. We then constructed a diagnostic panel using a combined diagnostic score of cell-free DNA (cfDNA) that showed high sensitivity and specificity. The healthy controls had a significantly lower combined diagnostic score (cd-score) than LUSC patients. Additionally, based on the methylation profiles, LUSC could be classified into two subgroups, C1 and C2. The methylation profile of the C2 group was not distinct from the healthy controls, which had a significantly lower cd-score than did the C1 group. Conclusions: LUSC-specific methylation patterns could potentially discriminate between peritumoral tissue, distant normal tumor tissue, and tumor tissues. This preliminary study also supported the potential utility of cfDNA methylation analysis in diagnosing LUSC.

The impact of factor Xa inhibitors on bleeding risk in patients with respiratory diseases.

It is unclear which factor Xa (FXa) inhibitors are associated with higher bleeding risk in patients with respiratory diseases, and there are no studies on the association between prothrombin time-international normalized ratio (PT-INR) and bleeding risk. We conducted a retrospective cohort study comparing 1-year-outcomes and PT-INR between patients with respiratory diseases treated with rivaroxaban (R group, n = 82) or edoxaban (E group, n = 138) for atrial fibrillation or venous thromboembolism from 2013 to 2021. The most frequent event of all bleeding discontinuations was respiratory bleeding in both groups (7.3 and 4.3%, respectively). The cumulative incidence of bleeding discontinuation was significantly higher in the R group (25.6%) than in the E group (14.4%) (hazard ratio [HR], 2.29; 95% confidence interval [CI] 1.13-4.64; P = 0.023). PT-INR after initiation of therapy significantly increased and was higher in the R group than in the E group (median value, 1.4 and 1.2, respectively; P < 0.001). Multivariate analysis using Cox proportional hazards and Fine-Gray models revealed that PT-INR after initiation of therapy was an independent risk factor of bleeding discontinuation events (HR = 4.37, 95% CI 2.57-7.41: P < 0.001). Respiratory bleeding occasionally occurs in patients receiving FXa inhibitors, and monitoring the PT-INR may need to ensure safety.

Subcortical hemorrhage caused by cerebral amyloid angiopathy compared with hypertensive hemorrhage.

OBJECTIVES: Most published reports on lobular hemorrhage in cerebral amyloid angiopathy (CAA) include patients diagnosed only by imaging studies. This study analyzed patients with subcortical hemorrhage histologically diagnosed as CAA or non-CAA (hypertensive). METHODS: This is a retrospective study analyzing data from 100 craniotomy cases. Tissue of hematoma cavity wall was collected for histological investigation in hematoma removal by surgery in patients with subcortical hemorrhage. Statistical analyses of blood pressure, hematoma location and volume, outcome, and mortality was performed in CAA and non-CAA groups. RESULTS: There were 47 CAA and 53 non-CAA cases, and average age was significantly older in the CAA group (p < 0.01). Blood pressure was significantly lower (p < 0.01) but hematoma volume was significantly greater (p < 0.05) in the CAA group. Rebleeding occurred in two CAA cases and one non-CAA case, but no re-operations were required. Average score of modified Rankin Scale, which is used to measure the degree of disability in patients who have had a stroke, at three months after surgery was not significantly different between the two groups (CAA: 3.94 ± 1.28, non-CAA: 3.58 ± 1.50). There were seven deaths in the CAA and six in the non-CAA group, and intraventricular hemorrhage highly complicated in the death cases in both groups. In the CAA group, average age of the fatal cases was significantly older than that of the surviving cases (p < 0.05) and six cases demonstrated dementia before onset of hemorrhage. CONCLUSIONS: Surgical removal of a subcortical hemorrhage caused by CAA is not contraindicated. However, age > 80 years, complication with intraventricular hemorrhage, hematoma volume ≥ 50 ml, and dementia before onset of hemorrhage contribute to high mortality, and craniotomy should be carefully considered for such patients. A limitation of this study is that comparison between CAA and non-CAA groups was performed in the patients with only surgically indicated ICH, and does not evaluate entire ICH cases with CAA. However, this study appropriately compared pathologically diagnosed CAA and non-CAA in patients with moderate to severe lobular ICH with surgical indications.

Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy and Heart Failure.

Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca2+/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.

Midline Shift Induced by the Drainage of Cerebrospinal Fluid in Three Patients With External Decompression.

It is not rare that progressive hydrocephalus worsens clinical conditions in a patient with external decompression and drainage or shunt surgery is required. However, spinal drainage or shunt surgeries potentially carry a risk of causing paradoxical herniation in a patient with decompressive craniectomy, particularly in a comatose case with wide craniectomy. Careful and strict observations are necessary for such patients. In our three comatose cases with craniectomy, paradoxical herniation occurred due to excessive drainage after 5-7 days of shunt surgery and lumbar drainage, although the drainage pressure was set at more than 10 cmH2O. Fortunately, in the three cases, the herniation improved within a few days after the drain was clamped and the bed was flattened. However, the Trendelenburg position and epidural blood patch might be necessary if paradoxical herniation occurs acutely after lumbar puncture or drainage because delayed resolution can be fatal in the herniation.

Initial experience of transpapillary gallbladder biopsy using newly designed device delivery system.

Transpapillary gallbladder biopsy has been reported for the diagnosis of gallbladder disease, and this procedure requires special biopsy forceps or a large-diameter pusher catheter. We retrospectively examined consecutive patients who underwent transpapillary gallbladder biopsy using a newly designed device delivery system (Endosheather; Piolax Medical Device, Kanagawa, Japan). We evaluated 11 patients (median age, 71 years [28-85]) who underwent transpapillary gallbladder biopsy from June 2021 to July 2022. The selective gallbladder cannulation and delivery system insertion success rate was 90.9% (10/11). The target lesion biopsy success rate was 63.6% (7/11). The biopsy time (i.e., time to completion of biopsy after successful guidewire placement) was 8.7 (5.4-32.7) min. In 1 patient in whom all 6 gallbladder bile juice cytology results were benign, the biopsy result was suspicious of adenocarcinoma. The final diagnosis for this patient was gallbladder cancer. Adverse events occurred in 2 patients. In 1 patient, acute cholecystitis occurred and required emergency surgery. Transpapillary gallbladder biopsy using the Endosheather is a potential option for the diagnosis of gallbladder disease. A good indication for this technique is considered to be wall thickening at the gallbladder fundus, where it is difficult to differentiate between benign and malignant lesions by imaging modalities such as ultrasonography or endoscopic ultrasound. The addition of transpapillary gallbladder biopsy may be advantageous when performing bile juice cytology using a nasogallbladder drainage tube for the diagnosis of gallbladder disease.

Clinical factors associated with acute abdominal symptoms induced by gastric anisakiasis: a multicenter retrospective cohort study.

BACKGROUND: Gastric anisakiasis typically causes severe abdominal symptoms; however, we incidentally detected asymptomatic gastric anisakiasis cases during esophagogastroduodenoscopy. The factors associated with developing acute abdominal symptoms induced by gastric anisakiasis remain unclear. Therefore, this study aimed to investigate the clinical factors associated with abdominal symptoms of gastric anisakiasis by comparing symptomatic and asymptomatic cases. METHODS: This was a retrospective cohort study involving 264 patients diagnosed with gastric anisakiasis at nine hospitals in Japan between October 2015 and October 2021. We analyzed patients' medical records and endoscopic images and compared the clinical factors between the symptomatic and asymptomatic groups. RESULTS: One hundred sixty-five patients (77.8%) were diagnosed with abdominal symptoms, whereas 47 (22.2%) were asymptomatic. Older age, male sex, diabetes mellitus, gastric mucosal atrophy, and gastric mucosal atrophy of the Anisakis penetrating area were significantly more common in the asymptomatic group than in the symptomatic group. Multivariate analysis revealed that age (p = 0.007), sex (p = 0.017), and presence or absence of mucosal atrophy (p = 0.033) were independent factors for the occurrence of acute abdominal symptoms. In addition, cases that were Helicobacter pylori naïve, with an elevation of white blood cells, or without an elevation of eosinophils were more common in the symptomatic group than in the asymptomatic group. CONCLUSIONS: Age, sex, and presence or absence of gastric mucosal atrophy were the clinical factors associated with the occurrence of acute abdominal symptoms. Older and male patients and those with gastric mucosal atrophy were less likely to show abdominal symptoms. The mechanisms of the occurrence of symptoms induced by gastric anisakiasis remain unclear; however, our results will help clarify this issue in the future.

Clinical complete response maintained for more than 5 years after aggressive chemoradiotherapy for advanced rectal cancer with necrotizing fasciitis: a case report.

We report the case of a 65-year-old male diagnosed with advanced rectal cancer associated with necrotizing fasciitis (NF). Since radical surgery, total pelvic exenteration with sacrectomy, was rejected because of detrimental effects on quality of life, chemoradiotherapy (CRT) was chosen as anti-cancer treatment after urgent debridement. Although CRT was paused unintentionally just after delivering the total dose of radiation owing to the relapse of NF, the patient has maintained clinical complete response (cCR) without any distant metastasis for >5 years. Advanced rectal cancer is recognized as an NF risk factor. No definitive treatment strategies have been reported for NF-inducing rectal cancer; however, some reports have demonstrated curative extended surgery. Thus, CRT may be a less-invasive treatment option for NF-inducing rectal cancer, whereas severe adverse effects including re-infection after debridement should be closely monitored.

Prognostic Role of Circulating LTBP-2 in Patients With Dilated Cardiomyopathy: A Novel Biomarker Reflecting Extracellular Matrix LTBP-2 Accumulation.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease related to heart failure. Extracellular matrix proteins have an important role in the pathogenesis of DCM. Latent transforming growth factor beta-binding protein 2 (LTBP-2), a type of extracellular matrix protein, has not been investigated in DCM. METHODS: First, we compared plasma LTBP-2 levels in 131 patients with DCM who underwent endomyocardial biopsy and 44 controls who were matched for age and sex and had no cardiac abnormalities. Next, we performed immunohistochemistry for LTBP-2 on endomyocardial biopsy specimens and followed the DCM patients for ventricular assist device (VAD) implantation, cardiac death, and all-cause death. RESULTS: Patients with DCM had elevated plasma LTBP-2 levels compared with controls (P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen. When patients with DCM were divided into 2 groups according to LTBP-2 levels, Kaplan-Meier analysis demonstrated that patients with high plasma LTBP-2 were associated with increased incidences of cardiac death/VAD and all-cause death/VAD. In addition, patients with high myocardial LTBP-2-positive fractions were associated with increased incidences of these adverse outcomes. Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with adverse outcomes. CONCLUSIONS: Circulating LTBP-2 can serve as a biomarker to predict adverse outcomes, reflecting extracellular matrix LTBP-2 accumulation in the myocardium in DCM.