Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade.

Anti-thyroglobulin antibodies (TgAb) and/or anti-thyroid peroxidase antibodies (TPOAb) positivity at baseline is a risk marker for thyroid immune-related adverse events (thyroid-irAEs) in anti-programmed cell death-1 antibody (PD-1-Ab) treatment; however, it is unknown if TgAb and TPOAb titers are associated with clinical characteristics of thyroid-irAEs. Among 586 patients treated with PD-1-Ab at Nagoya University Hospital between 2 November 2015 and 30 September 2021, 57 patients developed thyroid-irAEs (thyrotoxicosis [n = 38]; hypothyroidism without prior thyrotoxicosis {isolated hypothyroidism} [n = 19]) in whom thyroid function, and TgAb and TPOAb titers were determined at baseline and at the onset. The changes in TgAb (median, 54.8 vs. 0.2 IU/mL; p = 0.002) and TPOAb titers (31.6 vs. 0 IU/mL; p = 0.032) from baseline to onset of developing thyroid-irAEs were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism. Higher TgAb and TPOAb titers, and the TgAb titer at baseline were associated with an earlier onset of thyrotoxicosis and higher peak free thyroxine levels, respectively. Twenty-eight patients who developed hypothyroidism after thyrotoxicosis had higher TgAb (54.5 vs. 10.7 IU/mL; p = 0.011) and TPOAb titers at baseline (46.1 vs. 9.0 IU/mL; p < 0.001) and greater changes in TgAb (61.7 vs. 7.8 IU/mL; p = 0.025) and TPOAb titers (52.8 vs. -0.8 IU/mL; p < 0.001) than patients who did not develop hypothyroidism. The TgAb titer at baseline and changes in the TgAb and TPOAb titers were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism, suggesting that the magnitude of the thyroid autoimmune response reflects the clinical types of thyroid-irAEs.

Guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance in Japan: A tiered approach for the assessment of clinically meaningful driving impairment.

In December 2022, the Ministry of Health, Labour and Welfare (MHLW) of Japan issued and implemented the guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance. This guideline recommends the use of a tiered approach to assess clinically meaningful driving impairment. It is noted that adverse events cannot be solely explained by pharmacokinetics, as the onset and duration of these events vary. Among these adverse events, those affecting alertness, such as drowsiness caused by psychotropic drugs on driving performance, are more frequently observed during initial treatment stages and dose escalation. Hence, when evaluating the effects of psychotropic drugs on driving performance, it becomes crucial to assess the persistence of clinically meaningful impairment. Therefore, the MHLW guideline, developed by the authors, emphasizes the need to assess the temporal profile of adverse events affecting driving in all clinical trials. Additionally, the guideline states that when conducting driving studies, the timing of multiple dosing should consider not only the pharmacokinetics of the investigational drug but also its tolerance.

Clinical impact of malnutrition according to the Global Leadership Initiative on Malnutrition criteria combined with kidney dysfunction to determine mortality in inpatients.

OBJECTIVE: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). METHODS: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and incidence of all-cause mortality was evaluated using multivariate Cox proportional hazards (CPH) models. Malnutrition was defined as at least one phenotype (weight loss, low body mass index (BMI), or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). RESULTS: Multivariate CPH models showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted HR = 1.84, 95% CI: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. CONCLUSION: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

Assessing the Real-World, Long-Term Impact of Lemborexant on Sleep Quality in a Home-Based Clinical Study.

Purpose: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment. Patients and Methods: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires. Results: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment. Conclusion: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.

Right heart reserve function assessed with fluid loading predicts late right heart failure after left ventricular assist device implantation.

BACKGROUND: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid loading test with right heart catheterization (RHC) to evaluate right heart pre-load reserve function and investigate its impact on LRHF. METHODS: Patients aged > 18 who received continuous-flow LVAD between November 2007 and December 2022 at our institution and underwent RHC with saline loading (10ml/kg for 15 min) 1 month after LVAD implantation were included. RESULTS: Overall, 31 LRHF or deaths (RHF group) have occurred in 149 patients. Comparing the RHF and non-RHF groups, pulmonary artery pulsatility index (PAPi) at rest (1.8±0.89 vs. 2.5±1.4, p=0.02) and right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96±0.32 vs. 1.1±0.20, p=0.03) was significantly different. The PAPi at rest and RVSWi change ratio with saline loading were identified as the postoperative risks for LRHF or death. The cohort was divided into three groups based on whether the PAPi at rest and RVSWi change ratio were low. The event-free curve significantly differed between the three groups (p<0.001). CONCLUSIONS: Hemodynamic assessment with saline loading can evaluate the right ventricular pre-load reserve function of patients with LVAD. The low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation.

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer.

PURPOSE: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. METHODS: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. RESULTS: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. CONCLUSION: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

Impact of prolonged cardiopulmonary resuscitation on outcomes in heart transplantation with higher risk donor heart.

OBJECTIVES: To evaluate the influence of prolonged cardiopulmonary resuscitation (CPR) on outcomes in heart transplantation with higher risk donor hearts (HRDHs). METHODS: Patients transplanted in our hospital between May 2006 and December 2019 were divided into 2 groups, HRDH recipients and non HRDH recipients. HRDH was defined as meeting at least one of the following criteria: (1) donor left ventricular ejection fraction ≤ 50%, (2) donor-recipient predicted heart mass ratio < 0.8 or > 1.2, (3) donor age ≥ 55 years, (4) ischemic time > 4 h and (5) catecholamine index > 20. Recipients of HRDHs were divided into 3 groups according to the time of CPR (Group1: non-CPR, Group 2: less than 30 min-CPR, and Group 3: longer than 30 min CPR). RESULTS: A total of 125 recipients were enrolled in this study, composing of HRDH recipients (n = 97, 78%) and non HRDH recipients (n = 28, 22%). Overall survival and the rate of freedom from cardiac events at 10 years after heart transplantation were comparable between two groups. Of 97 HRDH recipients, 54 (56%) without CPR, 22 (23%) with CPR < 30 min, and 21 (22%) with CPR ≥ 30 min were identified. One-year survival rates were not significantly different among three groups. The 1-year rate of freedom from cardiac events was not also statistically different, excluding the patients with coronary artery disease found in early postoperative period, which was thought to be donor-transmitted disease. Multivariate logistics regression for cardiac events identified that the CPR duration was not a risk factor even in HRDH-recipients. CONCLUSION: The CPR duration did not affect the outcomes after heart transplantation in HRDH recipients.

Effect of single-administration of D-sorbitol pretreatment on the bitterness and continued willingness to take asenapine: a randomized, single-blind, placebo-controlled, crossover trial.

BACKGROUND: Asenapine has unique orally-related side effects, such as a bitter taste induced by sublingual administration, which often results in discontinuation of the medication. While the FDA has approved black-cherry-flavored asenapine, several countries have prescribed only unflavored versions. Specifically, Asians commonly report experiencing the bitterness of asenapine because they are more sensitive to bitter tastes than other ethnic groups. In this study, with the aim of improving adherence by reducing the bitterness of asenapine, we investigated the effects of D-sorbitol, which reduced the bitterness parameters of taste sensors in our previous basic study on the bitterness and continuity of asenapine among patients with schizophrenia. METHODS: Twenty adult patients with schizophrenia were included in this single-blind, placebo-controlled, crossover trial. Participants rinsed their mouths with single-administration of D-sorbitol or a placebo prior to each administration of asenapine. We then conducted the questionnaires and assessed changes in the bitterness of asenapine (primary end point) and willingness to continue its use (secondary end point). RESULTS: D-sorbitol significantly improved the bitterness of asenapine (p = 0.038). Although it did not significantly increase the willingness to continue asenapine (p = 0.180), it did show improvement over the placebo in enhancing willingness to continue, especially in patients who were not accustomed to its taste. CONCLUSION: Our findings indicate that single-administration of D-sorbitol significantly reduces the bitterness of asenapine. In countries where flavored asenapine is not available, this finding could benefit patients who were not accustomed to its bitter taste. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (jRCTs041210019) on May 14, 2021.

Prospective Analysis of Immunosuppressive Therapy in Cardiac Sarcoidosis With Fluorodeoxyglucose Myocardial Accumulation: The PRESTIGE Study.

BACKGROUND: Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) can noninvasively assess active inflammatory myocardium in patients with cardiac sarcoidosis (CS). Prednisolone (PSL) is the initial drug of choice for active CS; however, its efficacy has not been prospectively evaluated. Moreover, there are no alternative systematic treatment strategies. OBJECTIVES: The goal of this study was to evaluate the efficacy of methotrexate (MTX) in patients refractory to PSL assessed by using cardiac metabolic activity (CMA) in 18F-FDG-PET. METHODS: A total of 59 patients with active CS were prospectively enrolled. CMA (standardized uptake value × accumulation area) was used as an indicator of active inflammation, and a 6-month regimen of PSL therapy was introduced, followed by a second FDG scan. Poor responders to PSL therapy (CMA reduction rate <70%) and patients with recurrent CS (CMA reduction rate ≥70% after initial PSL therapy but CMA recurred after an additional 6 months of therapy) were randomly assigned to the MTX or repeat PSL (re-PSL) therapy groups for another 6 months. RESULTS: Fifty-six patients completed the initial 6-month PSL therapy regimen. Median CMA reduced from 203.3 to 1.0 (P < 0.001), and 47 patients were allocated to the response group, 9 to the poor response group, and 2 to the recurrent group. Accordingly, 11 patients were randomly assigned to the MTX (n = 5) or re-PSL (n = 6) groups. After 6 months, neither group showed a significant reduction in CMA values. MTX was comparable to re-PSL in reducing CMA. CONCLUSIONS: The 6-month regimen of PSL was a potent therapeutic tool for active CS. When MTX was added to low-dose PSL in patients refractory to the initial PSL therapy, there was no significant difference compared with re-PSL. Further studies are needed to evaluate the therapeutic potential of MTX for active CS, including how MTX works when it is administered in higher doses or for longer periods.

Dual decline in subjective gait speed and domain-specific cognition is associated with higher risk of incident dementia in older Japanese adults: A 15-year age-specific cohort study.

OBJECTIVES: Dual decline in gait speed and cognition has been found to have higher dementia risk than no decline or pure decline. However, evidence from the Asian population is lacking. Therefore, we aimed to investigate the association of dual decline from age 65 to 70 years with late-life dementia in older Japanese adults with different personal characteristics. METHODS: Data were collected from an age-specific cohort study conducted in 482 Japanese 65-year-old adults. We investigated participant demographics, medical histories, lifestyles, subjective gait speed, and cognition at both 64/65 and 70/71 years old, and confirmed dementia until age of 85 years. Cox proportion hazard models were used to estimate the risk of dementia, with adjustments for covariates, and death was treated as a competing risk. RESULTS: After a mean follow-up period of 12.5-years, 111 participants developed dementia. Older adults with dual decline are more likely to have hyperlipidemia, diabetes, and smoking habits. And we found that dual decline in gait speed and domain-specific cognition was associated with a higher risk of dementia compared with no decline in most cognitive tests, with the highest risk observed for gait speed combined with memory (sub-distribution hazard ratio:3.89, 95 %, confidence intervals: [1.68-9.01]). However, significant differences only existed in men after stratification by sex. CONCLUSIONS: A dual decline in subjective gait speed and cognition may serve as a robust predictor of dementia over a decade prior to its onset, particularly in men. These findings highlighted the importance of screening for dual decline at an early age.

LPS and its relationship with subjective-objective discrepancies of sleep onset latency in patients with psychiatric disorders.

Subjective-objective discrepancies in sleep onset latency (SOL), which is often observed among psychiatric patients, is attributed partly to the definition of sleep onset. Recently, instead of SOL, latency to persistent sleep (LPS), which is defined as the duration from turning out the light to the first consecutive minutes of non-wakefulness, has been utilized in pharmacological studies. This study aimed to determine the non-awake time in LPS that is most consistent with subjective sleep onset among patients with psychiatric disorders. We calculated the length of non-awake time in 30-s segments from lights-out to 0.5-60 min. The root mean square error was then calculated to determine the most appropriate length. The analysis of 149 patients with psychiatric disorders showed that the optimal non-awake time in LPS was 12 min. On the other hands, when comorbid with moderate or severe obstructive sleep apnea (OSA), the optimal length was 19.5 min. This study indicates that 12 min should be the best fit for the LPS non-awake time in patients with psychiatric disorders. When there is comorbidity with OSA, however, a longer duration should be considered. Measuring LPS minimizes discrepancies in SOL and provides important clinical information.

Association between reduced left ventricular ejection fraction and peritoneal dialysis related peritonitis: a single center retrospective cohort study in Japan.

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16-3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51-23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54-2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.

A novel pathogenic variant located just upstream of the C-terminal Ser423-X-Ser425 phosphorylation motif in SMAD3 causing Loeys-Dietz syndrome.

OBJECTIVE: Loeys-Dietz syndrome (LDS) is a heritable disorder of connective tissue closely related to Marfan syndrome (MFS). LDS is caused by loss-of-function variants of genes that encode components of transforming growth factor-ß (TGF-ß) signaling; nevertheless, LDS type 1/2 caused by TGFBR1/2 pathogenic variants is frequently found to have paradoxical increases in TGF-ß signaling in the aneurysmal aortic wall. Here, we present a Japanese LDS family having a novel SMAD3 variant. METHODS: The proband was tested via clinical, genetic, and histological analyses. In vitro analysis was performed for pathogenic evaluation. RESULTS: The novel heterozygous missense variant of SMAD3 [c.1262G>A, p.(Cys421Tyr)], located just upstream of the C-terminal Ser423-X-Ser425 phosphorylation motif, was found in this instance of LDS type 3. This variant led to reduced phospho-SMAD3 (Ser423/Ser425) levels and transcription activity in vitro; however, a paradoxical upregulation of TGF-ß signaling was evident in the aortic wall. CONCLUSIONS: Our results revealed the presence of TGF-ß paradox in this case with the novel loss-of-function SMAD3 variant. The precise mechanism underlying the paradox is unknown, but further research is warranted to clarify the influence of the SMAD3 variant type and location on the LDS3 phenotype as well as the molecular mechanism leading to LDS3 aortopathy.

Improved glycemic control after the use of flash glucose monitoring accompanied by improved treatment satisfaction in patients with non-insulin-treated type 2 diabetes: A post-hoc analysis of a randomized controlled trial.

AIMS: In our previously reported randomized controlled trial in patients with noninsulin-treated type 2 diabetes, the use of flash glucose monitoring (FGM) improved glycated hemoglobin (HbA1c), and the improvement was sustained after the cessation of glucose monitoring. In this post-hoc analysis, we examined data from our trial to identify the factors that influenced FGM efficacy. METHODS: We analyzed data for 48 of 49 participants of the FGM group who completed the trial to clarify the changes in various parameters and factors related to HbA1c improvement with the use of FGM. RESULTS: Analyses of the FGM data during the 12-week FGM provision period showed that the weekly mean blood glucose levels considerably decreased as early as at 1 week compared with the baseline values, and this decline continued for 12 weeks. An enhancement in the Diabetes Treatment Satisfaction Questionnaire regarding "willingness to continue the current treatment" score was significantly associated with the improvement in HbA1c at 12 (p = 0.009) and 24 weeks (p = 0.012). CONCLUSIONS: Glycemic control was improved soon after FGM initiation, accompanied by improved satisfaction with continuation of the current treatment in patients with noninsulin-treated type 2 diabetes.

Lymphopenia is a risk factor for severe infections in older patients with microscopic polyangiitis: a retrospective cohort study in Japan.

Objective: Previous studies have identified the predictors of severe infections in ANCA-associated vasculitis. However, lymphopenia has not been fully evaluated as a predictor of subsequent severe infections in patients with microscopic polyangiitis (MPA). The aim of this study was to assess the association between lymphopenia and severe infections requiring hospitalization after receiving immunosuppressive therapy for MPA. Methods: This single-centre retrospective cohort study included 130 consecutive patients with newly diagnosed MPA from Aichi Medical University Hospital, Japan, who received immunosuppressive therapy between March 2004 and December 2020. The relationship between lymphopenia and subsequent severe infections was assessed using time-dependent multivariate Cox proportional hazard models adjusted for clinically relevant factors. Results: During the follow-up period (median: 38 months; interquartile range: 15-63 months), 56 severe infectious episodes occurred in 51 patients (39.2%). Time-dependent multivariate Cox proportional hazard analyses identified older age [adjusted hazard ratio (HR) = 1.74 per 10 years, 95% CI: 1.13, 2.67], methylprednisolone pulse therapy (adjusted HR = 2.04, 95% CI: 1.03, 4.02), moderate lymphopenia (vs normal, adjusted HR = 7.17, 95% CI: 3.10, 16.6) and severe lymphopenia (vs normal, adjusted HR = 36.1, 95% CI: 11.8, 110.9) as significant predictors of severe infection. Conclusion: Lymphopenia is a predictor of subsequent severe infections in patients with MPA who receive immunosuppressive therapy. These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.

Efficacy of the latest new stimulation patterns of spinal cord stimulation for intractable neuropathic pain compared to conventional stimulation: study protocol for a clinical trial.

BACKGROUND: Spinal cord stimulation (SCS) is one of the neuromodulation therapies for chronic neuropathic pain. The conventional paresthesia-based SCS involves the application of tonic stimulation that induces a sense of paresthesia. Recently, new SCS stimulation patterns without paresthesia have been developed. Differential target multiplexed (DTM) stimulation and fast-acting subperception therapy (FAST) stimulation are the latest paresthesia-free SCS patterns. METHODS: A single-center, open-label, crossover, randomized clinical trial to investigate the superiority of SCS using the latest new stimulation patterns over conventional tonic stimulation for neuropathic pain is planned. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). In the SCS trial, participants will be randomly assigned to 4 groups receiving stimulation, including tonic, DTM, and FAST. Each stimulation will then be performed for 2 days, and a visual analog scale (VAS) for pain will be evaluated before and after each stimulation pattern. A stimulation-off period for 1 day is set between each stimulation pattern to wash out the residual previous stimulation effects. Pain improvement is defined as more than 33% reduction in the pain VAS. The primary analysis will compare pain improvement between the new stimulation patterns and the conventional tonic stimulation pattern in the SCS trial. The secondary outcomes will be evaluated as follows: (1) the relationships between causative disease and improvement rate by each stimulation pattern; (2) comparison of pain improvement between the DTM and FAST stimulation patterns in all cases and by causative disease; (3) changes in assessment items preoperatively to 24 months after the implantation; (4) preoperative factors associated with long-term effects defined as continuing for more than 12 months; and (5) adverse events related to this study 3 months after the implantation. DISCUSSION: This study aims to clarify the effectiveness of the latest new stimulation patterns compared to the conventional tonic stimulation. In addition, which stimulation pattern is most effective for which kind of causative disease will be clarified. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 1,042,220,094. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is an approved member of the Primary Registry Network of WHO ICTRP.

A Multicenter Randomized Phase II Trial Investigating the Effect of Polyglycolic Acid Sheet on the Prevention of Pancreatic Fistula After Gastrectomy with Prophylactic Lymph Node Dissection.

Pancreatic fistula after gastrectomy with lymph node dissection is associated with prolonged hospital stay and critical complications such as intra-abdominal bleeding and sepsis. Polyglycolic acid (PGA) sheets are absorbable suture reinforcement materials. A randomized Phase II trial has been planned to evaluate the effect of PGA sheets on preventing postoperative pancreatic fistula. A total of 320 patients will be recruited from thirteen institutions. Patients who are scheduled to undergo distal or total gastrectomy will be randomly allocated into the PGA group or control group, and the dissected area around the pancreas will be covered by the PGA sheet in the PGA group. The primary endpoint will be the maximum value of drain amylase concentration up to 5 days after surgery. The secondary endpoints will be as follows: transition of value of amylases of drain discharge, incidence of pancreatic fistula, incidence of intra-abdominal abscess, white blood cell count, value of C-reactive protein, incidence of postoperative complication, duration of antibiotic agents administration, duration of abdominal drainage, usage of octreotide, duration of hospital stay, incidence of bleeding in abdominal cavity, mortality, and incidence of reoperation.

Effect of renal function under left ventricular assist device support on the cardiac function and clinical events after heart transplantation.

AIM: We investigated the effects of pre-transplantation renal dysfunction under left ventricular assisted device (LVAD) support on post-transplantation cardiac function, and patient prognosis after heart transplantation (HTx). METHOD: All patients who were bridged by LVAD and underwent HTx at our hospital between 2007 and 2022 were included in this study. Patients were classified into two groups based on estimated glomerular filtration rate (eGFR) before HTx: renal dysfunction (RD) group (eGFR < 60 mL/min/1.73 m2 ) and non-renal dysfunction (NRD) group. RESULT: A total of 132 patients were analyzed, of whom 48 were classified into the RD group and 84 into the NRD group (RD group, 47.9 ± 10.1 years; NRD group, 38.4 ± 11.9 years, p < .0001). Under LVAD support before HTx, the RD group tended to have a history of right ventricular failure (RD group, nine (19%); NRD group, seven (8%); p = .098). After HTx, the echocardiographic parameters did not differ between the two groups in the long term. Furthermore, more concise hemodynamic parameters, exemplified by right heart catheterization, were not significantly different between the two groups. Regarding graft rejection, no significant differences were found in acute cellular rejection and cardiac allograft vasculopathy following HTx. In contrast, patients with RD before HTx had significantly increased mortality in the chronic phase after HTx and initiation of maintenance dialysis, without any overt changes in cardiac function. CONCLUSION: Pre-transplantation renal dysfunction under LVAD support significantly affected clinical course after HTx without any overt changes in graft cardiac function.

Rationale and study design of a randomized controlled trial to investigate the renoprotective effect of canagliflozin assessed by test of renal hemodynamics in diabetic kidney disease (the FAGOTTO study).

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are considered to have the potential to maintain renal function by correcting glomerular hypertension in patients with diabetic kidney disease (DKD). The aim of this study is to demonstrate the renoprotective effect of SGLT2i by measuring renal hemodynamics, including glomerular filtration fraction (FF), in type 2 diabetic patients with moderate renal dysfunction. METHODS: Renoprotective effect of canagliflozin derived from test of renal hemodynamics in diabetic kidney disease (FAGOTTO) study is a 12-week multicenter, open-label, randomized (1:1), parallel-group trial of type 2 diabetic patients with diabetic kidney disease (30 ≤ estimated glomerular filtration rate [eGFR] ≤ 60 mL/min/1.73 m2). A total of 110 patients are to be randomly allocated to receive once-daily canagliflozin 100 mg or control (standard therapy). FF will be calculated by dividing the measured GFR (mGFR) by the effective renal plasma flow (eRPF). mGFR and eRPF will be measured by the clearance of inulin and para-aminohippuric acid (PAH), respectively. The primary endpoint of this trial is the percentage change in FF after 4 weeks of treatment in the canagliflozin and control groups. DISCUSSION: The FAGOTTO study will elucidate the mechanism of the renoprotective action of SGLT2i. The background, rationale, and study design of this trial are presented. To date, > 80 patients have been enrolled in this trial. The study will end in 2025. TRIAL REGISTRATION: jRCT (Japan Registry Of Clinical Trials) jRCTs041200069. Date of registration: November 27, 2020.

Temporal change in the association between life satisfaction and functional decline with gender differences: an age-specific prospective cohort study.

BACKGROUND: Although life satisfaction (LS) has been shown to predict mortality, research studying the relationship between LS and functional decline is scarce. This study examined the association between LS and functional decline across four time points in young-old Japanese adults. METHODS: We analysed 1,899 community-dwelling 65-year-olds in this age-specific cohort study conducted between 2000 and 2005. The Life Satisfaction Index K was used to evaluate LS and was classified into quartiles. Functional decline was determined using the Japanese Long-Term Care Insurance (LTCI) system: 1) mild disability; 2) severe disability; 3) all-cause mortality; 4) mild or severe disability; 5) severe disability or death; 6) mild or severe disability, or death. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. The analyses were conducted in the 8th, 10th, 12th, and 14th years to assess the effect of LS on functional decline across time points. RESULTS: The impact of LS gradually weakened over time. In the 8th year (aged 72-73), a higher LS was associated with a lower risk of mild or severe disability among the women participants (adjusted HR [95% CI] = 0.30 [0.11-0.81]). However, the effect disappeared gradually (adjusted HR [95% CI] = 0.55 [0.27-1.14]) in the 10th year (aged 74-75), 0.72 (0.41-1.26) in the 12th year (aged 76-77), and 0.68 (0.41-1.14) in the 14th year (aged 78-79). This trend continued in severe disability or death (adjusted HR [95% CI] = 0.24 [0.06-0.70], 0.31 [0.11-0.76], 0.57 [0.28-1.14], and 0.60 [0.32-1.12]) and mild or severe disability, or death (adjusted HR [95% CI] = 0.30 [0.14-0.68], 0.46 [0.24-0.87], 0.67 [0.41-1.10], and 0.65 [0.42-1.02]) in the 8th, 10th, 12th, and 14th years, respectively. No statistically significant association was found among men at any time points or in any classification of outcomes. CONCLUSIONS: Higher LS scores in 65-year-old women were associated with a lower risk for functional decline in any combination of mild disability, severe disability, or death. Additionally, the effect of LS was observed to weaken over time. TRIAL REGISTRATION: This is not an intervention survey and does not require registration.