The Clinical Utility of 18F-Fluciclovine PET/CT in Biochemically Recurrent Prostate Cancer: an Academic Center Experience Post FDA Approval.

PURPOSE: To evaluate the diagnostic performance and clinical utility of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). METHODS: 18F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging (18F-NaF PET/CT (n = 12), 68Ga-PSMA11 PET/CT (n = 5), 18F-DCFPyL PET/CT (n = 20), and 68Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated. RESULTS: The overall positivity rate of 18F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA < 0.5), 50 % (0.5 ≤ PSA < 1), 56 % (1 ≤ PSA < 2), 68 % (2 ≤ PSA < 5), and 94 % (PSA ≥ 5), respectively. One hundred and two patients (62 %) had changes in clinical management based on 18F-fluciclovine PET findings. Twelve of these patients (12 %) had lesion localization on 18F-fluciclovine PET, despite negative conventional imaging. Treatment plans of 14 patients with negative 18F-fluciclovine PET were changed based on additional PET imaging with a different radiopharmaceutical. CONCLUSION: 18F-Fluciclovine PET/CT remains a useful diagnostic tool in the workup of patients with BCR PC, changing clinical management in 62 % of participants in our cohort.

Prospective Evaluation of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer in an Academic Center: A Focus on Disease Localization and Changes in Management.

18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52-91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18F-fluciclovine PET/CT (18), or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results:18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with 18F-DCFPyL, whereas 18F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or 18F-NaF PET scans were congruent with 18F-DCFPyL PET, whereas 18F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or 18F-NaF PET scans. In 8 of 18 (44%) patients, 18F-fluciclovine PET had located the same lesions as did 18F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative 18F-fluciclovine findings had positive 18F-DCFPyL PET findings and 1 of 18 (6%) patients with negative 18F-DCFPyL findings had uptake in the prostate bed on 18F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, 18F-DCFPyL and 18F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative results on conventional imaging. Conclusion:18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration-approved currently available imaging modalities and its impact on clinical management in 60% of patients.

Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer.

Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.

Assessing the Efficacy of Prothrombin Complex Concentrate in Multiply Injured Patients With High-Energy Pelvic and Extremity Fractures.

OBJECTIVES: Prothrombin complex concentrate (PCC) is being increasingly used for reversing induced coagulopathy of trauma. However, the use of PCC for reversing coagulopathy in multiply injured patients with pelvic and/or lower extremity fractures remains unclear. The aim of our study was to assess the efficacy of PCC for reversing coagulopathy in this group of patients. DESIGN: Two-year retrospective analysis. SETTING: Our level I trauma center. PATIENTS/PARTICIPANTS: All coagulopathic [International normalized ratio (INR) ≥1.5] trauma patients. Patients with femur, tibia, or pelvic fracture were included. Patients were divided into 2 groups: PCC (single dose) and fresh frozen plasma (FFP). Patients in the 2 groups were matched using propensity score matching. MAIN OUTCOME MEASUREMENTS: Time to correction of INR, time to intervention, development of thromboembolic complications, mortality, and cost of therapy. RESULTS: A total of 81 patients (PCC: 27, FFP: 54) were included. Patients who received PCC had faster correction of INR and shorter time to surgical intervention in comparison to patients who received FFP. PCC therapy was also associated with lower overall blood product requirement (P = 0.02) and lower transfusion costs (P = 0.0001). CONCLUSIONS: In a matched cohort of multiply injured patients with pelvic and/or lower extremity fractures, administration of a single dose of PCC significantly reduced the time to correction of INR and time to intervention compared with patients who received FFP therapy. This may allow orthopaedic surgeons to more safely proceed with early, definitive fixation strategies. LEVEL OF EVIDENCE: Therapeutic level III. See Instructions for Authors for a complete description of levels of evidence.

Web Page Content and Quality Assessed for Shoulder Replacement.

The Internet has become a major source for obtaining health-related information. This study assesses and compares the quality of information available online for shoulder replacement using medical (total shoulder arthroplasty [TSA]) and nontechnical (shoulder replacement [SR]) terminology. Three evaluators reviewed 90 websites for each search term across 3 search engines (Google, Yahoo, and Bing). Websites were grouped into categories, identified as commercial or noncommercial, and evaluated with the DISCERN questionnaire. Total shoulder arthroplasty provided 53 unique sites compared to 38 websites for SR. Of the 53 TSA websites, 30% were health professional-oriented websites versus 18% of SR websites. Shoulder replacement websites provided more patient-oriented information at 48%, versus 45% of TSA websites. In total, SR websites provided 47% (42/90) noncommercial websites, with the highest number seen in Yahoo, compared with TSA at 37% (33/90), with Google providing 13 of the 33 websites (39%). Using the nonmedical terminology with Yahoo's search engine returned the most noncommercial and patient-oriented websites. However, the quality of information found online was highly variable, with most websites being unreliable and incomplete, regardless of search term.

Developmental nicotine exposure enhances inhibitory synaptic transmission in motor neurons and interneurons critical for normal breathing.

Nicotine exposure in utero negatively affects neuronal growth, differentiation, and synaptogenesis. We used rhythmic brainstems slices and immunohistochemistry to determine how developmental nicotine exposure (DNE) alters inhibitory neurotransmission in two regions essential to normal breathing, the hypoglossal motor nucleus (XIIn), and preBötzinger complex (preBötC). We microinjected glycine or muscimol (GABAA agonist) into the XIIn or preBötC of rhythmic brainstem slices from neonatal rats while recording from XII nerve roots to obtain XII motoneuron population activity. Injection of glycine or muscimol into the XIIn reduced XII nerve burst amplitude, while injection into the preBötC altered nerve burst frequency. These responses were exaggerated in preparations from DNE animals. Quantitative immunohistochemistry revealed a significantly higher GABAA receptor density on XII motoneurons from DNE pups. There were no differences in GABAA receptor density in the preBötC, and there were no differences in glycine receptor expression in either region. Nicotine, in the absence of other chemicals in tobacco smoke, alters normal development of brainstem circuits that are critical for normal breathing.

Early thromboembolic prophylaxis in patients with blunt solid abdominal organ injuries undergoing nonoperative management: is it safe?

BACKGROUND: The aim of this study was to compare the safety of early (≤48 hours), intermediate (48 to 72 hours), and late (≥72 hours) venous thromboembolism prophylaxis in patients with blunt abdominal solid organ injury managed nonoperatively. METHODS: We performed a 6-year (2006 to 2011) retrospective review of all trauma patients with blunt abdominal solid organ injuries. Patients were matched using propensity score matching in a 2:1:1 (early:intermediate:late) for age, gender, systolic blood pressure, Glasgow Coma Scale, Injury Severity Score, and type and grade of organs injured. Our primary outcome measures were: hemorrhage complications and need for intervention (operative intervention and/or angioembolization). RESULTS: A total of 116 patients (58 early, 29 intermediate, and 29 late) were included. There were no differences in age (P = .5), Injury Severity Score (P = .6), type (P = .1), and grade of injury of the organ (P = .6) between the 3 groups. There were 67 liver (43.2%), 63 spleen (40.6%), 49 kidney (31.6%), and 24 multiple solid organ (15.4%) injuries. There was no difference in operative intervention (P = .8) and postprophylaxis blood transfusion (P = .3) between the 3 groups. CONCLUSIONS: Early enoxaparin-based anticoagulation may be a safe option in trauma patients with blunt solid organ injury. This study showed no significant correlation between early anticoagulation and development of bleeding complications.

Developmental nicotine exposure alters AMPA neurotransmission in the hypoglossal motor nucleus and pre-Botzinger complex of neonatal rats.

Developmental nicotine exposure (DNE) impacts central respiratory control in neonates born to smoking mothers. We previously showed that DNE enhances the respiratory motor response to bath application of AMPA to the brainstem, although it was unclear which brainstem respiratory neurons mediated these effects (Pilarski and Fregosi, 2009). Here we examine how DNE influences AMPA-type glutamatergic neurotransmission in the pre-Bötzinger complex (pre-BötC) and the hypoglossal motor nucleus (XIIMN), which are neuronal populations located in the medulla that are necessary for normal breathing. Using rhythmic brainstem slices from neonatal rats, we microinjected AMPA into the pre-BötC or the XIIMN while recording from XII nerve rootlets (XIIn) as an index of respiratory motor output. DNE increased the duration of tonic activity and reduced rhythmic burst amplitude after AMPA microinjection into the XIIMN. Also, DNE led to an increase in respiratory burst frequency after AMPA injection into the pre-BötC. Whole-cell patch-clamp recordings of XII motoneurons showed that DNE increased motoneuron excitability but did not change inward currents. Immunohistochemical studies indicate that DNE reduced the expression of glutamate receptor subunits 2 and 3 (GluR2/3) in the XIIMN and the pre-BötC. Our data show that DNE alters AMPAergic synaptic transmission in both the XIIMN and pre-BötC, although the mechanism by which this occurs is unclear. We suggest that the DNE-induced reduction in GluR2/3 may represent an attempt to compensate for increased cell excitability, consistent with mechanisms underlying homeostatic plasticity.