Preoperative imaging of cervical pedicles: comparison of accuracy of oblique radiographs versus axial CT scans

In spite of concerns about safety during their insertion, cervical spine pedicle screws have demonstrated biomechanical superiority over lateral mass screws in several biomechanical studies. One of the concerns for placement of cervical pedicle screws is their small size. Preoperative planning with computed tomography to assess pedicle width has been shown to be extremely accurate and is recommended by several authors. To date there has been no study assessing the accuracy of oblique radiographs for pedicle measurement. We sought to compare accuracy of the oblique radiographic measurements of cervical pedicle width with axial CT scan measurements. Five fresh-frozen human cadaveric cervical spines C3–C7 were studied. Thin cut 1.25 mm computed tomography axial cuts were made through the pedicle isthmus. Oblique radiographs at 35°, 45°, and 55° angles were taken of the right and left pedicles of each specimen using a standardized technique. Each radiograph contained a pin of known length to correct for magnification. All pedicles were again measured and corrected for magnification using the standard pin. Corrected oblique radiograph measurements were compared to CT for each specimen. The outer pedicle width was measured and agreed upon by consensus. The radiograph measurements were on average significantly larger than CT measurements for the pedicles indicating that the pin standard did not completely correct magnification. Plain radiographic data failed to reveal that one oblique angle was favorable to another in terms of magnification or precision. Plain radiographs at oblique angles do not provide accurate measurements of subaxial cervical pedicles at 35°, 45°, or 55° angles. We recommend that thin cut axial CT scans be obtained on all patients prior to transpedicular fixation in the cervical spine. This research was supported by Evanston Northwestern Healthcare Medical Group Orthopaedic Faculty Practice Institutional funds.     

Allogeneic hematopoietic cell transplantation for metastatic breast cancer

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.     

A luminescent bioassay for thyroid blocking antibodies

OBJECTIVE: Thyroid blocking antibodies (TBAb) have a role in the development of hypothyroidism and in the neonate are responsible for transient hypothyroidism. Specific measurement of TBAb requires a bioassay, but current methods are lengthy and cumbersome. We describe a rapid luciferase-based method for the detection of TBAb using the lulu* cell line which is suitable for the provision of a clinical service PATIENTS AND MEASUREMENTS: Chinese hamster ovary (CHO) cells were transfected with human TSH-R together with G418 resistance and a cAMP responsive luciferase construct. Stable pools of transfected cells were selected and clones identified by limiting dilution. Clone lulu* gave the best response to stimulation by TSH and was used to develop a bioassay for TBAb. The luminescent bioassay conditions have been optimized and validated using 12 serum samples from patients found to be TBAb positive in a bioassay using an established method quantifying cAMP by radioimmunoassay (RIA). The effect of thyroid stimulating antibodies (TSAb) on the calculation of Inhibition Index (InI) using two previously described formulae have been investigated and we have used serum containing both TSAb and TBAb to investigate detection of TBAb in samples containing more than one type of activity. RESULTS: Lulu* displays a dose dependent increase in luciferase expression in response to stimulation with bovine (b) TSH which is more effective in serum free medium than in salt free buffer. TSH stimulated luciferase expression can be inhibited by TBAb in either serum or an immunoglobulin preparation. Using optimized assay conditions, challenging 10% serum against 1 U/l bTSH in culture medium, we have tested 31 euthyroid sera to determine a reference range: InI values >23% were considered positive. Twelve samples previously shown to contain TBAb by an established method quantifying cAMP by RIA were positive by the luciferase-based assay. Of control sera, 20/20 systemic lupus erythematosus, 13/14 rheumatoid arthritis, 12/12 multinodular goitre were negative. We demonstrated that if more complex formulae are used to calculate InI, false positive TBAb results can be obtained in samples containing only TSAb. Finally, when sera contain both TSAb and TBAb, the net activity of stimulating and blocking antibodies is detected in the bioassay. Where TSAb are also present, analysis of serum may be required at several dilutions to detect TBAb. CONCLUSIONS: We describe the production of a new cell line, lulu*, and its use to develop a luminescent bioassay for TBAb suitable for clinical use. Comparing two established methods of calculating TBAb, we found that they do not give identical results. In light of this, the high prevalence reported for TBAb in some studies has to be considered with caution.     

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.     

Myeloablative conditioning regimens for AML allografts: 30 years later

During the last three decades, several myeloablative conditioning regimens have been used for AML allografts. In this review, we systematically examine the data from studies reporting on myeloablative conditioning regimens for AML allografts. High-dose busulfan combined with cyclophosphamide (BuCy) and cyclophosphamide in combination with total body irradiation (CyTBI) are the two most commonly used conditioning regimens for AML allografts. From the available data, there are no significant differences in survival with these two regimens. A small benefit of decreased relapse rate with CyTBI is counterbalanced by a nonsignificant increase in treatment-related mortality. The incidence of veno-occlusive disease is significantly higher in patients treated with BuCy. Therapeutic monitoring of busulfan was not reported in any of the studies comparing the regimens. Either of the regimens can be used for AML allografts, and the choice may ultimately depend on local availability and expertise. Further improvements may be possible from modifications of the standard regimens. Data from these latter studies seem to be encouraging, but are not based on comparative randomized trials.     

Transmission of donor illness by stem cell transplantation: should screening be different in older donors?

With increasing donor age, the potential of transmitting diseases from donor to recipient reaches new dimensions. Potentially transmittable diseases from donors include infections, congenital disorders, and acquired illnesses like autoimmune diseases or malignancies of hematological or nonhematological origin. While established nonmalignant or malignant diseases might be easy to discover, early-stage hematological diseases like CML, light-chain multiple myelomas, aleukemic leukemias, occult myelodysplastic syndromes and other malignant and nonmalignant diseases might not be detectable by routine screening but only by invasive, new and/or expensive diagnostic tests. In the following article, we propose recommendations for donor work-up, taking into consideration the age of the donors. In contrast to blood transfusions, stem cells from donors with abnormal findings might still be acceptable for HCT, when no other options are available and life expectancy is limited. This issue is discussed in detail in relation to the available donor and stem cell source. Finally, the recommendations presented here aim at harmonized worldwide work-up for donors to insure high standard quality.     

Diaphragmatic Hernia Masquerading as a Pulmonary Metastasis

Iatrogenic injury accounts for the second most common cause of acquired diaphragmatic hernias after penetrating trauma. An increased incidence of these hernias has been observed with the widespread use of laparoscopic surgery. We present the case of a 65-year-old woman who initially underwent sigmoid resection for an adenocarcinoma and a subsequent liver resection for metastasis. She was noted to have a left lower lobe pulmonary nodule on surveillance computed tomography, for which she underwent a mini-thoracotomy for a planned resection. At the time of surgery, the pulmonary nodule was discovered to be a diaphragmatic hernia, most probably of iatrogenic origin. We discuss the difficulty in diagnosis given her history and the location of such a lesion.