Pitfalls in MR morphology of the sterno-costo-clavicular region using whole-body MRI.

AIM: To analyse the imaging findings at the sterno-costo-clavicular (SCC) joint region using whole-body (WB) magnetic resonance imaging (MRI) in healthy individuals to minimize misinterpretation as changes due to spondyloarthritis (SpA). MATERIALS AND METHODS: As part of a cross-sectional study of 122 SpA patients, 75 healthy individuals (42/33 males/females; median age 30.3 years; range 17.7-63.8 years) were scanned using sagittal and coronal WB short tau inversion recovery (STIR) and T1-weighted MRI sequences. The SCC region was analysed independently by seven readers for bone marrow oedema (BMO), erosions, subchondral fat signal intensity (FSI), and joint fluid accumulation. RESULTS: SCC changes simulating inflammation were reported by four or more of the seven readers in 15 (20%) healthy individuals (12 male/three female; median age 32.1 years; range 20.2-48 years). Thirteen individuals (17%) had changes at the manubriosternal joint (MSJ); five had BMO, one BMO + erosion, four erosion, two erosion + FSI, and one FSI only. Changes at the sternoclavicular joint occurred in three individuals (4%) encompassing erosion, erosion + FSI + BMO, and joint fluid accumulation, respectively. One patient had both MSJ and sternoclavicular joint changes. CONCLUSIONS: Findings mimicking inflammatory changes occurred in healthy individuals, particularly in the MSJ. Awareness of this is important in recognition of SCC inflammation in SpA.

Frequency and risk factors of lower limb lymphedema following lymphadenectomy in patients with gynecological malignancies.

OBJECTIVE: Lower limb lymphedema (LLL) is a major cause of morbidity in patients with gynecological malignancies after surgical treatment involving lymph node (LN) dissection. The aim of this study was to estimate the prevalence of LLL in such patients and detect risk factors for its occurrence. MATERIALS AND METHODS: A retrospective analysis of all patients undergoing lymphadenectomy in newly-diagnosed gynecological malignancies at the University Hospital of Zurich between 2000 and 2007 was performed. Data from 313 patients were collected. Twenty patients with pre-existing edema or missing information were excluded before analysis. Time-to-LLL was estimated using the Kaplan-Meier estimate and potential risk factors were evaluated by a Cox regression model. RESULTS: Estimated prevalence of LLL one year after surgery was 32%, increasing to 58% eight years after surgery. Median time to diagnosis of LLL was 5.2 years. The number of removed lymph nodes was significantly associated with time-to-LLL. Diagnosis of postoperative lymphocysts and local infections were accompanied by a significantly elevated risk for the development of LLL. Furthermore, time-to-LLL decreased with a higher body mass index (BMI) of the patient. In contrast, chemo- and radiotherapy, age, positive LNs, site of lymphadenectomy, and type of cancer were not observed to be associated with the occurrence of LLL. CONCLUSIONS: LLL is a frequent postoperative complication in patients undergoing lymphadenectomy for gynecological malignancies. It is thus imperative to sufficiently educate patients about the risk and symptoms of LLL prior to surgery. The data clearly show an association between time-to-LLL and number of dissected LNs, stressing the need to prospectively analyze the prevalence of LLL and carefully plan LN sampling as increasing knowledge is gained regarding the therapeutic benefit of sentinel and systemic lymphadenectomy in patients with different stages of gynecological malignancies.

Does increased tumor burden of sentinel nodes in breast cancer affect detection procedure?

Numerous studies have shown that sentinel lymph node biopsy (SLN) has a high level of detection sensitivity. Successful detection procedure depends on the amount of radioactivity and accumulation of blue dye in the SN. Our aim was to relate the differences observed in intraoperative SN presentation to tumor burden, characteristics of the primary tumor and patient attributes. Our retrospective analysis included 369 patients undergoing SLN in the Department of Gynecology of the University Hospital of Zurich within five years. Data was collected from the patients (age, BMI), the primary tumor (size, grading, hormone receptors, HER2 status) and the SNs removed (counts per second [cps], blue dye, size of nodular metastasis, extracapsular involvement, number of SNs excised). Because patients typically had more than one SN, a linear mixed-effects model was used to account for the clustering within one patient. SNs presented with significantly lower radioactivity in elderly (-1.8%/year, p < 0.001) and obese patients (-3.9%/kg/m2, p = 0.006) as well as in G3 primary tumors (p = 0.002). Radiocolloid accumulation decreased with increasing metastasis size (-6.1%/mm, p = 0.006). In conclusion the detection procedure of SNs is mainly affected by the patient's age and BMI and by nodular metastasis' size. Phagocytotic activity in the lymph node may increase radiotracer accumulation, showing the highest tracer signals in micrometastatic SNs. In large SN metastasis the lymph flow appears obstructed, reducing the axillary drainage and therefore making detection procedure difficult.

On the effectiveness of treatment options in epistaxis: an analysis of 678 interventions.

BACKGROUND: Epistaxis represents one of the most common emergencies in ENT clinics around the world. It creates great physical and emotional stress to the patient as well as a financial burden on health-care systems. A lot of research has been performed with regard to aetiology and possible treatment, however, not much effort has been put into analysing the effectiveness of common treatment forms. It is the objective of this study to clarify which of these treatment forms is reliable. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: 2b. METHODS: Between 03/2007 and 04/2008, all epistaxis therapies including relapses and treatment failures at the University Hospital of Zurich have been documented using a computerised questionnaire. Different treatments were compared to each other. RESULTS: An analysis of 678 interventions in 537 patients was performed with emphasis on failure proportions and time to occurrence. The estimated failure proportions of coagulation in anterior epistaxis accounts for 14%. Successful treatment of epistaxis in posterior bleedings could be achieved in 62% by packing and in 97% by surgery with a statistically significant difference between the respective groups. CONCLUSION: Using our treatment options, anterior epistaxis can be cured reliably by cauterisation. Surgical therapies in posterior bleedings are able to successfully salvage failed packing therapies.

Radiological changes and signs of osteoarthritis in the fingers of male performance sport climbers.

AIM: The aim of this study was to investigate the radiological changes and signs of osteoarthritis in the fingers of performance sport climbers that felt to be from acute mechanical stress placed on the fingers and intense training regime over years. METHODS: A total of 31 male sport climbers who were either strong rock climbers or former members of the Swiss climbing team, and 67 non-climbers participated in the study. Fisher's exact test was used to compare the proportions of signs of osteoarthritis between climbers and non-climbers. For the evaluation of radiological changes, antero-posterior and lateral radiographs were taken of both hands. Distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints of the fingers Dig. II-V on the antero-posterior radiographs were scored for signs of osteoarthritis using an atlas (Altman) method. Osteophytes at the DIP and PIP joints were also evaluated on lateral radiographs and compared to the findings on the antero-posterior radiographs. RESULTS: According to the Kellgren-Lawrence method, 6 out of 31 climbers had evidence of clear signs of osteoarthritis in the fingers, whereas none of the non-climbers developed any signs of osteoarthritis (P≤0.001). Twenty-three climbers had definite signs of osteophytosis using antero-posterior radiographs compared to 31 climbers using lateral radiographs. Lateral radiographs have shown to be more accurate in finding, localizing and rating of osteophytes than antero-posterior radiographs. CONCLUSION: Male climbers have more signs of osteoarthritis compared to male non-climbers at similar age. Development of osteophytes seems to be ordinary in every climber. Lateral radiographs are more accurate in diagnosing osteophytes in climbers than using traditional antero-posterior radiographs.

A score regression approach to assess calibration of continuous probabilistic predictions.

Calibration, the statistical consistency of forecast distributions and the observations, is a central requirement for probabilistic predictions. Calibration of continuous forecasts is typically assessed using the probability integral transform histogram. In this article, we propose significance tests based on scoring rules to assess calibration of continuous predictive distributions. For an ideal normal forecast we derive the first two moments of two commonly used scoring rules: the logarithmic and the continuous ranked probability score. This naturally leads to the construction of two unconditional tests for normal predictions. More generally, we propose a novel score regression approach, where the individual scores are regressed on suitable functions of the predictive variance. This conditional approach is applicable even for certain nonnormal predictions based on the Dawid-Sebastiani score. Two case studies illustrate that the score regression approach has typically more power in detecting miscalibrated forecasts than the other approaches considered, including a recently proposed technique based on conditional exceedance probability curves.

Randomized clinical trial comparing venous cutdown with the Seldinger technique for placement of implantable venous access ports.

BACKGROUND: The aim of this randomized controlled study was to compare the primary success rate between venous cutdown and the Seldinger technique for placement of the totally implantable venous access port (TIVAP). METHODS: A total of 152 patients were randomized to receive TIVAP placement by either venous cutdown or the Seldinger technique. The main endpoint was the primary success rate. Secondary endpoints included overall success rate, procedure time and perioperative complication rates. Multiple logistic regression analysis was undertaken to assess the influence of different variables on primary success. RESULTS: The primary success rate was 71 per cent for venous cutdown and 90 per cent for the Seldinger technique (P = 0.007). The mean procedure time was significantly shorter for the Seldinger technique (48.9 versus 64.8 min; P < 0.001). The overall success rate was 97.4 per cent. The rate of perioperative complications was similar for the two approaches (5 per cent), but was higher when a procedure was converted. The variables sex, body mass index, implantation side and surgeon experience had no impact on the primary success rate. CONCLUSION: The Seldinger technique was more effective and quicker than venous cutdown, and should be regarded as the method of choice for TIVAP placement. REGISTRATION NUMBER: NCT00272623 (http://www.clinicaltrials.gov).

Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease.

A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.

Quality of analgesic treatment in patients with advanced prostate cancer: do we do a better job now? The Swiss Group for Clinical Cancer Research (SAKK) experience.

GOALS OF WORK: The aim of this study was to evaluate pain intensity and the application of the WHO guidelines for cancer pain treatment in patients with prostate cancer treated at Swiss cancer centers. MATERIALS AND METHODS: We analyzed a series of five multicenter phase II clinical trials which examined the palliative effect of different chemotherapies in patients with advanced hormone-refractory prostate carcinoma. Of 170 patients, 1,018 visits were evaluable for our purpose, including ratings of pain intensity by patients and prescribed analgesics. MAIN RESULTS: No or mild pain was indicated by patients in 36 to 55% of the visits, more than mild pain in 30 to 46%. In 21% of the visits, the WHO pain treatment criteria (treatment according to one of the three steps; oral, rectal or transdermal application of the main dose; administration on a regular schedule) were fulfilled, and the Cleeland index was positive according to all recommendations. In 6% of the visits, neither the WHO criteria were fulfilled nor was the Cleeland index positive. This indicates insufficient pain treatment not following the WHO guidelines and that the prescribed analgesics were not sufficiently potent for the rated pain intensity. CONCLUSIONS: In this selective Swiss sample, the standard of analgesic treatment is high. However, there is still scope for improvement. This cannot solely be solved by improving the knowledge of the physicians. Programs to change the patients' attitude towards cancer pain, training to improve the physicians' communication skills, and institutional changes may be promising strategies.

Endocrine symptom assessment in women with breast cancer: what a simple "yes" means.

GOALS OF WORK: To investigate the self-reported symptoms related to endocrine therapy in women with early or advanced breast cancer and the impact of these symptoms on quality of life (QL) indicators. MATERIALS AND METHODS: Symptom occurrence was assessed by the Checklist for Patients on Endocrine Therapy (C-PET) and symptom intensity was assessed by linear analogue self-assessment (LASA) indicators. Patients also responded to global LASA indicators for physical well-being, mood, coping effort and treatment burden. Associations between symptoms and these indicators were analysed by linear regression models. MAIN RESULTS: Among 373 women, the distribution of symptom intensity showed considerable variation in patients reporting a symptom as present. Even though patients recorded a symptom as absent, some patients reported having experienced that symptom when responding to symptom intensity, as seen for decreased sex drive, tiredness and vaginal dryness. Six of 13 symptoms and lower age had a detrimental impact on the global indicators, particularly tiredness and irritability. CONCLUSIONS: Patients' experience of endocrine symptoms needs to be considered both in patient care and research, when interpreting the association between symptoms and QL.

Protein synthesis in jejunum and liver of neonatal calves fed vitamin A and lactoferrin.

Rates of protein synthesis (PS) and turnover are more rapid during the neonatal period than during any other stage of postnatal life. Vitamin A and lactoferrin (Lf) can stimulate PS in neonates. However, newborn calves are vitamin A deficient and have a low Lf status, but plasma vitamin A and Lf levels increase rapidly after ingestion of colostrum. Neonatal calves (n = 6 per group) were fed colostrum or a milk-based formula without or with vitamin A, Lf, or vitamin A plus Lf to study PS in the jejunum and liver. l-[(13)C]Valine was intravenously administered to determine isotopic enrichment of free (nonprotein-bound) Val (AP(Free)) in the protein precursor pool, atom percentage excess (APE) of protein-bound Val, fractional protein synthesis rate (FSR) in the jejunum and liver, and isotopic enrichment of Val in plasma (APE(Pla)) and in the CO(2) of exhaled air (APE(Ex)). The APE, AP(Free), and FSR in the jejunum and liver did not differ significantly among groups. The APE(Ex) increased, whereas APE(Pla) decreased over time, but there were no group differences. Correlations were calculated between FSR(Jej) and histomorphometrical and histochemical data of the jejunum, and between FSR(Liv) and blood metabolites. There were negative correlations between FSR(Liv) and plasma albumin concentrations and between FSR(Jej) and the ratio of villus height:crypt depth, and there was a positive correlation between FSR(Jej) and small intestinal cell proliferation in crypts. Hence, there were no effects of vitamin A and Lf and no interactions between vitamin A and Lf on intestinal and hepatic PS. However, FSR(Jej) was correlated with histomorphometrical traits of the jejunum and FSR(Liv) was correlated with plasma albumin concentrations.

Single agent rituximab in patients with follicular or mantle cell lymphoma: clinical and biological factors that are predictive of response and event-free survival as well as the effect of rituximab on the immune system: a study of the Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: Predictive factors of rituximab efficacy and its effect on the immune system are still not defined. PATIENTS AND METHODS: Three hundred and six patients with follicular or mantle cell lymphoma received four weekly doses of rituximab (induction) and no further treatment (arm A) or four more doses at 2-month intervals (arm B). RESULTS: Response rate to induction was 44%. Independent predictive factors for response were disease bulk <5 cm, follicular histology, normal hemoglobin and low lymphocyte count. Factors associated with event-free survival (EFS) were having responded to induction, having received not more than one line of therapy, Ann Arbor stage I-III, high lymphocyte count, disease bulk <5 cm, Fc-gamma receptor genotype VV and receiving prolonged treatment. B cells were suppressed by treatment but recovered after a median of 12 months in arm A and 18 months in arm B. The median IgM level after 1 year was normal in arm A but was decreased to 73% of baseline in arm B. We observed 24 serious adverse events, equally distributed between arms. Ten patients receiving induction only and six patients receiving prolonged treatment developed a second tumor. CONCLUSIONS: We defined the characteristics predicting response and EFS to rituximab. Prolonged treatment results in longer EFS at the cost of a longer reduction in B cell and IgM levels, but without additional clinical toxicity.