Therapeutic Advances in Chronic Disease最新文献

Background: Patients with primary aldosteronism (PA) exhibit a high prevalence of diabetes mellitus (DM). However, the relationship between visceral adipose tissue (VAT) and new-onset diabetes mellitus (NODM) in PA patients remains unclear.

Objectives: To explore the association between VAT and the risk of NODM in PA patients.

Design: This is a prospective cohort study spanning 10 years (2010-2020).

Methods: A total of 342 PA patients were enrolled prospectively. Abdominal adiposity indexes, including VAT area, VAT ratio, subcutaneous adipose tissue (SAT) area, and SAT ratio, were measured using a computed tomography-based software at diagnosis.

Results: Of 342 PA patients (46.2% male, mean age 50.8 ± 11.2 years), 35 (10.2%) developed NODM over a mean follow-up of 7.4 years. A positive nonlinear association between NODM risk and Log (VAT ratio) ⩾ -0.72 was observed (high-VAT group). High VAT (odds ratio (OR), 6.09; p = 0.005), older age (OR, 1.09; p < 0.001), higher body mass index (OR, 1.24; p < 0.001), higher waist-to-hip ratio (OR, 1.11, p < 0.001), lower baseline aldosterone (OR, 0.99, p = 0.011), higher diastolic blood pressure (OR, 1.05, p = 0.012), and lower systolic blood pressure (OR, 0.98, p = 0.045) as risk factors for high VAT. Adrenalectomy did not significantly associate with reduced NODM risk (OR, 0.49; p = 0.292).

Conclusion: Our findings highlight that 10.2% of PA patients develop NODM over a mean follow-up of 7.4 years, with high VAT increasing the risk. Baseline VAT is a key determinant of NODM development in PA patients, regardless of targeted treatments.

Background: Hepatosteatosis is a common condition that can lead to cirrhosis and liver cancer. Galectin-3 (GAL-3) has been implicated in liver fibrosis and inflammation.

Objectives: The purpose of this study was to investigate the association between GAL-3 and hepatosteatosis.

Design: This study is a retrospective secondary analysis of data from a community health screening program.

Methods: A total of 766 participants were included in the final analysis. Hepatosteatosis was diagnosed using ultrasonography, and GAL-3 levels were measured using enzyme-linked immunosorbent assay. Logistic regression analysis was used to examine the association between GAL-3 levels and the presence of hepatosteatosis, adjusting for age, sex, and other potential confounding factors.

Results: The prevalence of moderate-to-severe hepatosteatosis in the study population was 31.5%. The participants with hepatosteatosis had a significantly higher mean level of GAL-3 compared to those without hepatosteatosis (16.6 ± 7.3 vs 13.5 ± 7.3 ng/ml; p < 0.001). After adjusting for age, sex, body mass index, and other potential confounding factors, a higher level of GAL-3 was significantly associated with an increased risk of moderate-to-severe hepatosteatosis (adjusted odds ratio (aOR) 1.24, 95% confidence interval (CI) 1.05-1.46, p = 0.010). The coexistence of alanine transaminase/aspartate transaminase ratio >1 and GAL-3 >14.4 ng/ml was associated with a significantly increased risk (aOR 3.37, 95% CI: 1.90-5.99, p < 0.001).

Conclusion: Our findings suggest that GAL-3 level is significantly associated with the presence of moderate-to-severe hepatosteatosis, independent of other known cardiometabolic risk factors.

Background: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease that affects up to 30% of patients with psoriasis. Diagnosis and treatment could be improved by implementing an interdisciplinary dermatological-rheumatological consultation (IDRC).

Objectives: This study aimed to assess the effect of a face-to-face IDRC involving both a dermatologist and a rheumatologist evaluating patients in a single visit, on disease activity and burden in patients with PsA.

Design: Prospective, single-center, cohort study.

Methods: 202 patients with psoriasis were enrolled, among whom 115 individuals with psoriasis and musculoskeletal symptoms underwent an IDRC. Disease manifestations, comorbidities, and both objective and subjective disease activity scores were evaluated.

Results: Out of the participants, 56 were diagnosed with definite PsA, while the remaining 146 had psoriasis. Nail involvement was associated with axial PsA (odds ratio 4.11; 95% CI 1.22-13.82; p = 0.02). Patients with PsA often experienced a prolonged time to diagnosis (mean 187 weeks) and had a significant psychosocial burden (mean Hospital Anxiety and Depression Index Scale [HADS]-Anxiety score of 7.66 and mean HADS-Depression score of 5.63). Post-IDRC, both objective and subjective disease parameters showed improvement, and patients required less time for consultations with healthcare professionals compared to before the IDRC.

Conclusion: These findings suggest that an IDRC approach could effectively expedite and optimize the diagnosis and treatment of patients with psoriasis and musculoskeletal symptoms.

Growth factors were introduced to increase predictability in periodontal regeneration and have since been widely applied in dentistry. This narrative review article highlights histological and latest findings of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth factor-2 (rhFGF-2) for periodontal regeneration. rhPDGF-BB enhances the proliferation and chemotaxis of periodontal ligament and alveolar bone cells. The optimal dose for rhPDGF-BB, in combination with beta-tricalcium phosphate, is 0.3 mg/ml. It is approved in the United States, Canada, and Taiwan for use in periodontal regeneration and treatment of gingival recession. rhFGF-2 promotes periodontal wound healing through mitogenic and angiogenic effects on mesenchymal cells in the periodontal ligament. It is approved in Japan at an optimal dose of 0.3% for periodontal regeneration in intrabony defects. Both recombinant growth factors show histological evidence of new bone, cementum, and periodontal ligament. Clinical studies demonstrate improved clinical attachment levels and defect resolution for treating intrabony and furcation periodontal defects. Presented clinical cases and consensus reports may serve as a reference for clinicians. rhPDGF-BB and rhFGF-2 are safe and effective biologics that can be applied to improve the outcomes of periodontal regeneration.

Background: Severe upper extremity paresis due to stroke is a significant clinical sequela. Neuromuscular electrical stimulation (NMES)-based rehabilitation has demonstrated promising results along with cortical plasticity. Transcranial alternating current stimulation (tACS) has gained attention due to its unique ability to entrain endogenous oscillatory brain rhythms with injected AC frequency, offering the potential for modifying brain conditions to enhance rehabilitative interventions. Because repetitive motor execution in rehabilitation training requires a smooth transition of the brain state despite often being impaired secondary to stroke, combining NMES and tACS may offer better treatment efficacy.

Aim: This study proposes a phase I/II trial of an outpatient comprehensive rehabilitative treatment combining the integrated volitional-control electrical stimulation (IVES), a closed-loop NMES, and the timing-specified focal tACS in individualized beta frequency (dynamic-precision tACS) targeting severe hand paresis in patients with chronic stroke, aiming to demonstrate the feasibility of combination treatment.

Design: Double-blind randomized cross-over trial.

Methods: The repetitive facilitative finger extension training utilizing closed-loop NMES is combined with dynamic-precision tACS on the primary motor cortex to assist post-movement beta-rebound. Together with regular occupational therapy, we propose a comprehensive outpatient neurorehabilitative regimen. Here, a total of 10 sessions will be conducted using a cross-over design using real and sham tACS.

Analysis: The perception and fatigue from stimulation will be investigated as the primary outcomes. The efficacy of improving sensorimotor function and their background physiological mechanisms will be evaluated as the secondary outcomes.

Discussion: This phase I/II trial will be the first to combine tACS and neurorehabilitation using functional electrical stimulation. A weekly outpatient protocol with cheap devices may offer a new treatment paradigm toward functional recovery for chronic stroke patients with severe upper extremity paresis.

Ethics and trial registration: This study was approved by the Ethics Committee of Kyorin University Faculty of Medicine (814-01). The trial was registered in a public database: UMIN000048274.

Background: Lumbar intervertebral disc and paravertebral muscle degeneration are common causes of chronic low back pain (CLBP). However, the exact etiology of CLBP in young patients remains unclear. Identifying the risk factors for CLBP in young patients could expedite the development of effective preventive recommendations.

Objectives: To identify the factors influencing the presence and severity of CLBP in young patients by analyzing the associations between the fat content of the paravertebral muscles, T2 value of the lumbar intervertebral disc (LIVD), and visual analog scale (VAS) score.

Design: Data for 23 patients diagnosed with CLBP were compared to those of 20 healthy young individuals.

Methods: The T2 values of the LIVD and fat content of the psoas major (PM), multifidus (MF), and erector spinae (ES) muscles for 23 young patients with CLBP and 20 healthy individuals were measured and compared using synthetic magnetic resonance imaging and proton density fat fraction analyses. Moreover, the factors (T2 values and fat content) associated with severe CLBP (assessed using the VAS score) were analyzed.

Results: The fat content of the right MF and ES was higher in patients with CLBP than in healthy individuals (p < 0.05). The T2 values of each LIVD in the CLBP and control groups were not significantly different (p > 0.05). Moreover, the VAS scores did not correlate with the T2 values of the patients (p > 0.05). The fat content of the bilateral MF and ES muscles was positively associated with the VAS score in young patients with CLBP (left MF: r = 0.506, p = 0.01; right MF: r = 0.532, p = 0.01; left ES: r = 0.636, p < 0.01; and right ES: r = 0.716, p < 0.01).

Conclusion: Degeneration of the MF and ES may contribute to CLBP in young patients. In addition, the severity of CLBP is positively correlated with the degree of fat infiltration in the MF and ES.

Background: The association between pyridoxal 5'-phosphate (PLP) and cardiovascular disease (CVD) remains a topic of discussion.

Objectives: This study aimed to explore the relationship between serum PLP levels and the incidence of all-cause mortality, cardiovascular mortality, and the risk of CVD among the US population.

Design: A population-based cohort study.

Methods: This study analyzed data from the National Health and Nutrition Examination Survey. Adjusted hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using weighted Cox proportional hazards regression models to assess the risk associated with all-cause and cardiovascular mortality. Weighted binary logistic regression was utilized to assess the relationship between serum PLP levels and the risk of CVD. Nonlinear associations were evaluated using multivariable-adjusted restricted cubic splines.

Results: There were 2546 cases of all-cause mortality and 867 cases of cardiovascular mortality over a mean follow-up of 11.36 years. In the fully adjusted model, the adjusted HRs with 95% CIs for all-cause mortality associated with increases in serum PLP levels corresponding to the interquartile ranges were 0.83 (0.74-0.93), 0.71 (0.63-0.80), and 0.64 (0.56-0.74), respectively. Similarly, cardiovascular mortality decreased by 0.78 (0.62-0.97), 0.63 (0.49-0.81), and 0.62 (0.50-0.77) with each quartile increase in serum PLP levels. Higher serum PLP levels confer protection against CVD risk (odds ratio: 0.87, 95% CI: 0.79-0.96). Serum PLP levels showed nonlinear relationships with risk of all-cause mortality, cardiovascular mortality, and CVD.

Conclusion: The results of this study provide evidence that serum PLP serves as a protective factor against all-cause mortality, cardiovascular mortality, and CVD in US adults, with dose-response relationships.

Background: Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus and is associated with an increased risk of end-stage renal disease (ESRD) and cardiovascular events. Early diagnosis and monitoring of DKD are crucial for implementing appropriate interventions. This study aimed to investigate the relationship between serum renalase (RNLS) levels, DKD, and diabetic macroangiopathy in patients with type 2 diabetes mellitus (T2DM).

Objectives: This study aims to evaluate the diagnostic value of serum renalase levels in DKD and diabetic macroangiopathy.

Design: This is a retrospective case-control study.

Methods: A total of 233 participants were recruited for the study, including 115 T2DM patients without DKD or diabetic retinopathy, and 118 T2DM patients with DKD. Serum RNLS levels were measured using an enzyme-linked immunosorbent assay. Kidney function parameters and diabetic macroangiopathy risk factors were evaluated in relation to serum RNLS levels.

Results: Serum RNLS levels were significantly higher in DKD patients compared to T2DM controls (34.82 (31.68, 39.37) vs 30.52 (28.58, 33.16), p < 0.01). Multiple linear regression analysis indicated that kidney function parameters and carotid intima-media thickness were independently related to RNLS levels. The study population was divided into four groups: no DKD and no diabetic macroangiopathy, DKD without diabetic macroangiopathy, diabetic macroangiopathy without DKD, and both DKD and diabetic macroangiopathy. Analysis results showed that patients with both DKD and diabetic macroangiopathy had the highest RNLS levels. Receiver operating characteristic curve analysis demonstrated the diagnostic value of RNLS for DKD (0.76 (95% confidence interval (CI) = 0.70-0.82, p < 0.01)) and diabetic macroangiopathy (0.75 (95% CI = 0.66-0.84, p < 0.01)).

Conclusion: Circulating RNLS levels were significantly increased in patients with DKD and diabetic macroangiopathy, suggesting that RNLS may serve as an early diagnostic marker.

Background: The criteria for remission in both clinical and pathological contexts for lupus nephritis (LN) remain controversial.

Objectives: To identify optimal short-term goals (remission criteria) for LN predicting long-term success at 5 years, using repeat kidney biopsy (Biopsy 2) and clinical data.

Design: Single-center observational study.

Methods: Twenty-three consecutive LN patients undergoing Biopsy 2 2 years post-induction therapy were evaluated. Two ideal long-term goals at 5 years were defined as: "A," Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) = 0 and prednisolone (PSL) ⩽5 mg/day, and "B," proteinuria ⩽0.2 g/day with a normal serum creatinine level and PSL ⩽5 mg/day. Histologically, the electron-dense deposit (EDD) score grades immune deposits based on their intensity, amount, and location. A score of ⩽1 was defined as "electron microscopy remission (ER)."

Results: Conventional renal indices failed to predict long-term goals. The short-term goals with an accuracy (area under the curve: 95% confidence interval) of ⩾0.8 predicted long-term goals: "A at 5 years" (A-5y), A-2y (0.91: 0.79-1.00), DORIS-R-2y (0.87: 0.72-1.00), EDD score (0.85: 0.70-1.00), B-2y (0.83: 0.66-0.99), and SLEDAI-R-2y (0.82: 0.66-0.98) as well as "B at 5 years" (B-5y), A-2y (0.87: 0.73-1.00), B-2y (0.87: 0.73-1.00), EDD score (0.85: 0.69-1.00), and DORIS-R-2y (0.83: 0.67-0.99). EDD scores predicted A-5y, B-5y, and PSL dose at 5 years in proportion to the score. The clinical and histological goals aligned.

Conclusion: The best predictive short-term goal was A-2y. Concordance between clinical remission (A-2y, B-2y, and DORIS-R-2y) and histological remission (ER) at 2 years suggests optimal short-term goals for LN.