Reinforcement learning-based adaptive beam alignment in a photodiode-integrated array antenna module.

We successfully demonstrated an intelligent adaptive beam alignment scheme using a reinforcement learning (RL) algorithm integrated with an 8 × 8 photonic array antenna operating in the 40 GHz millimeter wave (MMW) band. In our proposed scheme, the three key elements of RL: state, action, and reward, are represented as the phase values in the photonic array antenna, phase changes with specified steps, and an obtained error vector magnitude (EVM) value, respectively. Furthermore, thanks to the Q-table, the RL agent can effectively choose the most suitable action based on its prior experiences. As a result, the proposed scheme autonomously achieves the best EVM performance by determining the optimal phase. In this Letter, we verify the capability of the proposed scheme in single- and multiple-user scenarios and experimentally demonstrate the performance of beam alignment to the user's location optimized by the RL algorithm. The achieved results always meet the signal quality requirement specified by the 3rd Generation Partnership Project (3GPP) criterion for 64-QAM orthogonal frequency division multiplexing (OFDM).

Using peptide barcodes for simultaneous profiling of protein expression from mRNA.

RATIONALE: mRNA technology has begun to play a significant role in the areas of therapeutic intervention and vaccine development. However, optimizing the mRNA sequence that influences protein expression levels is a resource-intensive and time-consuming process. This study introduces a new method to accelerate the selection of sequences of mRNA for optimal protein expression. METHODS: We designed the mRNA sequences in such a way that a unique peptide barcode, corresponding to each mRNA sequence, is attached to the expressed protein. These barcodes, cleaved off by a protease and simultaneously quantified by mass spectrometry, reflect the protein expression, enabling a parallel analysis. We validated this method using two mRNAs, each with different untranslated regions (UTRs) but encoding enhanced green fluorescence protein (eGFP), and investigated whether the peptide barcodes could analyze the differential eGFP expression levels. RESULTS: The fluorescence intensity of eGFP, a marker of its expression level, has shown noticeable changes between the two UTR sequences in mRNA-transfected cells when measured using flow cytometry. This suggests alterations in the expression level of eGFP due to the influence of different UTR sequences. Furthermore, the quantified amount of peptide barcodes that were released from eGFP showed consistent patterns with these changes. CONCLUSIONS: The experimental findings suggest that peptide barcodes serve as a valuable tool for assessing protein expression levels. The process of mRNA sequence selection, aimed at maximizing protein expression, can be enhanced by the parallel analysis of peptide barcodes using mass spectrometry.

Characteristics of successful termination of atrial fibrillation by atrial antitachycardia pacing in patients with cardiac implantable electronic devices.

Asymptomatic paroxysmal atrial fibrillation (AF) is often found in patients implanted with cardiac implantable electronic devices (CIEDs). Second-generation atrial antitachycardia pacing (A-ATP) is effective in managing AF in patients implanted with CIEDs. The purpose of this study was to evaluate the efficacy and safety of A-ATP in patients implanted with CIEDs. This was a single-center retrospective study involving 91 patients (male 46 patients, mean age 74 ± 9 years) implanted with Reactive A-ATP equipped devices (84 patients with pacemakers, 6 with ICDs, and 1 with a CRT-D). The AF burden, rate of AF termination, and details of the activation of the A-ATP were analyzed in each patient. During a mean follow-up period of 21 ± 13 months, A-ATP was activated in 45 of 91 patients (49.5%). No patients had adverse events. Although the efficacy of the A-ATP varied among the patients, the median rate of AF termination was 44%. In comparison to the A-ATP start time, "0 min" had a higher AF termination rate by the A-ATP (39.4% vs. 24.4%, P = 0.011). The rate of termination by the A-ATP was high for AF with a long cycle length and a relatively regular rhythm. A-ATP successfully terminated AF episodes in some patients implanted with CIEDs. The optimal settings of the A-ATP will be determined in future studies.

Eculizumab for paediatric patients with atypical haemolytic uraemic syndrome: full dataset analysis of post-marketing surveillance in Japan.

BACKGROUND: Eculizumab was approved for atypical haemolytic uraemic syndrome (aHUS) in Japan in 2013. Post-marketing surveillance (PMS) was mandated by regulatory authorities to assess the safety and effectiveness of eculizumab in patients with aHUS in a real-world setting. METHODS: Paediatric patients in the PMS cohort who were <18 years of age at the first administration of eculizumab and diagnosed with aHUS [excluding Shiga toxin-producing Escherichia coli HUS, thrombotic thrombocytopaenic purpura and secondary thrombotic microangiopathy (TMA)] were included in the effectiveness and safety analysis. Clinical endpoints of effectiveness [complete TMA response, TMA event-free status, platelet (PLT) count and lactate dehydrogenase (LDH) normalization, serum creatinine (sCr) decrease and estimated glomerular filtration rate (eGFR) improvement] were analysed in patients treated with at least one dose of eculizumab. Serious adverse events (SAEs) were also evaluated. RESULTS: A total of 40 paediatric patients (median age 5 years) were included. The median eculizumab treatment duration was 66 weeks. PLT count, LDH and eGFR significantly improved at 10 days post-treatment. Complete TMA response, haematologic normalization, sCr decrease, eGFR improvement and TMA event-free status were achieved by 73.3%, 73.3%, 70.0%, 78.3% and 77.5% of patients, respectively. Discontinuation criteria were met by 18 patients: 13 patients maintained treatment discontinuation at the end of observation and 5 patients, including 1 patient with aHUS relapse, continued the treatment but extended the treatment interval. During eculizumab treatment, 59 SAEs (0.66/person-year) were reported. Although four deaths were reported, none of them were related to eculizumab. CONCLUSION: Eculizumab was well tolerated and effective for paediatric patients with aHUS in the real-world setting in Japan.

Analysis of the ratio of urinary beta-2-microglobulin to total protein concentration in children with isolated tubulointerstitial disease.

BACKGROUND: Proteinuria is broadly classified into glomerular and tubular proteinuria. Urinary beta-2-microglobulin (ß2-MG) is known as a marker for detecting tubulointerstitial diseases. However, tubulointerstitial damage can also lead to an increase in urinary ß2-MG level in some patients with glomerular diseases. This study aimed to determine the ratio of urinary ß2-MG to total protein (TP) concentration in patients with both isolated tubulointerstitial and glomerular disease. METHODS: This multicenter, retrospective study included children with Dent disease or lupus nephritis in five facilities. Their urinary ß2-MG levels were > 1000 µg/L. Urinary ß2-MG and TP concentrations were obtained, and the ratio of urinary ß2-MG to TP concentration (µg/mg) was calculated. The Mann-Whitney U test was performed to compare this ratio between these children. The optimal cutoff value of the ratio for considering the presence of glomerular disease was obtained from the receiver operating characteristic (ROC) curve. RESULTS: We obtained information on 23 children with Dent disease and 14 children with lupus nephritis. The median ratios of urinary ß2-MG to TP concentrations in children with Dent disease and lupus nephritis were 84.85 and 1.59, respectively. The ROC curve yielded the optimal cutoff value of this ratio for distinguishing between these diseases, and the cutoff value was found to be 22.3. CONCLUSION: In children with tubulointerstitial diseases, the urinary ß2-MG concentration may be approximately 8.5% of the TP concentration. The possibility of presenting with glomerular disease should be considered in patients with a ratio of urinary ß2-MG to TP concentration of < 22.3 (µg/mg).

Effects of adding a neurokinin-1 receptor antagonist to 5 mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis.

BACKGROUND: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy. METHODS: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching. RESULTS: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine. CONCLUSIONS: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based chemotherapy.

Serum albumin level is associated with mycophenolic acid concentration in children with idiopathic nephrotic syndrome.

Mycophenolate mofetil is effective for the treatment of pediatric idiopathic nephrotic syndrome (INS). The dosage of mycophenolate mofetil is adjusted according to the serum concentration of mycophenolic acid (MPA). Kidney function or cyclosporine (CsA) concentrations affect serum MPA levels. However, few studies have focused on the association between serum concentrations of MPA and albumin. This retrospective observational study aimed to evaluate the relationship between the serum concentrations of MPA and albumin in INS children. Subjects were children with INS who underwent the therapeutic drug monitoring of CsA and MPA. We obtained the serum albumin (sAlb) concentration, estimated glomerular filtration rate (eGFR), age, and MPA and CsA areas under concentration-time curves from 0 to 12 h (AUC0-12). Multiple linear regression analysis and generalized estimating equations were performed to predict values for MPA AUC0-12. We obtained information for 51 INS children with 261 MPA AUC0-12 measurements. The standardized regression coefficients of sAlb, eGFR, CsA AUC0-12, and age were 0.54, - 0.21, - 0.07, and 0.04, respectively. Furthermore, MPA AUC0-12 levels positively correlated with sAlb concentrations (p < 0.001) and were inversely correlated with eGFR values (p = 0.005) but not with CsA AUC0-12 (p = 0.24) and age (p = 0.65).Conclusion: Serum albumin concentration was strongly associated with total MPA concentration compared with kidney function or CsA values. Although patients with INS may have a low serum concentration of total MPA in the presence of low sAlb concentration, close attention should be paid to the interpretation of the low MPA values. What is Known: • The dosage of mycophenolate mofetil is adjusted according to the serum concentration of total mycophenolic acid. • Kidney function, cyclosporin concentrations, or serum albumin concentrations influence serum mycophenolic acid levels. What is New: • Serum albumin concentration is more strongly associated with total mycophenolic acid concentration than kidney function or cyclosporin values. • In children with nephrotic syndrome, the total mycophenolic acid concentration may not increase in the presence of severe hypoalbuminemia.

Mortality outcomes and clinical background of children on maintenance dialysis without receiving kidney transplantation.

BACKGROUND: Some pediatric patients on maintenance dialysis may need end-of-life care in the future because of being excluded from the indication of kidney transplantation and experiencing difficulty in continuation of their dialysis. This study aimed to thoroughly elucidate mortality outcomes of children on maintenance dialysis including the cause of death and clinical background of exclusion from indication of transplantation. PATIENTS AND METHODS: This single-center retrospective study enrolled 53 children who received kidney transplantation (5) or maintenance peritoneal dialysis (PD, 48) as initial renal replacement therapy (RRT). We examined the selected RRT modalities, mortality outcomes, clinical backgrounds of cause of death, and risk factors of excluding from future the indication of transplantation. RESULTS: Nine (17%) of all 53 patients, all receiving PD (9/48, 19%), were finally excluded from next RRT indication-7 were excluded due to severe extrarenal complications that indicated high risk for transplantation and 2 were excluded due to severe psychomotor retardation and at the guardians' discretion. Patients who were excluded from the indication had a younger age at PD induction and higher proportion of cerebral and cardiac complications or psychomotor retardation than patients who were included in the indication. Of the nine patients, seven died; of which, one patient died due to fatal progression of extrarenal complications and six died due to infectious or noninfectious dialysis-related complications. CONCLUSION: Patients with severe extrarenal complications or psychomotor retardation tend to be excluded from the indication of transplantation. Their condition becomes fatal because of the complications of long-term dialysis and progression in extrarenal complications.

Multi-IF-over-fiber transmission using a commercial TOSA for analog fronthaul networks aiming beyond 5G.

An IF-over-fiber (IFoF)-based analog transport technology for mobile fronthaul applications has recently attracted significant attention. However, most previous studies have employed discrete optical components. For the analog transport technology to be a more cost-effective and power-efficient solution, it is necessary to utilize existing integrated optical transceivers. In this paper, we demonstrate IFoF transmission using a commercial off-the-shelf transmitter optical sub-assembly (TOSA). Although the TOSA was developed for a digital system employing non-return-to-zero (NRZ) signals, we show that it is also possible for the TOSA to support high-capacity analog transmission. As a demonstration, by using the TOSA, we could successfully transmit 64- and 256-ary quadrature-amplitude-modulated (64/256QAM) orthogonal-frequency-division-multiplexed (OFDM) signals with net bit rates of 54.74 and 36.49 Gbps per wavelength, respectively. Since the TOSA has four wavelength channels, the total capacities are 218.94 and 145.98 Gbps, respectively. To the best of our knowledge, these rates are the highest among all the demonstrations using analog transport technology.

Photonic Armstrong method enabled by direct detection for wideband electrical PM generation.

Wideband signal generation using frequency/phase modulation (FM/PM) is the key fundamental function for various applications such as radar and analog communication systems. It is well known that analog FM/PM communication systems can dramatically improve signal quality by spectral expansion. In classical communication theories, the Armstrong indirect method is one of the most popular methods for bandwidth expansion of FM signals. In the Armstrong method, a narrowband signal is converted to a broadband signal with the help of a nonlinear frequency multiplier. In this paper, we propose a photonic Armstrong method enabled by direct detection. By utilizing the nonlinearity caused by direct detection, we can increase bandwidth so that it is double that of the original signal in the photonic Armstrong method. Also, it completely eliminates signal-to-signal beat interference (SSBI) at the same time. We conducted an experiment to verify the concept and confirmed these advantages experimentally.

Efficacy and safety of 5 mg olanzapine for nausea and vomiting management in cancer patients receiving carboplatin: integrated study of three prospective multicenter phase II trials.

BACKGROUND: The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine's efficacy and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine. METHODS: Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors. RESULTS: Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist. CONCLUSIONS: The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy.

The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, a long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report outcomes from a pediatric patient cohort from the ravulizumab clinical trial (NCT03131219) who were switched from chronic eculizumab to ravulizumab treatment. METHODS: Ten patients received a loading dose of ravulizumab on Day 1, followed by maintenance doses administered initially on Day 15, and then, every 4-8 weeks thereafter, depending on body weight. All patients completed the initial evaluation period of 26 weeks and entered the extension period. RESULTS: No patients required dialysis at any point throughout the study. The median estimated glomerular filtration rate values remained stable during the trial: 99.8 mL/min/1.73m2 at baseline, 93.5 mL/min/1.73m2 at 26 weeks, and 104 mL/min/1.73m2 at 52 weeks. At last available follow-up, all patients were in the same chronic kidney disease stage as recorded at baseline. Hematologic variables (platelets, lactate dehydrogenase, and hemoglobin) also remained stable throughout the initial evaluation period and up to the last available follow-up. All patients experienced adverse events; the most common were upper respiratory tract infection (40%) and oropharyngeal pain (30%). There were no meningococcal infections reported, no deaths occurred, and no patients discontinued during the study. CONCLUSIONS: Overall, treatment with ravulizumab in pediatric patients with aHUS who were previously treated with eculizumab resulted in stable kidney and hematologic parameters, with no unexpected safety concerns when administered every 4-8 weeks. TRIAL REGISTRATION: Trial identifiers: Trial ID: ALXN1210-aHUS-312 Clinical trials.gov : NCT03131219 EudraCT number: 2016-002499-29 Graphical abstract.

Clinical outcomes after balloon angioplasty with Crosser device for heavily calcified common femoral and popliteal artery disease.

Data on the mid-term clinical outcomes after endovascular treatment (EVT) using a Crosser catheter (C. R. Bard, Inc.) as a crossing or flossing device for a heavily calcified lesion in the common femoral artery (CFA) or popliteal artery (PA) are lacking. The aim of this study was to investigate the safety and efficacy of EVT using a Crosser catheter for isolated and heavily calcified CFA or PA disease. We retrospectively analyzed 64 consecutive patients (72 lesions; CFA 30, PA 42) who underwent EVT for heavily calcified CFA or PA lesions with Crosser catheters between April 2015 and April 2019. The primary endpoint was clinically driven target lesion revascularization (CD-TLR). The median follow-up was 18.5 months. The mean age of the study population was 70 ± 9.5 years, with a male prevalence of 73.6%. The mean Proposed Peripheral Artery Calcification Scoring System grade was 2.9 ± 0.9. Procedure success, defined as 50% or less residual stenosis without suboptimal results, was achieved in 94.4% of lesions. There were no cases of bailout stenting or target lesion-related complications. After EVT, the 1-year CD-TLR-free rate for CFA and PA lesions was 87.4 and 76.8%, respectively. The corresponding rates at 2 years were 82.2 and 62.8%, respectively. In the multivariate analysis used to define CD-TLR predictors for CFA and PA lesions, hemodialysis was the only independent predictor (HR 3.35, 95% CI 1.02-13.95, P = 0.045). EVT with a Crosser device for heavily calcified CFA and PA lesions seems to be safe and feasible.

Development of a novel T cell-oriented vaccine using CTL/Th-hybrid epitope long peptide and biodegradable microparticles, against an intracellular bacterium.

Antigen-specific CD8+ T-lymphocytes (cytotoxic T-lymphocytes: CTL), as well as CD4+ T-lymphocytes (helper T-lymphocytes: Th), simultaneously play an important role in the elimination of intracellular bacteria such as Mycobacterium tuberculosis and Listeria monocytogenes. Administration of T-cell epitope short peptide needs large numbers of peptides for effective vaccination due to its easily degradable nature in vivo. In this respect, biocompatible and biodegradable microparticles combined with CTL/Th-hybrid epitope long peptide (long peptide) have been used to diminish the degradation of loaded peptide. The aim of this study is to develop a novel T cell-oriented vaccine against intracellular bacteria that is composed of long peptide and poly (lactic-co-glycolic acid) (PLGA) microparticles. Mouse bone marrow-derived dendritic cells (BMDCs) were loaded with L. monocytogenes listeriolysin O (LLO)-derived or ovalbumin (OVA)-derived long peptide/PLGA or other comparative antigens. The antigen-loaded BMDCs were injected subcutaneously into the flank of mice twice, and then, the spleens were collected and lymphocyte proliferation and interferon-γ production were evaluated. The median diameter of the PLGA spheres was 1.38 µm. Both LLO- and OVA-long peptide/PLGA showed significantly more robust CTL and Th proliferations with higher interferon-γ production than the long peptide alone or CTL and Th short peptides/PLGA vaccination. Furthermore, the LLO-long peptide/PLGA vaccination showed a significantly lower bacterial burden in spleens compared with the long peptide alone or the CTL and Th short peptides/PLGA vaccination after the challenge of lethal amounts of L. monocytogenes. These results suggest that the novel vaccine taking advantages of CTL/Th-hybrid epitope long peptide and PLGA microparticle is effective for protection against intracellular bacteria.

Management of a Preterm Infant with Renal Tubular Dysgenesis: A Case Report and Review of the Literature.

Renal tubular dysgenesis (RTD) is the absence or poor development of the renal proximal tubules caused by gene mutations in the renin-angiotensin system. Although RTD has been considered fatal, improving neonatal intensive care management has enhanced survival outcomes. However, little has been reported on the survival of extremely preterm infants. This study reports the survival of an extremely preterm infant with RTD and discusses the appropriate management of RTD by reviewing the literature. A female infant weighing 953 g was delivered at 27 weeks' gestation by Cesarean section because of oligohydramnios. She exhibited severe persistent pulmonary hypertension, severe systemic hypotension, and renal dysfunction shortly after birth. Respiratory management was successfully undertaken using nitric oxide inhalation and high-frequency oscillatory ventilation. Desmopressin was effective in maintaining her blood pressure and urinary output. She was diagnosed with RTD based on genetic testing, which revealed a compound heterozygous mutation in the angiotensin-converting enzyme gene in exon 18 (c.2689delC; p.Pro897fs) and exon 20 (c.3095dupT; p.Leu1032fs). At 2 years, she started receiving oral fludrocortisone for treating persistently high serum creatinine levels, which was attributed to nephrogenic diabetes insipidus caused by RTD. Subsequently, her urine output decreased, and renal function was successfully maintained. Currently, there is no established treatment for RTD. Considering cases reported to date, treatment with vasopressin and fludrocortisone appears to be most effective for survival and maintenance of renal function in patients with RTD. This study presents the successful management of RTD using this strategy in an extremely preterm infant.

The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses.

HIV-1 CRF01_AE viruses are highly prevalent in Southeast Asia. However, vulnerability sites in Env of CRF01_AE viruses have not been investigated sufficiently. We examined the sensitivity of CRF01_AE viruses from Japan and Vietnam, together with subtype B viruses from Japan, to neutralization and Fc-mediated signaling. Neutralization coverage of broadly neutralizing antibodies (bnAbs), 2G12 and b12, was significantly low against CRF01_AE viruses, compared with subtype B viruses. In contrast, the conventional antibody targeting the CD4 binding site (CD4bs), 49G2, showed better neutralization and Fc-mediated signaling activities against CRF01_AE viruses than subtype B viruses. Fc-mediated signaling activity of anti-CD4 induced (CD4i) antibody, 4E9C, was also detected against CRF01_AE viruses more than subtype B viruses. These results suggest that conventional antibodies against CD4bs and CD4i may play an important role in the control of CRF01_AE viruses.

Hemodynamic and Lesion Characteristics Associated with Discordance between the Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

BACKGROUND: The instantaneous wave-free ratio (iFR) is an invasive coronary physiological index that is not inferior to fractional flow reserve- (FFR-) guided revascularization. The indexes of iFR and FFR are similar and closely correlated, but there are a few key differences. Previous studies suggested that patient characteristics and lesion severity could induce discordance between iFR and FFR. This study aimed to clarify the hemodynamics and lesion characteristics that influence discordance between iFR and FFR. METHODS: In this retrospective study, we enrolled 225 patients (304 lesions) who underwent clinically indicated invasive coronary angiography and both iFR and FFR examinations between 2012 and 2017. We included only patients who underwent right heart catheterization and had blood pressure and heart rates recorded immediately prior to iFR and FFR. RESULTS: Discordance (iFR ≤0.89 and FFR >0.8 or iFR >0.89 and FFR ≤0.8) was observed in 80 lesions (26.3%). The heart rate, rate-pressure product, and cardiac index tended to be higher in the iFR ≤0.89 group than in the iFR >0.89 group. These trends were not seen between the FFR ≤0.8 group and FFR >0.8 group. A multivariate analysis showed that independent predictors of iFR ≤0.89 and FFR >0.8 discordance were female sex and higher rate-pressure product. iFR >0.89 and FFR ≤0.8 discordance was rare in hemodialysis patients. CONCLUSION: Even if iFR is functionally significant in intermediate stenosis, additional FFR evaluations should be considered for women, especially those with a high rate-pressure product, to avoid unnecessary percutaneous coronary intervention. If iFR is not functionally significant with intermediate stenosis in hemodialysis patients, then further FFR evaluations are unnecessary.

Safety and Efficacy of Low-Dose Prasugrel as Part of Triple Therapy With Aspirin and Oral Anticoagulants in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention　- From the TWMU-AF PCI Registry.

BACKGROUND: Using the standard maintenance dose of prasugrel (10 mg/day) as part of triple therapy with aspirin and an oral anticoagulant (OAC) is not recommended in the current guidelines because it increases the risk of bleeding compared with clopidogrel. However, the safety and efficacy of low-dose prasugrel (3.75 mg/day) as part of triple therapy has not been reported. Methods and Results: We registered 816 consecutive patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) from January 2011 to June 2016 at 8 hospitals in Japan. We examined the clinical outcomes of patients who received either low-dose prasugrel (n=57) or clopidogrel (n=451) as part of triple therapy after PCI. The incidences of bleeding (TIMI major and minor) and major adverse cerebrocardiovascular events (MACCE; all-cause death, nonfatal myocardial infarction, stent thrombosis, unplanned revascularization, and stroke) were evaluated. The cumulative 1-year incidence of bleeding was not significantly different (prasugrel 5.6% vs. clopidogrel 8.1%, log-rank P=0.55). In addition, the cumulative 1-year incidence of MACCE was also not significantly different (prasugrel 11.5% vs. clopidogrel 12.3%, log-rank P=0.88). CONCLUSIONS: Low-dose prasugrel, as part of triple therapy, did not increase the risk of bleeding compared with clopidogrel. Therefore, it can be an alternative to clopidogrel for patients with AF undergoing PCI.

A review of clinical characteristics and genetic backgrounds in Alport syndrome.

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.

Clinical Characteristics and Long-Term Outcomes of Rotational Atherectomy　- J2T Multicenter Registry.

BACKGROUND: Rotational atherectomy (RA) is an adjunct tool for the management of heavily calcified coronary lesions during percutaneous coronary intervention (PCI), but the long-term clinical outcomes of RA use remain unclear in this drug-eluting stent era.Methods and Results:This multi-center registry assessed the characteristics and outcomes of patients treated by RA for calcified coronary lesions between 2004 and 2015. Among 1,090 registered patients, mean age was 70±10 years and 815 (75%) were male. Sixty percent of patients had diabetes mellitus and 27.7% were receiving hemodialysis. The procedure was successful in 96.2%. In-hospital death occurred in 33 patients (3.0%), and 14 patients (1.3%) developed definite/probable stent thrombosis. During the median follow-up period of 3.8 years, the incidence of major adverse cardiac events (MACE), defined as all-cause death, acute coronary syndrome, stent thrombosis, target vessel revascularization and stroke, was 46.7%. On multivariable Cox hazard analysis, hemodialysis (HR, 2.08; 95% CI: 1.53-2.86; P<0.0001) and age (HR, 1.03; 95% CI: 1.01-1.04; P<0.0001) were strong independent predictors of MACE. Conversely, statin treatment was associated with lower incidence of MACE (P=0.035). CONCLUSIONS: This study has provided the largest Japanese dataset for long-term follow-up of RA. Although RA in calcified lesions appears feasible with a high rate of procedural success, a high incidence of MACE was observed.