Development of an automated production process of [64Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications

Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [⁶⁴Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy. Various production and radiosynthesis methods of [⁶⁴Cu][Cu (ATSM)] exist in labs, but usually involved non-standardized equipment with varying production qualities and may not be easily implemented in wider hospital settings. [⁶⁴Cu][Cu (ATSM)] was synthesized on a modified GE TRACERlab FXN automated synthesis module. End-of-synthesis (EOS) molar activity of [⁶⁴Cu][Cu (ATSM)] was 2.2–5.5 Ci/μmol (HPLC), 2.2–2.6 Ci/μmol (ATSM-titration), and 3.0–4.4 Ci/μmol (ICP-MS). Radiochemical purity was determined to be >99% based on radio-HPLC. The final product maintained radiochemical purity after 20 h. We demonstrated a simple and feasible process development and quality control protocols for automated cyclotron production and synthesis of [⁶⁴Cu][Cu (ATSM)] based on commercially distributed standardized synthesis modules suitable for PET imaging and theranostic studies.     

Follow-Up Study of Over Three Years of Patients with Uveitis after Cataract Phacoemulsification: Outcomes and Complications

Purpose: To evaluate the rate and onset of intraoperative and postoperative complications post-phacoemulsification. Methods: One hundred sixty-two eyes of 145 patients with uveitis who underwent phacoemulsification between 2006 and 2009 were identified through surgical record review. Fifty-nine eyes of 46 patients met the inclusion criteria. Hazard ratio (HR) and Kaplan-Meier survival probability were calculated for each class of uveitis. Results: Macular edema (ME) resulted to be associated to chronic postoperative inflammation (r?=?0.6; p?=?0.00) and mostly related to patients who presented more than one postoperative relapse/year (r?=?0.2; p?=?0.02). Fuchs uveitis resulted to be a risk factor for posterior capsule opacification (PCO) (HR 3.36 IC95%1.0-10.5; p?=?0.03). Hypotony and elevated intraocular pressure (IOP) were detected in the anterior uveitis group (0.02 EY). Conclusion: The HR to develop ME was significantly related to chronic anterior uveitis. PCO and elevated IOP are most frequent in Fuchs uveitis. The postoperative visual acuity result was good among all the uveitis groups.     

Interpersonal Counseling in the Treatment of Adolescent Depression: A Randomized Controlled Effectiveness and Feasibility Study in School Health and Welfare Services

In order to offer early and accessible treatment for adolescents with depression, brief and effective treatments in adolescents’ everyday surroundings are needed. This randomized controlled trial studied the preliminary effectiveness, feasibility, and acceptability of interpersonal counseling (IPC) and brief psychosocial support (BPS) in school health and welfare services. The study was conducted in the 28 lower secondary schools of a large city in Southern Finland, randomized to provide either IPC or BPS. Help-seeking 12–16-year-old adolescents with mild-to-moderate depression, with and without comorbid anxiety, were included in the study. Fifty-five adolescents received either 6 weekly sessions of IPC or BPS and two follow-up sessions. Outcome measures included self- and clinician-rated measures of depression, global functioning, and psychological distress/well-being. To assess feasibility and acceptability of the treatments, adolescents’ and counselors’ treatment compliance and satisfaction with treatment were assessed. Both treatments were effective in reducing depressive disorders and improving adolescents’ overall functioning and well-being. At post-treatment, in both groups, over 50% of adolescents achieved recovery based on self-report and over 70% based on observer report. Effect sizes for change were medium or large in both groups at post-treatment and increased at 6-month follow-up. A trend indicating greater baseline symptom severity among adolescents treated in the IPC-providing schools was observed. Adolescents and counselors in both groups were satisfied with the treatment, and 89% of the adolescents completed the treatments and follow-ups. This trial suggests that both IPC and BPS are feasible, acceptable, and effective treatments for mild-to-moderate depression in the school setting. In addition, IPC seems effective even if comorbid anxiety exists. Our study shows that brief, structured interventions, such as IPC and BPS, are beneficial in treating mild-to-moderate depression in school settings and can be administered by professionals working at school.

Trial registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT03001245.

     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.