Two Decades Rituximab Therapy in Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis.

Remission failure and relapse numerate as one of the main problems in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAVs). The need for new agents that provide effective and safe induction accompanied by sustained remission seems to be urgent in clinical care. The efficacy and safety of rituximab (RTX) for AAVs therapy has been reported in various studies. RTX therapy offers several advantages to treating AAVs patients compared to other therapeutic approaches including reduction of Glucocorticoids (GCs) and conventional Immunosuppressive therapy (IST) usage during both the induction of remission and maintenance phases. This reduction can lead to a lower rate of serious complications making RTX therapy a safer option. It seems that RTX may provide improved clinical outcomes in these patients mediated via B-lymphocyte depletion, Proteinase 3-antineutrophilic cytoplasmic antibody (PR3-ANCA), and myeloperoxidase-antineutrophilic cytoplasmic antibody (MPO-ANCA) titers reduction. In this regard, some uncertainties have been reported to validate the association between such depletion and clinical improvement, as suggested by other sources of autoreactive B cells that did not target with RTX. Due to the prolonged B cell depletion, fixed intervals and adjusted dosage of RTX may be required in patients with AAVs. In this narrative review, we aimed to insight better understand regarding the efficacy of RTX for effective induction and sustained remission in patients with AAVs. It seems that discovering new biomarkers predicting relapse in AAVs patients can lead to future targeted therapy.

The clinical utility of autologous tumor lysate-loaded dendritic cell vaccination for patients with glioma: A systematic review and meta-analysis.

BACKGROUND: Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta-analysis examined DC vaccine efficacy and safety for gliomas. METHODS: This systematic review and meta-analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated. RESULTS: A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6-month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%-100%]. Respectively, 12-month OS reported 75% [95%CI: 65%-85%] but declined to 32% [95%CI: 20%-43%] for 24-month OS. 6- and 12-month progression-free survival reached 49% [95%CI: 21%-77%] and 19% [95%CI:8%-30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%-42%], and 26% [95%CI: 10%-42%], though stable disease reached 33% [95%CI: 15%-51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%-57%]. CONCLUSIONS: In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.

Anti-PD-1/PD-L1 inhibitor therapy for melanoma brain metastases: a systematic review and meta-analysis.

Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.

The complex role of macrophages in pancreatic cancer tumor microenvironment: a review on cancer progression and potential therapeutic targets.

Pancreatic cancer (PC) is one of the deadliest cancers worldwide with low survival rates and poor outcomes. The treatment landscape for PC is fraught with obstacles, including drug resistance, lack of effective targeted therapies and the immunosuppressive tumor microenvironment (TME). The resistance of PC to existing immunotherapies highlights the need for innovative approaches, with the TME emerging as a promising therapeutic target. The recent advancements in understanding the role of macrophages, this context highlight their significant impact on tumor development and progression. There are two important types of macrophages: M1 and M2, which play critical roles in the TME. Therapeutics strategies including, depletion of tumor-associated macrophages (TAMs), reprogramming TAMs to promote anti-tumor activity, and targeting macrophage recruitment can lead to promising outcomes. Targeting macrophage-related pathways may offer novel strategies for modulating immune responses, inhibiting angiogenesis, and overcoming resistance to chemotherapy in PC treatment.

Role of T follicular helper cells in autoimmune rheumatic Diseases: A systematic review on immunopathogenesis and response to treatment.

BACKGROUND: T follicular helper (Tfh) cells are a subdivision of T helper cells involved in antigen-specific B cell immunity. Tfh cells play an essential role in the interaction of T cells/B cells in the germinal centers (GC), and dysregulation of Tfh actions can offer pathogenic autoantibody formation and lead to the development of autoimmune diseases. This study seeks to evaluate changes in Tfh frequency and its related cytokines in autoimmune disease, its association with disease phase, severity, prognosis, and the effect of immunosuppressive treatment on the Tfh population. METHOD: The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. Electronic databases, including PubMed, Scopus, Web of Science, and Embase, were systematically searched for potentially eligible studies up to January 1, 2024. RESULTS: We identified 4998 articles in the initial search, from which 1686 similar titles were removed. A total of 3312 articles were initially screened, and 3051 articles were excluded by title/abstract screening. A total of 261 studies were considered for full-text assessment, and 205 articles were excluded by reason. Finally, a total of 56 studies were included in our review. CONCLUSION: The population of Tfh cells is generally higher in autoimmune diseases versus Health control. Moreover, the number of Tfh cells is associated with the disease severity and can be considered for determining the prognosis of studies. Also, peripheral blood circulating Tfh (cTfh) cells are an available sample that can be used as an indicator for diagnosing diseases.

The effects of tumor-derived supernatants (TDS) on cancer cell progression: A review and update on carcinogenesis and immunotherapy.

Tumors can produce bioactive substances called tumor-derived supernatants (TDS) that modify the immune response in the host body. This can result in immunosuppressive effects that promote the growth and spread of cancer. During tumorigenesis, the exudation of these substances can disrupt the function of immune sentinels in the host and reinforce the support for cancer cell growth. Tumor cells produce cytokines, growth factors, and proteins, which contribute to the progression of the tumor and the formation of premetastatic niches. By understanding how cancer cells influence the host immune system through the secretion of these factors, we can gain new insights into cancer diagnosis and therapy.

Effect of Iron Deficiency Anemia on Blood Glucose and Insulin Resistance in Women with Type II Diabetes: A Single-group, Clinical Interventional Study.

AIMS: Iron deficiency anemia (IDA) is one of the disorders recently associated with an increase in insulin resistance (IR) and, consequently, diabetes mellitus (DM) affection by causing oxidative stress. In this study, we look at how IDA may contribute to developing type II diabetes mellitus (T2DM), controlling diabetes, and reducing IR in women with T2DM. METHODS: In this single group, clinical interventional study, we enrolled 40 women with T2DM and IDA. Before and after intervention with ferrous sulfate tablets, their blood glucose (BG) levels and IR levels were evaluated. This study was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1397.031) and registered at the Iranian Center for Clinical Trials (No. IRCT20170215032587N3). A significant level was considered p <0.05. RESULT: The mean age of patients was 48.18 ± 4.6 years, with 5.3-5.8 years duration of T2DM. After the intervention, the mean fasting blood glucose (FBG) level reached 198.53 ± 48.11 to 170.93 ± 37.41, which was significant (p <0.0001). Also, hemoglobin A1C level reached from 8.49 ± 0.9 to 7.96 ± 0.58, which was significant (p <0.0001). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) demonstrating a significant reduction of IR levels after intervention with ferrous sulfate tablets (p <0.018). CONCLUSIONS: IDA treatment in patients with T2DM can significantly reduce the BG and IR levels. To better control BG, checking iron status and its correction may provide better clinical outcomes in these patients.

WITHDRAWN: Comparison of the Efficacy of Oral Magnesium with Oral Ketorolac for Postoperative Pain Management in Anorectal Surgery: A Double-blinded Randomized Clinical Trial

The article has been withdrawn at the request of the editor of the journal Reviews on Recent Clinical Trials.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Comparison of the Effects of Govarcin Herbal Capsule and Metoclopramide for Alleviating Gastrointestinal Symptoms in Patients with Functional Dyspepsia: A Randomized Double-blind Clinical Trial.

BACKGROUND: Functional dyspepsia (FD) is felt as a discomfort or pain on the center line or upper abdomen. In this study, we aimed to compare the effects of Govarcin herbal capsule and Metoclopramide for alleviating gastrointestinal symptoms in patients with FD. METHODS: Totally, 106 patients enrolled in a double-blind, clinical trial study. The participants had FD and were divided into two groups receiving Govarcin and Metoclopramide by block randomization. The patients were treated for four weeks, taking one Govarcin capsule or Metoclopramide tablet after each meal. The rate of improvement in patients was assessed by mitigation of clinical symptoms, including epigastric pain, fullness, discomfort, nausea, vomiting and heartburn. Also, before and after intervention, we used Nepin questionnaire and ROME III. SPSS statistics 25 software was used for data analyzing. RESULTS: Clinical symptom score changes between Govarcin and Metoclopramide patients' groups showed that there was no significant difference in any of the clinical symptom scores (except for heartburn, p-value=0.012) between the study groups. Nepean score in Govarcin group before and after treatment were 19.3±4.8 and 8.9±2.8, respectively (p-value<0.001). For Metoclopramide group, these values were 19.8±3.5 and 9.4±2.1 respectively (p-value<0.001). No significant difference was found in terms of Nepean score between the Govarcin and Metoclopramide groups (p-value=0.995). CONCLUSION: Govarcin herbal capsule can be used to remedy symptoms in patients with FD. It seems that Govarcin is as effective as Metoclopramide in fighting symptoms of FD as no significant difference in efficacy has been demonstrated between them.

Effects of Pregabalin as a Neural Pathway Inhibitor for the Treatment of Resistant Subacute and Chronic Cough: A Pilot Clinical Trials Study.

BACKGROUND: Cough hypersensitivity syndrome is one of the causes of chronic cough. Small clinical trials have suggested the effects of pregabalin as a neural pathway inhibitor in treating subacute and chronic cough resistance. METHODS: This study is an 8-week, pilot study randomized, double-blind clinical trial on 30 patients' resistant to treatment of the underlying cause who were referred to an ultra-specialized lung clinic, Shahid Beheshti Hospital, between 2021-2022. The samples were randomly divided into control (dextromethorphan and placebo) and intervention (dextromethorphan and pregabalin). Patients were evaluated at the beginning, during, and after eight weeks of treatment, using the modified standard Leicester Cough Questionnaire (LCQ) regarding the changes and the rate of recovery compared to before Participation in the study. FINDINGS: The quality of life score of patients eight weeks after treatment had a significant difference and was higher in the intervention group (In the pregabalin group) than in the control group (p =0.006). The recovery rate of cough in 26% of patients was equal to 70%, but others were reported up to 50%. CONCLUSION: Pregabalin increases the quality of life in patients with subacute and chronic cough resistant to standard treatment and increases the rate of recovery in these patients.

The effect of interferon in the therapy of severe coronavirus infection.

BACKGROUND: So far, several protocols have been used for the treatment of coronavirus disease-2019 (COVID-19). In this study, we aimed to study the effect of interferon on the treatment of hypoxemia caused by COVID-19. MATERIALS AND METHODS: This was a quasi-experiment with a nonequivalent group design. All participants were admitted to Shahid Beheshti Hospital, Qom province. In total, 60 patients were enrolled in the study, and inclusion criteria were age over 18 years, positive PCR test result, pulmonary involvement in computed tomography (CT) scan, and SpO2 level below 93%. Individuals were divided into two control (hydroxychloroquine + lopinavir/ritonavir [Kaletra]) and intervention (hydroxychloroquine + lopinavir/ritonavir [Kaletra] + interferon-ß 1a [recigen]) groups. The data were analyzed in Stata/SE 14.2 using Chi-square, t-test, and Mann-Whitney U test. RESULTS: The mean ± standard deviation (SD) age of patients was 63 ± 16.12 years and 43.3% were male. In terms of outcome variables, 20% of patients in the intervention group and 53.3% of subjects in the control group died and this difference was significant (P = 0.007). According to the quick sequential organ failure assessment (qSOFA) score, the severe cases were 16.7% in the intervention group and 50% in the control group (P = 0.006). In addition, the median days of hospitalization were 11.5 days-significantly higher than those in the control group (5.5 days) (P < 0.001). CONCLUSION: Based on the results of this study, the use of interferon in the treatment of COVID-19 can improve health and reduce the severity of the disease and mortality.

Immunopathogenesis of viral infections in neurological autoimmune disease.

Autoimmune diseases develop due to self-tolerance failure in recognizing self and non-self-antigens. Several factors play a role in inducing autoimmunity, including genetic and environmental elements. Several studies demonstrated the causative role of viruses; however, some studies showed the preventive effect of viruses in the development of autoimmunity. Neurological autoimmune diseases are classified based on the targets of autoantibodies, which target intracellular or extracellular antigens rather than neurons. Several theories have been hypothesized to explain the role of viruses in the pathogenesis of neuroinflammation and autoimmune diseases. This study reviewed the current data on the immunopathogenesis of viruses in autoimmunity of the nervous system.

Discharge of Confirmed COVID-19 Patients Based on WHO or Regional Criteria? A Cohort Study.

BACKGROUND: Increasing the number of COVID-19 patients raises concerns about the capacity of the health care system. This issue emphasizes reducing the admission rate and expediting patient discharge. OBJECTIVE: This study aimed to develop a discharge protocol for COVID-19 patients based on the existing capacity of the healthcare system and to assess its post-discharge outcomes. METHODS: This is a multicenter cohort study. All COVID-19 patients referred to selected medical centers in Qom, Iran, from Feb. 19 to Apr. 19, 2020, were target populations. Eligible patients were classified into a) the criterion group and b) the non-criterion group. Patients were followed up daily for 14 days after discharge by phone, and the required data was gathered and recorded in follow-up form. Univariate (chi-square and t-tests) and multivariate multiple (multivariate probit regression) analysis were used. RESULTS: A total of 2775 patients were included in the study (1440 people in the criterion group and 1335 in the non-criterion group). Based on multivariate probit regression, death was statistically associated with discharge outside our criteria (p<0.001), rising age (p<0.001), and being male (p=0.019), and readmission were associated with discharge outside our criteria (p<0.001), rising age (p=0.009), and having the history of underlying diseases (p=0.003). Furthermore, remission had statistically significant associations with discharge based on our criteria (p<0.001), decreasing age (p=0.001), and lack of a history of underlying diseases (p<0.001). CONCLUSION: Mortality and readmission were significantly lower according to our discharge criteria. Our designed criteria apply to less developed and developing countries due to the limited capacity and resources available in the health care system.

Comparing the Sensitivity and Specificity of Lung CT-scan with RT-PCR for Diagnosis of COVID-19.

BACKGROUND: The lung is one of the major organs affected by the SARS-CoV-2 virus. Lung CT scan and RT-PCR are the most valuable diagnostic methods in the early diagnosis and management of COVID-19. Due to the possible inconsistency of the false-negative results for the RT-PCR test, in our study, we aimed to evaluate the sensitivity and specificity of lung CT-scan as an accurate diagnostic method of COVID-19. METHODS: In this cross-sectional study, patients suspected of COVID-19 and referred to Shahid Beheshti Hospital in Qom city from February 26 to April 13, 2020, were enrolled. For a definitive diagnosis of COVID-19, chest CT scan and RT-PCR testing was performed for 644 patients, and both sensitivity and specificity of lung CT scan were evaluated. RESULTS: According to the findings, and comparing to the RT-PCR test as the gold standard, sensitivity, specificity as well as, positive predictive and negative predictive values of lung CT-scan were found as follow; 94.47% (95% CI: 90.73 - 97.02%), 24.71% (95% CI: 20.70 - 29.07%), 40.73% (95% CI: 36.58 - 44.99%), 89.08% (95% CI: 82.4 - 94.05%), respectively. CONCLUSION: According to the findings, the lung CT scan has a better diagnostic value than RTPCR in symptomatic patients who were referred to the hospital for COVID-19 diagnosis. Performing lung CT-scan in patients with negative RT-PCR tests should be assessed.

Choosing the Right Protocol to Establish MCF-7 Tumor Xenograft in Nude Mice.

BACKGROUND: Xenografts of various human cancers in nude mice provide a helpful model in cancer research. This study aimed to develop a xenograft mouse model of MCF-7 breast cancer using injectable estradiol valerate. METHODS: Thirty healthy female C57 nu/nu mice were engrafted with three protocols to establish an MCF-7 tumor. Injectable estradiol valerate (10 mg/ml) was used as a substitute for estradiol pellets. The development of tumors was recorded daily, and data were statistically analyzed. Histology of bladder, kidney, and tumors was used to estimate tumor establishment and probable urinary adverse effects. RESULTS: According to the findings, the duration of MCF-7 tumor growth was the lowest for protocol B (tumor tissue). Also, this protocol had the highest xenograft yield within the shortest time duration (37 days for protocol B vs. 73 days for protocol A) without causing urinary adverse effects. CONCLUSION: Our findings revealed that estradiol valerate, which is way less expensive than estradiol pellets, can be used as a tumor proliferator to establish MCF-7 tumors with the highest yield when MCF-7 tumors have been used for xenograft.

Patient-related post-ERCP pancreatitis (PEP) risk factors between two groups of patients: Prophylactic pancreatic stent and rectal indomethacin.

Background: Pancreatitis is one of the most crucial complications following endoscopic retrograde cholangiopancreatography (ERCP). The purpose of the current study was to investigate patient-related post-ERCP pancreatitis (PEP) risk factors in two groups of patients: prophylactic pancreatic stent and rectal indomethacin. Methods: Two different prophylactic modalities were planned and complications were assessed based on the defined inclusion criteria. In this study, the patients were evaluated for the procedure and patient-related risk factors in post-ERCP pancreatitis in the recipient groups of the prophylactic pancreatic stent and rectal indomethacin. Results: Pancreatitis was confirmed in 27 of all 170 selected patients after ERCP. By univariate analysis, two variables were significant with the development of PEP. Regarding the patient-related risk factors, unique subjects with common bile duct (CBD) dilated 10mm were more exposed to an increased chance of PEP (P=0. 015); meanwhile, other factors did not correlate with the increased possibility of PEP in both groups. The only procedure-related risk factor for PEP was the deep cannulation of the pancreatic duct in both groups during the procedure with an incremental significant incidence of pancreatitis (P=0.005). Comparison of prophylactic pancreatic stent and rectal indomethacin showed no effects in term of post ERCP pancreatitis reduction. Additionally, there was no significant difference between these two strategies in the rate of PEP. Conclusion: Prophylactic pancreatic duct stents and administration of rectal indomethacin cannot have particular approaches for reducing the possible occurrence of PEP. The increase in time of deep cannulation and the presence of CBD dilation <10mm could be considered as important risk factors.

Comparison of the Sedative Effect of Ketamine, Magnesium Sulfate, and Propofol in Patients Undergoing Upper Gastrointestinal Endoscopy: Double-Blinded Randomized Clinical Trial

BACKGROUND: Endoscopy provides valuable diagnostic information and intervention therapies for gastroenterologists. Therefore, various drugs have been used to induce sedation in patients undergoing endoscopy, whereas none have been considered preferred by endoscopists. In the current study, we decided to use the combination of magnesium sulfate, ketamine, and their synergistic effects for creating partial analgesia to increase the satisfaction of endoscopists and patients. METHODS: This study is a Double-Blind Randomized Clinical Trial that investigates the sedative effect of ketamine, magnesium sulfate, and propofol in endoscopy. Patients were selected from individuals over 12 years old and with American Society of Anesthesia (ASA) physical status I or II. The study was performed on 210 patients classified as ASA (I have no underlying disease) or II (with underlying controlled disease). The whole group was relieved of pain through sedation according to Ramsay criteria, satisfaction with the operation, duration, recovery, nausea and vomiting, hypotension, and decreased oxygen saturation were compared. RESULTS: A total of 155 patients were enrolled in our study, including 51 patients (midazolam and propofol), 55 patients (midazolam and ketamine), and 49 patients (midazolam and ketamine and magnesium). The results showed that preoperative heart rate, intraoperative systolic blood pressure, intraoperative diastolic blood pressure, postoperative heart rate, postoperative systolic blood pressure, and postoperative heart rate were significantly different between the groups. CONCLUSION: The satisfaction of the endoscopic was achieved to a great extent, mainly in the group receiving midazolam and propofol and in the group receiving midazolam and ketamine. In most cases, the satisfaction of the endoscopic was acceptable, and the low satisfaction of the endoscopic was more in the group receiving midazolam. Ketamine and magnesium were observed. The two compounds midazolam-ketamine, and midazolam-propofol, have a more favorable effect than the combination of midazolam, ketamine, and magnesium.

Various Aspects of Fasting on the Biodistribution of Radiopharmaceuticals.

It is demonstrated that fasting can alter the biodistribution of radiopharmaceuticals in nuclear medicine. Various studies have highlighted that fasting is interpreted to be easy for physicians during PET study, fasting is one of the most important factors determining the usefulness of this protocol. It is well documented that fasting can suppress normal 18F-FDG PET uptake during nuclear cardiology. However, there is no consensus about the usefulness of fasting on radiopharmaceuticals, especially on 18F-FDG in PET imaging, but special attention should be paid to the setting of the fasting duration. Nevertheless, it does seem we still need extensive clinical studies in the future. The present study aims to review the various aspects of fasting, especially metabolic alteration on radiopharmaceutical biodistribution. In this study, we focused more on the effect of fasting on 18F-FDG biodistribution, which alters its imaging contrast in cardiology and cancer imaging. Therefore, shifting substrate metabolism from glucose to free fatty acids during fasting can be an alternative approach to suppress physiological myocardial uptake.