Mitochondrial Fission Promotes the Continued Clearance of Apoptotic Cells by Macrophages.

Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. We show here that uptake of multiple ACs by macrophages requires dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, which is triggered by AC uptake. When mitochondrial fission is disabled, AC-induced increase in cytosolic calcium is blunted owing to mitochondrial calcium sequestration, and calcium-dependent phagosome formation around secondarily encountered ACs is impaired. These defects can be corrected by silencing the mitochondrial calcium uniporter (MCU). Mice lacking myeloid Drp1 showed defective efferocytosis and its pathologic consequences in the thymus after dexamethasone treatment and in advanced atherosclerotic lesions in fat-fed Ldlr-/- mice. Thus, mitochondrial fission in response to AC uptake is a critical process that enables macrophages to clear multiple ACs and to avoid the pathologic consequences of defective efferocytosis in vivo.

Smad2 and Smad3 Inversely Regulate TGF-ß Autoinduction in Clostridium butyricum-Activated Dendritic Cells.

Colonization with a mixture of Clostridium species has been shown to induce accumulation of induced regulatory T (iTreg) cells in the colon. Transforming growth factor-ß (TGF-ß) is an essential factor for iTreg cell induction; however, the relationship between Clostridium species and TGF-ß remains to be clarified. Here we demonstrated that a gram-positive probiotic bacterial strain, Clostridium butyricum (C. butyricum), promoted iTreg cell generation in the intestine through induction of TGF-ß1 from lamina propria dendritic cells (LPDCs). C. butyricum-mediated TGF-ß1 induction was mainly Toll-like receptor 2 (TLR2) dependent, and the ERK-AP-1 kinase pathway played an important role. In addition, the autocrine TGF-ß-Smad3 transcription factor signal was necessary for robust TGF-ß expression in DCs, whereas Smad2 negatively regulated TGF-ß expression. Smad2-deficient DCs expressed higher concentrations of TGF-ß and were tolerogenic for colitis models. This study reveals a novel mechanism of TGF-ß induction by Clostridia through a cooperation between TLR2-AP-1 and TGF-ß-Smad signaling pathways.

Preserved seasonal variation in glycemic control in patients with type 2 diabetes mellitus during COVID-19: a 3-year-long retrospective cohort study in older adults in Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed our lifestyle by imposing restrictions, such as physical distancing. The effect of COVID-19 prevalence on seasonal variations in glycemic control in patients with diabetes mellitus (DM) remains unknown. METHODS: This single-center retrospective cohort study evaluated glycemic control in patients with type 2 DM who visited Sugi Cardiovascular Hospital in December 2021. We evaluated the clinical findings of all patients treated regularly between March 1, 2019, and December 31, 2021, including the periods both before and after the COVID-19 pandemic. All the standard treatments were approved. Furthermore, seasonal changes in hemoglobin A1c (HbA1c) levels were evaluated using stratified analyses based on age. RESULTS: This study analyzed 86 patients (mean age, 69.6 ± 9.2 years; men, 57). Median HbA1c (National Glycohemoglobin Standardization Program [Union of Clinical Chemistry]) levels in spring (March) were 7.70% (interquartile range (IQR):7.23%-8.30%) [60.6 mmol/mol (IQR:55.4-67.2 mmol/mol)], 7.35% (IQR:6.90%-7.90%) [56.8 mmol/mol (IQR:51.9-62.8 mmol/mol)], and 7.50% (IQR:7.10%-8.00%) [58.5 mmol/mol (IQR:54.1-63.9 mmol/mol)] in 2019, 2020, and 2021, respectively. During these periods, HbA1c levels and body mass index (BMI) revealed significant seasonal variations "high in spring" and "low in autumn." Median HbA1c levels in spring (March) and autumn (September) were 7.86% [61.2 mmol/mol] and 7.48% [57.4 mmol/mol] in 2019 (P < 0.001), 7.50% [57.7 mmol/mol] and 7.17% [54.2 mmol/mol] in 2020 (P < 0.001), and 7.61% [58.3 mmol/mol] and 7.19% [53.8 mmol/mol] in 2021 (P < 0.001). Seasonal variations in HbA1c levels and BMI were maintained over the past 3 years, including the pandemic period. None of the patients in this study developed COVID-19 during the study period. CONCLUSIONS: Seasonal variations in glycemic control in patients with DM were not influenced by lifestyle modifications associated with COVID-19. Maintenance of physical activity is necessary to prevent the development of sarcopenia. Moreover, seasonal variations in glycemic metabolism should be considered an independent factor for DM management. Additional extensive multifacility investigations are necessary to corroborate our findings.

[A Case of Conversion Surgery for Unresectable Advanced Gastric Cancer of Which Metastatic Site Was Disappear by Chemotherapy but the Primary Site Was Enlarged after Five Years].

A 77-year-old man presented to our hospital with a chief complaint of stomachache. He received a diagnosis of unresectable advanced gastric cancer classified as cT3, N+, M1(LYM, HEP, OSS), Stage ⅣB. He underwent first-line chemotherapy with SOX, second-line treatment with PTX plus Ram, and third-line treatment with nivolumab. The primary tumor showed a reduction in size, and liver and lymph node metastases were not detectable. However, after 5 years of chemotherapy, a re- enlargement was observed in the primary gastric lesion without progression of liver and lymph node metastases. Subsequently, conversion surgery was performed. Based on the pathological analysis, the diagnosis was ypT1b2(SM2), N0(0/17), M0, ypStage ⅠA, R0. After nivolumab administration postoperatively for 5 months, chemotherapy was discontinued as there was no recurrence.

Aggressive surgical intervention may improve prognosis in patients with ovarian metastasis from colorectal cancer.

PURPOSE: The current study aimed to investigate the prognostic clinicopathological factors of synchronous and metachronous ovarian metastasis (OM) from colorectal cancer (CRC) in patients with and without oophorectomy. METHODS: Female patients with OM from CRC who underwent primary tumor resection at our institution from January 2013 to December 2020 were evaluated. RESULTS: Of 661 female patients, 22 (3.3%) were diagnosed with OM. Among 22 patients with OM, 12 underwent OM resection. Twenty (91%) patients had extra OM upon diagnosis. Thirteen (59%) patients in the non-surgery group had peritoneal dissemination at surgery or on computed tomography scan or positron emission tomography-computed tomography. Two patients in the OM surgery group had emergency surgery because of abdominal pain. Four patients had postoperative complications, and the median duration of hospital admission was 16.5 days. The median survival time from OM diagnosis to mortality was 20.9 months. Then, the association between the clinicopathological factors and overall survival (OS) was investigated. Tumor location and surgery were found to be related to OS (p = 0.03, 0.006, respectively) in the univariate analysis. However, only surgery was associated with OS (p = 0.02) in the multivariate analysis. CONCLUSION: Surgery is an important prognostic clinicopathological factor of OM from CRC. OM tumors should be resected because OM surgery is less likely to cause complications and symptoms.

Iliopsoas muscle to visceral fat ratio on CT predicts Cushing's syndrome in elderly females with adrenal tumors.

There is no computed tomography (CT)-based numerical index for predicting Cushing's syndrome (CS) in patients with adrenal incidentalomas. We tested the hypothesis that the iliopsoas muscle (Ip-M) to visceral fat (V-fat) ratio (IVR) on CT may predict CS in elderly female patients with adrenal tumors. We examined the V-fat area, subcutaneous fat (S-fat) area, Ip-M area, V-fat/S-fat ratio, and IVR at the third lumbar vertebra (L3) level using abdominal CT in female patients aged ≥50 years with cortisol-producing adrenal tumor diagnosed with CS or non-functioning adrenal tumor (NFT) in the derivation cohort. We performed receiver operating characteristic (ROC) analysis to evaluate the diagnostic value of the V-fat/S-fat ratio and IVR for predicting CS. We assessed the usefulness of the IVR in a separate validation cohort. In the derivation cohort, the IVR was significantly lower in the 9 patients with CS than in the 15 patients with NFT (p < 0.001). In ROC analysis with a cut-off value of 0.067, the IVR showed a sensitivity of 100%, specificity of 80.0%, positive likelihood ratio (PLR) of 5.000, and negative likelihood ratio (NLR) of 0.000. The area under the curve was significantly higher for the IVR than for the V-fat/S-fat ratio (0.933 vs. 0.704, respectively, p = 0.036). In 23 patients in the validation cohort, the IVR demonstrated a PLR of 5.714 and an NLR of 0.327. The novel IVR index, based on single-slice CT at the L3 level, predicted CS in elderly female patients with adrenal tumors.

Dynamin-related protein 1 differentially regulates FcεRI- and substance P-induced mast cell activation.

BACKGROUND: The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro, but its functions in MCs activated by various stimuli in vivo have not yet been examined. OBJECTIVE: We sought to analyze Drp1 function in both mouse and human MCs. METHODS: We used human peripheral blood-derived cultured MCs and 2 genetic mouse models in which MCs were depleted of Drp1: Drp1fl/flMcpt5cre+/- mice and Drp1fl/flCpa3cre+/- mice. RESULTS: In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P-stimulated MC activation in vitro and in vivo. This was also true in human peripheral blood-derived cultured MCs in vitro after pharmacologic inhibition of Drp1. CONCLUSION: Drp1 differentially regulates MC activation by various stimuli. Promoting Drp1 activation might therefore represent a novel therapy for suppressing IgE-dependent MC activation. Further, inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P.

Simple Detection and Culture of Circulating Tumor Cells from Colorectal Cancer Patients Using Poly(2-Methoxyethyl Acrylate)-Coated Plates.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II-IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

[A Case of Advanced Gastric Cancer in Which Tumor Relapse Was Observed after Discontinuation of Nivolumab Due to Complete Response, and for Which Re-Administration Was Initiated].

A 61-year-old male was diagnosed with unresectable advanced gastric cancer(cT4b[SI; panc], N+, M0, cStage ⅣA). However he was administered S-1 plus oxaliplatin as a primary treatment and ramucirumab plus paclitaxel as a secondary treatment, the primary tumor and lymph nodes were enlarged. We judged PD and switched to the third-line treatment with nivolumab. After starting nivolumab, both the primary tumor and the lymph nodes shrank, and the PET-CT scan after 24 courses showed no FDG accumulation in the primary tumor or lymph nodes, so we judged the response as CR. The patient requested discontinuation of nivolumab, and nivolumab administration was stopped. Twenty months later after nivolumab administration was discontinued, CT scan showed re-growth of the primary tumor, and nivolumab administration was resumed. After resumption, he received 22 courses of nivolumab for 10 months with maintenance of SD.

María Teresa Miras Portugal: a pioneer for vesicular nucleotide storage.

Chromaffin granules are secretory granules present in adrenal medulla chromaffin cells. They contain high contents of catecholamines and nucleotides and have been regarded as a model system for the study of vesicular transmitter uptake and release. In 1988, Dr. María Teresa Miras Portugal, when studying catecholamine biosynthesis, detected a novel group of nucleotides, the diadenosine polyphosphates, in the adrenal chromaffin granules. Based on this finding, she unraveled the existence of diadenosine polyphosphate-mediated chemical transmission, leading to a paradigm shift in the field of purinergic signaling. She is also a pioneer in the studies on vesicular nucleotide storage. First, María Teresa and her group characterized nucleotide transport in chromaffin granules and synaptic vesicles using fluorescent nucleotide derivatives such as 1, N6-ethenoadenosine triphosphates. Then, they revealed the presence of a hypothetical vesicular nucleotide transporter with unique properties in terms of substrate specificity. In this article, we will describe her contributions to vesicular nucleotide storage and the foundations she laid for future studies.

Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery for descending colon cancer: a propensity score-matched analysis.

BACKGROUND: The clinical impact of single-incision laparoscopic surgery (SILS) for descending colon cancer (DCC) is unclear. The aim of this study was to evaluate the clinical outcomes of SILS for DCC compared with multi-port laparoscopic surgery (MPLS). METHODS: We retrospectively analyzed 137 consecutive patients with stage I-III DCC who underwent SILS or MPLS at two high-volume multidisciplinary tertiary hospitals between April 2008 and December 2018, using propensity score-matched analysis. RESULTS: After propensity score-matching, we enrolled 88 patients (n = 44 in each group). SILS was successful in 97.7% of the matched cohort. Compared with the MPLS group, the SILS group showed significantly less blood loss and a greater number of harvested lymph nodes. Morbidity rates were similar between groups. Recurrence pattern did not differ between groups. No significant differences were found between groups in terms of 3-year disease-free and overall survivals. CONCLUSION: SILS appears safe and feasible and can provide satisfactory oncological outcomes for patients with DCC.

Impact of antithrombotic agents on short-term outcomes following minimally invasive colorectal cancer surgery: a propensity score-matched analysis.

BACKGROUND: It remains unclear whether minimally invasive colorectal cancer (CRC) surgery under the suitable management of perioperative antithrombotic therapy (ATT) is safe and feasible in patients treated with chronic ATT. The present study aimed to assess the impact of ATT on short-term outcomes following minimally invasive CRC surgery. METHODS: We retrospectively analyzed 1495 consecutive patients who underwent elective minimally invasive CRC surgery between 2011 and 2021, using propensity score-matched analysis. RESULTS: Overall, 230 patients had chronically received ATT. After propensity score matching, we enrolled 412 patients (n = 206 in each group). Before matching, significant group-dependent differences were observed in terms of sex (p < 0.01), age (p < 0.01), American Society of Anesthesiologists' physical status (p < 0.01), body mass index (p < 0.01), and pathological N classification (p = 0.03). The frequencies of overall postoperative complications, bleeding events, and thromboembolic events were significantly higher in the ATT group than in the Non-ATT group (p < 0.01). After matching, no significant differences were found between the groups in terms of clinical or surgical characteristics, or in terms of the frequency of overall postoperative complications, bleeding events, thromboembolic events, length of postoperative stay, or any other postoperative complication. Multivariate analysis identified no significant risk factors for postoperative bleeding events or severe postoperative complications associated with ATT. CONCLUSIONS: Patients treated with chronic ATT showed acceptable short-term outcomes for minimally invasive CRC surgery compared with those not receiving ATT. Minimally invasive CRC surgery appears safe and feasible under the suitable management of perioperative ATT regardless of whether the patient has a history of ATT.

[A Resected Case of the Sigmoid Colon Cancer after the Endovascular Aneurysm Repair in Which Intraoperative Indocyanine Green Fluorescence Method Was Useful for Evaluating the Blood Flow in the Colon].

A man in his 70s underwent an endovascular aneurysm repair(EVAR)for abdominal aortic aneurysm. Blood test revealed an anemia and an increased tumor marker. Enhanced computed tomography revealed the wall thickening in the sigmoid colon and the Type Ⅱ endoleak after EVAR. Colonoscopy showed the wall thickening in the sigmoid colon, and biopsy indicated a diagnosis of adenocarcinoma. We performed open sigmoid colectomy with D3 lymph node dissection and ileostomy. We performed intraoperative indocyanine green (ICG) fluorescence method for evaluating the blood flow in the colon before the high ligation of the inferior mesenteric artery and the creation of the anastomosis, and perfusion of the colon was visualized. He was discharged postoperative day 14, and was performed closure of ileostomy 5 months later. Intraoperative ICG fluorescence method was safety and useful for evaluating the blood flow in the colon.

[A Case of Synchronous Secondary Lymph Node Metastasis in the Mesentery of the Ileum with cCR Achievement after Surgery for Sigmoid Colon Cancer].

A 71-year-old woman was hospitalized with loose stools and lightheadedness. She was subsequently diagnosed with sigmoid colon cancer for which we performed a laparoscopic sigmoid colectomy, small intestine partial resection, partial bladder resection, and open conversion. The intraoperative findings and histopathological analysis showed secondary lymph node metastasis in the mesentery of the ileum, and the surgery resulted in R2 resection. Chemotherapy(CAPOX plus Bev) was initiated thereafter, and the L-OHP and Bev were discontinued over time. A complete response was achieved at 1 year postoperative. Capecitabine alone was continued, and no signs of recurrence were noted at 2 years postoperative.

[Outcome of Hepatectomies for Non-Colorectal Liver Metastases].

We performed 16 cases of non-colorectal liver metastasis resection(19 resections)between January 2011 and December 2021. Among the 16 cases, the primary lesions were as follows: gastric cancer in 7 cases; GIST in 2 cases; and neuroendocrine tumor, renal cancer, pancreatic cancer(acinic cell carcinoma), cholangiocarcinoma, breast cancer, ovarian cancer, and leiomyosarcoma in 1 case each. The median time from primary lesion resection to the diagnosis of liver metastasis was 20.6 months. In cases of neuroendocrine tumors and renal cancer, hepatectomy was performed with a preoperative diagnosis of hepatocellular carcinoma. Four cases underwent laparoscopic hepatectomy, and 10 cases underwent anatomical liver resection. Postoperative chemotherapy was performed in 8 cases. Recurrence of liver metastasis was observed in 7 cases. One case of gastric cancer and 1 case of neuroendocrine tumor underwent repeat hepatectomy. The median relapse-free survival was 13.8 months, and the median overall survival was 55.7 months.

[A Case of Resection of Sigmoid Colon Metastasis from Pancreatic Cancer].

A 73-year-old man underwent distal pancreatectomy for invasive pancreatic ductal carcinoma in 2018. He showed stenosis of sigmoid colon due to recurrence of pancreatic cancer and received transverse colostomy in 2020. One year after initiation of gemcitabine monotherapy, he complained of abdominal pain. CT images and colonoscopy revealed accumulation of mucus in sigmoid colon due to stenotic lesions. Because conservative treatment using antibiotics was not effective, we performed sigmoidectomy. Histological examination revealed that tubular adenocarcinoma located mainly in the muscularis propria invaded into the colonic mucosa. Immunohistochemical analysis showed positive staining for CK7, and negative for CK20. We diagnosed sigmoid colon metastases of pancreatic cancer.

[Metachronous Ovarian Metastasis of Colorectal Cancer at Our Hospital].

Among the cases that underwent primary tumor resection(PTR)of colorectal cancer at our hospital between January 2010 and December 2020, we examined 6 cases that involved ovarian metastasis(OM)surgery. The period from PTR to recurrence of OM was 2-28 months. Bilateral oophorectomy or bilateral salpingo-oophorectomy was performed in 5 cases, and unilateral oophorectomy was performed in 1. The reasons for surgery were symptom development and progressive disease. The period from recurrence of OM to OM surgery was short, that of 0-6 months. In 5 cases, peritoneal dissemination and other distant metastases were observed during OM surgery; R0 resection was performed in 2 cases. Postoperative complications associated with OM surgery were not observed. The median time required from the day of OM surgery to the resumption of chemotherapy was 33 days, and it was possible to resume chemotherapy early. The median survival time after OM surgery was approximately 11 months, which is considered to be owing to the influence of complications of peritoneal dissemination and other distant metastases.

Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor.

AIMS/HYPOTHESIS: Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. METHODS: We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. RESULTS: MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. CONCLUSIONS/INTERPRETATION: We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH.

Smad2 and Smad3 expressed in skeletal muscle promote immobilization-induced bone atrophy in mice.

Skeletal muscle is known to regulate bone homeostasis through muscle-bone interaction, although factors that control this activity remain unclear. Here, we newly established Smad3-flox mice, and then generated skeletal muscle-specific Smad2/Smad3 double conditional knockout mice (DcKO) by crossing Smad3-flox with skeletal muscle-specific Ckmm Cre and Smad2-flox mice. We show that immobilization-induced gastrocnemius muscle atrophy occurring due to sciatic nerve denervation was partially but significantly inhibited in DcKO mice, suggesting that skeletal muscle cell-intrinsic Smad2/3 is required for immobilization-induced muscle atrophy. Also, tibial bone atrophy seen after sciatic nerve denervation was partially but significantly inhibited in DcKO mice. Bone formation rate in wild-type mouse tibia was significantly inhibited by immobilization, but inhibition was abrogated in DcKO mice. We propose that skeletal muscle regulates immobilization-induced bone atrophy via Smad2/3, and Smad2/3 represent potential therapeutic targets to prevent both immobilization-induced bone and muscle atrophy.

A new diagnostic indication device of a biomarker growth differentiation factor 15 for mitochondrial diseases: From laboratory to automated inspection.

Mitochondrial diseases (MDs) are occasionally difficult to diagnose. Growth differentiation factor 15 (GDF15) has been reported as a biomarker useful for not only diagnosing MDs, but also evaluating disease severity and therapeutic efficacy. To enable the measurement of serum GDF15 concentrations at medical institutions, we developed a new latex-enhanced turbidimetric immunoassay (LTIA) as an automated diagnostic indication test for MDs. We also examined the equivalency of specificity and sensitivity in measuring serum GDF15 concentrations between a commercially available enzyme-linked immunosorbent assay (ELISA) kit and a novel LTIA device in patients with MDs, disease controls, and healthy controls. A clinical performance study used a newly developed LTIA device and an existing ELISA kit to measure the concentrations of GDF15 in 35 MD patients, 111 disease controls, and 86 healthy controls. The median (first quartile-third quartile) of serum GDF15 concentrations measured with the LTIA device was significantly higher (P < .001) in MD patients (1389.0 U/mL [869.5-1776.0 U/mL]) than in healthy controls (380.5 U/mL [330.2-471.8 U/mL]); the interquartile ranges did not overlap between MD patients and healthy controls. The areas under the curve in disease and healthy controls were 0.812 (95% confidence interval [CI]: 0.734-0.886) and 0.951 (95% CI: 0.910-0.992), respectively. The automated, high-throughput technology-based LTIA device has definite advantages over the ELISA kit in shorter processing time and lower estimated cost per sample measurement. The LTIA device of GDF15 may be a sufficiently reliable, frontline, diagnostic indicator of individuals with suspected MDs in the general population.