Improving quantitative MRI using self-supervised deep learning with model reinforcement: Demonstration for rapid T1 mapping.

PURPOSE: This paper proposes a novel self-supervised learning framework that uses model reinforcement, REference-free LAtent map eXtraction with MOdel REinforcement (RELAX-MORE), for accelerated quantitative MRI (qMRI) reconstruction. The proposed method uses an optimization algorithm to unroll an iterative model-based qMRI reconstruction into a deep learning framework, enabling accelerated MR parameter maps that are highly accurate and robust. METHODS: Unlike conventional deep learning methods which require large amounts of training data, RELAX-MORE is a subject-specific method that can be trained on single-subject data through self-supervised learning, making it accessible and practically applicable to many qMRI studies. Using quantitative T 1 $$ {\mathrm{T}}_1 $$ mapping as an example, the proposed method was applied to the brain, knee and phantom data. RESULTS: The proposed method generates high-quality MR parameter maps that correct for image artifacts, removes noise, and recovers image features in regions of imperfect image conditions. Compared with other state-of-the-art conventional and deep learning methods, RELAX-MORE significantly improves efficiency, accuracy, robustness, and generalizability for rapid MR parameter mapping. CONCLUSION: This work demonstrates the feasibility of a new self-supervised learning method for rapid MR parameter mapping, that is readily adaptable to the clinical translation of qMRI.

Long-Term Outcomes of Endovascular Repair Within and Outside the Instructions for Use in Korean Patients With Abdominal Aortic Aneurysm.

OBJECTIVE: Endovascular aneurysm repair (EVAR) has been used worldwide to treat abdominal aortic aneurysms (AAAs). Outcomes after EVAR within and outside the instruction for use (IFU) remain controversial. We analyzed long-term outcomes of EVAR within-the-IFU compared with that outside-the-IFU and baseline clinical/anatomical characteristics that influence outcomes of EVAR. METHODS: The study included 546 patients who underwent EVAR for infrarenal AAA from 1997 to 2021 at 2 Korean medical centers. The primary endpoint was graft-related adverse events (GRAEs), including type 1 or 3 endoleak, reintervention (included open conversion), aneurysm sac enlargement, aneurysm-related mortality (ARM), rupture, stent-graft migration, and stent thrombotic occlusion. RESULTS: The patients who underwent EVAR outside the IFU were 287 (52.6%). A neck angle of >60° was most common outside the IFU criteria (n=146, 50.9%). This study revealed that patients outside the IFU had a higher rate of GRAEs compared with patients within the IFU (hazard ratio [HR]: 1.879; 95% confidence interval [CI]: 1.045-2.386). A neck angle of >60° was a significant risk factor for GRAEs (adjusted HR: 2.229; 95% CI: 1.418-3.503), type 1 or 3 endoleak (adjusted HR: 2.640; 95% CI: 1.343-5.189), and reintervention (adjusted HR: 1.891; 95% CI: 1.055-3.388). CONCLUSIONS: Our study revealed EVAR with outside the IFU was associated with increased GRAEs, mainly attributed to endoleak and ARM, compared with EVAR with within the IFU. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak, and reintervention. CLINICAL IMPACT: Our study revealed endovascular aneurysm repair (EVAR) with outside-the-instruction for use (IFU) was associated with increased graft-related adverse events (GRAEs) compared with EVAR with within-the-IFU. In the low-risk population, the incidence of GRAEs and Aneurysm related mortality were higher in the outside-the-IFU group rather than within-the-IFU group. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak and reintervention.

Comparison of circulating tumor DNA between African American and Caucasian patients with metastatic castrate-resistant prostate cancer post-abiraterone and/or enzalutamide.

BACKGROUND: African American men are much more likely than Caucasian men to be diagnosed with and to die of prostate cancer. Genetic differences likely play a role. The cBioPortal database reveals that African American men with prostate cancer have higher rates of CDK12 somatic mutations compared to Caucasian men. However, this does not account for prior prostate cancer treatments, which are particularly important in the castrate-resistant setting. We aimed to compare somatic mutations based on circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC) between African American and Caucasian men after exposure to abiraterone and/or enzalutamide. METHODS: This single-institution retrospective study characterizes the somatic mutations detected on ctDNA for African American and Caucasian men with mCRPC who had progressed after abiraterone and/or enzalutamide from 2015 through 2022. We evaluated the gene mutations and types of mutations in this mCRPC cohort. RESULTS: There were 50 African American and 200 Caucasian men with CRPC with available ctDNA data. African American men were younger at the time of diagnosis (p = 0.008) and development of castration resistance (p = 0.006). African American men were more likely than Caucasian men to have pathogenic/likely pathogenic (P/LP) mutations in CDK12 (12% vs. 1.5%; p = 0.003) and copy number amplifications and P/LP mutations in KIT (8.0% vs. 1.5%; p = 0.031). African American men were also significantly more likely to have frameshift mutations (28% vs. 14%; p = 0.035). CONCLUSIONS: Compared to Caucasian men, African American men with mCRPC after exposure to abiraterone and/or enzalutamide had a higher incidence of somatic CDK12 P/LP mutations and KIT amplifications and P/LP mutations based on ctDNA. African American men also had more frameshift mutations. We hypothesize that these findings have potential implications for tumor immunogenicity.

B1 inhomogeneity-corrected T1 mapping and quantitative magnetization transfer imaging via simultaneously estimating Bloch-Siegert shift and magnetization transfer effects.

PURPOSE: To introduce a method of inducing Bloch-Siegert shift and magnetization Transfer Simultaneously (BTS) and demonstrate its utilization for measuring binary spin-bath model parameters free pool spin-lattice relaxation ( T 1 F $$ {T}_1^{\mathrm{F}} $$ ), macromolecular fraction ( f $$ f $$ ), magnetization exchange rate ( k F $$ {k}_{\mathrm{F}} $$ ) and local transmit field ( B 1 + $$ {B}_1^{+} $$ ). THEORY AND METHODS: Bloch-Siegert shift and magnetization transfer is simultaneously induced through the application of off-resonance irradiation in between excitation and acquisition of an RF-spoiled gradient-echo scheme. Applying the binary spin-bath model, an analytical signal equation is derived and verified through Bloch simulations. Monte Carlo simulations were performed to analyze the method's performance. The estimation of the binary spin-bath parameters with B 1 + $$ {B}_1^{+} $$ compensation was further investigated through experiments, both ex vivo and in vivo. RESULTS: Comparing BTS with existing methods, simulations showed that existing methods can significantly bias T 1 $$ {T}_1 $$ estimation when not accounting for transmit B 1 $$ {B}_1 $$ heterogeneity and MT effects that are present. Phantom experiments further showed that the degree of this bias increases with increasing macromolecular proton fraction. Multi-parameter fit results from an in vivo brain study generated values in agreement with previous literature. Based on these studies, we confirmed that BTS is a robust method for estimating the binary spin-bath parameters in macromolecule-rich environments, even in the presence of B 1 + $$ {B}_1^{+} $$ inhomogeneity. CONCLUSION: A method of estimating Bloch-Siegert shift and magnetization transfer effect has been developed and validated. Both simulations and experiments confirmed that BTS can estimate spin-bath parameters ( T 1 F $$ {T}_1^{\mathrm{F}} $$ , f $$ f $$ , k F $$ {k}_{\mathrm{F}} $$ ) that are free from B 1 + $$ {B}_1^{+} $$ bias.

Improved intra-atrial conduction delay after successful ablation for atrial fibrillation by scar homogenization in right atrium.

Atrial fibrosis in the right atrium (RA) presenting as a low-voltage zone might be the mechanism of atrial fibrillation (AF) and intra-atrial conduction delay. The impact of scar homogenization in RA on intra-atrial conduction delay is unknown. We describe a patient with paroxysmal AF and significant intra-atrial conduction delay with repetitive atrial flutter, triggered from the lateral free wall in the RA between the significant low-voltage zone and slow conduction area after pulmonary vein isolation. Linear ablation along the trabeculated lateral free wall in the RA to homogenize the scar was successfully performed, and the intra-atrial conduction delay improved ultimately.

Targeted Alpha-Particle Therapy: A Review of Current Trials.

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.

Safety and Efficacy of Post-Dilation in Percutaneous Coronary Intervention Using Polymer-Free Ultrathin Strut Sirolimus-Probucol Coated Drug-Eluting Stents.

Background and Objectives: Polymer-free ultrathin strut sirolimus- and probucol-eluting stents (PF-SES) are recognized as safe and effective in diverse patient populations, although the implications of post-dilation during stent implantation remain underexamined. Materials and Methods: In this study, patients implanted with PF-SES at Gachon University Gil Medical Center between December 2014 and February 2018 were evaluated. Major adverse cardiovascular events (MACE), encompassing nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular death were identified as primary outcomes, with secondary outcomes including target vessel revascularization (TVR), target lesion revascularization (TLR), and in-stent restenosis (ISR). Results: Of the 384 initial patients, 299 were considered eligible for analysis. The groups, delineated by those undergoing post-dilation (143 patients) and those not (156 patients), exhibited comparable rates of primary outcomes [hazard ratio (HR), 2.17; 95% confidence interval (CI), 0.40 to 11.87; p = 0.37]. The outcomes remained consistent irrespective of the post-dilation status and were similarly unaffected in multivariate analyses (HR, 2.90; 95% CI, 0.52 to 16.34; p = 0.227). Conclusions: These results suggest that the clinical outcomes of patients with post-dilation were similar to that of those without post-dilation in those with the polymer-free sirolimus- and probucol-eluting stents.

Efficacy of enfortumab vedotin in advanced urothelial cancer: Analysis from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study.

BACKGROUND: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials. METHODS: UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy. RESULTS: The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression-free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06). CONCLUSIONS: In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate < 30 mL/min and significant comorbidities. LAY SUMMARY: Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real-world setting, and support the use of this drug in broader patient populations.

Multi-institutional Analysis of the Clinical and Genomic Characteristics of Black Patients with Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: The outcomes of metastatic hormone-sensitive prostate cancer (mHSPC) have significantly improved through treatment intensification, yet Black representation in those studies is suboptimal. METHODS: A multi-institutional, retrospective analysis of Black men with mHSPC was conducted, focusing on baseline demographics, treatment patterns, genomic profiles, clinical outcomes including prostate-specific antigen response, time to castrate-resistant prostate cancer (CRPC), and subsequent treatments. RESULTS: A total of 107 patients, median age 64 years, 62% with de novo metastases at diagnosis and 64% with high-volume disease, were included. Twenty-nine patients (27%) were treated with androgen deprivation therapy (ADT) with and without first generation anti-androgens, while 20%, 38% and 5% received chemotherapy, abiraterone, and enzalutamide, respectively. At time of data cut-off, 57 (54%) patients had developed CRPC, with a median time to CRPC of 25.4 months (95% CI 20.3-30.4). The median time to CRPC was 46.3 months (18.9-73.7) and 23.4 months (18.6-28.2) for patients who received ADT with or without first-generation anti-androgens and treatment intensification, respectively. The 2-year survival rate was 93.3%, and estimated median overall survival of was 74.9 months (95% CI, 68.7-81.0). Most patients (90%) underwent germline testing; the most frequent known alterations were found within the DNA repair group of genes. Somatic testing revealed pathogenic alterations of interest, notably TP53 (24%) and CDK12 (12%). CONCLUSION: In our cohort, Black men with mHSPC presented with a high proportion of de novo metastases and high-volume disease. Treatment outcomes were very favorable with ADT-based regimens. The genomic landscape suggests different molecular profile relative to White patients with potential therapeutic implications.

Long-Term Clinical Outcomes and Its Predictors Between the 1- and 2-Stent Strategy in Coronary Bifurcation Lesions　- A Baseline Clinical and Lesion Characteristic-Matched Analysis.

BACKGROUND: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions.Methods and Results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (pinteraction=0.008) and side branch calcification (pinteraction=0.010). CONCLUSIONS: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.

Unexpected paced wide QRS complex rhythm after successful implantation of cardiac resynchronization therapy; what is the mechanism?

The adaptive CRT (aCRT) is an innovative algorithm that was developed to avoid unnecessary right ventricular (RV) pacing through continuous intracardiac delay evaluation. We present a case of unexpected wide QRS paced rhythm after successful implantation of CRT in patients with right bundle branch block (RBBB) and describe the reasons and the programming changes required to resolve it.

New Trends in Dyslipidemia Treatment.

Dyslipidemia is one of the most important risk factors for cardiovascular (CV) disease. Statin therapy has dramatically improved CV outcomes and is the backbone of current lipid-lowering therapy, but despite well-controlled low-density lipoprotein cholesterol (LDL-C) levels through statin administration, up to 40% patients still experience CV disease. New therapeutic agents to tackle such residual cholesterol risk by lowering not only LDL-C but triglycerides (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp(a)) are being introduced. Ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, PCSK9 small interference RNA (siRNA), and bempedoic acid added to statin therapy have shown additional improvement to CV outcomes. Recent trials administering eicosapentaenoic acid to patients with high TG despite statin therapy have also demonstrated significant CV benefit. Antisense oligonucleotide (ASO) therapies with hepatocyte-specific targeting modifications are now being newly introduced with promising lipid-lowering effects. ASOs targeting TG/TRL, such as angiopoietin-like 3 or 4 (ANGPTL3 or ANGPTL4), apolipoprotein C-III (APOC3), or Lp(a) have effectively lowered the corresponding lipid profiles without requiring high or frequent doses. Clinical outcomes from these novel therapeutics are yet to be proven. Here, we review current and emerging therapeutics targeting LDL-C, TG, TRL, and Lp(a) to reduce the residual CV risk.

Lipoprotein(a) and Cardiovascular Diseases　- Revisited.

Two decades ago, it was recognized that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However, the importance of Lp(a) was not strongly established due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent advances in clinical and genetic research have revealed the crucial role of Lp(a) in the pathogenesis of CVD. Mendelian randomization studies have shown that Lp(a) concentrations are causal for different CVDs, including coronary artery disease, calcified aortic valve disease, stroke, and heart failure, despite optimal low-density lipoprotein cholesterol (LDL-C) management. Lp(a) consists of apolipoprotein (apo) B100 covalently bound to apoA. Thus, Lp(a) has atherothrombotic traits of both apoB (from LDL) and apoA (thrombo-inflammatory aspects). Although conventional pharmacological therapies, such as statin, niacin, and cholesteryl ester transfer protein, have failed to significantly reduce Lp(a) levels, emerging new therapeutic strategies using proprotein convertase subtilisin-kexin type 9 inhibitors or antisesnse oligonucleotide technology have shown promising results in effectively lowering Lp(a). In this review we discuss the revisited important role of L(a) and strategies to overcome residual risk in the statin era.

Femoral neuropathy following venoarterial-extracorporeal membrane oxygenation therapy: a case report.

BACKGROUND: Although life-threatening complications of extracorporeal membrane oxygenation (ECMO) are well described, non-life threatening complications are less known. Herein, we report a case of femoral neuropathy (FN) due to nerve compression caused by cannula compression and deep vein thrombosis (DVT) after successful ECMO therapy, which seriously undermined one's quality of life. CASE PRESENTATION: A 70-year old male presented to the emergency department for chest pain. The patient had cardiac arrest before percutaneous coronary intervention (PCI) and was inserted with ECMO. Although he was successfully weaned from ECMO 4 days after PCI, he consistently complained swelling, abnormal sensation, and weakness in his right lower extremity, where the cannulas were inserted. Imaging studies showed deep vein thrombosis (DVT) in his right leg, which was further treated with anticoagulants. Symptoms, however, remained after the regression of DVT. Nerve conduction study revealed femoral neuropathy, which may have been caused by ECMO cannula compression and tissue swelling. CONCLUSION: The current case proposes that non-life threatening complications of ECMO therapy can seriously affect quality of life. Venous drainage distant from the arterial cannula may prevent such complications.

Comparison of Intracardiac Echocardiography and Transesophageal Echocardiography for Image Guidance in Percutaneous Patent Foramen Ovale Closure.

Background and Objectives: Transesophageal echocardiography (TEE) guidance is the current gold standard for catheter-based procedures in the treatment of structural heart diseases. Intracardiac echocardiography (ICE), which can be performed under local anesthesia, has been recently introduced and is becoming more widely used. We aimed to compare the efficacy and safety of ICE and TEE in patent foramen ovale (PFO) device closure. Materials and Methods: All 74 patients with a history of cryptogenic stroke undergoing PFO closure for secondary prophylaxis were selected from our registry. Intraprocedural TEE was performed by echocardiographer-cardiologists with the patient under general anesthesia. Conversely, ICE was performed with the patient under local anesthesia. Baseline characteristics, procedural details, and immediate outcomes were compared between the TEE and ICE groups (n = 49 and n = 25, respectively). Results: Although patients in the ICE group were older (47 ± 10 vs. 57 ± 7 years, p < 0.001), sex and comorbidity variables were similar between the two groups. The degree of inducible right-to-left shunt via the PFO, assessed using preprocedural TEE, was also comparable. Notably, fluoroscopy time (22 ± 18 vs. 16 ± 7 min, p = 0.030), radiation dose (498 ± 880 vs. 196 ± 111 mGy, p = 0.022), and total procedural time in the catheter laboratory (99 ± 30 vs. 67 ± 12 min, p < 0.001) were significantly lower in the ICE group than those in the TEE group. The entire hospital stay was similar between groups (3.8 ± 2.2 vs. 3.4 ± 1.3 days, p = 0.433). No procedural complications, such as device embolization, pericardial hemorrhage, major bleeding, mortality, or access-related vascular injury were reported in either group. Conclusions: ICE-guided PFO device closure is quicker and less hazardous in terms of radiation exposure than the TEE-guided procedure, with similar procedural outcomes and duration of hospital stay.

Designing 3D selective adiabatic radiofrequency pulses with single and parallel transmission.

PURPOSE: To introduce a method of designing single and parallel transmit (pTx) 3D adiabatic π pulses for inverting and refocusing spins that are insensitive to transmit B1 ( B1+) inhomogeneity. THEORY AND METHODS: A 3D adiabatic pulse is created by replacing each piece-wise constant element (or sub-pulse) of an adiabatic full passage (AFP) by a 2D selective pulse. In this study, the parent AFP is an HS1 and each sub-pulse is a 2D pulse derived from a jinc function designed using a spiral k-trajectory. Spatial selectivity in the third direction is achieved by blipping the slab-selective gradient between sub-pulses, yielding a rectangular slab profile identical to that of the parent AFP. The slew-rate limited sub-pulse can be undersampled utilizing pTx, thus shortening the overall pulse width. Simulations and experiments demonstrate the quality of spatial selectivity and adiabaticity achievable. RESULTS: The 3D adiabatic pulse inverts and refocus spins in a sharply demarcated cylindrical volume. When stepping RF amplitude, an adiabatic threshold is observed above which the flip angle remains π. Experimental results demonstrate that pTx is an effective means to significantly improve pulse performance. CONCLUSION: A method of designing 3D adiabatic pulses insensitive to B1 inhomogeneity has been developed. pTx can shorten these pulses while retaining their adiabatic character. Magn Reson Med 79:701-710, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Routine Indwelling Urethral Catheterization in Acute Heart Failure Patients Is Associated With Increased Urinary Tract Complications Without Improved Heart Failure Outcomes.

BACKGROUND: Indwelling urethral catheters (IUC) are routinely inserted for the purpose of monitoring urine output in patients with acute heart failure (AHF). The benefit of IUC in patients capable of complying with urine collection protocols is unclear, and IUC carry multiple risks. This study describes the impact of IUC on AHF treatment.Methods and Results:A total of 540 records were retrospectively analyzed. After exclusion criteria were applied, 316 patients were propensity matched to establish groups of 100 AHF patients who either did (IUC(+)) or did not receive an IUC (IUC(-)) upon admission. Hospital length of stay (9 vs. 7 days), in-hospital urinary complications (24 vs. 5%), and 1-year urinary tract infection rate (17 vs. 6%; HR, 3.145; 95% CI: 1.240-7.978) were significantly higher in the IUC(+) group (P<0.05 for all). There were no differences in 30-day rehospitalization (6 vs. 6%; HR, 0.981; 95% CI: 0.318-3.058; P=0.986) or major adverse cardiac/cerebrovascular events at 1 year (37 vs. 32%, HR, 1.070; 95% CI: 0.636-1.799; P=0.798). CONCLUSIONS: Based on this retrospective analysis, the routine use of IUC may increase length of stay and UTI complications in AHF patients without reducing the risk for major cardiovascular and cerebrovascular events or 30-day rehospitalization rate.

Requirement for autophagy in the long-term persistence but not initial formation of memory B cells.

Autophagy is required for the long-term maintenance of Ag-specific memory B cells. However, whether autophagy is also important for the initial formation of memory B cells remains unclear. In this study, we show that newly generated memory B cells do not display active autophagy but are capable of forming Ab-secreting cells after rechallenge with Ags. Increases in autophagy took place over time after the initial formation of memory B cells. The expression of transcription factors involved in autophagy, but not changes in epigenetic regulation by DNA methylation, was required for autophagy gene expression and the development of active autophagy in memory B cells. This indicates that autophagy is not critical for the initial generation of memory B cells but is required for their long-term persistence. Our results suggest that promoting autophagy to improve Ab-dependent immunological memory is more effective during memory B cell maintenance stage.

Transmurally differentiated measurement of ATP hydrolysis rates in the in vivo porcine hearts.

PURPOSE: Compare the transmural distribution of forward creatine kinase reaction (kf,CK ) and ATP hydrolysis rate (kr,ATPase ) in the myocardium of normal porcine heart. Rate constants were extracted from partially relaxed spectra by applying the T1nom method, effectively reducing data acquisition time by up to an order of magnitude. THEORY AND METHODS: T1nom method for double saturation of PCr and Pi is introduced and validated through simulations. Bioenergetics was measured in vivo utilizing one-dimensional chemical shift imaging (1D-CSI) magnetic resonance (31) P spectroscopy. RESULTS: At basal conditions, there was no significant difference between subepicardial layers (EPI) vs. the subendocardial layers (ENDO) for both fluxf,CK and fluxr,ATPase . At high cardiac workload (HWL), where the rate pressure product increased 2.6-fold, PCr/ATP ratio and fluxf,CK showed no significant change in both EPI and ENDO layers, while fluxr,ATPase increased significantly (baseline: 1.11 ± 0.12 and 1.12 ± 0.13 µmol/g/s, EPI and ENDO, respectively; to HWL: 2.35 ± 0.27 and 2.21 ± 0.08 µmol/g/s, EPI and ENDO, respectively, each P < 0.01 vs. baseline). CONCLUSION: In the normal heart, increase of cardiac work state is accompanied by an increase in ATP hydrolysis rate with no changes in CK flux rate. There are no significant differences between EPI vs. ENDO concerning the ATP hydrolysis rate or CK flux rate in both baseline and high cardiac work states.