PSA bounce after <Superscript>125</Superscript>I-brachytherapy for prostate cancer as a favorable prognosticator

Background

Permanent low-dose-rate brachytherapy (BT) with iodine 125 is an established curative treatment for localized prostate cancer. After treatment, prostate-specific antigen (PSA) kinetics may show a transient rise (PSA bounce). Our aim was to investigate the association of PSA bounce with biochemical control.

Patients and methods

Patients treated with BT in Switzerland were registered in a prospective database. Only patients with a follow-up of at least 2 years were included in our analysis. Clinical follow-up and PSA measurements were assessed after 1.5, 3, 6, and 12 months, and annually thereafter. If PSA increased, additional follow-up visits were scheduled. Cases of PSA bounce were defined as a rise of at least 0.2 ng/ml above the initial PSA nadir with a subsequent decline to or below the initial nadir without treatment. Biochemical failure was defined as a rise to nadir +?2 ng/ml.

Results

Between March 2001 and November 2010, 713 patients with prostate cancer undergoing BT with at least 2 years of follow-up were registered. Median follow-up time was 41 months. Biochemical failure occurred in 28 patients (3.9?%). PSA bounce occurred in 173 (24.3?%) patients; only three (1.7?%) patients with PSA bounce developed biochemical failure, in contrast to 25 (4.6?%) patients without previous bounce (p?<?0.05). The median time to bounce was 12 months, the median time to biochemical failure was 30 months. The median bounce increase was 0.78 ng/ml. Twenty-eight patients with bounce (16.5?%) had a transient PSA rise of +?2 ng/ml above the nadir.

Conclusion

In most cases, an early increase in PSA after BT indicates PSA bounce and is associated with a lower risk of biochemical failure.

     

Relative Femoral Neck Lengthening Improves Pain and Hip Function in Proximal Femoral Deformities With a High-riding Trochanter

BackgroundComplex proximal femoral deformities, including an elevated greater trochanter, short femoral neck, and aspherical head-neck junction, often result in pain and impaired hip function resulting from intra-/extraarticular impingement. Relative femoral neck lengthening may address these deformities, but mid-term results of this approach have not been widely reported.Questions/purposesDo patients who have undergone relative femoral neck lengthening show (1) less hip pain and greater function; (2) improved radiographic parameters; (3) significant complications requiring subsequent surgery; and (4) progression of osteoarthrosis (OA) or conversion to total hip arthroplasty (THA) at mid-term followup?MethodsWe retrospectively reviewed 40 patients (41 hips) with isolated relative femoral neck lengthening between 1998 and 2006 with sequelae of Legg-Calvé-Perthes disease (38 hips [93%]), slipped capital femoral epiphysis (two hips [5%]), and postseptic arthritis (one hip [2%]). During this time, the general indications for this procedure included a high-riding greater trochanter with a short femoral neck with abductor weakness and symptomatic intra-/extraarticular impingement. Mean patient followup was 8 years (range, 5–13 years), and complete followup was available in 38 patients (39 hips [95%]). We evaluated pain and function with the impingement test, limp, abductor force, Merle d’Aubigné-Postel score, and range of motion. Radiographic parameters included trochanteric height, alpha angle, and progression of OA. Subsequent surgeries, complications, and conversion to THA were summarized.ResultsThe proportion of positive anterior impingement tests decreased from 93% (38 of 41 hips) preoperatively to 49% (17 of 35 hips) at latest followup (p = 0.002); the proportion of limp decreased from 76% (31 of 41 hips) to 9% (three of 35 hips; p < 0.001); the proportion of normal abductor strength increased from 17% (seven of 41 hips) to 91% (32 of 35 hips; p < 0.001); mean Merle d’Aubigné-Postel score increased from 14 ± 1.7 (range, 9–17) to 17 ± 1.5 (range, 13–18; p < 0.001); mean internal rotation increased to 25° ± 15° (range, 0°–60°; p = 0.045), external rotation to 32° ± 14° (range, 5°–70°; p = 0.013), and abduction to 37° ± 13° (range, 10°–50°; p = 0.004). Eighty percent of hips (33 of 41 hips) showed normal trochanteric height; alpha angle improved to 42° ± 10° (range, 27°–90°). Two hips (5%) had subsequent surgeries as a result of lack of containment; four of 41 hips (10%) had complications resulting in reoperation. Fourteen of 35 hips (40%) showed progression of OA; four of 40 hips (10%) converted to THA.ConclusionsRelative femoral neck lengthening in hips with combined intra- and extraarticular impingement results in reduced pain, improved function, and improved radiographic parameters of the proximal femur. Although lack of long-term complications is gratifying, progression of OA was not prevented and remains an area for future research.

Level of Evidence

Level IV, therapeutic study.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-014-4032-9) contains supplementary material, which is available to authorized users.     

2015 Marshall Urist Young Investigator Award: Prognostication in Patients With Long Bone Metastases: Does a Boosting Algorithm Improve Survival Estimates?

Background

Survival estimation guides surgical decision-making in metastatic bone disease. Traditionally, classic scoring systems, such as the Bauer score, provide survival estimates based on a summary score of prognostic factors. Identification of new factors might improve the accuracy of these models. Additionally, the use of different algorithms—nomograms or boosting algorithms—could further improve accuracy of prognostication relative to classic scoring systems. A nomogram is an extension of a classic scoring system and generates a more-individualized survival probability based on a patient’s set of characteristics using a figure. Boosting is a method that automatically trains to classify outcomes by applying classifiers (variables) in a sequential way and subsequently combines them. A boosting algorithm provides survival probabilities based on every possible combination of variables.

Questions/purposes

We wished to (1) assess factors independently associated with decreased survival in patients with metastatic long bone fractures and (2) compare the accuracy of a classic scoring system, nomogram, and boosting algorithms in predicting 30-, 90-, and 365-day survival.

Methods

We included all 927 patients in our retrospective study who underwent surgery for a metastatic long bone fracture at two institutions between January 1999 and December 2013. We included only the first procedure if patients underwent multiple surgical procedures or had more than one fracture. Median followup was 8 months (interquartile range, 3-25 months); 369 of 412 (90%) patients who where alive at 1 year were still in followup. Multivariable Cox regression analysis was used to identify clinical and laboratory factors independently associated with decreased survival. We created a classic scoring system, nomogram, and boosting algorithms based on identified variables. Accuracy of the algorithms was assessed using area under the curve analysis through fivefold cross validation.

Results

The following factors were associated with a decreased likelihood of survival after surgical treatment of a metastatic long bone fracture, after controlling for relevant confounding variables: older age (hazard ratio [HR], 1.0; 95% CI, 1.0–1.0; p < 0.001), additional comorbidity (HR, 1.2; 95% CI, 1.0–1.4; p = 0.034), BMI less than 18.5 kg/m² (HR, 2.0; 95% CI, 1.2–3.5; p = 0.011), tumor type with poor prognosis (HR, 1.8; 95% CI, 1.6–2.2; p < 0.001), multiple bone metastases (HR, 1.3; 95% CI, 1.1–1.6; p = 0.008), visceral metastases (HR, 1.6; 95% CI, 1.4–1.9; p < 0.001), and lower hemoglobin level (HR, 0.91; 95% CI, 0.87–0.96; p < 0.001). The survival estimates by the nomogram were moderately accurate for predicting 30-day (area under the curve [AUC], 0.72), 90-day (AUC, 0.75), and 365-day (AUC, 0.73) survival and remained stable after correcting for optimism through fivefold cross validation. Boosting algorithms were better predictors of survival on the training datasets, but decreased to a performance level comparable to the nomogram when applied on testing datasets for 30-day (AUC, 0.69), 90-day (AUC, 0.75), and 365-day (AUC, 0.72) survival prediction. Performance of the classic scoring system was lowest for all prediction periods.

Conclusions

Comorbidity status and BMI are newly identified factors associated with decreased survival and should be taken into account when estimating survival. Performance of the boosting algorithms and nomogram were comparable on the testing datasets. However, the nomogram is easier to apply and therefore more useful to aid surgical decision making in clinical practice.

Level of Evidence

Level III, prognostic study.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-015-4446-z) contains supplementary material, which is available to authorized users.     

Pharmacological and ablative hybrid therapy of atrial fibrillation. Long-term effect on quality of life and arrhythmia-related symptoms

The pharmacological and ablative hybrid therapy of atrial fibrillation (AF) consists of radiofrequency catheter ablation of antiarrhythmic drug-induced typical atrial flutter (AFl) and continuation of drug therapy. The purpose of this study was to determine the effect of this therapy on AF symptoms and quality of life (QoL). Forty-six patients were monitored after isthmus-ablation of drug-induced typical AFl and continuation of their antiarrhythmic drug treatment over a mean follow-up of 22.4+/-11.6 months. AF characteristics, symptoms and QoL before and after ablation were evaluated by the SF-36 question- naire, the Symptoms Checklist-Frequency and Severity Scale and the analysis of ECG recordings. 63% of patients demonstrated recurrences of AF. However, the frequency and duration of symptomatic episodes significantly decreased in 82.6 and 76% of patients. All categories of the SF-36 improved significantly and the AF symptomatology showed a relevant attenuation in 65.8% of the study population. CONCLUSION: The pharmacological and ablative hybrid therapy significantly reduced the mean number and the duration of symptomatic AF episodes as well as AF-correlated symptoms and was associated with significant QoL improvement.     

N-terminal pro-brain natriuretic peptide predicts myocardial ischemia and is related to postischemic left-ventricular dysfunction in patients with stable coronary artery disease.

BACKGROUND: The N-terminal-pro-B natriuretic peptide (Nt-pro-BNP) is of diagnostic and prognostic value in coronary artery disease (CAD). We assessed the relationship between Nt-pro-BNP and (1) the extent of ischemia on stress myocardial perfusion imaging (MPI), and (2) changes between the basal and postexercise ejection fraction (EF), in stable patients with a normal EF. METHODS AND RESULTS: One hundred and two patients with stable, documented CAD (EF, 62% +/- 8%) underwent an exercise-rest thallium-201 gated-MPI and serial Nt-pro-BNP assays. Myocardial perfusion imaging produced abnormal results in 57 patients (56%; group 1), and normal results in 45 patients (44%; group 2). Median baseline, immediate postexercise, and 3-hour postexercise Nt-pro-BNP values were higher in group 1 than in group 2: 182 vs 85, 201 vs 86, and 212 vs 99 pg/mL, respectively (P < .001 for all). Postexercise EF decreased in group 1 (53% +/- 11% vs 62% +/- 10%, P < .001), but not in group 2 (61% +/- 9% vs 62% +/- 7%, NS). The Nt-pro-BNP ruled out significant ischemia with a negative predictive value of 0.90, whereas patients within the higher tertile of Nt-pro-BNP had a fivefold higher risk of ischemia compared with patients within the lower tertile. CONCLUSIONS: The post-stress increase in Nt-pro-BNP is related to myocardial ischemia and to postischemic left-ventricular dysfunction, and accurately predicts the presence or absence of myocardial perfusion defects.     

Real-time assessment of acute myocardial ischaemia by an intra-thoracic 6-lead ECG: evaluation of a new diagnostic option in the implantable defibrillator.

AIM: In the presence of coronary artery disease, implantable cardioverter-defibrillators (ICD) are used effectively for treating life-threatening tachyarrhythmias. Continuous monitoring of myocardial ischaemia would provide a new diagnostic option in future ICD generations. METHODS AND RESULTS: In 22 selected patients undergoing coronary angioplasty, percutaneous transluminal coronary angioplasty (PTCA), three electrodes, similar to those used in the ICD, were inserted aiming to create six intra-thoracic ECG (IT-ECG) leads according to Einthoven and Goldberger. In total, 27 PTCA were conducted. The diagnostic efficacy for ischaemia assessment was compared with the surface ECG. The IT-ECG proved to be more sensitive than conventional ECG in early and overall ischaemia assessment. At 30 s of coronary artery occlusion, ischaemic ST-segment alterations (> or =0.25 mV) were present in the IT-ECG 2.3 times more often (23 vs. 10/27 PTCA attempts, P<0.01) and at 90 s 1.4 times more often compared with conventional ECG leads (18 vs. 26/27, P<0.05). Intra-thoracic Einthoven 2 (SVC+RVA vs. ICD-housing) and Goldberger 3 (SVC+ICD-housing vs. RVA) had the highest sensitivity (88/85%). Using > or =4 IT-ECG, ischaemia monitoring was independent of severity and site of origin. IT-ECG signals showed double ST-T signal amplitude (4.19+/-0.6 vs. 2.15+/-0.3 mV, ratio: 1.95, P<0.01) at a QRS/ST amplitude ratio similar in the two ECG techniques. CONCLUSION: This study provides strong evidence that the ICD-based IT 6-lead ECG would provide a new and efficient means of assessing a patient's daily ischaemic burden.     

Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting

Aims

Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of–function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.

Methods and Results

137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y₁₂ inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient’s informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y₁₂ inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.

Conclusion

The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y₁₂ receptor inhibition.     

Kidney dysfunction and deterioration of ejection fraction pose independent risk factors for mortality in implantable cardioverter-defibrillator recipients for primary prevention

Background:

A growing number of patients with advanced heart failure fulfill a primary‐prevention indication for an implantable cardioverter‐defibrillator (ICD). This study seeks to identify new predictors of overall mortality in a Sudden Cardiac Death in Heart Failure Trial (SCD‐HeFT)‐like collective to enhance risk stratification.

Hypothesis:

An impaired renal function and severely depressed left ventricular ejection fraction pose relevant risk factors for mortality in primary prevention ICD recipients.

Methods:

Ninety‐four consecutive ICD patients with New York Heart Association class II–III heart failure and depressed left ventricular function (left ventricular ejection fraction [LVEF] ≤35%) with no history of malignant ventricular arrhythmias were followed for 34 ± 20 months.

Results:

During this period, 30 patients died (32%). Deceased patients revealed a significantly worse renal function before ICD implantation (1.55 ± 0.7 mg/dL vs 1.1 ± 0.4 mg/dL; P = 0.007), suffered more often from coronary artery disease (53 vs 29; P = 0.006), and were older (69.5 ± 8 y vs 67 ± 12 y; P = 0.0002) than surviving patients. Furthermore, increased serum creatinine at baseline (2 mg/dL vs 1 mg/dL; odds ratio [OR]: 3.96, 95% confidence interval [CI]: 1.2–13.04, P = 0.02), presence of coronary artery disease (OR: 8.6, 95% CI: 1.1–65, P = 0.036), and low LVEF (OR per 5% baseline LVEF deterioration: 1.4, 95% CI: 1–1.8, P = 0.034) represented strong and independent predictors for overall mortality.

Conclusions:

Impaired renal function, the presence of coronary artery disease, and reduced LVEF before implantation represent independent predictors for mortality in a cohort of patients with advanced systolic heart failure. These conditions still bear a high mortality risk, even if ICD implantation effectively prevents sudden arrhythmic death. Indeed, in patients suffering from several of the identified “high‐risk” comorbidities, primary‐prevention ICD implantation might have a limited survival benefit. The possible adverse effects of these comorbidities should be openly discussed with the potential ICD recipient and his or her close relatives. Clin. Cardiol. 2012 doi: 10.1002/clc.22018 The authors have no funding, financial relationships, or conflicts of interest to disclose.