Usefulness Differs Between the Visual Assessment and Specific Binding Ratio of 123I-Ioflupane SPECT in Assessing Clinical Symptoms of Drug-Naïve Parkinson’s Disease Patients

Background: In clinical practice, assessment of the striatal accumulation in 123I-ioflupane single photon emission computed tomography (SPECT) is commonly performed calculating the specific binding ratio (SBR) for the whole striatum. On the other hand, visual assessment of striatal accumulation in the SPECT was recently established. However, correlations of visual assessment with motor and cognitive functions in Parkinson’s disease (PD) have rarely been examined. Differences in the usefulness of these assessments at clinics are uncertain.Objective: We performed this study to compare correlations of cognitive and motor functions in drug-naive PD between the SBR and visual assessment using 123I-ioflupane SPECT.Methods: Cognitive and motor assessments and 123I-ioflupane SPECT were performed in 47 drug-naïve PD patients with Mini-mental State Examination scores of ≥25. Cognitive function was assessed using the total score and 6 subscores of the Montreal Cognitive Assessment (MoCA) and 10 separate subtests of the Neurobehavioral Cognitive Status Examination (COGNISTAT). Motor function was assessed using the Hoehn and Yahr scale and Unified Parkinson’s Disease Rating Scale. Accumulation of 123I-ioflupane was determined by visual assessment based on five grades: 1, burst striatum; 2, egg-shaped; 3, mixed type; 4, eagle wing; 5, normal striatum; and by calculating SBR averaged for the bilateral striatum using the DaTView computer software commonly used in clinical practice. Each SPECT assessment was compared with each subscore for cognitive and motor assessments.Results: Spearman correlation analysis showed SBR was significantly correlated with the MoCA subscores of visuospatial function and attention, and with COGNISTAT subtests of attention. Visual assessment showed significant negative correlation with the Hoehn and Yahr scale. Mean score of postural instability in patients with visual grade of 1 was significantly higher than those in patients with visual grades of 2 and 3.Conclusion: Clinical symptoms reflected by 123I-ioflupane SPECT differ between the SBR and visual assessment. SBR reflects some cognitive functions, whereas a visual assessment grade of 1, which signifies decreased uptake of 123I-Ioflupane in the caudate nucleus, reflects postural instability. Thus, the caudate nucleus may play an important role in posture maintenance. Our results suggest that performing both assessments is of value

Retrospective Comparison of the Efficacy of Tonsillectomy with and without Steroid-pulse Therapy in IgA Nephropathy Patients.

著者最終原稿版Objective Tonsillectomy and steroid-pulse (TSP) therapy have been proposed as a curative treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, we sometimes encounter patients who reject steroid-pulse therapy because of concerns about the side effects of corticosteroids. Here, we examined the efficacy of TSP therapy and tonsillectomy alone for IgAN with urinary abnormalities. Methods Data on 40 IgAN patients diagnosed by renal biopsies, who presented glomerular hematuria and proteinuria at baseline and underwent bilateral palatine tonsillectomy, were analyzed retrospectively. Twenty of them underwent TSP therapy (TSP group), and 20 underwent tonsillectomy alone (T group). We examined associations between therapies, changes in urinary findings and renal function, and subsequent clinical remission (CR), defined as negative proteinuria and urinary erythrocytes of less than 5/high-power field. Results TSP group showed a significant decrease in proteinuria and hematuria earlier than T group. The rates of CR were significantly higher in TSP group compared with T group on the final observation period (75% vs. 45%, p<0.05). There was a significant difference between CR group and non-CR group only in the rate of receiving TSP therapy. Conclusion TSP therapy significantly increased the probability of CR compared with tonsillectomy alone in IgAN patients with urinary abnormalities

Combined Treatment with Curcumin and Ferulic Acid Suppressed the A&beta;-Induced Neurotoxicity More than Curcumin and Ferulic Acid Alone

Alzheimer&rsquo;s disease (AD) is a neurodegenerative disease that leads to progressive cognitive decline. Several effective natural components have been identified for the treatment of AD. However, it is difficult to obtain conclusive evidence on the safety and effectiveness of natural components, because a variety of factors are associated with the progression of AD pathology. We hypothesized that a therapeutic effect could be achieved by combining multiple ingredients with different efficacies. The purpose of this study was thus to evaluate a combination treatment of curcumin (Cur) and ferulic acid (FA) for amyloid-&beta; (A&beta;)-induced neuronal cytotoxicity. The effect of Cur or FA on A&beta; aggregation using thioflavin T assay was confirmed to be inhibited in a concentration-dependent manner by Cur single or Cur + FA combination treatment. The effects of Cur + FA on the cytotoxicity of human neuroblastoma (SH-SY5Y) cells induced by A&beta; exposure were an increase in cell viability, a decrease in ROS and mitochondrial ROS, and repair of membrane damage. Combination treatment showed an overall higher protective effect than treatment with Cur or FA alone. These results suggest that the combined action mechanisms of Cur and FA may be effective in preventing and suppressing the progression of AD

The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by A&beta; Oligomers

In Alzheimer&rsquo;s disease (AD), accumulation of amyloid &beta;-protein (A&beta;) is one of the major mechanisms causing neuronal cell damage. Disruption of cell membranes by A&beta; has been hypothesized to be the important event associated with neurotoxicity in AD. Curcumin has been shown to reduce A&beta;-induced toxicity; however, due to its low bioavailability, clinical trials showed no remarkable effect on cognitive function. As a result, GT863, a derivative of curcumin with higher bioavailability, was synthesized. The purpose of this study is to clarify the mechanism of the protective action of GT863 against the neurotoxicity of highly toxic A&beta; oligomers (A&beta;o), which include high-molecular-weight (HMW) A&beta;o, mainly composed of protofibrils in human neuroblastoma SH-SY5Y cells, focusing on the cell membrane. The effect of GT863 (1 &mu;M) on A&beta;o-induced membrane damage was assessed by phospholipid peroxidation of the membrane, membrane fluidity, membrane phase state, membrane potential, membrane resistance, and changes in intracellular Ca2+ ([Ca2+]i). GT863 inhibited the A&beta;o-induced increase in plasma-membrane phospholipid peroxidation, decreased membrane fluidity and resistance, and decreased excessive [Ca2+]i influx, showing cytoprotective effects. The effects of GT863 on cell membranes may contribute in part to its neuroprotective effects against A&beta;o-induced toxicity. GT863 may be developed as a prophylactic agent for AD by targeting inhibition of membrane disruption caused by A&beta;o exposure

The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers

In Alzheimer’s disease (AD), accumulation of amyloid β-protein (Aβ) is one of the major mechanisms causing neuronal cell damage. Disruption of cell membranes by Aβ has been hypothesized to be the important event associated with neurotoxicity in AD. Curcumin has been shown to reduce Aβ-induced toxicity; however, due to its low bioavailability, clinical trials showed no remarkable effect on cognitive function. As a result, GT863, a derivative of curcumin with higher bioavailability, was synthesized. The purpose of this study is to clarify the mechanism of the protective action of GT863 against the neurotoxicity of highly toxic Aβ oligomers (Aβo), which include high-molecular-weight (HMW) Aβo, mainly composed of protofibrils in human neuroblastoma SH-SY5Y cells, focusing on the cell membrane. The effect of GT863 (1 μM) on Aβo-induced membrane damage was assessed by phospholipid peroxidation of the membrane, membrane fluidity, membrane phase state, membrane potential, membrane resistance, and changes in intracellular Ca2+ ([Ca2+]i). GT863 inhibited the Aβo-induced increase in plasma-membrane phospholipid peroxidation, decreased membrane fluidity and resistance, and decreased excessive [Ca2+]i influx, showing cytoprotective effects. The effects of GT863 on cell membranes may contribute in part to its neuroprotective effects against Aβo-induced toxicity. GT863 may be developed as a prophylactic agent for AD by targeting inhibition of membrane disruption caused by Aβo exposure

Fulvestrant with or without anti‐HER2 therapy in patients in a postmenopausal hormonal state and with ER‐positive HER2‐positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG‐C06)

Abstract Background The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)‐positive, human epidermal growth factor receptor 2 (HER2)‐positive advanced or metastatic breast cancer (AMBC) is unclear. Methods We analyzed the data from 94 patients with ER‐positive HER2‐positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER‐positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti‐HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first‐line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. Results The TTF was longer in the patients treated with F500 as first‐ or second‐line therapy (n = 20) than in those who received later‐line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti‐HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. Conclusions In patients with ER‐positive HER2‐positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first‐ or second‐line therapy. In patients who received chemotherapy‐free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut‐off for indicating clinical outcomes

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC