Trabecular Bone Score and Hip Structural Analysis in Patients With Atypical Femur Fractures

Bisphosphonate use has declined dramatically in recent years, partly because of fear of rare side effects like atypical femur fractures (AFFs). It is therefore desirable to have a diagnostic method to identify those at risk of AFF to prevent this serious complication. We compared trabecular microarchitecture and hip geometry between 30 patients with AFF and 141 controls of similar age and sex, using bisphosphonates. Trabecular bone score (TBS) and hip structural analysis (HSA) were used to assess trabecular microarchitecture and macroscopic hip geometry from dual-energy X-ray absorptiometry images of the lumbar spine and hip, respectively. General characteristics, TBS, and HSA were compared between patients with AFF and controls using Student's t tests and chi-square statistics. Associations between AFF and TBS and femur geometric characteristics by HSA were adjusted for sex, age, height, weight, ethnicity, duration of bisphosphonate use, and glucocorticoid use. Additionally, the analysis of TBS was adjusted for lumbar spine bone mineral density and the time difference between dual-energy X-ray absorptiometry scanning and the diagnosis of AFF. Patients with AFF had significantly higher body mass index than controls, had used bisphosphonates longer, and glucocorticoids and proton pump inhibitors more frequently. Sex-specific T-score was significantly higher in patients with AFF at the lumbar spine (p?=?0.004), but not at the femoral neck (p?=?0.190) after adjustment for age, height, and weight. TBS did not differ significantly between patients with AFF and controls. Neither neck shaft angle nor any geometric variables at the femoral shaft measured by HSA differed between patients with AFF and controls. At the narrow neck, patients with AFF had lower buckling ratio and higher centroid position, consistent with a lower risk of classical fragility hip fractures. The findings at narrow neck and higher bone mineral density might be explained by the fact that the majority of patients with AFF used bisphosphonates to prevent glucocorticoid-induced osteoporosis. Based on our results, TBS and HSA do not appear to have value in detecting patients at risk of AFF.     

The role of complete surgical resection in stage IV neuroblastoma

The purpose of this study was to examine the outcome of attempted radical surgical resection in patients with stage IV neuroblastoma. Between 1989 and 2003, 20 (median age 2.4 years, range 0.5–8.7 years) children with stage IV neuroblastoma were treated at the Department of Pediatrics. Surgery was performed in 7 consecutive children (6 male and 1 female) between July 1997 and February 2002 at the Department of Urology in Bonn. Mean age at diagnosis was 57 months (21–104 months). Mean age at the time of surgery was 54 months (8–390 months). Follow-up was available for all patients (100%) and mean follow-up after the operation was 32.5 months (4–56 months). Primary localization of the tumor was retroperitoneal in all cases; 4 out of 7 patients (57%) also had additional adrenal, 3 out of 7 (42%) paraganglion and 1 out of 7 (14%) thoracic primaries. Bone marrow and lymph node metastases were found in all patients (100%). Surgery led to complete tumor resection in 6 out of 7 patients (85%). Surgical approach was abdominal (chevron incision) in 6 out of 7 (85%) of the patients, in one patient the approach was thoraco-abdominal. After induction chemotherapy and delayed surgery, 6 out of 7 (86%) patients showed a complete remission (CR) and the mean CR lasted for about 27.7 months (range 3.1–55.4 months). At the last time of follow-up 5 out of 7 (71%) patients were alive, 2 had died due to recurrent disease. Mean time to recurrent disease was 24 and 51 months, respectively. Mean overall survival time since diagnosis was 38.3 months (11–64 months) and mean event-free survival was 34.5 months (11–60.3 months). The final outcome, overall survival and event-free survival time was influenced by metastatic or local relapse. Tumor resection is beneficial but the value of surgery can only be judged when we are able to control metastatic disease in stage IV neuroblastoma. The final outcome may rely on the extent of complete surgical resection, but is also related to treatment of metastases. A longer follow-up period is indicated to detect long term outcome.     

The impact of surgical excision in chest wall rhabdomyosarcoma: a report from the Children's Oncology Group

Aims

Rhabdomyosarcoma (RMS) is the most common soft tissue tumor of childhood. Patient age, size, histologic finding, and site of the tumor are primary determinants of prognosis in RMS. Chest wall RMS is a site in which the limitations of surgical excision are realized. We aim to determine the impact of surgical excision in chest wall RMS.

Methods

A retrospective chart review was conducted of all 130 pediatric patients enrolled in the Intergroup Rhabdomyosarcoma Study (IRS) with chest wall rhabdomyosarcoma from the first (I) through fourth (IV) IRS with follow-up to June 2005. Median follow-up was 12.1 years (4.6-27.2 years).

Results

There was a significant improvement in failure-free survival (FFS) and overall survival (OS) between the first IRS study, I, and IRS-IV. The estimated FFS and OS at 5 years in IRS I was 30% and 40%, respectively, compared to 68% and 78%, respectively, in IRS-IV (P = .03 and P = .05, respectively). There was no association between histologic finding or size and FFS or OS. However, all patients who presented without metastasis had an FFS and OS of 49% and 61%, respectively, compared with metastatic patients, 7% and 7%, respectively (P < .001). Five-year FFS of group I, II, and III patients was 52%, 52%, and 45%, respectively, and OS was 65%, 60%, and 59%, respectively. There was no significant difference in 5-year FFS or OS in patients who had a complete resection (group I), complete resection with positive microscopic margins (group II), or biopsy or partial resection only (group III). In groups I to III patients, the local and regional failure rate at 5 years is 25% and 6%, respectively.

Conclusions

The most significant impact on outcome in chest wall RMS patients is metastatic disease at diagnosis. The locoregional failure rate is high but does not appear to impact survival. Alternative treatment strategies are needed for chest wall RMS, but aggressive surgical excision may not be necessary.     

Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991-2000)

BACKGROUND: There is concern about the rising prevalence of type 2 diabetes mellitus and of the resultant nephropathy. This study uses data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry to provide information on the epidemiology and outcome of renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetic nephropathy (DN). METHODS: Data from the following 10 registries: Austria, French-speaking Belgium, Denmark, Finland, Greece, Norway, Scotland (UK), Catalonia (Spain), Sweden, and The Netherlands were combined. Average annual changes (%) were estimated by Poisson regression. Analyses of mortality were performed by Cox regression. RESULTS: An increase in patients with type 2 DN entering RRT has been observed (+11.9% annually, P < 0.05), while large differences in RRT incidence in this disease continue to exist between countries in Europe. There was a reduction in mortality during the first 2 years on dialysis therapy among patients with type 2 DN (AHR 0.96, 95%CI 0.94-0.97 annually). The mortality among transplant recipients decreased for both type 1 DN and nondiabetic ESRD (non DN) within the 1995-1998 cohort (type 1 DN: AHR 0.49, 95% CI 0.35-0.68; non DN: AHR 0.79, 95% CI 0.69-0.90) compared to the 1991-1994 cohort. CONCLUSION: This report has shown that during the last decade there has been a marked increase in the incidence of RRT for type 2 DN. Survival analysis showed that over the period 1991-1999 the mortality rates of all dialysis patients and of type 1 diabetic and nondiabetic renal transplant recipients have fallen.     

Sentence intelligibility in noise for listeners with normal hearing and hearing impairment: influence of measurement procedure and masking parameters

Speech intelligibility measurements strongly depend on several procedural parameters. In order to obtain comparable results from different test procedures, these parameters must be investigated as to which should be standardized and which could be set freely. This study investigates the influence of noise level, noise type, and presentation mode on speech reception thresholds (SRTs), and intelligibility function slopes in noise for normal-hearing and hearing-impaired subjects. The noise presentation level had no significant influence on either SRTs or slope values, provided that the presentation level exceeded hearing threshold. Two stationary, speech-shaped noises produced identical results. Speech-simulating fluctuating noise yielded about 14 dB lower SRTs for normal-hearing subjects and about 10 dB lower SRTs for 20% of the heating-impaired subjects. Of the hearing-impaired subjects, 30% did not benefit from the modulations and showed similar SRTs as for stationary noise. Using continuous noise yielded lower SRTs compared to gated noise. However, the difference between the results in continuous and gated noise was not significant for the hearing-impaired subjects. A presentation level of 65 dB SPL (normal-hearing subjects) or 80 dB SPL (hearing-impaired subjects) and an interfering noise with a spectrum similar to the mean long-term average speech spectrum (LTASS) is suggested for comparable adaptive measurement procedures. A fluctuating, speech-shaped noise is recommended to differentiate between subjects.     

Phototherapy and photochemotherapy of sclerosing skin diseases

The treatment of sclerosing skin diseases [systemic sclerosis, localized scleroderma, lichen sclerosus et atrophicus, sclerodermoid graft-vs.-host disease, scleredema adultorum (Buschke), scleromyxedema and necrobiosis lipoidica] is difficult and remains a great challenge. Numerous treatments, some with potentially hazardous side effects, are currently used with only limited success. The introduction of phototherapy and photochemotherapy for sclerosing skin diseases has considerably enriched the therapeutic panel and proven useful in a number of sclerosing skin diseases especially in localized scleroderma. Two phototherapeutic modalitites are used for the treatment of sclerosing skin diseases, long-wave ultraviolet A and psoralen plus ultraviolet A (PUVA). This article reviews current knowledge about the application of phototherapy and photochemotherapy to various sclerosing skin disorders.     

Cosmetic results of histographically controlled excision of non‐melanoma skin cancer in the head and neck region

Background: Beside the primary goal of complete eradication, the cosmetic result is an important aspect of the treatment of non‐melanoma skin tumors especially in the head and neck region. Patients and Methods: From 1990 to 2000, we treated a total of 5,227 large basal cell carcinomas (BBC) and 1,189 squamous cell carcinomas (SCC) in the head and neck region by surgical excision in 4,239 inpatients at the Department of Dermatology, University of Tübingen. The procedure used in all patients was a conservative excision controlled by complete three dimensional histology of all margins (3D‐histology) and specifically targeted follow‐up surgery where required (histographic surgery). As part of the prospective tumor follow‐up, we asked the treating outdoor physician one and four years later to evaluate the results of our surgical procedures. Results: Of the 5,565 follow‐up questionnaires sent back, 4,868 contained answers regarding the cosmetic result. The data from both answers were pooled. In 1,972 (40,5 %) patients the cosmetic result was evaluated as “excellent”, in 1,992 (40,9 %) as “good”, in 662 (13,6 %) as “satisfactory”, in 191 (3,9 %) as “mediocre” and in 51 (< 1,0 %) as “poor”. In 697 of the responses, the physician did not comment the cosmetic results or the patient was lost for follow up. Conclusion: With respect to both long term safety and cosmetic outcome, tumor surgery with 3D‐histology of excisional margins has set very high quality standards in the treatment of non‐melanoma skin cancer of the head and neck area.     

The M1/M4 preferring muscarinic agonist xanomeline modulates functional connectivity and NMDAR antagonist-induced changes in the mouse brain

Cholinergic drugs acting at M1/M4 muscarinic receptors hold promise for the treatment of symptoms associated with brain disorders characterized by cognitive impairment, mood disturbances, or psychosis, such as Alzheimer’s disease or schizophrenia. However, the brain-wide functional substrates engaged by muscarinic agonists remain poorly understood. Here we used a combination of pharmacological fMRI (phMRI), resting-state fMRI (rsfMRI), and resting-state quantitative EEG (qEEG) to investigate the effects of a behaviorally active dose of the M1/M4-preferring muscarinic agonist xanomeline on brain functional activity in the rodent brain. We investigated both the effects of xanomeline per se and its modulatory effects on signals elicited by the NMDA-receptor antagonists phencyclidine (PCP) and ketamine. We found that xanomeline induces robust and widespread BOLD signal phMRI amplitude increases and decreased high-frequency qEEG spectral activity. rsfMRI mapping in the mouse revealed that xanomeline robustly decreased neocortical and striatal connectivity but induces focal increases in functional connectivity within the nucleus accumbens and basal forebrain. Notably, xanomeline pre-administration robustly attenuated both the cortico-limbic phMRI response and the fronto-hippocampal hyper-connectivity induced by PCP, enhanced PCP-modulated functional connectivity locally within the nucleus accumbens and basal forebrain, and reversed the gamma and high-frequency qEEG power increases induced by ketamine. Collectively, these results show that xanomeline robustly induces both cholinergic-like neocortical activation and desynchronization of functional networks in the mammalian brain. These effects could serve as a translatable biomarker for future clinical investigations of muscarinic agents, and bear mechanistic relevance for the putative therapeutic effect of these class of compounds in brain disorders.Subject terms: Schizophrenia, Translational research, Preclinical research