Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose.Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis. Paired baseline and on-treatment skin and tumor biopsy samples were collected for PD analyses.Results: Eighty patients with chemotherapy-refractory solid tumors were enrolled. One dose-limiting toxicity was noted, but a maximum-tolerated dose was not identified. Grade 1 to 3 hyperglycemia, responsive to metformin, occurred in 15 (19%) patients. At dose levels or more than 5 mg/kg, dalotuzumab mean terminal half-life was 95 hours or more, mean C min was more than 25 mg/mL, clearance was constant, and serum exposures were approximately dose proportional. Decreases in tumor IGF-1R, downstream receptor signaling, and Ki67 expression were observed.18 F-Fluorodeoxy-glucose positron emission tomography metabolic responses occurred in three patients. One patient with Ewing's sarcoma showed a mixed radiologic response. The recommended phase II doses were 10, 20, and 30 mg/kg for the weekly, every other week, and every third week schedules, respectively. Conclusions: Dalotuzumab was generally well-tolerated, exhibited dose-proportional PK, inhibited IGF-1R pathway signaling and cell proliferation in treated tumors, and showed clinical activity. The low clearance rate and long terminal half-life support more extended dosing intervals.

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Background Performance of point-of-care tests in different clinical scenarios and on different samples remains undetermined. We comprehensively evaluated the performance of the nasopharyngeal Panbio COVID-19 antigen Rapid-Test-Device. Method Prospective study including consecutive patients attending three primary care centers (PCC) and an emergency department. The antigen test was performed at point-of-care in nasopharyngeal and nasal swabs, and in saliva. Positive and negative percent agreement (PPA, NPA) were calculated with the RT-PCR assay as reference standard. Results Of 913 patients included, 296 (32.3%) were asymptomatic and 690 (75.6%) came from the PCC. Nasopharyngeal swabs were collected from 913, nasal swabs from 659, and saliva from 611 patients. RT-PCR was positive in 196 (21.5%) nasopharyngeal samples (NPS). Overall PPA (95% CI) in NPS was 60.5% (53.3-67.4), and it was lower in nasal swabs (44.7%) and saliva (23.1%). Test performance in NPS was largely dependent on the cycle threshold (Ct) in RT-PCR, with PPA of 94% for Ct≤25 and 80% for Ct<30. In symptomatic patients, the PPA was 95% for Ct≤25; 85% for Ct<30, and 89% for the symptom triad of fever, cough and malaise. Performance was also dependent on age, with PPA of 100% in symptomatic patients >50 years with Ct<25. In asymptomatic patients, the PPA was 86% for Ct<25. In all cases, NPA was 100%. Conclusion The nasopharyngeal Panbio COVID-19 antigen test performed at point-of-care has a good sensitivity in symptomatic patients with Ct<30 and older age. The test was useful to identify asymptomatic patients with lower Ct values.

We report a case of successful percutaneous treatment of a congenital splenic cyst using alcohol as the sclerosing agent. A 14-year-old female adolescent presented with a nonsymptomatic cystic mass located in the spleen that was believed to be congenital. After ultrasonography, a drainage catheter was placed in the cavity. About 250 ml of serous liquid was extracted and sent for microbiologic and pathologic studies to rule out an infectious or malignant origin. Immediately afterwards, complete drainage and local sclerotherapy with alcohol was performed. This therapy was repeated 8 days later, after having observed 60 ml of fluid in the drainage bag. One year after treatment the cyst has practically disappeared. We believe that treatment of splenic cyst with percutaneous puncture, ethanolization, and drainage is a valid option and it does not rule out surgery if the conservative treatment fails.

BackgroundPerformance of point-of-care tests in clinical practice remains undetermined. We aimed to evaluate the performance of the nasopharyngeal Panbio COVID-19 antigen Rapid Test Device in real-life conditions in different clinical scenarios.MethodProspective study conducted in three primary care centers (PCC) and an emergency department. The antigen test was performed at point-of-care in nasopharyngeal and nasal swabs, and in saliva. Positive and negative percent agreement (PPA, NPA) were calculated with the RT-PCR assay as reference standard.ResultsOf 913 patients included, 296 (32.3%) were asymptomatic and 690 (75.6%) came from the PCC. Nasopharyngeal swabs were collected from 913, nasal swabs from 659, and saliva from 611 patients. RT-PCR was positive in 196 (21.5%) nasopharyngeal samples (NPS). Overall PPA (95% CI) in NPS was 60.5% (53.3-67.4), and it was lower in nasal swabs (44.7%) and saliva (23.1%). Test performance in NPS was largely dependent on the cycle threshold (Ct) in RT-PCR, with PPA>90% for Ct≤25 and ≥80% for Ct<30. In symptomatic patients, the PPA was 95% for Ct≤25; ≥85% for Ct<30, and 89% for the symptom triad of fever, cough and malaise. Performance was also dependent on age, with PPA of 100% in symptomatic patients >50 years with Ct<25. In asymptomatic patients, the PPA was 86% for Ct<25. In all cases, NPA was 100%.ConclusionThe nasopharyngeal Panbio COVID-19 antigen test performed at point-of-care is highly sensitive in symptomatic patients, particularly with Ct<30 and older age. The test was useful to identify asymptomatic patients with lower Ct values and therefore with contagious risk.Key pointsThe nasopharyngeal Panbio-COVID-19 antigen test performed in real-life conditions at point-of-care is highly sensitive in symptomatic patients, particularly with Ct<30 and older age. The test is useful to identify asymptomatic patients with lower Ct values and therefore with contagious risk.