Journal of clinical medicine research最新文献

Background: The aim of the present study was to conduct a prospective observational study to explore the effects of imeglimin on systemic energy metabolism/body composition and to identify potential mitochondria-related biomarkers of the efficacy of the drug in clinical settings.

Methods: In this prospective observational study, 16 participants with type 2 diabetes mellitus in the diabetes clinic of Kyoto University Hospital were enrolled. Individuals were started on imeglimin as monotherapy or add-on therapy.

Results: After 3 months under imeglimin treatment, there was no significant change in basal metabolism or body composition. However, serum levels of growth differentiation factor 15 (GDF15) were higher while those of serum fibroblast growth factor 21 and urine 8-hydroxy-2'-deoxyguanosine were not changed. Additional in vitro examination revealed that imeglimin induces GDF15 protein release from human hepatocytes.

Conclusions: Three-month imeglimin treatment increased serum GDF15 levels in clinical type 2 diabetes mellitus patients along with little change in basal metabolism or body composition, suggesting GDF15 as a potential marker for the efficacy of imeglimin.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for type 2 diabetes, have emerged as a promising treatment for heart failure with reduced ejection fraction (HFrEF). They show significant cardiovascular benefits, including reduced cardiovascular mortality and heart failure hospitalizations. This review consolidates knowledge on the efficacy of SGLT2 inhibitors in HFrEF, focusing on their mechanisms of action, clinical benefits, and patient outcomes. To consolidate existing knowledge on the efficacy of SGLT2 inhibitors in reducing cardiovascular mortality in HFrEF, with an emphasis on pathophysiology, clinical benefits, and patient outcomes, major medical databases such as PubMed, Scopus, and Web of Science were reviewed, prioritizing research published from 2020 to 2024. Key studies and clinical trials, including DAPA-HF and EMPEROR-Reduced, were analyzed to understand the impacts of SGLT2 inhibitors on HFrEF management. The review highlights the multifaceted mechanisms by which SGLT2 inhibitors exert their cardiovascular benefits, including osmotic diuresis, natriuresis, improved myocardial energetics, and anti-inflammatory and antifibrotic effects. Clinical trials have consistently demonstrated significant reductions in cardiovascular mortality and hospitalizations among HFrEF patients treated with SGLT2 inhibitors. These benefits are observed across diverse demographic and clinical subgroups, indicating their broad applicability in clinical practice. SGLT2 inhibitors significantly advance HFrEF management, reducing cardiovascular mortality and hospitalizations. However, gaps remain in long-term outcomes, early diagnostic indicators, and mechanisms of action. Future research should address these gaps and explore personalized medicine to optimize treatment. Integrating SGLT2 inhibitors into standard HFrEF management guidelines, supported by updated policies and educational initiatives for healthcare providers, will be crucial to maximize their therapeutic potential and improve patient outcomes.

Background: Despite sharing common pathophysiological risk factors, the relationship between gallstones and depression requires further evidence for a clearer understanding. This study combines the National Health and Nutrition Examination Survey 2017 - 2020 observational data and Mendelian randomization (MR) analysis to shed light on the potential correlation between these conditions.

Methods: By analyzing the National Health and Nutrition Examination Survey 2017 - 2020 data through weighted multivariable-adjusted logistic regression, we examined the association between depression and gallstone risk. MR was subsequently applied, utilizing genetic instruments from a large genome-wide association study on depression (excluding 23andMe, 500,199 participants) and gallstone data (28,627 cases, 348,373 controls), employing the main inverse variance-weighted method alongside other MR methods to explore the causal relationship. Sensitivity analyses validated the study's conclusions.

Results: Among the 5,303 National Health and Nutrition Examination Survey participants, a significant association was found between depressive symptoms and increased gallstone risk (initial odds ratio (OR) = 2.001; 95% confidence interval (CI) = 1.523 - 2.598; P < 0.001), with the association persisting after comprehensive adjustments (final OR = 1.687; 95% CI = 1.261 - 2.234; P < 0.001). MR findings also indicated a causal link between genetically predicted depression and higher gallstone risk (OR = 1.164; 95% CI = 1.053 - 1.286; P = 0.003).

Conclusions: Depression is significantly associated with a higher risk of gallstones, supported by genetic evidence suggesting a causal link. These findings highlight the importance of considering depression in gallstone risk assessments and management strategies.

In the pharmacologic treatment of primary aldosteronism (PA), titration of mineralocorticoid receptor antagonist (MRA) dosing is necessary to reverse the renin suppression caused by high aldosterone levels. However, we often encounter cases in which the plasma renin activity (PRA) does not achieve the target level, even with the maximum dose of MRA. In this setting, sacubitril/valsartan, a combination of a neprilysin inhibitor and an angiotensin II type 1 receptor blocker that is approved for use as adjunctive therapy with an MRA, has been reported to inhibit aldosterone secretion both in vitro and in vivo. If sacubitril/valsartan proves to be effective in this context, it may offer a promising treatment for PA. However, there are few reports on the use of sacubitril/valsartan in this disease. We used add-on sacubitril/valsartan in three patients with PA, in whom blood pressure was insufficiently reduced and PRA remained suppressed despite administering the maximum dose of MRA. With the addition of sacubitril/valsartan, the decrease in plasma aldosterone concentration (PAC) was more marked than the increase in PRA. Because MRAs do not suppress aldosterone production but instead act by blocking mineralocorticoid receptors, use of these agents actually promotes the renin-angiotensin system and leads to increased PAC resulting from positive feedback. The pathological significance of the phenomenon whereby PAC increases with MRA administration but decreases with the addition of sacubitril/valsartan is unclear. In PA, more effective treatment may be possible by suppressing aldosterone with sacubitril/valsartan and blocking the action of aldosterone with MRAs.

Background: The aim of this study is to investigate whether vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in the prevention of colorectal cancer (CRC) risk.

Methods: The case-control design was employed, including 650 CRC cases and 650 controls aged 35 to 70 years, comprising both men and women. The study encompasses sociodemographic data, clinical information, radiological diagnoses, and biochemical measurements.

Results: Statistically significant differences were observed between CRC and controls in terms of age, diagnostic radiology, tomography, positron emission tomography/computed tomography (PET/CT), colonoscopy, CRC awareness, risk factors, age, genetics, exposure to chemicals, inadequate nutrition, smoking, hookah and alcohol use. Significant differences were also identified in intestinal inflammations, obesity, processed foods (P < 0.001), abdominal pain and cramps, diarrhea, constipation, blood in stool, bloating (gas), irritable bowel, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Regarding biochemical parameters, statistically significant differences were found between CRC and controls in terms of hemoglobin, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), vitamin D, neutrophil level, red blood cell (RBC), white blood cell (WBC), platelet level, platelet count, hematocrit, potassium, sodium (Na), calcium, creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), bilirubin, uric acid, iron (Fe), ferritin, C-reactive protein (CRP), total protein, systolic blood pressure (SBP), and diastolic blood pressure (DBP) parameters (P < 0.001). Multivariate stepwise regression analysis was performed to find the best risk factors for the diagnosis of CRC as the dependent variable. As a result of the analysis, intestinal inflammation (P < 0.001), nausea/vomiting (P < 0.001), stomach pain (P = 0.003), hookah-smoking (P = 0.034), uric acid (P < 0.001), bilirubin (P < 0.001), cigarette smoke exposure (P = 0.033), processed food consumption (P = 0.002), calcium levels (P = 0.029), vitamin D deficiency (P < 0.001), and ferritin (P < 0.001) levels were identified as significant determinants for CRC.

Conclusions: The current study demonstrated that vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in reducing the risk of CRC prevention. The increase in CRC rates may be associated with lifestyle, environmental and hereditary factors, nutrition, alcohol consumption, hookah use, and cigarette smoking.

Background: The high prevalence of traditional cardiovascular risk factors among the patients without cardiovascular disease (CVD) allows us to predict an increase in cardiovascular morbidity rate in the future. Arterial stiffness is one of the most important predictors and pathogenetic mechanisms of CVD development. The aim of our study was to evaluate the predictive differences of age-related and age-independent (universal) cardio-ankle vascular index (CAVI) reference values for detecting increased arterial stiffness in individuals without CVD.

Methods: The study included 600 patients (43% men and 57% women, mean age 36.0 ± 18.3 years). All the patients underwent anthropometric measurements with obesity markers evaluation, assessment of arterial stiffness by sphygmomanometry. To create predictive models, we used universal and age-related CAVI thresholds: ≥ 9.0 (CAVI^{≥ 9}) and CAVI^Age according to the "Consensus of Russian experts on the evaluation of arterial stiffness in clinical practice".

Results: In the < 50 years group, both the CAVI^Age and CAVI^{≥ 9} models were significant (CAVI^Age: b = 4.8, standard error b (st.err.b) = 0.27, P < 0.001; CAVI^{≥ 9}: b = 3.2, st.err.b = 1.6, P < 0.001). The CAVI^Age model demonstrated high sensitivity and specificity (> 70%) compared to the CAVI^{≥ 9} model (sensitivity 62%, specificity 58%). In the receiver operating characteristic (ROC) curve analysis, the CAVI^Age model had a significantly higher area under the ROC curve (AUC) = 0.802 than the CAVI^{≥ 9} model: AUC = 0.674. In the ≥ 50 years group, both models were significant: CAVI^Age (b = 2.6, st.err.b = 1.13, P < 0.001) and CAVI^{≥ 9} (b = 5.3, st.err.b = 0.94, P < 0.001). Both models demonstrated high sensitivity and specificity (> 70%). When ROC curves were analyzed for the CAVI^Age model, the AUC value of 0.675 was significantly lower when compared to the CAVI^{≥ 9} model (AUC = 0.787, P = 0.031).

Conclusions: In the < 50 years group, the model based on age-specific CAVI thresholds has the higher predictive value, sensitivity, and specificity for identifying individuals with increased arterial stiffness. In contrast, in the ≥ 50 years group, a predictive model using a universal threshold value of CAVI^{≥ 9} has advantages.

The goal of combination therapy for moderate-to-severe lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) is to ease both the dynamic and static symptoms by using agents that have complementary mechanisms of action. Similar to prescribing other drugs, LUTS/BPH combination therapy has been affected by multiple factors. Previous qualitative research discussed the individual perspectives that influenced combination therapy administration. Yet, until recently, there has been limited interest in clinical reasons that physicians have to consider before prescribing LUTS/BPH combination treatment. This systematic review aimed to identify the clinical considerations that influence the decision to prescribe combination therapy of tamsulosin 0.4 mg + dutasteride 0.5 mg for Asian men with LUTS/BPH. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was performed in databases Medline, CINAHL, the Cochrane Library, and Embase from inception until January 2024 using Medical Subject Headings (MeSH) terms and keywords with truncation for alternative acronyms. A citation search was performed to gather works of literature on LUTS/BPH combination treatment in addition to the "PICO" framework for search terms. Five English-language primary randomized controlled trials (RCTs) were included in the narrative analysis using the Critical Appraisal Skills Program (CASP) checklist after critical appraisal. Several dosages of tamsulosin (0.2 mg and 0.4 mg) have been administered in LUTS/BPH combination treatment over the last few decades despite 0.2 mg tamsulosin being standardized as an effective regime in Asian countries. A remarkable correlation between prostate volume (PV) and prostate-specific antigen (PSA) was found in Asian men, which requires higher PSA secretion to enlarge each prostate unit and causes an increased risk of moderate-to-severe LUTS. Additionally, BPH baseline variables may lead to a different response to combination therapy, especially the PV and PSA differences. In conclusion, compared with Caucasian men, a significantly higher risk of moderate-to-severe LUTS was found in Asian men. Initiation of combination therapy, especially dutasteride, depends on a larger PV (≥ 30 mL); it is possible, therefore, that earlier PV and PSA examinations and baseline variables assessments ought to be performed by physicians before the combination therapy prescription. Alternative treatment options may be considered for a patient who prefers an active pattern of sexual activity during their BPH combined pharmacotherapy. These clinical considerations may influence the prescription of tamsulosin 0.4 mg + dutasteride 0.5 mg combination therapy for Asian men with moderate-to-severe LUTS/BPH. This study was registered on PROSPERO (CRD42024575528).

The aim of the present study was to report the remodeling of the basement membrane through physiological stimulus during the treatment of fibrosis in a lower limb with lymphedema. A clinical trial was conducted involving the evaluation of the basement membrane in skin biopsies before and after treatment for clinical stage II lower limb lymphedema using the Godoy method for the reversal of lymphedema and skin fibrosis. The samples were stained with Gomori's reticulin stain and evaluated using Weibel's multipoint morphometric method at the Godoy Clinic. Prior to treatment for lymphedema, rupture and important discontinuity of the basement membrane was found. After treatment, structural continuity and thickness had returned to the regions of previous rupture. The difference was statistically significant (P < 0.05, paired t-test). The present study reports that physiological stimuli targeting the lymphatic system led to the clinical reversal of fibrosis, as well as stimulate the synthesis of extracellular matrix proteins and the reconstruction of the basal lamina of the skin.

Granulomatosis with polyangiitis (GPA) has three clinicopathological features, namely, necrotizing granulomatosis of the upper respiratory tract and lungs, focal segmental necrotizing glomerulonephritis of the kidney, and necrotizing vasculitis of small vessels throughout the body. A 92-year-old man with clinically diagnosed probable Alzheimer's disease (AD) exhibited subacute deterioration in cognitive function. On admission, he was diagnosed with acute renal failure with an elevated creatinine level (5.48 mg/dL) as well as severe disturbance of consciousness. Antineutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3-ANCA) were highly positive with ≥ 350 U/mL. The patient was diagnosed with GPA and was managed with steroid pulse therapy. However, he died without any improvement in renal function. As a result of the autopsy, the patient was diagnosed with definite AD, and his impaired consciousness was found not to be caused by central nervous system involvement due to GPA. As necrotizing crescentic glomerulonephritis was observed, the cause of the acute progressive renal failure was found to be PR3-ANCA-positive GPA. The autopsy revealed no GPA-related lesions in other parts of the body aside from the kidneys. It is rare to encounter cases of PR3-ANCA-positive GPA with renal-limited vasculitis and acute renal failure as the initial manifestation, as in the present case. Making an accurate clinical diagnosis of older patients suffering from various diseases in multiple organs is challenging. Although autopsy has the limitation of a terminal image, it is extremely useful in elucidating the pathophysiology of the older patient in this case.