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PURPOSE: The diagnostic performance of large language artificial intelligence (AI) models when utilizing radiological images has yet to be investigated. We employed Claude 3 Opus (released on March 4, 2024) and Claude 3.5 Sonnet (released on June 21, 2024) to investigate their diagnostic performances in response to the Radiology's Diagnosis Please quiz questions. MATERIALS AND METHODS: In this study, the AI models were tasked with listing the primary diagnosis and two differential diagnoses for 322 quiz questions from Radiology's "Diagnosis Please" cases, which included cases 1 to 322, published from 1998 to 2023. The analyses were performed under the following conditions: (1) Condition 1: submitter-provided clinical history (text) alone. (2) Condition 2: submitter-provided clinical history and imaging findings (text). (3) Condition 3: clinical history (text) and key images (PNG file). We applied McNemar's test to evaluate differences in the correct response rates for the overall accuracy under Conditions 1, 2, and 3 for each model and between the models. RESULTS: The correct diagnosis rates were 58/322 (18.0%) and 69/322 (21.4%), 201/322 (62.4%) and 209/322 (64.9%), and 80/322 (24.8%) and 97/322 (30.1%) for Conditions 1, 2, and 3 for Claude 3 Opus and Claude 3.5 Sonnet, respectively. The models provided the correct answer as a differential diagnosis in up to 26/322 (8.1%) for Opus and 23/322 (7.1%) for Sonnet. Statistically significant differences were observed in the correct response rates among all combinations of Conditions 1, 2, and 3 for each model (p < 0.01). Claude 3.5 Sonnet outperformed in all conditions, but a statistically significant difference was observed only in the comparison for Condition 3 (30.1% vs. 24.8%, p = 0.028). CONCLUSION: Two AI models demonstrated a significantly improved diagnostic performance when inputting both key images and clinical history. The models' ability to identify important differential diagnoses under these conditions was also confirmed.
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PURPOSE: Large language models (LLMs) are rapidly advancing and demonstrating high performance in understanding textual information, suggesting potential applications in interpreting patient histories and documented imaging findings. As LLMs continue to improve, their diagnostic abilities are expected to be enhanced further. However, there is a lack of comprehensive comparisons between LLMs from different manufacturers. In this study, we aimed to test the diagnostic performance of the three latest major LLMs (GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro) using Radiology Diagnosis Please Cases, a monthly diagnostic quiz series for radiology experts. MATERIALS AND METHODS: Clinical history and imaging findings, provided textually by the case submitters, were extracted from 324 quiz questions originating from Radiology Diagnosis Please cases published between 1998 and 2023. The top three differential diagnoses were generated by GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro, using their respective application programming interfaces. A comparative analysis of diagnostic performance among these three LLMs was conducted using Cochrane's Q and post hoc McNemar's tests. RESULTS: The respective diagnostic accuracies of GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro for primary diagnosis were 41.0%, 54.0%, and 33.9%, which further improved to 49.4%, 62.0%, and 41.0%, when considering the accuracy of any of the top three differential diagnoses. Significant differences in the diagnostic performance were observed among all pairs of models. CONCLUSION: Claude 3 Opus outperformed GPT-4o and Gemini 1.5 Pro in solving radiology quiz cases. These models appear capable of assisting radiologists when supplied with accurate evaluations and worded descriptions of imaging findings.
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PURPOSE: To assess the performance of GPT-4 Turbo with Vision (GPT-4TV), OpenAI's latest multimodal large language model, by comparing its ability to process both text and image inputs with that of the text-only GPT-4 Turbo (GPT-4 T) in the context of the Japan Diagnostic Radiology Board Examination (JDRBE). MATERIALS AND METHODS: The dataset comprised questions from JDRBE 2021 and 2023. A total of six board-certified diagnostic radiologists discussed the questions and provided ground-truth answers by consulting relevant literature as necessary. The following questions were excluded: those lacking associated images, those with no unanimous agreement on answers, and those including images rejected by the OpenAI application programming interface. The inputs for GPT-4TV included both text and images, whereas those for GPT-4 T were entirely text. Both models were deployed on the dataset, and their performance was compared using McNemar's exact test. The radiological credibility of the responses was assessed by two diagnostic radiologists through the assignment of legitimacy scores on a five-point Likert scale. These scores were subsequently used to compare model performance using Wilcoxon's signed-rank test. RESULTS: The dataset comprised 139 questions. GPT-4TV correctly answered 62 questions (45%), whereas GPT-4 T correctly answered 57 questions (41%). A statistical analysis found no significant performance difference between the two models (P = 0.44). The GPT-4TV responses received significantly lower legitimacy scores from both radiologists than the GPT-4 T responses. CONCLUSION: No significant enhancement in accuracy was observed when using GPT-4TV with image input compared with that of using text-only GPT-4 T for JDRBE questions.
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Radiología , Humanos , Japón , Radiología/educación , Consejos de Especialidades , Competencia Clínica , Evaluación Educacional/métodosRESUMEN
BACKGROUND AND PURPOSE: The rise of large language models such as generative pre-trained transformers (GPTs) has sparked significant interest in radiology, especially in interpreting radiological reports and image findings. While existing research has focused on GPTs estimating diagnoses from radiological descriptions, exploring alternative diagnostic information sources is also crucial. This study introduces the use of GPTs (GPT-3.5 Turbo and GPT-4) for information retrieval and summarization, searching relevant case reports via PubMed, and investigates their potential to aid diagnosis. MATERIALS AND METHODS: From October 2021 to December 2023, we selected 115 cases from the "Case of the Week" series on the American Journal of Neuroradiology website. Their Description and Legend sections were presented to the GPTs for the two tasks. For the Direct Diagnosis task, the models provided three differential diagnoses that were considered correct if they matched the diagnosis in the diagnosis section. For the Case Report Search task, the models generated two keywords per case, creating PubMed search queries to extract up to three relevant reports. A response was considered correct if reports containing the disease name stated in the diagnosis section were extracted. McNemar's test was employed to evaluate whether adding a Case Report Search to Direct Diagnosis improved overall accuracy. RESULTS: In the Direct Diagnosis task, GPT-3.5 Turbo achieved a correct response rate of 26% (30/115 cases), whereas GPT-4 achieved 41% (47/115). For the Case Report Search task, GPT-3.5 Turbo scored 10% (11/115), and GPT-4 scored 7% (8/115). Correct responses totaled 32% (37/115) with three overlapping cases for GPT-3.5 Turbo, whereas GPT-4 had 43% (50/115) of correct responses with five overlapping cases. Adding Case Report Search improved GPT-3.5 Turbo's performance (p = 0.023) but not that of GPT-4 (p = 0.248). CONCLUSIONS: The effectiveness of adding Case Report Search to GPT-3.5 Turbo was particularly pronounced, suggesting its potential as an alternative diagnostic approach to GPTs, particularly in scenarios where direct diagnoses from GPTs are not obtainable. Nevertheless, the overall performance of GPT models in both direct diagnosis and case report retrieval tasks remains not optimal, and users should be aware of their limitations.ABBREVIATIONS: AI = Artificial Intelligence, GPT = generative pretrained transformer, LLM = large language model.
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After the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic emerged, the virus spread rapidly worldwide, and outbreaks continued to occur intermittently. Here, we present the case of a 5-year-old boy with acute disseminated encephalomyelitis (ADEM) and initial symptoms of dysphoria and pain in the right lower extremity. Around the time of this episode, the patient exhibited no fever or respiratory symptoms. Brain magnetic resonance imaging (MRI) revealed multiple T2-weighted image/fluid-attenuated inversion recovery high-signal areas bilaterally subcortical to the deep white matter, corpus callosum, and bilateral basal ganglia. MRI of the cervical and thoracic regions indicated a long lesion with continuous T2WI high signal intensity in the central gray matter. Serum aquaporin-4 antibody and serum myelin oligodendrocyte glycoprotein antibody tests were negative and positive, respectively. A polymerase chain reaction test using nasopharyngeal swab fluid upon admission was positive for SARS-CoV-2. Patients with severe coronavirus disease 2019 (COVID-19) in the acute phase may show central nervous system symptoms. There have been no previous reports of ADEM in the subacute phase of COVID-19, lacking symptoms in the acute phase, as in the present case. Notably, ADEM can develop in the subacute phase of asymptomatic COVID-19 infection.
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New Ru-Pd heterobimetallic complexes were synthesized and structurally characterized utilizing 6,6â³-bis(phosphino)-2,2':6',2â³-terpyridine as a scaffold for the metal-metal bond. The dicationic Ru-Pd complex was found to exhibit high catalytic activity as a photocatalyst for photochemical reduction of CO2 to CO under visible light irradiation. This study established a new design of transition metal catalysts that tune photoredox catalysis with metalloligands.
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BACKGROUND: Previous research applying large language models (LLMs) to medicine was focused on text-based information. Recently, multimodal variants of LLMs acquired the capability of recognizing images. OBJECTIVE: We aim to evaluate the image recognition capability of generative pretrained transformer (GPT)-4V, a recent multimodal LLM developed by OpenAI, in the medical field by testing how visual information affects its performance to answer questions in the 117th Japanese National Medical Licensing Examination. METHODS: We focused on 108 questions that had 1 or more images as part of a question and presented GPT-4V with the same questions under two conditions: (1) with both the question text and associated images and (2) with the question text only. We then compared the difference in accuracy between the 2 conditions using the exact McNemar test. RESULTS: Among the 108 questions with images, GPT-4V's accuracy was 68% (73/108) when presented with images and 72% (78/108) when presented without images (P=.36). For the 2 question categories, clinical and general, the accuracies with and those without images were 71% (70/98) versus 78% (76/98; P=.21) and 30% (3/10) versus 20% (2/10; P≥.99), respectively. CONCLUSIONS: The additional information from the images did not significantly improve the performance of GPT-4V in the Japanese National Medical Licensing Examination.
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Concesión de Licencias , Medicina , Japón , LenguajeRESUMEN
INTRODUCTION: The purpose of this study was to clarify the relationship between seasonal variation and distal radius fractures using diagnosis procedure combination data in Japan. MATERIALS AND METHODS: The participants were hospitalized patients who underwent surgical treatment for distal radius fracture as the primary injury at hospitals that introduced the diagnosis procedure combination system between April 2011 and March 2016. We obtained a summary table of the month of admission, region of residence, age at admission, and sex of the patients from the Ministry of Health, Labour and Welfare and evaluated it by month, region, age group, and sex. RESULTS: The total number of patients for the 5 years from 2011 to 2016 was 105,025. There were 29,224 male and 75,801 female participants, with a female-to-male ratio of 2.6. The mean age was 60.2 (standard deviation, 20.8) years. Distal radius fractures occurred more frequently in the winter, especially among female individuals in eastern Japan. Female participants aged ≥ 50 years tended to have a higher incidence of distal radius fracture in winter. The incidence of distal radius fracture among male participants aged 0-19 years was higher from spring to autumn. CONCLUSION: Surgically treated distal radius fractures occur frequently during the winter months among female individuals in eastern Japan or those aged ≥ 50 years and increase from school age to adolescence, especially in male individuals from spring to autumn. We should be aware of the high incidence of distal radius fractures in winter, especially in regions with snowfall and cold temperatures.
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Fracturas del Radio , Fracturas de la Muñeca , Adolescente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estaciones del Año , Estudios Transversales , Fracturas del Radio/epidemiología , Fracturas del Radio/cirugía , Pacientes Internos , Japón/epidemiologíaRESUMEN
PURPOSE: The purpose of this study was to investigate the longitudinal MRI characteristic of COVID-19-vaccination-related axillary lymphadenopathy by evaluating the size, T2-weighted signal intensity, and apparent diffusion coefficient (ADC) values. METHODS: COVID-19-vaccination-related axillary lymphadenopathy was observed in 90 of 433 health screening program participants on the chest region of whole-body axial MRIs in 2021, as reported in our previous study. Follow-up MRI was performed at an interval of approximately 1 year after the second vaccination dose from 2022 to 2023. The diameter, signal intensity on T2-weighted images, and ADC of the largest enlarged lymph nodes were measured on chest MRI. The values were compared between the post-vaccination MRI and the follow-up MRI, and statistically analyzed. RESULTS: Out of the 90 participants who had enlarged lymph nodes of 5 mm or larger in short axis after the second vaccination dose, 76 participants (45 men and 31 women, mean age: 61 years) were enrolled in the present study. The median short- and long-axis diameter of the enlarged lymph nodes was 7 mm and 9 mm for post-vaccination MRI and 4 mm and 6 mm for follow-up MRI, respectively. The median signal intensity relative to the muscle on T2-weighted images decreased (5.1 for the initial post-vaccination MRI and 3.6 for the follow-up MRI, P < .0001). The ADC values did not show a notable change and remained in a normal range. CONCLUSION: The enlarged axillary lymph nodes decreased both in size and in signal intensity on T2-weighted images of follow-up MRI. The ADC remained unchanged. Our findings may provide important information to establish evidence-based guidelines for conducting proper assessment and management of post-vaccination lymphadenopathy.
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AIM: Clinical trials showed the efficacy of sodium-glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat-AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium-glucose cotransporter 2 inhibitor, ipragliflozin. METHODS: Adults with T1D (n = 25) took 50-mg open-labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed-meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C-peptide, glucagon and ß-hydroxybutyrate. RESULTS: The area under the curve from fasting (0 min) to 120 min (AUC0-120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial ß-hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0-120min) from baseline to 12 weeks were significantly correlated with those in ß-hydroxybutyrate levels. CONCLUSIONS: Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied.
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Diabetes Mellitus Tipo 1 , Glucagón , Glucósidos , Tiofenos , Adulto , Humanos , Ácido 3-Hidroxibutírico , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucagón/metabolismo , Glucosa , Control Glucémico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Insulina/uso terapéutico , Estudios ProspectivosRESUMEN
BACKGROUND/AIM: The recurrence rate following the excision of tenosynovial giant cell tumors (TSGCT) of the hand is very high. Intraoperative application of a surgical microscope has been reported. However, to date, there are no reports of medium-term outcomes related to this technique. This study aimed to evaluate the medium-term outcomes of tumor excision using surgical microscope for TSGCT of the hand. PATIENTS AND METHODS: A total of 27 patients, who underwent an initial surgery for histologically-confirmed TSGCT of the hand, between 2008 and 2020, were included and evaluated. The mean follow-up time postoperatively was 6.8 years. Tumor recurrence and preoperative tumor characteristics were assessed. RESULTS: All tumors were adherent to tendons, tendon sheaths, neurovascular structures or periarticular ligaments and capsules. Bony lesions were observed in 11 tumors. The surgical microscope was used in 13 tumors. Recurrences were observed in three tumors (overall recurrence rate: 11%). Tumor characteristics were similar in both groups, but the recurrence rate in the group treated using the surgical microscope was 0%, whereas the recurrence rate in the group treated without the surgical microscope was 21%. Re-operations using the surgical microscope for recurrent tumors were performed, without recurrence postoperatively. CONCLUSION: Among patients with TSGCT of the hand treated with tumor excision using the surgical microscope, the postoperative recurrence rate was 0%. Based on the results of this study, the surgical microscope might be used for excision of TSGCTs of the hand.
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Tumor de Células Gigantes de las Vainas Tendinosas , Tumores de Células Gigantes , Humanos , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Tumor de Células Gigantes de las Vainas Tendinosas/diagnóstico por imagen , Tumor de Células Gigantes de las Vainas Tendinosas/cirugía , Tumor de Células Gigantes de las Vainas Tendinosas/patología , Mano/cirugía , Mano/patología , Reoperación , Microscopía , Tumores de Células Gigantes/cirugíaRESUMEN
Spinal epidural abscess (SEA) is an abscess that forms between the dura mater and vertebrae. SEA is characterized by back pain and neuropathy associated with fever, of which early diagnosis and treatment are necessary to avoid irreversible neurological sequelae. However, its diagnosis is often difficult because specific symptoms are rarely present in the early stages of the disease. A 25-month-old boy, healthy by nature and free of risk factors, was referred and admitted for fever symptoms only, without back pain or neurological symptoms. We focused on the residual activation of the coagulation-fibrinolytic system, which was contrary to the response to therapy, and were able to establish a diagnosis of SEA. After the initiation of antibiotics, the patient responded well to treatment and made a mild recovery without the need for surgical intervention. To date, there are no reported cases of SEA with only febrile symptoms without localized spinal cord tenderness. SEA is easily overlooked and should be considered in the differential diagnosis of pediatric fever of unknown origin. Although imaging studies have drawbacks, such as radiation exposure and sedation, they should be immediately performed if SEA is suspected.
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BACKGROUND AIMS: Monocytes, derived from hematopoietic stem cells (HSCs), play a pivotal role in the immune response to cancer. Although they are an attractive source of cell therapy for cancer, a method for ex vivo expansion has not yet been established. Monocytes differentiated from pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs), can be an alternative source of HSC-derived monocytes because of their self-renewal and pluripotency. To develop a standardized method for the generation of iPSC-derived monocytes for future clinical applications, we aim to control the size of the iPSC colony. METHODS: To this end, we developed a plate with multiple dots containing a chemical substrate for the iPSC scaffold. iPSCs placed in the plate expanded only on the dots and created colonies of the same size. The cells were then differentiated into monocytes by adding cytokines to the colonies. RESULTS: The dot plate substantially reduced variability in monocyte-like cell generation when compared with cultivating cells on a plate with the substrate covering the entire surface area. Furthermore, more monocyte-like cells were obtained by adjusting the dot size and the distance between the dots. The iPSC-derived monocyte-like cells phagocytosed cancer cells and secreted proinflammatory cytokines. The cells also expressed Fc receptors and exerted immunoglobulin G-mediated killing of cancer cells with the corresponding antibodies. CONCLUSIONS: The dot plate enabled the control of iPSC colony size in two-dimensional culture, which resulted in a reduction in the generation-variation of functional monocyte-like cells. This standardized method for generating iPSC-derived monocyte-like cells using the dot plate could also facilitate the development of an automated closed system on a large scale for clinical applications.
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Células Madre Pluripotentes Inducidas , Monocitos , Leucocitos , Diferenciación Celular , CitocinasRESUMEN
The rate of cell proliferation is a crucial factor in cell production under good manufacturing practice (GMP) control. In this study, we identified a culture system for induced pluripotent cells (iPSCs) that supports cell proliferation and viability and maintains the cells in an undifferentiated state even at 8 days after seeding. This system involves the use of dot pattern culture plates that have been coated with a chemically defined scaffold which has high biocompatibility. Under cell starvation conditions, where medium exchange was not performed for 7 days or where the amount of medium exchange was reduced to half or a quarter, iPSC viability and lack of differentiation were maintained. The rate of cell viability in this culture system was greater than generally obtained by standard culture methods. The cells in this compartmentalized culture system could be induced to differentiate in a controlled and consistent manner: differentiation of endoderm occurred in a controlled and consistent manner: endoderm, mesoderm, and ectoderm could be consistently induced to differentiate in the cultures. In conclusion, we have developed a culture system that supports high viability in iPSCs and allows their controlled differentiation. This system has the potential for use in GMP-based production of iPSCs for clinical purposes.
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Células Madre Pluripotentes Inducidas , Diferenciación Celular , Técnicas de Cultivo de Célula/métodos , Medios de CultivoRESUMEN
The prediction of gene structure within the genome sequence is the starting point of genome analysis, and its accuracy has a significant impact on the quality of subsequent analyses. Gene structure prediction is roughly divided into RNA-Seq-based methods, ab initio-based methods, homology-based methods, and the integration of individual prediction methods. Integrated methods are mainstream in recent genome projects because they improve prediction accuracy by combining or taking the best individual prediction findings; however, adequate prediction accuracy for eukaryotic species has not yet been achieved. Therefore, we developed an integrated tool, GINGER, that solves various issues related to gene structure prediction in higher eukaryotes. By handling artefacts in alignments of RNA and protein sequences, reconstructing gene structures via dynamic programming with appropriately weighted and scored exon/intron/intergenic regions, and applying different prediction processes and filtering criteria to multi-exon and single-exon genes, we achieved a significant improvement in accuracy compared to the existing integration methods. The feature of GINGER is its high prediction accuracy at the gene and exon levels, which is pronounced for species with more complex gene architectures. GINGER is implemented using Nextflow, which allows for the efficient and effective use of computing resources.
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Zingiber officinale , Zingiber officinale/genética , Eucariontes , Genoma , Exones , Intrones , Algoritmos , Programas InformáticosRESUMEN
BACKGROUND AND OBJECTIVES: Few studies exist on resistant starch in rice grains. The Okinawa Institute of Science and Technology Graduate University (OIST) has developed a new rice (OIST rice, OR) rich in resistant starch. This study aimed to clarify the effect of OR on postprandial glucose concentrations. METHODS AND STUDY DESIGN: This single-center, open, randomized, crossover comparative study included 17 patients with type 2 diabetes. All participants completed two meal tolerance tests using OR and white rice (WR). RESULTS: The median age of the participants was 70.0 [59.0-73.0] years, and the mean body mass index was 25.9±3.1 kg/m2. The difference in total area under the curve (AUC) of plasma glucose was -8223 (95% confidence interval [CI]: -10100 to -6346, p<0.001) mg·min/dL. The postprandial plasma glucose was significantly lower with OR than with WR. The difference in the AUC of insulin was -1139 (95% CI: -1839 to -438, p=0.004) µU·min/mL. The difference in the AUC of total gastric inhibitory peptide (GIP) and total glucagon-like peptide-1 (GLP-1) was -4886 (95% CI: -8456 to -1317, p=0.011) and -171 (95% CI: -1034 to 691, p=0.673) pmol·min/L, respectively. CONCLUSIONS: OR can be ingested as rice grains and significantly reduced postprandial plasma glucose compared to WR independent of insulin secretion in patients with type 2 diabetes. OR could have escaped absorption not only from the upper small intestine but also from the lower small intestine.
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Diabetes Mellitus Tipo 2 , Oryza , Humanos , Persona de Mediana Edad , Anciano , Incretinas/farmacología , Insulina , Glucemia , Almidón Resistente/farmacología , Periodo Posprandial , Estudios CruzadosRESUMEN
INTRODUCTION: The amino acid 5-aminolevulinic acid (5-ALA) is the first heme biosynthetic precursor. The combination of 5-ALA with sodium ferrous citrate (SFC) enhances heme production, leading to increased adenosine triphosphate (ATP) production in mitochondria. We investigated whether administering 5-ALA/SFC improves glucose tolerance with an increase in insulin secretion in patients with maternally inherited diabetes and deafness (MIDD), which is characterized by an insulin secretory disorder due to impaired mitochondrial ATP production. METHODS: This was a single-arm, open-label, interventional study. We prospectively administered the oral glucose tolerance test (OGTT) twice in five patients with MIDD who had received intensive insulin therapy: before and 24 weeks after an administration of 5-ALA/SFC (200/232 mg per day). We measured the concentrations of glucose, insulin, C-peptide, and proinsulin at fasting, and 30, 60, and 120 min after glucose load in each OGTT. The primary endpoint was the changes in the area under the curve (AUC) of serum insulin from 0 to 120 min during OGTT from baseline to 24 weeks. RESULTS: The serum insulin AUC (µU/mL) during the 120-min OGTT tended to increase from baseline to 24 weeks but not significantly (17.1 ± 13.7 versus 22.3 ± 13.4, p = 0.077). The plasma glucose AUC (mg/dL) during the 120-min OGTT at 24 weeks was not significantly decreased; the late phase of glucose excursion from 60 to 120 min was significantly decreased compared with baseline (357 ± 42 versus 391 ± 50, p = 0.041). The mean level of glycated hemoglobin (HbA1c) decreased from 8.3 ± 1.2% at baseline to 7.9 ± 0.3% at 24 weeks (p = 0.36) without increasing the daily dose of insulin injections. CONCLUSION: The 24-week administration of 5-ALA/SFC did not demonstrate a significant improvement in insulin secretion in patients with MIDD. Further investigations with a larger number of patients and a placebo control group are required to clarify the potential efficacy of 5-ALA/SFC for ameliorating mitochondrial dysfunctions in MIDD. TRIAL REGISTRATION: UMIN-CTR000040581 and jRCT071200025.
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We reported two patients with acute ischemic stroke who had presented with symptoms of thyroid storm. Case1: A 43-year-old man abruptly developed left hemiparesis caused by the right middle cerebral artery occlusion. Cardiac evaluations revealed atrial fibrillation and left atrial enlargement. He had successful recanalization after reperfusion therapies. Case 2: A 66-year-old woman with severe bilateral middle cerebral artery stenosis presented with right hemiparesis and dysarthria. MRI revealed the acute infarction in the left frontal and parietal lobe. In both cases, protein C activity was decreased which could be related to severe hyperthyroidism. They concomitantly had arterial lesions where blood stasis could occur. Severe hyperthyroidism which could evoke the decreasing of protein C activity could be responsible to develop acute ischemic stroke.
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Fibrilación Atrial , Hipertiroidismo , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Masculino , Femenino , Humanos , Anciano , Adulto , Proteína C , Hipertiroidismo/complicaciones , Paresia , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiologíaRESUMEN
We reported in 2018 that among several extracellular matrices, fibronectin, type I collagen, type IV collagen, laminin I, fibrinogen, and bovine serum albumin, fibronectin is particularly useful for adhesion of porcine pancreatic tissue. Subsequently, we developed a technology that enables the chemical coating of the constituent motifs of fibronectin onto cell culture dishes. In this experiment, we used islets (purity ≥ 90%), duct epithelial cells (purity ≥ 60%), and acinar cells (purity ≥ 99%) isolated from human pancreas according to the Edmonton protocol published in 2000 and achieved adhesion to the constituent motifs of fibronectin. A solution including cGMP Prodo Islet Media was used as the assay solution. In islets, adhesion was enhanced with the constitutive motifs of fibronectin compared with uncoated islets. In the functional evaluation of islets, insulin mRNA expression and insulin secretion were enhanced by the constitutive motif of fibronectin compared with non-coated islets. The stimulation index was comparable between non-coated islets and fibronectin motifs. In duct epithelial cells, adhesion was mildly promoted by the fibronectin component compared with non-coated component, while in acinar cells, adhesion was inhibited by the fibronectin component compared with the non-coated component. These data suggest that the constitutive motifs of fibronectin are useful for the adhesion of islets and duct epithelial cells.