Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents, affecting ~560 young patients in the United States annually. The term OS describes a diverse array of subtypes with varying prognoses, but the majority of tumors are high grade and aggressive. Perhaps because the true etiology of these aggressive tumors remains unknown, advances in OS treatment have reached a discouraging plateau, with only incremental improvements over the past 40 years. Thus, research surrounding the pathogenesis of OS is essential, as it promises to unveil novel therapeutic targets that can attack tumor cells with greater specificity and lower toxicity. Among the candidate molecular targets in OS, the retinoblastoma (RB) pathway demonstrates the highest frequency of inactivation and thus represents a particularly promising avenue for molecular targeted therapy. This review examines the present thinking and practices in OS treatment and specifically highlights the relevance of the RB pathway in osteosarcomagenesis. Through further investigation into RB pathway-related novel therapeutic targets, we believe that a near-term breakthrough in improved OS prognosis is possible.

Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experimental hypoglycemia (2.8 mmol/L) for 120 min. Cardiac vagal baroreflex function was assessed using the modified Oxford method before the initiation of the hypoglycemic-hyperinsulinemic clamp protocol and during the last 30 min of hypoglycemia. During hypoglycemia, compared with baseline euglycemic conditions, 1) baroreflex sensitivity decreases significantly (19.2 ± 7.5 vs. 32.9 ± 16.6 ms/mmHg, P < 0.005), 2) the systolic blood pressure threshold for baroreflex activation increases significantly (the baroreflex function shifts to the right; 120 ± 14 vs. 112 ± 12 mmHg, P < 0.005), and 3) the maximum R-R interval response (1,088 ± 132 vs. 1,496 ± 194 ms, P < 0.001) and maximal range of the R-R interval response (414 ± 128 vs. 817 ± 183 ms, P < 0.001) decrease significantly. These findings indicate reduced vagal control and impaired cardiovascular homeostasis during hypoglycemia.

Background Many surgical procedures have been described for the treatment of thumb carpometacarpal (CMC) joint osteoarthritis, with significant variation. To date, none has proven to be superior. The purpose of this study was to report long-term follow-up results of suture suspension arthroplasty (SSA). Methods The SSA technique uses a single incision, trapeziectomy, and an intra-articular suture suspension sling anchored into the insertions of the flexor carpi radialis (FCR) and abductor pollicis longus (APL), which serves to stabilize the base of the thumb metacarpal, correct subluxation deformity, and maintain arthroplasty space. Ninety of 153 SSA reconstructions (59% recall) were evaluated at long-term follow-up (mean, 12.6 years). Data were analyzed for functional outcomes, including preoperative and postoperative grip and pinch strength, radiographs, complications, and postoperative Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores. Results The mean age at date of surgery was 61.7 ± 7.6 years (82% women). Significant improvement was noted in grip strength (preoperative mean, 25.0 kg; postoperative mean, 28.0 kg; P < .0001), key pinch (preoperative, 4.2 kg; postoperative, 5.1 kg; P < .0001), and tip pinch (preoperative, 2.9 kg; postoperative, 3.6 kg; P < .0001). Radiographic subsidence averaged 35% (0-90). Postoperative QuickDASH scores (mean, 6.6; range, 0-50) revealed good to excellent pain relief and function. One revision was performed, and postoperative FCR rupture occurred in 3 reconstructions. Conclusions The SSA technique for thumb CMC arthritis reconstruction yields good to excellent long-term clinical outcomes. Potential advantages of the SSA include short operative time, a single incision, minimal cost, and no need for tendon harvesting, pin fixation, or implantable hardware.