Assessment of the healing of conservatively-treated scaphoid fractures using HR-pQCT.

Improving the clinical outcome of scaphoid fractures may benefit from adequate monitoring of their healing in order to for example identify complications such as scaphoid nonunion at an early stage and to adjust the treatment strategy accordingly. However, quantitative assessment of the healing process is limited with current imaging modalities. In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for the first time to assess the changes in bone density, microarchitecture, and strength during the healing of conservatively-treated scaphoid fractures. Thirteen patients with a scaphoid fracture (all confirmed on HR-pQCT and eleven on CT) received an HR-pQCT scan at baseline and three, six, twelve, and 26 weeks after first presentation at the emergency department. Bone mineral density (BMD) and trabecular microarchitecture of the scaphoid bone were quantified, and failure load (FL) was estimated using micro-finite element analysis. Longitudinal changes were evaluated with linear mixed-effects models. Data of two patients were excluded due to surgical intervention after the twelve-week follow-up visit. In the eleven fully evaluable patients, the fracture line became more apparent at 3 weeks. At 6 weeks, individual trabeculae at the fracture region became more difficult to identify and distinguish from neighboring trabeculae, and this phenomenon concerned a larger region around the fracture line at 12 weeks. Quantitative assessment showed that BMD and FL were significantly lower than baseline at all follow-up visits with the largest change from baseline at 6 weeks (-13.6% and - 23.7%, respectively). BMD remained unchanged thereafter, while FL increased. Trabecular thickness decreased significantly from baseline at three (-3.9%), six (-6.7%), and twelve (-4.4%) weeks and trabecular number at six (-4.5%), twelve (-7.3%), and 26 (-7.9%) weeks. Trabecular separation was significantly higher than baseline at six (+13.3%), twelve (+19.7%), and 26 (+16.3%) weeks. To conclude, this explorative HR-pQCT study showed a substantial decrease in scaphoid BMD, Tb.Th, and FL during the first 6 weeks of healing of conservatively-treated scaphoid fractures, followed by stabilization or increase in these parameters. At 26 weeks, BMD, trabecular microarchitecture, and FL were not returned to baseline values.

Improved Detection of Scaphoid Fractures with High-Resolution Peripheral Quantitative CT Compared with Conventional CT.

BACKGROUND: Computed tomography (CT), magnetic resonance imaging, and bone scintigraphy are second-line imaging techniques that are frequently used for the evaluation of patients with a clinically suspected scaphoid fracture. However, as a result of varying diagnostic performance results, no true reference standard exists for scaphoid fracture diagnosis. We hypothesized that the use of high-resolution peripheral quantitative CT (HR-pQCT) in patients with a clinically suspected scaphoid fracture could improve scaphoid fracture detection compared with conventional CT in the clinical setting. METHODS: The present study included 91 consecutive patients (≥18 years of age) who presented to the emergency department with a clinically suspected scaphoid fracture between December 2017 and October 2018. All patients were clinically reassessed within 14 days after first presentation, followed by CT and HR-pQCT. If a scaphoid fracture was present, the fracture type was determined according to the Herbert classification system and correlation between CT and HR-pQCT was estimated with use of the Kendall W statistic or coefficient of concordance (W) (the closer to 1, the higher the correlation). RESULTS: The cohort included 45 men and 46 women with a median age of 52 years (interquartile range, 29 to 67 years). HR-pQCT revealed a scaphoid fracture in 24 patients (26%), whereas CT revealed a scaphoid fracture in 15 patients (16%). Patients with a scaphoid fracture were younger and more often male. The correlation between CT and HR-pQCT was high for scaphoid fracture type according to the Herbert classification system (W = 0.793; 95% confidence interval [CI], 0.57 to 0.91; p < 0.001) and very high for scaphoid fracture location (W = 0.955; 95%, CI 0.90 to 0.98; p < 0.001). CONCLUSIONS: In the present study, the number of patients diagnosed with a scaphoid fracture was 60% higher when using HR-pQCT as compared with CT. These findings imply that a substantial proportion of fractures-in this study, more than one-third-will be missed by the current application of CT scanning in patients with a clinically suspected scaphoid fracture. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Ciprofloxacin is used as antimicrobial prophylaxis in pediatric acute lymphoblastic leukemia (ALL) to decrease infections with gram-negative bacteria. However, there are no clear guidelines concerning prophylactic dose. AIMS: To determine the pharmacokinetics and pharmacodynamics (PKPD) of ciprofloxacin prophylaxis in a pediatric ALL population. The effect of patient characteristics and antileukemic treatment on ciprofloxacin exposure, the area under the concentration time curve over minimal inhibitory concentration (AUC24/MIC) ratios, and emergence of resistance were studied. METHODS: A total of 615 samples from 129 children (0-18 years) with ALL were collected in a multicenter prospective study. A population pharmacokinetic model was developed. Microbiological cultures were collected prior to and during prophylaxis. An AUC24/MIC of ≥125 was defined as target ratio. RESULTS: A 1-compartment model with zero-order absorption and allometric scaling best described the data. No significant (P < .01) covariates remained after backward elimination and no effect of asparaginase or azoles were found. Ciprofloxacin AUC24 was 16.9 mg*h/L in the prednisone prophase versus 29.3 mg*h/L with concomitant chemotherapy. Overall, 100%, 81%, and 18% of patients at, respectively, MIC of 0.063, 0.125, and 0.25 mg/L achieved AUC24/MIC ≥ 125. In 13% of the patients, resistant bacteria were found during prophylactic treatment. CONCLUSION: Ciprofloxacin exposure shows an almost 2-fold change throughout the treatment of pediatric ALL. Depending on the appropriateness of 125 as target ratio, therapeutic drug monitoring or dose adjustments might be indicated for less susceptible bacteria starting from ≥ 0.125 mg/L to prevent the emergence of resistance and reach required targets for efficacy.

Incidence of arcuate line hernia in patients with abdominal complaints: radiological and clinical features.

INTRODUCTION: Acute abdominal complaints are a frequent cause for consultation in the emergency department, with a large differential diagnosis. One cause is arcuate line herniation, but this entity is little known and rarely considered during initial analysis. The incidence of arcuate line herniation in this population is unknown. METHODS: A retrospective cohort study was performed. All patients who presented to the emergency department for surgical consultation during an 18-month period with abdominal complaints in who no diagnosis was found after analysis, and who had computed tomography imaging of the abdomen were included. CT scans were reviewed with a focus on abdominal wall pathology and correlated with clinical features. RESULTS: Eight hundred and ten patients presented with abdominal complaints, 415 of these had CT scans available for review and were included in the study. In 47 patients (11.3%), an arcuate line anomaly was found, and in 14 patients (3.4%), a frank arcuate line herniation (grades 2 or 3) was found. Retrospective correlation with clinical complaints was found in 50% of these patients. Patients with arcuate line hernia had a significantly higher BMI, and diabetes mellitus and aortic aneurysm were more prevalent in these patients. CONCLUSION: Arcuate line herniation has a higher incidence than previously thought in patients with acute abdominal complaints and should be considered when evaluating these patients.

Locally advanced rectal cancer: is diffusion weighted MRI helpful for the identification of complete responders (ypT0N0) after neoadjuvant chemoradiation therapy?

OBJECTIVES: To determine retrospectively the additional value of DWI-MRI toT2-MRI for predicting complete response (ypT0N0 = CR) after chemoradiation-therapy (CRT) in locally advanced rectal cancer. METHODS: Seventy locally advanced rectal cancer patients underwent CRT followed by restaging MRI and resection. Two readers with different experience levels independently scored T2 images for CR and, in a second reading, combined T2 and DWI. A 5-point confidence-level score was used to generate ROC curves. Areas under the ROC curves (AUC) and interobserver agreement were compared for both readings. Histology served as reference standard. RESULTS: The interobserver agreement increased after addition of DWI from 0.35 to 0.58 but the AUC improved only for the experienced reader (0.77 to 0.89, p = 0.005 vs. 0.74 to 0.70, p > 0.05). Sensitivity and NPV improved from 20-30 % to 40-70 %, respectively 88 % to 91-95 %. Specificity and PPV improved only for the experienced reader (87 to 93 % respectively 27 to 63 %). CONCLUSION: Adding DWI to T2-MRI improves consistency between readers and has potential to improve readers' accuracy dependent on his/her experience. DWI could be of additional value, particularly in ruling out CR (high NPV), but considering the sub-optimal PPV one should be cautious about relying solely on MRI for the clinical decision to offer a wait-and-see strategy.

Assessment of residual tumour by FDG-PET: conventional imaging and clinical examination following primary chemotherapy of large and locally advanced breast cancer.

BACKGROUND: The aim of this was to evaluate FDG-PET (2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography) for assessment of residual tumour after primary chemotherapy of large and locally advanced breast cancer in comparison with conventional imaging modalities. METHODS: In a prospective multicentre trial, 99 patients underwent one or more breast imaging modalities before surgery in addition to clinical examination, namely, FDG-PET (n=89), mammography (n=47), ultrasound (n=46), and magnetic resonance imaging (MRI) (n=46). The presence of residual tumour by conventional imaging, dichotomised as positive or negative, and the level of FDG uptake (standardised uptake values, SUV) were compared with histopathology, which served as the reference standard. Patients with no residual tumour or only small microscopic foci of residual tumour were classified as having minimal residual disease and those with extensive microscopic and macroscopic residual tumour tissue were classified as having gross residual disease. RESULTS: By applying a threshold SUV of 2.0, the sensitivity of FDG-PET for residual tumour was 32.9% (specificity, 87.5%) and increased to 57.5% (specificity, 62.5%) at a threshold SUV of 1.5. Conventional imaging modalities were more sensitive in identifying residual tumour, but had a low corresponding specificity; sensitivity and specificity were as follows: MRI 97.6 and 40.0%, mammography 92.5 and 57.1%, ultrasound 92.0 and 37.5%, respectively. Breast MRI provided the highest accuracy (91.3%), whereas FDG-PET had the lowest accuracy (42.7%). CONCLUSIONS: FDG-PET does not provide an accurate assessment of residual tumour after primary chemotherapy of breast cancer. Magnetic resonance imaging offers the highest sensitivity, but all imaging modalities have distinct limitations in the assessment of residual tumour tissue when compared with histopathology.

Blood coagulation and cancer: thrombosis and survival, clinical relevance and impact. An introduction.

There is a strong association between deep venous thrombosis and cancer. In this review, we will discuss the increased incidence of cancer following an idiopathic venous thrombotic event (VTE) and the increased incidence of VTE and its recurrence in cancer patients. Furthermore, we will review the adverse impact VTE has on cancer patients' morbidity and mortality. Finally, the potential influence of anticoagulation on survival of cancer patients is discussed. Although the data are encouraging, anticoagulation is still of limited value for routine clinical practice in anticancer treatment.

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.

Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (P<0.001). This correlation was found for Snail expression as well (P<0.001). There was a significant (P=0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P=0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P=0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.

Classical operative therapy for Zenker's diverticulum.

Zenker's diverticulum is a rare disease usually described in elderly patients. The "gold standard" is endoscopic treatment. We describe a 77-year-old patient treated by classical operative therapy. Patient history showed weight loss of 22 kilograms within a year. Physical examination showed a swelling in the neck of 7 by 2 centimeters. Gastroscopic examination demonstrated a Zenker's diverticulum, but this could not be passed with the scope. Classical surgical resection was performed with excellent results 6 months after surgery.

Immigration policy in a global economy.

The author discusses trends in immigration policy making. "The state has been transformed by the growth of a transnational economic system. Because immigration policy is deeply rooted in state sovereignty, it is critical to examine the implications of global transformations as national legal innovation lags behind systemic change." Sections are included on the state and the new economic regime, constraint on states' policy making, and when different regimes intersect.

New employment regimes in cities: the impact on immigrant workers.

"The major cities of highly developed countries exhibit marked changes in job supplies and employment relations. It is frequently held that post-industrial societies require plentiful supplies of highly educated workers and will hold no openings for the low skilled. It is this latter category of jobs that immigrants have tended to fill in recent decades. Empirical data on major cities in advanced economies negate this supposition, revealing that there is an ongoing demand for immigrant labour and a continuing stream of employment opportunities which do not require high educational levels and which pay low wages. The article examines whether this job supply is merely a residue, to some extent augmented by the supply of low wage workers themselves, or whether it is a feature of a reconfigured labour market in advanced urban economies, i.e. a systemic development."

[Immigration in the world economy]. / Die Immigration in der Weltwirtschaft.

PIP: "Immigration is at least partly an outcome of the actions of the governments and major private economic actors of the developed countries. The case of Japan is of interest here because it allows us to capture the intersection of economic internationalization and immigration in its inception.... This paper argues that [Japan's] new immigration is part of the globalisation of [its] economy. Japan is a major presence in a regional Asian economic system where it is the leading investor, foreign aid donor, and exporter of consumer goods (including cultural products). The new immigration to Japan is not unrelated to these processes of internationalization. Internationalization provides a context within which bridges are built with the countries of origin of potential emigrants and internationalization contributes to make the Japanese economy more porous, particularly so in the case of large cities." (EXCERPT)^ieng

The new illegal immigration in Japan, 1980-1992.

"This article presents some of the latest available figures on illegal immigration in Japan, a process that did not assume significant proportions until the mid-1980s. It also discusses briefly the latest developments around 'immigration' policy--more precisely, the law on the entry and exit of aliens."

Economic internationalization: the new migration in Japan and the United States.

"The general proposition argued in this paper is that international migrations are embedded in larger social, economic and political processes.... The first section of the paper addresses the impact of economic internationalization on the formation of new immigration flows into the U.S. during the last 25 years. The second section examines both the magnitude and forms of Japan's recent economic presence in South and Southeast Asia. The third and fourth sections briefly review questions of policy in the U.S. and Japan during the last few years.... The fifth section conveys evidence of illegal immigration to Japan. The sixth section discusses conditions in receiving countries that make possible the adaptation of immigrants with a view to understanding how illegal immigrants in Japan could become part of the Japanese economy involving Japanese employers deeply steeped in an anti-immigration culture." (SUMMARY IN FRE AND SPA)

America's immigration "problem.".

PIP: Immigration has traditionally aroused strong passions in the US. Though Americans profess pride in their history as a nation of immigrants, each new wave of immigrants is met with strenuous opposition. Sassen points out that this opposition underestimates the US's capacity to absorb more people and fails to appreciate the political and economic forces that give rise to immigration. The outcry over rising illegal immigration culminated in the 1986 Immigration Reform and Control Act. So far, the law's effectiveness has been limited. 1.8 million immigrants applied to regularize their status. However, there is growing evidence that the employer sanctions program is resulting in discrimination against minority workers who are US citizens, and in various abuses against undocumented workers. Meanwhile, illegal immigration continues to rise. The 1986 law, like earlier laws, is based o a faulty understanding of immigration causes. The US played a crucial role in the 1960s and 1970s in developing today's global economic system. This system contributed to the creation of pools of potential immigrants and to the formation of links between the industrialized and developing countries. In sum, foreign investment and promotion of export-oriented growth i the US in developing countries has served to increase immigration to the US. A workable US immigration policy would be based o the recognition that the US bears a certain amount of responsibility for international labor migrations. The precise features of a fair immigration policy will have to be elaborated. However, it is clear that US immigration policy will continue to be counterproductive as long as it places the responsibility for the formation of international migrations exclusively upon the migrants themselves.^ieng