Correction to: The Effect of Rifampin on the Pharmacokinetics and Safety of Lorlatinib: Results of a Phase One, Open-Label, Crossover Study in Healthy Participants.

In the original article, the reference 4 has been published and cited incorrectly.

GLUT1 expression in high-risk prostate cancer: correlation with 18F-FDG-PET/CT and clinical outcome.

BACKGROUND: Tumour 18F-FDG-uptake is of prognostic value in high-risk and metastatic prostate cancer (PCa). The aim of this study is to investigate the underlying glucose metabolism mechanisms of 18F-FDG-uptake on PET/CT imaging in PCa. METHODS: Retrospective analysis was conducted for 94 patients diagnosed with a Gleason sum ≥8 adenocarcinoma of the prostate at biopsy between July 2011 and July 2014 who underwent 18F-FDG-PET/CT imaging before radical prostatectomy (RP). 18F-FDG-uptake in primary lesion was measured by a blinded reader using maximum standardised uptake value (SUVmax). GLUT1, GLUT12 and HK2 expression were blindly scored after immunohistochemistry on specimens RP by three pathologists. Correlations between GLUT1, GLUT12 and HK2, and SUVmax were assessed using Spearman's rank correlation test. Survival probabilities were based on the Kaplan-Meier method. RESULTS: With a median follow-up of 4.5 years, 56% (n = 53) of patients had biochemical recurrence (BCR), 7% (n = 7) progressed to castration-resistant prostate cancer (CRPC) disease, 13% (n = 12) developed metastasis and 6% (n = 6) died. Correlation was found between GLUT1 expression and SUVmax level (r = 0.25, p = 0.02). In addition, SUVmax was significantly higher in tumours with high GLUT1 expression (n = 17, 5.74 ± 1.67) than tumours with low GLUT1 expression (n = 71, 2.68 ± 0.31, p = 0.004). Moreover, a significant association was found between GLUT1 expression levels and SUVmax level (p = 0.005), lymph node status (p = 0.05), volume of cancer (p = 0.01), CRPC disease progression (p = 0.02) and metastasis development (p = 0.04). No significant difference between GLUT12 and HEX2 expression and SUVmax have been found. CONCLUSIONS: GLUT1 expression in PCa tumours correlates with 18F-FDG-uptake and poor prognostic factors. These results suggest that this transporter is involved in the molecular mechanism of 18F-FDG-uptake in high-risk PCa and raise interest in targeting metabolic dependencies of PCa cells as a selective anticancer strategy.

Efficacy of different cerclage suture materials in reducing preterm birth.

Objective: To compare the efficacy of monofilament suture, braided polyester thread, and 5 mm tape suture in reducing preterm birth (PTB).Study design: Women who received a cerclage at Touro Infirmary, New Orleans, LA, USA, between 1 January, 2011 and 31 December, 2016 were identified using ICD-9/10 codes. All charts were reviewed for demographic and obstetrical variables including gestational age (GA) at delivery.Results: Of 145 women who received a cerclage, 36 were excluded due to incomplete charts leaving 109 for analysis. There was no significant difference in gestational age at cerclage placement or delivery among women with monofilament, braided, or 5 mm tape cerclages (p = .936 and p = .919, respectively) nor was there a difference in the proportion who delivered at ≥32, 34, or 37 weeks across groups with differing cerclage material (p = .270, p = .275, and p = .419, respectively). There was no difference in GA at delivery for patients who received 17-OHP compared to those who did not (p = .362). There were also no differences with respect to birth outcomes such as birthweight (p = .938), Apgar scores (p = .477, p = .430) or neonatal intensive care admission rates (NICU) (p = .304). Analysis revealed no difference in characteristics between groups including history of PTB or indication for removal (p = .371, p = .317).Conclusion: We found no difference in pregnancy prolongation when comparing different suture material used for indicated cerclages. We also found no differences with respect to rates of maternal infection or adverse neonatal outcomes among groups.RationaleThis study was conducted to evaluate the efficacy of different suture materials in increasing gestational age at delivery and reducing preterm birth.

The Effect of Rifampin on the Pharmacokinetics and Safety of Lorlatinib: Results of a Phase One, Open-Label, Crossover Study in Healthy Participants.

INTRODUCTION: Lorlatinib is a third-generation tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer; cytochrome P450 (CYP) 3A plays an important role in the metabolism of lorlatinib. METHODS: This phase 1, open-label, two-period, crossover study estimated the effect of oral rifampin (a strong CYP3A inducer) on the pharmacokinetics and safety of oral lorlatinib (NCT02804399). Healthy participants received single-dose lorlatinib 100 mg in period 1 followed by rifampin 600 mg/day (days 1-12) and single-dose lorlatinib 100 mg (day 8) in period 2. Blood samples were collected for 120 h after each dose of lorlatinib. RESULTS: When a single dose of lorlatinib was administered during daily dosing with rifampin (period 2), the area under the plasma concentration-time profile extrapolated to infinity (AUCinf) and maximum plasma concentration (Cmax) of lorlatinib were 14.74% [90% confidence interval (CI) 12.78%, 17.01%] and 23.88% (90% CI 21.58%, 26.43%), respectively, of those in period 1 (lorlatinib alone). A single dose of lorlatinib was well tolerated in period 1, but elevations in transaminase values were observed in all participants (grade 2-4 in 11 participants) within 1-3 days after a single dose of lorlatinib was administered with ongoing rifampin in period 2. Rifampin dosing was therefore halted. Transaminase levels subsequently returned to normal (median time to recovery: 15 days). No elevations in bilirubin were observed. CONCLUSIONS: The addition of a single dose of lorlatinib to daily dosing with rifampin significantly reduced lorlatinib plasma exposure relative to a single dose of lorlatinib administered alone and was associated with severe but self-limiting transaminase elevations in all healthy participants. These observations support the contraindication in the product label against concomitant use of lorlatinib with all strong CYP3A inducers. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02804399.

Increased Prostate Cancer Glucose Metabolism Detected by 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Localised Gleason 8-10 Prostate Cancers Identifies Very High-risk Patients for Early Recurrence and Resistance to Castration.

BACKGROUND: The accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to stage prostate cancer (PCa) is limited. However, Gleason 8-10 PCa and more aggressive metastatic PCa have been shown to exhibit a higher glycolytic activity. OBJECTIVE: To evaluate the potential of intraprostatic FDG uptake to prognose Gleason 8-10 PCa patients prior to prostatectomy, based on tumour intrinsic biology. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET/CT and a bone scan were performed as a staging procedure prior to prostatectomy in 148 consecutive patients diagnosed with PCa with a Gleason sum of ≥8 at biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The FDG-PET/CT images were blind reviewed. Lymph node (LN) metastasis and intraprostatic FDG uptake were systematically recorded, and correlated with the patients' clinicopathological characteristics. RESULTS AND LIMITATIONS: FDG-PET/CT detected foci of intraprostatic FDG uptake in 66% of patients. An intraprostatic FDG uptake of maximum intraprostatic standardised uptake value (SUVmax) of ≥4.6 was statistically significantly associated with a higher pathological Gleason ≥8, extracapsular extension, seminal vesicle invasion, and pathological LN metastasis. In multivariate analysis, an intraprostatic SUVmax of ≥4.6 was associated with a two-fold increased risk of biochemical recurrence in the year following surgery. Patients with an intraprostatic SUVmax of ≥4.6 had estimated median biochemical recurrence-free survival (BFS) of 11.3mo compared with 49.5mo for those with a lower SUVmax. Finally, high intraprostatic FDG uptake was associated with shorter time to castration resistance following radical prostatectomy (RP). CONCLUSIONS: Preoperative intraprostatic FDG uptake is an integrator of adverse pathological prognostic factors, predicting BFS and castration resistance following RP in patients with a Gleason score ≥8 PCa at biopsy. These results support the use of preoperative FDG-PET/CT as a tool to distinguish at diagnosis very high-risk Gleason 8-10 PCa patients in whom novel neoadjuvant or adjuvant therapies should be explored. PATIENT SUMMARY: This study shows that an increased use of glucose by prostate cancer cells detected by 18F-fluorodeoxyglucose positron emission tomography molecular imaging can identify aggressive prostate cancers.

The use of urodynamic studies for the followup of neurogenic bladders treated with onabotulinumtoxinA.

INTRODUCTION: Intradetrusor injection of onabotulinumtoxinA (BoNTA) is well-established as treatment for patients with neurogenic bladders. Urodynamics (UDS) is used at regular intervals during followup to monitor intravesical pressure. With regards to the discomfort and risks associated with UDS, our objective was to assess if UDS done at regular intervals in the followup of neurogenic bladders treated with BoNTA had an impact on management. METHODS: We retrospectively analyzed the medical records of adult patients with neurological disorders treated with BoNTA for either detrusor overactivity or low bladder compliance at the Institut de Réadaptation en Déficience Physique de Québec (IRDPQ). At our centre, UDS was routinely performed at baseline, three months after the first treatment, then three months after every fifth set of injections. RESULTS: We identified 57 patients with neurological disorder treated with intravesical BoNTA. Each patient had between one and 19 sets of injections (mean 5.61 injections) and 1-6 followup UDS (mean 2.09). Of the 119 followup UDS reviewed at our centre, three UDS (2.5%) resulted in a modification of the urinary tract management from BoNTA to bladder augmentation. Two regimens were suspended and one was ended due to patient preference. CONCLUSIONS: Our study showed that UDS at pre-set intervals for followup of patients receiving BoNTA injections were rarely associated with modifications in the treatment course. Therefore, UDS should only be performed in cases where there are changes in the patient's symptoms or if the urologist suspects that the treatment response is suboptimal.

Metabolic Imaging of Prostate Cancer Reveals Intrapatient Intermetastasis Response Heterogeneity to Systemic Therapy.

Although intrapatient heterogeneity of prostate cancer (PCa) has recently been characterized via genomic and transcriptomic studies, the heterogeneity of systemic treatment responses has yet to be reported or imaged. Our objective was to evaluate the intrapatient intermetastasis response to systemic treatment among patients with metastatic PCa. We evaluated the metabolic response for each individual metastatic lesion (n=165) in 15 patients with metastatic PCa who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before and at least 3 mo after initiation of a systemic therapy that did not change in that period. Intermetastasis heterogeneity was defined as opposite metabolic responses for at least two metastases from the same compartment (bone or soft tissue) between the two time points. We found intrapatient intermetastasis response heterogeneity in 40% of the cases in our retrospective series. Our results suggest that systemic therapies can induce heterogeneous responses among individual metastases in patients with PCa, supporting the polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be useful in identifying clinical resistance early after therapy initiation and could also allow targeted biopsy of resistant clones for molecular analysis. PATIENT SUMMARY: Systemic therapies can lead to heterogeneous responses in individual metastases of prostate cancer in a patient. Molecular imaging may be useful for identifying heterogeneity and could allow targeted biopsy for molecular analysis or therapy.

Anticholinergic use in children: Persistence and patterns of therapy.

INTRODUCTION: Overactive bladder (OAB) symptoms are complex and generally require long-term therapy. Nevertheless, it has been demonstrated that persistence rates of antimuscarinic drug use are low in adults. Better understanding of the treatment patterns of children treated with antimuscarinics could help to improve drug management. Our objective was to evaluate persistence rates of patients under 20 years of age on antimuscarinic therapy over a four-year period. METHODS: Patients having received a first-ever antimuscarinic drug prescription between April 2007 and March 2008 were identified using IMS Brogan's Public and Private Drug Plans database. Canadian drug claims data from Private Drug Plans, Régie de l'Assurance Maladie du Québec, and Ontario Public Drug Plans were analyzed retrospectively. Patients were followed for four years to assess the prescribed drugs, the lines of treatment, and the duration of each treatment. RESULTS: Data were available for 374 patients. The most prescribed drug as a first-line therapy was oxybutynin (87.2%), followed by tolterodine LA (5.9%). Patients refilled their index prescriptions for an average of 429 days. Solifenacin had the highest mean duration of index therapy (765 days). The median number of antimuscarinics prescribed was one. At the end of the followup, 44 patients were still on therapy. Reasons for discontinuation of treatment were not available. CONCLUSIONS: Overall discontinuation rate of antimuscarinic therapy in children is comparable to what has been reported in adult patients with OAB. However, children seem to persist on the medication for a longer duration before adherence rates start declining. The low rate of persistence highlights the need to identify the reasons for discontinuation of therapy in children in order to obtain better persistence rates.

Intrascrotal extratesticular schwannoma: A first pediatric case.

Scrotal nerve sheath tumours unassociated with neurofibromatosis or schwannomatosis are extremely rare. Very few cases of benign intrascrotal and extratesticular schwannomas have been reported, but none of them occurred in childhood. This current report describes for the first time a case of benign intrascrotal extratesticular solitary schwannoma in a 16-year-old male.