Cholesterol metabolism in pathogenesis of osteoarthritis disease

Several lines of research indicate that osteoarthritis (OA) is not only a joint disorder associated with mechanical stress and aging but also a ‘metabolic syndrome’ in which several risk factors work together to contribute to disease initiation and/or development. One such metabolic risk factor could be high cholesterol levels in the body. Even though high cholesterol level is a well‐known risk factor for cardiovascular disorders, its possible role in musculoskeletal diseases, particularly OA, is not clear. The authors discuss the fundamental viewpoints on cholesterol involvement in the pathogenesis of OA, stressing the need for understanding the molecular mechanisms behind this association. This is the area of research needed to provide knowledge on how one should live to prevent OA development as well as to suggest new targets for drug therapy.     

A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.     

Intensity-modulated radiotherapy for recurrent and second primary head and neck cancer in previously irradiated territory

Purpose

To evaluate re-irradiation using IMRT for recurrent and second primary head and neck cancer in previously irradiated territory.

Materials and methods

Between 1997 and 2008, 84 patients with recurrent and second primary head and neck cancer were treated with IMRT to a median dose of 69 Gy. Median time interval between initial radiotherapy and re-irradiation was 49.5 (5.2-298.3) months. Salvage surgery preceded re-irradiation in 19 patients; 17 patients received concurrent chemotherapy.

Results

Median follow-up of living patients was 19.8 (1.9-76.1) months. Five-year locoregional control and overall survival were 40% and 20%, respectively. Five-year disease-specific survival and disease-free survival were 29% and 15%, respectively. Stage T4 (p = 0.015), time interval between initial treatment and re-irradiation (p = 0.011) and hypopharyngeal cancer (p = 0.013) were independent prognostic factors for worse overall survival in multivariate analysis. Twenty-six and 11 patients developed Grade ?3 acute and late toxicity, respectively. No Grade 5 acute toxicity was encountered. There were 2 fatal vascular ruptures during follow-up.

Conclusions

High-dose IMRT for recurrent and second primary head and neck cancer in previously irradiated territory leads to ≈20% long-term survival in a non-selected patient population. Identification of patients who would benefit most of curative IMRT is warranted.     

Sirolimus rescue for tacrolimus-associated post-transplant autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) has been reported to occur after renal transplantation, and typically does so in the first few weeks post-transplant. We report on a 3-yr-old child who developed cold AIHA nearly 1 yr after an ABO identical, living donor renal transplant from his mother. Numerous transfusions, pulse steroids, repeat plasma exchange treatments, and IVIG were unsuccessful. Nearly 3 wk into his illness, tacrolimus was changed to cyclosporine, and then to sirolimus, and resulted in a prompt response. He currently has a normal renal function and a normal hemoglobin level on sirolimus monotherapy.     

Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies

Since its introduction more than a decade ago, intensity-modulated radiotherapy (IMRT) has spread to most radiotherapy departments worldwide for a wide range of indications. The technique has been rapidly implemented, despite an incomplete understanding of its advantages and weaknesses, the challenges of IMRT planning, delivery, and quality assurance, and the substantially increased cost compared with non-IMRT. Many publications discuss the theoretical advantages of IMRT dose distributions. However, the key question is whether the use of IMRT can be exploited to obtain a clinically relevant advantage over non-modulated external-beam radiation techniques. To investigate which level of evidence supports the routine use of IMRT for various disease sites, we did a review of clinical studies that reported on overall survival, disease-specific survival, quality of life, treatment-induced toxicity, or surrogate endpoints. This review shows evidence of reduced toxicity for various tumour sites by use of IMRT. The findings regarding local control and overall survival are generally inconclusive.     

Primitive neuroectodermal tumor of the sternum in a child: resection and reconstruction

Pediatric primary malignancies of the sternum are rare. They represent less than 1% of all bone tumors. Primitive neuroectodermal tumor of the chest wall or Askin's tumor is more often seen in the ribs than in the sternum. Surgical treatment involves resection of the tumor followed by primary reconstruction. We report the case of a 16-year-old adolescent boy who was diagnosed to have primitive neuroectodermal tumor of the sternum and underwent resection with primary reconstruction of the anterior chest wall. We describe for the first time the use of a 2-mm Gore-Tex Dualmesh plus biomaterial (W.L. Gore and Associates, Flagstaff, Ariz) and locking mandibular multiperforated titanium plates with screws (Stryker-Leibinger, Freiburg, Germany) for primary sternal reconstruction in a child. Despite having a wide resection, he did not require postoperative ventilation and had an uncomplicated recovery. The reconstructed chest wall has a normal contour with normal pulmonary physiology.