Ventricular dyssynchrony late after the Fontan operation is associated with decreased survival.

BACKGROUND: Ventricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation. METHODS: Single-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and an age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death, heart transplant or heart transplant listing (D/HTx). RESULTS: A total of 503 cases (15 y; IQR 10, 21) and 42 controls (16 y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx. CONCLUSIONS: Compared to control LVs, single right and mixed morphology ventricles in the Fontan circulation exhibit a higher degree of mechanical dyssynchrony as evaluated by CMR-FT. Dyssynchrony indices correlate with ventricular size and function and are associated with death or need for heart transplantation. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.

2 Cases of Spontaneous Coronary Artery Dissection in Neonates.

Spontaneous coronary artery dissection in infants is a rare phenomenon. We present 2 neonates with severe ventricular dysfunction due to coronary artery dissection. Neither patient had evidence of extracardiac fibromuscular dysplasia or other comorbidities that would explain the presentation. (Level of Difficulty: Advanced.).

Multiple Sclerosis Wellness Shared Medical Appointment Model: A Pilot Study.

BACKGROUND: Shared medical appointments (SMAs) are group medical visits combining medical care and patient education. We examined the impact of a wellness-focused pilot SMA in a large multiple sclerosis (MS) clinic. METHODS: We reviewed data on all patients who participated in the SMA from January 2016 through June 2019. The following data were collected 12 months pre/post SMA visits: demographics, body mass index, patient-reported outcomes, and health care utilization. Data were compared using the Wilcoxon rank sum test. RESULTS: Fifty adult patients (mean ± SD age, 50.1 ± 12.3 years) attended at least one MS wellness SMA. Most patients had private insurance (50%), and 26% had Medicaid coverage. The most common comorbidity was depression/anxiety (44%). Pre/post SMA outcomes showed a small but significant reduction in body mass index (30.2 ± 7.3 vs 28.8 ± 7.1, P = .03), and Patient Health Questionnaire-9 scores decreased from 7.3 ± 5.5 to 5.1 ± 5.6 (P = .001). The number of emergency department visits decreased from 13 to two (P = .0005), whereas follow-up visits increased with an attendees' primary care provider from 19 to 41 (P < .001), physical therapist from 15 to 27 (P = .004), and psychologist from six to 19 (P = .003). CONCLUSIONS: This pilot MS wellness SMA was associated with improved physical and psychological outcomes. There was increased, lower-cost health care utilization with reduced acute, high-cost health care utilization, suggesting that SMAs may be a cost-effective and beneficial method in caring for patients with MS.

Optimal sequencing of docetaxel and abiraterone in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Recent advances have yielded multiple new life-prolonging treatments for men with metastatic castration-resistant prostate cancer (mCRPC) including chemotherapy, next-generation hormonal therapy, immunotherapy, and radiopharmaceutical products. However, the optimal sequencing of these agents to maximize clinical benefit remains unclear. Recent data from the CHAARTED and STAMPEDE studies suggest that early use of docetaxel in men with metastatic hormone-sensitive prostate cancer (mHSPC) significantly improves survival, but whether early compared with delayed use of chemotherapy also provides a survival advantage in mCRPC is unknown. METHODS: A retrospective analysis of consecutive mCRPC patients treated at Johns Hopkins is reported. Patients included were treated with sequential docetaxel and abiraterone, in either order. The combined progression-free survival (combined PFS: PFS1 + PFS2) of abiraterone-to-docetaxel is compared to the reverse sequence, where PFS1 and PFS2 represent progression-free survival on the first and second agents respectively. Overall survival (OS) from the start of the first therapy to death is compared between groups. Baseline characteristics are reported prior to the start of the first agent in the sequence. Propensity score-weighted multivariable models and Kaplan-Meier analysis are used for evaluation of the primary and secondary outcomes. RESULTS: Fifty-eight patients who began treatment for mCRPC between January 2011 (the year of abiraterone's FDA-approval) and February 2015 were identified: 26 were in the docetaxel-to-abiraterone group and 32 were in the abiraterone-to-docetaxel group. Patients in the abiraterone-to-docetaxel group had more Gleason 8-10 tumors, greater metastatic burden in bone, and higher median PSAs than those in the docetaxel-to-abiraterone group. Propensity score-weighted univariate analyses for combined PFS (HR 0.82; 95%CI 0.50-1.33; P = 0.41) and OS (HR 0.79; 95%CI 0.50-1.25; P = 0.31) do not identify any significant differences based on treatment sequence. Propensity score-weighted multivariate analyses for combined PFS (HR 0.91; 95%CI 0.52-1.60; P = 0.74) and OS (HR 0.98; 95%CI 0.59-1.63; P = 0.95) also do not identify any significant differences between groups. CONCLUSIONS: We do not observe differences in clinical outcomes based on alternative sequencing of abiraterone and docetaxel in men with mCRPC. Treatment sequencing should be determined by patient and disease characteristics, comorbidities and end-organ function, ability to tolerate side effects, and patient preferences. Studies evaluating biomarkers to inform optimal treatment sequencing in men with mCRPC are urgently needed.

The influence of prior abiraterone treatment on the clinical activity of docetaxel in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Taxanes may partly mediate their effect in castration-resistant prostate cancer (CRPC) through disruption of androgen-receptor trafficking along microtubules. This raises the possibility of cross-resistance between androgen-directed agents and docetaxel. OBJECTIVE: To evaluate docetaxel efficacy after abiraterone treatment in CRPC patients. DESIGN, SETTING, AND PARTICIPANTS: This was a single-institution, retrospective analysis in CRPC patients (N=119) who either received abiraterone before docetaxel (AD) (n=24) or did not receive abiraterone before docetaxel (docetaxel-only; n=95). Men initiated docetaxel between December 2007 (the date abiraterone was first used at our center) and May 2013. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary efficacy end points were prostate-specific antigen progression-free survival (PSA-PFS) and clinical/radiographic progression-free survival (PFS) on docetaxel. Differences between groups were assessed using univariate and multivariable analyses. RESULTS AND LIMITATIONS: Men in the AD group had a significantly higher risk for progression than those in the docetaxel-only group. Median PSA-PFS was 4.1 mo in the AD group and 6.7 mo in the docetaxel-only group (p=0.002). Median PFS was also shorter in the AD group (4.4 mo vs 7.6 mo; p=0.003). In multivariable analysis, prior abiraterone treatment remained an independent predictor of shorter PSA-PFS (hazard ratio [HR]: 3.48; 95% confidence interval [CI], 1.36-8.94; p=0.01) and PFS (HR: 3.62; 95% CI, 1.41-9.27; p=0.008). PSA declines ≥50% were less frequent in the AD group (38% vs 63%; p=0.02). The small size and retrospective nature of this study may have introduced bias. CONCLUSIONS: Men receiving abiraterone before docetaxel were more likely to progress on docetaxel and less likely to achieve a PSA response than abiraterone-naïve patients. Cross-resistance between abiraterone and docetaxel may explain these findings; however, larger, more definitive studies are still needed to confirm this. PATIENT SUMMARY: We examined the efficacy of docetaxel in castration-resistant prostate cancer patients who either did or did not receive prior abiraterone. We found that men receiving abiraterone before docetaxel were less likely to achieve a PSA response and were more likely to progress sooner on docetaxel than abiraterone-untreated patients. This may be due to cross-resistance.

Long-term results of a prospective, Phase II study of long-term androgen ablation, pelvic radiotherapy, brachytherapy boost, and adjuvant docetaxel in patients with high-risk prostate cancer.

PURPOSE: We report the long-term results of a prospective, Phase II study of long-term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. METHODS AND MATERIALS: Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate-specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m(2) per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). RESULTS: From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9-7.8 years) and 6.3 years (range, 4-7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3-5) was 7.7%. CONCLUSIONS: The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a multi-institutional setting.