Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

How to define pathologic pelvic floor descent in MR defecography during defecation?

Abdominal Radiology - To assess the extents of pelvic floor descent both during the maximal straining phase and the defecation phase in healthy volunteers and in patients with pelvic floor...     

MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos

BACKGROUNDColorectal cancer (CRC) ranks third in terms of incidence and second in mortality worldwide. In CRC, the silencing of mismatch repair genes, including the mutL homolog 1 (hMLH1) has been linked to microsatellite instability (MSI), the lengthening or shortening of microsatellite repeats. Very limited data have been presented so far on the link of hMLH1 methylation and MSI in Southeast Asia populations with sporadic CRC, and on its clinical significance.AIMTo investigate the significance of the MSI status and hMLH1 methylation in CRC Filipino patients.METHODSFifty-four sporadic CRC patients with complete clinical data were included in this study. Genomic DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting (HRM) analysis using the Bethesda Panel of Markers (BAT25, BAT26, D2S123, D5S346, and D17S250). hMLH1 methylation screening was performed using bisulfite conversion and methylation specific polymerase chain reaction. Statistical analysis was conducted to calculate their associations to clinicopathological characteristics and survival relevance (Kaplan-Meier curves and the log-rank test).RESULTS hMLH1 methylation was observed in 9% and 35% of CRC and normal samples, respectively. Higher incidence of consistently methylated hMLH1 found in both normal and CRC was noticed for relation to location of tumor (P < 0.05). As for MSI status, D2S123 the most common unstable microsatellite and MSI-high (MSI-H) was the most common MSI profile, counted for 46% and 50% of normal and CRC tissues, respectively. The presence of MSI-low (MSI-L) and microsatellite stable (MSS) was 43% and 11% for normal, and 31% and 19% for CRC samples. The mean month of patients’ survival was shorter in patients whose normal and tumor tissues had methylated compared to those with unmethylated hMLH1 and with MSI-H compared to those with MSI-L/MSS (P < 0.05). This was supported by significant difference in Kaplan-Meier with log-rank analysis. This data indicated that hMLH1 methylation and high MSI status have prognostic value.CONCLUSIONThis study showed the clinical significance of hMLH1 methylation and MSI status in sporadic CRC Filipino patients, especially in the normal part of the tumor.     

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

The distribution of hepatitis B virus (HBV) in the populations of island Southeast Asia is of medical and anthropological interest and is associated with an unusually high genetic diversity. This study examined the association of this HBV genetic diversity with the ethnogeography of the populations of the Indonesian archipelago. Whole genome analysis of 21 HBV isolates from East Nusa Tenggara and Papua revealed two recently reported HBV/B subgenotypes unique to the former, B7 (7 isolates) and B8 (5 isolates), and uncovered a further novel subgenotype designated B9 (4 isolates). Further isolates were collected from 419 individuals with defined ethnic backgrounds representing 40 populations. HBV/B was predominant in Austronesian-language-speaking populations, whereas HBV/C was the major genotype in Papua and Papua-influenced populations of Moluccas; HBV/B3 was the predominant subgenotype in the western half of the archipelago (speakers of the Western Malayo-Polynesian [WMP] branch of Austronesian languages), whereas B7, B8 and B9 were specific to Nusa Tenggara (Central Malayo-Polynesian (CMP)). The result provides the first direct evidence that the distribution of HBV genotypes/subgenotypes in the Indonesian archipelago is related to the ethnic origin of its populations and suggests that the HBV distribution is associated with the ancient migratory events in the peopling of the archipelago.     

Quick PTH assay cannot predict incomplete parathyroidectomy in patients with renal hyperparathyroidism

BACKGROUND: Contradictory reports on the value of intraoperative quick parathyroid hormone (PTH) monitoring in renal hyperparathyroidism have been published. METHODS: Thirty-five consecutive patients underwent total parathyroidectomy, central neck dissection, bilateral thymectomy, and immediate autotransplantation. PTH levels were measured by PTH assay at induction of anesthesia (baseline level) and in 5-minute intervals after excision of the last parathyroid gland. Parathyroidectomy was considered "total" in patients with PTH levels <10 pg/mL (subgroup 1), "subtotal" between 10 and 65 pg/mL (subgroup 2) and "insufficient" at >65 pg/mL (subgroup 3) within the first postoperative week. RESULTS: Fifteen minutes after excision of the last gland, PTH levels dropped to 19.4 +/- 15.7% (subgroup 1), 14.9 +/- 5.9% (subgroup 2), and 18 +/- 6.7% (subgroup 3) from baseline among 22 patients on hemodialysis, to 22.1 +/- 18.7% and 17.5% in 9 patients (subgroups 1 and 2) after successful kidney transplantation, and to 10.7% and 17.5% (subgroup 1) and 12.8% and 31.4% (subgroup 2) in 4 patients with reduced renal function after kidney transplantation. CONCLUSIONS: Currently available QPTH assays are not useful to predict insufficient resection of hyperfunctioning parathyroid tissue.     

Multiregional sampling reveals a homogenous distribution of Ki-67 proliferation rate in pituitary adenomas

Summary. Ki-67 antigen is used as a marker of proliferative activity that is linked to growth rate, invasiveness and prognosis of pituitary adenomas. So far the distribution of Ki-67 index within an individual adenoma has not been investigated. If Ki-67 antigen expression differs significantly within an individual pituitary adenoma, a sampling error may result when assessing small fragments of adenoma tissue. Such a potential error would diminish the value of Ki-67 as a tool for postoperative patient management considerations. The aim of the present study was to assess Ki-67 proliferation rates in different regions of pituitary adenomas and to statistically analyse these data for potential regional differences within each tumor.Ki-67 proliferation index was assessed in smear preparations of 100 specimens of 26 consecutive patients operated on for pituitary adenoma in the Department of Neurosurgery, Medical University Vienna. Depending on the size and extent of the tumor, a mean of 4 tissue samples (range 2–8) was selected intraoperatively from each adenoma from endosellar, suprasellar, parasellar, and basal sellar dural locations.Overall mean cell proliferation rate measured by Ki-67 was 1.81±0.90% (range 0.33–3.43%). Histologically invasive adenomas had significantly higher mean Ki-67 proliferation index in all samples from the same tumor than non-invasive adenomas (2.01±0.91% vs. 1.11±0.59%; P=0.024). Multiregional sampling revealed a homogenous distribution of Ki-67 index throughout an individual adenoma with no significant differences between any two different regions on t-test.Our data confirm that location of a biopsy does not influence Ki-67 index. Therefore, Ki-67 index of a single biopsy is representative for the whole individual adenoma. Thus Ki-67 index can be considered a reliable parameter for assessment of cell proliferation rate in adenoma biopsies and may be used for postoperative patient management considerations.     

Maintenance Therapy with 13-cis Retinoid Acid in High-Grade Glioma at Complete Response After First-Line Multimodal Therapy – A Phase-II Study

BACKGROUND: Approximately 5% of patients with malignant glioma achieve complete response (CR) after first-line combined modality treatment. Although these patients will invariably suffer from tumor recurrence, they usually do not receive any further treatment to maintain remission. According to in vitro and in vivo clinical studies, 13-cis retinoic acid (cRA) may be a promising agent for maintenance therapy in these patients. OBJECTIVE: We initiated a clinical study to evaluate the feasibility and toxicity of high-dose cRA as maintenance therapy in patients with high-grade glioma in complete remission after first-line multimodal treatment. METHODS: A prospective single-arm phase-II study in patients with CR after combined first-line therapy (neurosurgery, radio- and chemotherapy) was performed. Patients were treated with cRA at 60 mg/m2 BS from day 1 to 21 in four-weekly cycles with a dose escalation of up to 100 mg/m2 BS until tumor recurrence. Clinical controls were performed every 4 weeks, magnetic resonance imaging every 8 weeks. RESULTS: Twenty-three patients (10, grade IV; 13, grade III) were evaluable using an intention-to-treat analysis. Treatment was well tolerated for up to 149 weeks with moderate dermatological symptoms in all patients. No grade 4 toxicities were observed. Median time to progression was 41 weeks, median overall survival 74 weeks after inclusion in the protocol. DISCUSSION: There is an urgent need for strategies maintaining remission in patients with malignant glioma. Maintenance therapy with high-dose cRA is feasible and well tolerated over long periods of time. A controlled clinical trial to test the efficacy of cRA as a maintenance treatment in malignant glioma is warranted.     

Scapular Notching on Kinematic Simulated Range of Motion After Reverse Shoulder Arthroplasty Is Not the Result of Impingement in Adduction

Impingement after reverse shoulder arthroplasty (RSA) is believed to occur from repetitive contact in adduction between the humeral component and the inferior scapular pillar. The primary purpose of this biomechanical study was to confirm the presence of different types of impingement and to examine which daily-life movements are responsible for them. A secondary aim was to provide recommendations on the type of components that would best minimize notching and loss of range of motion (ROM).The study included 12 fresh frozen shoulder specimens; each had a computed tomography (CT) image of the entire scapula and humerus in order to acquire topological information of the bones before RSA implantation. Cyclic tests were run postimplantation with 3 shoulders in each modalities. To quantify bone loss due to impingement, 3-dimensional anatomical models of the scapula were reconstructed from the CT scans and compared to their intact states.We found 8 bony impingements in 7 specimens: 2 at the lateral acromion, 1 at the inferior acromion, 4 scapular notching, and 1 with the glenoid resulting to wear at the 3:00 to 6:00 clock-face position. Impingements occurred in all kinds of tested motions, except for the internal/external rotation at 90° of abduction. The 3 specimens tested in abduction/adduction presented bone loss on the acromion side only. Scapular notching was noted in flexion/extension and in internal/external rotation at 0° of abduction. The humeral polyethylene liner was worn in 2 specimens—1 at the 6:00 to 8:00 clock-face position during internal/external rotation at 0° of abduction and 1 at the 4:00 clock-face position during flexion/extension.The present study revealed that 2 types of impingement interactions coexist and correspond to a frank abutment or lead to a scapular notching (friction-type impingement). Scapular notching seems to be caused by more movements or combination of movements than previously considered, and in particular by movements of flexion/extension and internal/external rotation with the arm at the side. Polyethylene cups with a notch between 3 and 9 o’clock and lower neck-shaft angle (145° or 135°) may play an important role in postoperative ROM limiting scapular notching.