Differential pattern of response in mood symptoms and suicide risk measures in severely ill depressed patients assigned to citalopram with placebo or citalopram combined with lithium: role of lithium levels

The assumption that antidepressants may reduce suicide risk by reducing depressive symptoms is not based on data. Further, it is unclear if the retrospectively based anti-suicidal effects of lithium can be prospectively evaluated using lithium as an augmenting agent to antidepressants.To verify our hypothesis, we designed and conducted an exploratory proof of concept trial of four weeks duration using a randomized, double-blind, parallel group method. Forty patients were assigned to citalopram + lithium and 40 were assigned to citalopram + placebo. The primary dependent measures were the Sheehan-Suicidality Tracking Scale (S-STS) and the Montgomery-Asberg Depression Rating Scale (MADRS).The reduction of S-STS scores was large (43%) and twice that seen in MADRS scores (25%) among the eighty patients included in the trial. Both response (χ² = 8.8, p < 0.01) and remission (χ² = 4.6, p = 0.03) rates showed similar patterns.There were no significant differences in mean total S-STS change scores among patients assigned to citalopram with placebo (4.8 ± 5.1) and patients assigned to citalopram with lithium (5.1 ± 5.2). When explored further, a subgroup of the patients assigned to citalopram and lithium achieved therapeutic serum levels and had significantly higher S-STS remission rates (45% compared to 19%, p < 0.05).There were no deaths by suicide or other causes indicating that trials enrolling acutely suicidal patients are feasible. These results suggest that citalopram may have a direct therapeutic effect on suicidal thoughts and behaviors. Further, lithium when used in therapeutic doses may augment such effects. These data warrant further exploration of lithium and an antidepressant combination for anti-suicidal effects.     

The evolution of three-dimensional technology in musculoskeletal oncology

Musculoskeletal tumours pose considerable challenges for the orthopaedic surgeon during pre-operative planning, resection and reconstruction. Improvements in imaging technology have improved the diagnostic process of these tumours. Despite this, studies have highlighted the difficulties in achieving consistent resection free margins especially in tumours of the pelvis and spine when using conventional methods. Three-dimensional technology – three-dimensional printing and navigation technology – while relatively new, may have the potential to prove useful in the musculoskeletal tumour surgeon's arsenal. Three-dimensional printing (3DP) allows the production of objects by adding material layer by layer rather than subtraction from raw materials as performed conventionally. High resolution imaging, computer tomography (CT) and magnetic resonance imaging (MRI), are used to print highly complex and accurate items. Powder-based printing, vat polymerization-based printing and droplet-based printing are the common 3DP technologies applied. 3DP has been utilized pre-operatively in surgical planning and intra-operatively for patient specific instruments and custom made prosthesis. Pre-operative 3DP models transfer information to the surgeon in a concise yet exhaustive manner. Patient specific instruments are customized 3DP instruments utilized with the intention to easily replicate surgical plans. Complex musculoskeletal tumours pose reconstructive challenges and standard implants are often unable to reconstruct defects satisfactorily. The ability to use custom materials and tailor the pore size, elastic modulus and porosity of the 3DP prosthesis to be comparable to the patient's bone allows for a potential patient-specific prosthesis with unique incorporation and longevity properties. Similarly, navigation technology utilizes CT or MRI images to provides surgeons with real time intraoperative three-dimensional calibration of instruments. It has been shown to potentially allow surgeons to perform more accurate resections. These technological advancements have the potential to greatly impact the management of musculoskeletal tumours. 3D planning models, patient-specific instruments and customized 3DP implants and navigation should not be thought of as separate, but rather, patient-specific adaptation of relevant modes of application should be selected on a case-by-case basis when taking all unique factors of each case into consideration.