Mesna, Doxorubicin, Ifosfamide and Dacarbazine (MAID) Combination Chemotherapy for Retroperitoneal Sarcoma: A Single-center Experience.

BACKGROUND/AIM: There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population. PATIENTS AND METHODS: We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized. RESULTS: At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm2 Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients. CONCLUSION: MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.

Frailty and Exacerbation of Chronic Obstructive Pulmonary Disease: Is There Any Association?

Purpose: This study investigated if individuals with chronic obstructive pulmonary disease (COPD) and frailty are more likely to have acute exacerbations of COPD or require hospitalization for exacerbation than those without frailty. Patients and Methods: Data on 135 outpatients with stable COPD were analyzed with the Cox proportional hazards model to assess the risk of future events. The Kihon Checklist was administered at baseline to classify the participants as robust, pre-frail, or frail. The follow-up period was a maximum of six and a half years. Results: In all, 76 patients (56.3%) experienced an exacerbation and 46 (34.1%) were hospitalized due to it. Multivariate Cox proportional hazards analysis that accounted for FEV1 and sex showed that the frail group was more likely to face future risks of COPD exacerbations [Hazard ratio 1.762 (95% CI 1.011-3.070), p=0.046] and hospitalizations for exacerbation [2.238 (1.073-4.667), p=0.032] than the robust group. No significant differences were observed when comparing robust patients to those who were pre-frail or pre-frail to frail either in exacerbations or hospitalizations. When comparing the C-indices for frailty and FEV1, the former index (exacerbation 0.591 and hospitalization 0.663) did not exceed the latter (0.663 and 0.769) in either analysis. Conclusion: Frail COPD patients have a more unfavorable future risk of acute exacerbations of COPD and hospitalizations for exacerbation than robust patients. However, no significant differences were observed when comparing robust patients to those who were pre-frail or pre-frail to frail, suggesting that the future risk for COPD patients with frailty is only higher compared to those who are considered robust. Additionally, FEV1 was found to be a more reliable predictor of future events than measures of frailty.

Impact of body composition on outcomes of immune checkpoint inhibitor combination therapy in patients with previously untreated advanced renal cell carcinoma.

BACKGROUND: Data on the association between body composition and outcomes in patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitor (ICI) combination therapy are limited. METHODS: We retrospectively evaluated the clinical and radiographic data of 159 patients with advanced RCC, including 84 receiving ICI dual combination therapy (immunotherapy [IO]-IO group) and 75 receiving combinations of ICIs with tyrosine kinase inhibitors (TKIs) (IO-TKI group). Pretreatment computed tomography images were used to calculate body composition, including skeletal muscle mass and fat tissue area. Sarcopenia was defined based on skeletal muscle and psoas muscle indexes. The total fat index, subcutaneous fat index (SFI), and visceral fat index were also calculated. RESULTS: In the IO-IO treatment group, there was no significant association between body composition and survival or tumor response (P > 0.05). In the IO-TKI treatment group, the high SFI was associated with longer progression-free survival (hazard ratio, 2.70; P = 0.0091) and overall survival (hazard ratio, 26.0; P = 0.0246) than the low SFI, which remained significant after adjusting for covariates. Furthermore, in the high-SFI population, patients treated with IO-TKI therapy had longer progression-free survival (P = 0.0019) and overall survival (P = 0.0287) than those treated with IO-IO therapy, while there was no significant survival difference between the 2 treatment groups in the low-SFI population (P > 0.05). CONCLUSION: The SFI can be potentially utilized as an effective predictive and prognostic biomarker for first-line ICI combination therapy for advanced RCC.

Comparison of Disease Severity Classifications of Chronic Obstructive Pulmonary Disease: GOLD vs. STAR in Clinical Practice.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR), with four grades of severity in subjects with an FEV1/FVC ratio <0.70: STAR 1 ≥0.60 to <0.70, STAR 2 ≥0.50 to <0.60, STAR 3 ≥0.40 to <0.50, and STAR 4 <0.40. PURPOSE: The aim of this study was to compare the staging of COPD using the GOLD and STAR classifications in clinical practice. METHODS: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. RESULTS: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3 + 4 groups, with the GOLD 1 group used as the reference [hazard ratio 4.222 (95% CI 1.298-13.733), p = 0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3 + 4. St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3 + 4, but not between STAR 1 and STAR 2. CONCLUSION: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

First-line dual immune checkpoint inhibitor therapies versus combination therapies comprising immune checkpoint inhibitors and tyrosine kinase inhibitors for advanced renal cell carcinoma: a comparative analysis of the effectiveness using real-world data.

BACKGROUND: There are few comparative studies on dual immune checkpoint inhibitors (ICIs) (i.e., IO-IO) and combination therapies comprising ICIs plus tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI) for advanced renal cell carcinoma (RCC), especially in real-world settings. METHODS: We retrospectively evaluated data of 175 patients with IMDC intermediate-risk or poor-risk RCC; as first-line therapy, 103 received IO-IO, and 72 received IO-TKI. An inverse probability of treatment weighting (IPTW) analysis was conducted to balance patients' backgrounds in the IO-IO and IO-TKI groups. RESULTS: Based on the IPTW analysis, progression-free survival (PFS) was longer in the IO-TKI group than in the IO-IO group (median: 15.6 vs. 8.3 months; p = 0.0386). In contrast, overall survival was not different between groups (median: 46.7 vs. 49.0 months; p = 0.465). Although the IPTW-adjusted objective response rate was not significantly different (51.2% vs. 43.9%; p = 0.359), the progressive disease rate as the best overall response was lower in the IO-TKI group than in the IO-IO group (3.3% vs. 27.4%; p < 0.0001). Regarding the safety profile, the treatment interruption rate was higher in the IO-TKI group than in the IO-IO group (70.3% vs. 49.2%; p = 0.005). In contrast, the IO-IO group had a higher corticosteroid administration rate (43.3% vs. 20.3%; p = 0.001). CONCLUSION: IO-TKI therapy exhibited superior effectiveness over IO-IO therapy in terms of PFS improvement and immediate disease progression prevention and was associated with a higher risk of treatment interruption and a lower risk of needing corticosteroids.

Is Frailty a Mortality Predictor in Subjects with Chronic Obstructive Pulmonary Disease?

Background: Chronic obstructive pulmonary disease (COPD) has been frequently associated with frailty. The association between frailty and mortality in patients with COPD has not yet been fully elucidated and it remains controversial whether frailty or airflow limitation is more important in predicting mortality. Methods: A total of 141 subjects with stable COPD completed pulmonary function tests and the Kihon Checklist at baseline between 2015 and 2022 and were followed for a maximum of 95 months. Using the Kihon Checklist Total score, we classified patients' frailty status as robust (0-3), pre-frail (4-7), and frail (8-25). Results: At baseline, there were 67 (47.5%) in the robust group, 36 (25.5%) pre-frail, and 38 (27.0%) frail. Death was confirmed in 29 (20.5%). Univariate Cox proportional hazards analyses revealed that all predictive relationships of frailty and airflow limitation with mortality were statistically significant, and the C-index was similar, ranging from 0.63 to 0.66. According to the Log rank test and the Cox regression model, there was a significant difference between the frail and robust groups, (p=0.004 and p=0.005, respectively). No significant differences were found in either comparison with the pre-frail group. When stratification of frailty and FEV1 as well as sex were included as explanatory variables, multivariate Cox regression analysis showed a significant difference between the robust and frail groups with respect to mortality when the robust group was used as the reference (p=0.024). The robust and pre-frail groups did not differ significantly (p=0.163). Conclusion: The mortality of frail COPD patients is higher than those classed as robust. Despite frailty being a substantial mortality predictor, it is uncertain whether or not it is a better predictor than FEV1.

The Conceptual Independence of Health Status, Respiratory Symptoms and Dyspnea in Chronic Obstructive Pulmonary Disease in Real Clinical Practice.

The hypothesis that health status is the highest ranking concept, followed by respiratory symptoms and dyspnea as the lowest ranking concepts in subjects with chronic obstructive pulmonary disease (COPD) was tested in a real clinical setting with 157 subjects with stable COPD. Spearman's rank correlation coefficients for scores of health status using the COPD Assessment Test (CAT), respiratory symptoms using the COPD Evaluating Respiratory Symptoms (E-RS) and dyspnea using Dyspnea-12 (D-12) between any two were 0.6 to 0.7. Upon categorizing the patients as "abnormal" or "normal" according to the threshold, it was found that 30 patients (19.1%) had dyspnea, respiratory symptoms and impaired health status. Dyspnea was considered an important part of respiratory symptoms, though seven patients had dyspnea but no respiratory symptoms. There were 10 patients who had respiratory symptoms without dyspnea but without health status problems. Furthermore, there were six patients who had both dyspnea and respiratory symptoms but whose health status was classified as fine. Thus, the hypothesis was correct in approximately 85% of cases.

Special Issue "Diagnosis, Treatment, and Management of COPD and Asthma".

It has been my great pleasure to publish 17 papers in the Special Issue "Diagnosis, Treatment, and Management of COPD and Asthma" [...].

Comparison of Predictive Properties between Tools of Patient-Reported Outcomes: Risk Prediction for Three Future Events in Subjects with COPD.

BACKGROUND: Patient-reported outcome (PRO) measures must be evaluated for their discriminatory, evaluative, and predictive properties. However, the predictive capability remains unclear. We aimed to examine the predictive properties of several PRO measures of all-cause mortality, acute exacerbation of chronic obstructive pulmonary disease (COPD), and associated hospitalization. METHODS: A total of 122 outpatients with stable COPD were prospectively recruited and completed six self-administered paper questionnaires: the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Baseline Dyspnea Index (BDI), Dyspnoea-12, Evaluating Respiratory Symptoms in COPD and Hyland Scale at baseline. Cox proportional hazards analyses were conducted to examine the relationships with future outcomes. RESULTS: A total of 66 patients experienced exacerbation, 41 were hospitalized, and 18 died. BDI, SGRQ Total and Activity, and CAT and Hyland Scale scores were significantly related to mortality (hazard ratio = 0.777, 1.027, 1.027, 1.077, and 0.951, respectively). The Hyland Scale score had the best predictive ability for PRO measures, but the C index did not reach the level of the most commonly used FEV1. Almost all clinical, physiological, and PRO measurements obtained at baseline were significant predictors of the first exacerbation and the first hospitalization due to it, with a few exceptions. CONCLUSIONS: Measurement of health status and the global scale of quality of life as well as some tools to assess breathlessness, were significant predictors of all-cause mortality, but their predictive capacity did not reach that of FEV1. In contrast, almost all baseline measurements were unexpectedly related to exacerbation and associated hospitalization.

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

Mean pulmonary artery pressure estimated by echocardiogram rapidly exceeds 20 mmHg from the normal range in patients with connective tissue disease.

Earlier intervention for pulmonary hypertension (PH) has been reported to improve the prognosis of patients with connective tissue disease (CTD). However, it is not fully elucidated how rapidly PH develops in patients showing normal mean pulmonary arterial pressure (mPAP) at the index investigation. We evaluated 191 CTD patients with normal mPAP retrospectively. The mPAP was estimated by the formerly defined method employing echocardiography (mPAPecho). We investigated predictive factors that predict increasing mPAPecho at follow-up transthoracic echocardiography (TTE) using uni- and multi variable analysis. The mean age was 61.5 years old, and 160 patients were female. The percentage of patients in whom mPAPecho exceeded 20 mmHg at follow-up TTE was 38%. Multivariable analysis revealed that acceleration time/ejection time (AcT/ET) measured at the right ventricular outflow tract at initial TTE was independently associated with the consequent increase of mPAPecho at the follow-up TTE. When using 0.43 of best cutoff value in AcT/ET calculated by receiver operating characteristic analysis, the change in mPAPecho in patients with low AcT/ET was significantly higher than in those with high AcT/ET (3.05 mmHg in patients with AcT/ET < 0.43 and 1.00 mmHg in patients with AcT/ET ≥ 0.43, p < 0.001). Thirty-eight percent of CTD patients who show the normal estimated mPAP by TTE develop gradual elevation of mPAP to the level to consider early intervention within 2 years. AcT/ET at initial TTE can predict increasing mPAP at follow-up TTE.

Changes in mortality among patients with chronic obstructive pulmonary disease from the 1990s to the 2000s: a pooled analysis of two prospective cohort studies.

OBJECTIVES: This study aimed to identify and investigate changes in the mortality of patients with chronic obstructive pulmonary disease (COPD) at the same institute from the 1990s to the 2000s. We hypothesised that the improvement in long-term mortality of COPD was achieved due to the development of pharmacological and non-pharmacological treatments. DESIGN: This study was a retrospective analysis of two observational prospective cohort studies. One study enrolled subjects from 1995 to 1997 (the 1990s), and the other enrolled subjects from 2005 to 2009 (the 2000s). SETTING: Two studies from a single centre, which was the same university hospital in Japan. PARTICIPANTS: Patients with stable COPD. PRIMARY AND SECONDARY OUTCOME MEASURES: We analysed all-cause mortality data from the pooled database. Subanalyses were conducted by stratifying subjects into two groups according to airflow limitation severity as severe/very severe (per cent predicted value of forced expiratory volume in 1 s (%FEV1) <50%) or mild/moderate (%FEV1≥50%). RESULTS: In total, 280 male patients with COPD were enrolled. Patients in the 2000s (n=130) were significantly older (71.6 vs 68.7 years) and had milder disease (%FEV1; 57.6% vs 47.1%) than those in the 1990s (n=150). Almost all severe/very severe patients in the 2000s received long-acting bronchodilators (LABDs), and they had a significantly lower risk of mortality than those in the 1990s according to Cox proportional regression analyses (OR=0.34, 95% CI 0.13-0.78), with a 48% reduction in 5-year mortality (from 31.0% to 16.1%). Moreover, any LABD use had a significantly positive impact on prognosis, even after adjustments for age, FEV1, smoking status, dyspnoea, body size, oxygen therapy and study period. CONCLUSIONS: Trends indicating a better prognosis for patients with COPD in the 2000s were observed. This improvement may be associated with the usage of LABDs.

Plasma renin activity variation following admission predicts patient outcome in acute decompensated heart failure with reduced and mildly reduced ejection fraction.

Plasma renin activity (PRA) level at admission is reported to be a prognostic predictor of acute decompensated heart failure (ADHF) patients. Although PRA is affected during hospitalization by several factors including fluid volume and drug titration, whether the changes in PRA levels during hospitalization (ΔPRA) are associated with prognosis of ADHF patients are largely unknown. PURPOSE: Investigate the predictive impact of ΔPRA on the prognosis of ADHF patients with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF). METHODS: Retrospectively analyzed consecutive 116 HFrEF and HFmrEF patients admitted for ADHF. PRA measurements were acquired at admission and at discharge. The primary outcome was a composite of cardiovascular death and HF re-hospitalization. RESULTS: Out of 116 patients, 85 had PRA measurements both at admission and at discharge. Compared to admission, PRA level was significantly higher at discharge (0.8 (IQR 0.3-2.2) to 2.8 (IQR 1.0-7.2), p < 0.001). Tertiary groups ranked by PRA level on admission showed trend of poor prognosis in order of high, mid, and low PRA level (p = 0.07). On the contrary, PRA level at discharge significantly differentiated the prognosis and was poor in order of high, low, and mid (p = 0.026). Next, when the participants were divided into tertiary groups ranked by ΔPRA, prognosis worsened in the order of "minimal", "decreasing", and the "increasing" tier. Cubic splines analysis also indicate a similar tendency. CONCLUSIONS: In ADHF patients with HFrEF and HFmrEF, patients with minimal ΔPRA showed the better prognosis over the those with either increasing or decreasing.

Clinical utility of reticulocyte hemoglobin equivalent in patients with heart failure.

Anemia and iron deficiency (ID) are common in patients with heart failure (HF) and intravenous (IV) administration of iron to patients hospitalized for decompensated HF with ID improves outcome. The diagnosis of ID in routine practice is based on serum ferritin and transferrin saturation (TSAT) but both have limitations; alternatives should be considered. Reticulocyte hemoglobin equivalent (Ret-He) reflects iron content in reticulocytes but its clinical utility in patients with HF remains uncertain. We prospectively enrolled 142 patients hospitalized for decompensated HF. Sixty five percent had ID as defined in current international guidelines. Ret-He was directly correlated with serum iron and ferritin concentrations and with TSAT. There was a poor relationship between quartile of Ret-He and HF hospitalization or death but increases or decreases in Ret-He between admission and discharge were associated with a worse outcome. The clinical utility of Ret-He for identifying ID and predicting response to IV iron and prognosis for patients with HF requires further investigation.

Identification of cell cycle-associated and -unassociated regulators for expression of a hepatocellular carcinoma oncogene cyclin-dependent kinase inhibitor 3.

Human cyclin-dependent kinase inhibitor 3 (CDKN3) is a known oncogene in hepatocellular carcinoma (HCC) and its expression is promoted during tumor development. CDKN3 serves as a cell cycle regulator and its dysregulation is considered to be a causal factor for tumor progression. However, the molecular basis of the regulation of CDKN3 expression remains largely elusive. Using in silico approach, we identified CDKN3SE, a super enhancer (SE), and enhancer RNA (eRNA) candidates transcribed from this SE. Among the eRNA candidates, the expression of CDKN3eRNA was detected in the human HCC model cell line HepG2, and was found to facilitate the expression of CDKN3 without affecting the cell proliferation rate. In silico screening revealed two DNA-binding transcription factors, upstream stimulatory factor (USF) 1 and 2, involved in the regulation of CDKN3eRNA expression on CDKN3SE. A knock-down of USF1/USF2 expression in the HepG2 cells did not affect CDKN3eRNA expression, while the expression of CDKN3 was down-regulated. In a USF2 dominant negative HepG2 cell line generated by genome editing, a drastically altered cell shape and lowered cell proliferation rate were found; however, the expression of CDKN3eRNA appeared unaffected. Thus, the present study illustrated two regulators for CDKN3 expression: USF2, as a cell cycle-associated protein regulator, and CDKN3eRNA, as a cell cycle-unassociated RNA regulator.

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

OBJECTIVES: To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. PATIENTS AND METHODS: Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared. RESULTS: During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613). CONCLUSIONS: The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.

Successful withdrawal of catecholamine with ivabradine administration in catecholamine-dependent heart failure.

Ivabradine is a heart rate (HR)-lowering agent that blocks hyperpolarization-activated cyclic nucleotide-gated channel in the sinus node without a negative inotropic effect on cardiac function. Here we report a case of catecholamine-dependent heart failure, who was intolerant to ß blockers, and successfully withdrew catecholamine by administering ivabradine. A 39-year-old male acute decompensated heart failure (ADHF) patient with severe systolic cardiac failure, refractory to diuretic and dobutamine treatment was transferred to our hospital. In addition to titration of dobutamine support, intra-aortic balloon pump, mechanical ventilation, and continuous hemodiafiltration therapy were initiated. These mechanical supports could stabilize ADHF and were removed. Upon stabilization of ADHF, we attempted to initiate a low dose of bisoprolol and taper dobutamine, but the patient could not tolerate even a low dose of bisoprolol nor tapering of dobutamine. Since his HR was consistently above 100 beats per minute and ivabradine was reported to improve stroke volume (SV), we initiated ivabradine, and his SV remarkably increased after initiation. Consequently, the dose of dobutamine was successfully tapered. Also, additional clinical advantage of ivabradine, assessed through hemodynamic parameters, appeared to be a reduction in afterload. .

Assessment of Feasibility of Robot-assisted Radical Cystectomy in Patients With Advanced Bladder Cancer Treated With Maintenance Hemodialysis Therapy.

BACKGROUND/AIM: To clarify the perioperative and oncological outcomes of robot-assisted radical cystectomy (RARC) in advanced bladder cancer (BC) patients treated with maintenance hemodialysis (HD) therapy. PATIENTS AND METHODS: We retrospectively evaluated patients receiving HD therapy who had undergone RARC or open radical cystectomy (ORC) for BC between April 1988 and December 2021 at two affiliated institutions. We compared the surgical outcomes and survival after radical cystectomy between patients treated with RARC and those treated with ORC. RESULTS: Thirty-six patients were evaluated, and eight (22%) and 28 (78%) received RARC and ORC, respectively. RARC was more frequently conducted than ORC in elderly patients (median: 75.5 vs. 68.2 years, p<0.05). Regarding postoperative surgical outcomes, the estimated blood loss volume (median: 75 ml vs. 627 ml, p<0.05) was significantly lower in the RARC group than that in the ORC group. A lower blood transfusion rate (25% vs. 67%, p=0.170) was observed. Moreover, there were no differences in operative time (median: 255 vs. 294 min, p=0.232) or complication rate (Clavien-Dindo grade, any grade: 50% vs. 46%, p=0.858; grade 3 or more: 13% vs. 14%, p=0.897). The 11-year overall survival rate did not differ between the two groups (88% vs. 74%, p=0.365). CONCLUSION: The perioperative outcomes of RARC in patients undergoing HD therapy were comparable to those of ORC. RARC is a potentially feasible surgical option even in patients with high comorbidities.

A long non-coding RNA as a direct vitamin D target transcribed from the antisense strand of the human HSD17B2 locus.

Vitamin D (VD) exerts a wide variety of actions via gene regulation mediated by the nuclear vitamin D receptor (VDR) under physiological and pathological settings. However, the known target genes of VDR appear unlikely to account for all VD actions. We used in silico and transcriptomic approaches in human cell lines to search for non-coding RNAs transcriptionally regulated by VD directly. Four long non-coding RNAs (lncRNAs), but no microRNAs (miRNAs), were found, supported by the presence of consensus VDR-binding motifs in the coding regions. One of these lncRNAs (AS-HSD17ß2) is transcribed from the antisense strand of the HSD17ß2 locus, which is also a direct VD target. AS-HSD17ß2 attenuated HSD17ß2 expression. Thus, AS-HSD17ß2 represents a direct lncRNA target of VD.