Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60-89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03045406","term_id":"NCT03045406"}}NCT03045406.     

First imaging results of an intraindividual comparison of 11C-acetate and 18F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy

Purpose

¹⁸F-Fluorocholine (FCH) and ¹¹C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers.

Methods

The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤5 ng/ml) or RP and salvage RT (9 patients, PSA ≤5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307?±?16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994?±?72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results.

Results

PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen’s kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later.

Conclusion

Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.     

Clinical Situations in Which the Diagnosis of Autism is Debatable: An Analysis and Recommendations

The “autism spectrum disorder” (ASD) construct and its current diagnostic criteria have led to the inclusion of increasingly heterogeneous and decreasingly atypical individuals under its definition. This broad category, based on the polymorphic clinical expression of common genetic variants underpinning the risk of autism, is likely beneficial for certain individuals. However, determining the boundaries between ASD and typical individuals, as well as those with other neurodevelopmental conditions, remains an issue of which the importance is growing with the increase in ASD prevalence. We identified four clinical contexts associated with a questionable, poorly justified, or unhelpful ASD diagnosis: (1) those in which diagnostic instruments raise uncertainties, (2) in the context of a subclinical presentation, (3) when early autistic signs tend to fade away during development, and (4) when comorbidities are prominent. We argue that in certain cases, a diagnosis of ASD may not be the most suitable, timely, or helpful medical act and provide recommendations for clinical practice when facing such situations.     

Short-term perioperative outcomes after robot-assisted and laparoscopic distal pancreatectomy

Robotic surgery offers potential technical advantages that may facilitate pancreatic resection. The aim of this study was to evaluate the learning curve and short-term perioperative outcomes in patients who underwent laparoscopic and robot-assisted distal pancreatectomy. All perioperative variables were evaluated and compared retrospectively between laparoscopic (LDP) (n = 23) and robot-assisted (RDP) (n = 11) distal pancreatectomy. The mean total operative time was shorter in LDP (194 vs. 225 min; p = 0.017). All other perioperative criteria were similar between LDP and RDP patients (blood loss, transfusion rate, conversion, pancreatic fistula, postoperative morbidity, and duration of hospitalization). Non-adjusted CUSUM curve for composite events including operative time, conversion, postoperative morbidity and reoperation rates showed that the RDP learning curve corresponded to the first seven consecutive patients. During early experience, RDP was associated with longer operative time but similar short-term perioperative outcomes compared to conventional distal pancreatectomy.     

Targeting Jab1/CSN5 in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated head and neck cancer that is most common in eastern Asia. Epstein-Barr virus infection, environmental factors, and genetic susceptibility play important roles in NPC pathogenesis. Jab1/CSN5 is a multifunctional protein that participates in affecting integrin signaling, controlling cell proliferation and apoptosis, and regulating genomic instability and DNA repair. Correlation of Jab1/CSN5 overexpression with poor prognosis for NPC provides evidence that it is involved in the tumorigenic process. In this review, we highlight recent advances in studies of the oncogenic role of Jab1/CSN5 in NPC and its potential as a therapeutic target for this cancer.     

Arthroscopic posterior bone block: surgical technique

Posterior glenohumeral instability remains a difficult problem. There are still many controversies regarding surgical treatment, due to a lack of understanding the pathomechanical issues leading to posterior instability. This article presents a new arthroscopic technique of posterior bone block augmentation, which we found to be effective, repeatable and successful. This technique can be used for combined soft tissue and bony defects as well as for revisions after previous soft tissue reconstructions.