Provisional COVID-19 infrastructure induces large, rapid increases in cycling.

The bicycle is a low-cost means of transport linked to low risk of transmission of infectious disease. During the COVID-19 crisis, governments have therefore incentivized cycling by provisionally redistributing street space. We evaluate the impact of this new bicycle infrastructure on cycling traffic using a generalized difference in differences design. We scrape daily bicycle counts from 736 bicycle counters in 106 European cities. We combine these with data on announced and completed pop-up bike lane road work projects. Within 4 mo, an average of 11.5 km of provisional pop-up bike lanes have been built per city and the policy has increased cycling between 11 and 48% on average. We calculate that the new infrastructure will generate between $1 and $7 billion in health benefits per year if cycling habits are sticky.

No aggregate deforestation reductions from rollout of community land titles in Indonesia yet.

In Indonesia, 60 million people live within 1 km of state forest. The government of Indonesia plans to grant community titles for 12.7 million hectares of land to communities living in and around forests. These titles allow for using nontimber forest products, practicing agroforestry, operating tourism businesses, and selective logging in designated production zones. Here, we estimate the early effects of the program's rollout. We use data on the delineation and introduction date of community forest titles on 2.4 million hectares of land across the country. We find that, contrary to the objective of the program, community titles aimed at conservation did not decrease deforestation; if anything, they tended to increase forest loss. In contrast, community titles in zones aimed at timber production decreased deforestation, albeit from higher baseline forest loss rates.

Acupressure, a promising intervention for fatigue, within the European nursing care pathways (ENP): An integrative review.

AIMS: The aim of this study is to test whether acupressure for patients with fatigue is an efficient nursing intervention and if it can be implemented into the European nursing care pathways (ENP) nursing classification system. BACKGROUND: Previously, interventions for acupressure were included nonspecifically in ENP and therefore were not available for standardized nursing documentation in an electronic health record (EHR). INTRODUCTION: Acupressure is a nursing intervention that is increasingly used in specific settings. ENP is a nursing classification system that provides evidence-based nursing interventions for nursing diagnoses. METHODS: A systematic international literature search was conducted from May 2021 to December 2021. An iterative, hierarchical search process according to the 6S evidence pyramid was chosen. The results were reported following the PRISMA statement. RESULTS: Findings of 49 included publications that studied a total of 1,716 patients indicate that certain acupressure points may be efficient in treating fatigue. DISCUSSION: Acupressure is a useful nursing intervention and can really help patients experiencing fatigue. It is illustrated how the findings have been implemented in the development of ENP nursing interventions to document acupressure. CONCLUSION: The acupressure points most frequently used on the ear with positive effects in improving fatigue are Shen Men, liver, spleen, subcortex, endocrine, heart, and sympathetic, while the most common points on the body are ST 36, SP 6, LI 4, HT 7, KID 1, Ex-HN 3, Ex-HN, and KID 3. IMPLICATION FOR NURSING: In the future, nurses will be able to use ENP to quickly and easily document acupressure interventions for fatigue in the EHR. In the EHR, the documentation of the nursing process with ENP could help to promote research into evidence-based approaches to fatigue by generating mass data on the different concepts of acupressure, which could lead to a clearer determination of the evidence and contribute to the safety of care and patients.

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis.

OBJECTIVE: To compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA). METHODS: Prospective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks. RESULTS: TOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers. Both TOC (DAS28-ESR: baseline: 6.2±0.5; 52 weeks: 2.3±1.0) and ADA/MTX (6.3±0.6; 2.8±1.2) significantly reduced disease activity. Erosion volumes significantly decreased in the MCH and radius of patients with RA treated with TOC (p<0.001) but not in patients treated with ADA/MTX (p=0.77), where they remained stable in size. Mean decrease in erosion volume in TOC-treated patients was -1.0±1.1 mm3 and -3.3±5.9 mm3 in the MCH and radius of TOC-treated patients, respectively, and -0.05±0.9 mm3 and -0.08±4.1 mm3 in patients treated with ADA/MTX. CONCLUSIONS: The REBONE study shows that TOC monotherapy achieves more pronounced repair of existing bone erosions than ADA/MTX. Hence, IL-6 is a central factor for the disturbed bone homeostasis in the joints of patients with RA.

Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis.

OBJECTIVES: To search for structural bone changes in the joints of psoriasis patients without psoriatic arthritis (PsA). METHODS: 55 psoriasis patients without any current or past symptoms of arthritis or enthesitis and 47 healthy controls were examined by high-resolution peripheral quantitative CT scans of the metacarpophalangeal joints. Number, size and exact localisation of erosions and enthesiophytes were recorded by analysing axial scans of the metacarpal heads and phalangeal bases and were confirmed in additional coronal and/or sagittal sections. In addition, we collected demographic and clinical data including subtype, duration and severity of psoriasis. RESULTS: Psoriasis patients showed a larger and significantly increased number of enthesiophytes (total number 306; mean±SD/patient 5.62±3.30) compared with healthy controls (total number 138; mean±SD/patient 3.04±1.81, p<0.001). Enthesiophytes were typically found at the dorsal and palmar sides of the metacarpal heads where functional entheses related to extensor and flexor tendons are localised. Bone erosions were rare and not significantly different between psoriasis patients and healthy controls. If present, erosions were almost exclusively found at the radial side of the second metacarpal head in both psoriasis patients and healthy controls. CONCLUSIONS: Psoriasis patients without PsA show substantial signs of enthesiophyte formation compared with healthy controls. These changes represent new bone formation at mechanically exposed sites of the joint and substantiate the concept of the existence of a 'Deep Koebner Phenomenon' at enthesial sites in psoriasis patients.

Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis.

OBJECTIVES: To search for subclinical inflammatory joint disease in patients with psoriasis without psoriatic arthritis (PsA), and to determine whether such changes are associated with the later development of PsA. METHODS: Eighty-five subjects without arthritis (55 with psoriasis and 30 healthy controls) received high field MRI of the hand. MRI scans were scored for synovitis, osteitis, tenosynovitis and periarticular inflammation according to the PsAMRIS method. Patients with psoriasis additionally received complete clinical investigation, high-resolution peripheral quantitative CT for detecting erosions and enthesiophytes and were followed up for at least 1 year for the development of PsA. RESULTS: 47% of patients with psoriasis showed at least one inflammatory lesion on MRI. Synovitis was the most prevalent inflammatory lesion (38%), while osteitis (11%), tenosynovitis (4%) and periarticular inflammation (4%) were less frequent. The mean (±SD) PsAMRIS synovitis score was 3.0±2.5 units. Enthesiophytes and bone erosions were not different between patients with psoriasis with or without inflammatory MRI changes. The risk for developing PsA was as high as 60% if patients had subclinical synovitis and symptoms related to arthralgia, but only 13% if patients had normal MRIs and did not report arthralgia. CONCLUSIONS: Prevalence of subclinical inflammatory lesions is high in patients with cutaneous psoriasis. Arthralgia in conjunction with MRI synovitis constitutes a high-risk constellation for the development of PsA.

Automated three-dimensional registration of high-resolution peripheral quantitative computed tomography data to quantify size and shape changes of arthritic bone erosions.

OBJECTIVE: To monitor size and shape changes of bone erosions and changes in BMD in the vicinity of the erosion and in the periarticular trabecular compartment of patients with RA using high-resolution peripheral quantitative CT (HR-pQCT) imaging and to compare an automated three-dimensional (3D) image processing technique with manual measurements of erosion width and depth. METHODS: The shape of 40 bone erosions and composition of bone around the erosions were analysed in the MCP joints of 22 RA patients both manually and by semi-automated 3D image processing at two different time points. Periosteal segmentation was performed using volume growing and morphological operations. Image registration was applied for transfer of baseline segmentations to follow-up datasets. RESULTS: Eight erosions decreased in size, 6 increased and 28 remained stable. Increasing erosions were more spherical and smaller at baseline compared with decreasing or stable erosions. BMD in the vicinity of shrinking erosions increased, while it decreased next to expanding erosions. There was moderate agreement in the determination of erosion volume between semi-automated and manual measurements, but agreement was poor when assessing changes in volume over time. CONCLUSION: Longitudinal changes in erosion size and shape and of BMD in the vicinity of an erosion can be measured. BMD changes are associated with progression and regression of erosions. However, the semi-automated and manual approaches did not classify longitudinal changes of erosion volume in the same way. Further research is necessary to define the nature of these differences.

A comparative analysis of magnetic resonance imaging and high-resolution peripheral quantitative computed tomography of the hand for the detection of erosion repair in rheumatoid arthritis.

OBJECTIVES: To investigate whether MRI allows the detection of osteosclerosis as a sign of repair of bone erosions compared with high-resolution peripheral quantitative computed tomography (HR-pQCT) as a reference and whether the presence of osteosclerosis on HR-pQCT is linked to synovitis and osteitis on MRI. METHODS: A total of 103 RA patients underwent HR-pQCT and MRI of the dominant hand. The presence and size of erosions and the presence and extent (grades 0-2) of osteosclerosis were assessed by both imaging modalities, focusing on MCP 2 and 3 and wrist joints. By MRI, the presence and grading of osteitis and synovitis were assessed according to the Rheumatoid Arthritis MRI Score (RAMRIS). RESULTS: Parallel evaluation was feasible by both modalities on 126 bone erosions. Signs of osteosclerosis were found on 87 erosions by HR-pQCT and on 22 by MRI. False-positive results (MRI(+)CT(-)) accounted for 3%, while false-negative results (MRI(-)CT(+)) accounted for 76%. MRI sensitivity for the detection of osteosclerosis was 24% and specificity was 97%. The semi-quantitative scoring of osteosclerosis was reliable between MRI and HR-pQCT [intraclass correlation coefficient 0.917 (95% CI 0.884, 0.941), P < 0.001]. The presence of osteosclerosis on HR-pQCT showed a trend towards an inverse relationship to the occurrence and extent of osteitis on MRI [χ(2)(1) = 3.285; ϕ coefficient = -0.124; P = 0.070] but not to synovitis [χ(2)(1) = 0.039; ϕ coefficient = -0.14; P = 0.844]. CONCLUSION: MRI can only rarely detect osteosclerosis associated with bone erosions in RA. Indeed, the sensitivity compared with HR-pQCT is limited, while the specificity is high. The presence of osteitis makes osteosclerosis more unlikely, whereas the presence of synovitis is not related to osteosclerosis.

Bone anabolic changes progress in psoriatic arthritis patients despite treatment with methotrexate or tumour necrosis factor inhibitors.

OBJECTIVES: To investigate whether methotrexate or tumour necrosis factor inhibitors (TNFi) affect osteophyte formation in patients with psoriatic arthritis (PsA). METHODS: 41 patients with PsA were examined for the presence of osteophytes and erosions at the metacarpophalangeal joints by high-resolution micro-CT imaging. The size of each individual lesion was quantified at baseline and 1-year follow-up in PsA patients treated with TNFi (N=28) or methotrexate (N=13). Groups were comparable for age, sex, disease duration and activity and baseline burden of osteophytes. RESULTS: In total, 415 osteophytes (TNFi N=284, methotrexate N=131) were detected. Osteophyte size increased significantly from baseline to follow-up in the TNFi group (mean±SEM change +0.23±0.02 mm; p<0.0001) and the methotrexate group (+0.27±0.03 mm, p<0.0001). In both treatment groups, the majority of osteophytes showed progression (TNFi 54.3%, methotrexate 61.1%), whereas regression of lesions was rare (less than 10%). In contrast to osteophytes, clinical disease activity decreased in both groups of PsA patients and erosions showed an arrest of progression in both groups. CONCLUSIONS: Osteophytes progress in PsA patients treated with either methotrexate or TNFi. These data provide the first evidence that pathological bone formation in the appendicular skeleton of patients with PsA is not affected by current antirheumatic treatment strategies.

Energy conservation in the gut microbe Methanomassiliicoccus luminyensis is based on membrane-bound ferredoxin oxidation coupled to heterodisulfide reduction.

Methanomassiliicoccus luminyensis was originally isolated from human feces and belongs to the seventh order of methanogens, the Methanomassiliicoccales, which are only distantly related to other methanogenic archaea. The organism forms methane from the reduction of methylamines or methanol using molecular hydrogen as reductant. The energy-conserving system in M. luminyensis is unique and the enzymes involved in this process are not found in this combination in members of the other methanogenic orders. In this context our central question was how the organism is able to generate ATP. Energy transduction was dependent on a membrane-bound ferredoxin: heterodisulfide oxidoreductase composed of reduced ferredoxin as an electron donor, at least one protein in the membrane fraction and the heterodisulfide reductase HdrD, which reduced the electron acceptor CoM-S-S-CoB. Electron transfer of this respiratory chain proceeded with a rate of 145 nmol reduced heterodisulfide min-1 ·mg-1 membrane protein. Methanomassiliicoccus luminyensis is the first example of a methanogenic archaeon that does not require Na+ ions for energy conservation. Only protons were used as coupling ions for the generation of the electrochemical ion gradient. The membrane-bound F420 H2 :phenazine oxidoreductase complex (without the electron input module FpoF) probably catalyzed the oxidation of reduced ferredoxin and potentially acted as primary proton pump in this electron transport system. In summary, the energy-conserving system of M. luminyensis possesses features found in the pathways of hydrogenotrophic and methylotrophic/aceticlastic methanogenesis. Consequently, the composition of the enzymes involved in ion translocation across the cytoplasmic membrane is different from all other methanogenic archaea.

Simultaneous quantification of bone erosions and enthesiophytes in the joints of patients with psoriasis or psoriatic arthritis - effects of age and disease duration.

BACKGROUND: Comprehensive simultaneous quantification of bone erosion and enthesiophytes in the joints of patients with psoriatic arthritis (PsA) has not been performed. Herein, we aimed to compare the extent of bone erosion and enthesiophytes in patients with PsA, psoriasis (PSO) and healthy controls, assess the influence of age and disease duration on the development of erosions and enthesiophytes and define their impact on physical function. METHODS: Patients with PsA or with PSO and controls were analysed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The extent of bone erosions and enthesiophytes was assessed and plotted according to different categories of age, duration of PSO and duration of PsA, respectively. In addition, demographic and disease-specific data, including physical function (health assessment questionnaire) were collected. RESULTS: A total of 203 patients were analysed; 101 had PsA, 55 had PSO and 47 were healthy individuals. Patients with PsA had significantly more and larger erosions (p = 0.002/p = 0.003) and enthesiophytes (p < 0.001) compared to patients with PSO and healthy controls. Patients with PSO and healthy controls did not differ in erosions, while enthesiophytes were more frequent in patients with PSO than in healthy controls. Bone erosions, but not enthesiophytes, showed strong age-dependency in all three groups. In contrast, enthesiophytes were mostly influenced by the duration of PSO and PsA and, in contrast to bone erosions, were associated with poorer physical function. CONCLUSIONS: Bone erosions are age-dependent, enhanced in PsA and increase with disease duration. Enthesiophytes are less age-dependent, are enhanced in both PSO and PsA and strongly influenced by disease duration. Enthesiophytes impact physical function in PsA suggesting the need for early therapeutic interventions to prevent damage.

Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography and Interreader Reliability for Detection and Measurement.

OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size. METHODS: HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated. RESULTS: Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16-8.90) and mean depth was 1.86 mm (range 0.30-8.00). CONCLUSION: We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor.

The wingless-type mouse mammary tumor virus integration site family (Wnt) pathway plays a major role in the carcinogenesis of colorectal cancer (CRC). Its most important effector, the nuclear ß-catenin, influences not only transcription but also the proliferation and dedifferentiation of the colonic mucosa. This induces an epithelial-mesenchymal transition which ultimately can lead to the development of cancer and the formation of metastases. However, little is known about the exact interaction and context-sensitive expression of Wnt-pathway effectors in the primary tumor and corresponding metastasis. Therefore, this study assessed the expression of the three most important effectors of the Wnt pathway, ß-catenin, adenomatous polyposis coli (APC) and Wnt-1, in the primary tumor and corresponding metastasis of patients with CRC. Immunohistochemical staining of ß-catenin, APC and Wnt-1 was performed in paraffin-embedded tissue samples of the primary tumor, and the corresponding hepatic and nodal metastasis samples from 24 patients with metastatic CRC. Isotype antibodies were used as negative controls. The results were visualized using the ABC-method. Analysis of the primary tumor comprised of a separate evaluation of the central tumor area as well as the invasion front. There was a significant overexpression of nuclear ß-catenin at the tumor invasion front (P<0.001). Compared to normal colonic mucosa, expression of cytoplasmic ß-catenin was significantly higher in the primary tumor (P<0.001) as well as all the corresponding hepatic and lymphatic metastases (hepatic metastases, P=0.001; nodal metastases, P=0.017). By contrast, APC expression was significantly lower in all analyzed tumor compartments compared with normal colonic mucosa (primary tumor, P=0.022; hepatic metastases, P=0.006; nodal metastases, P=0.012). Finally, Wnt-1 protein expression was significantly lower in liver metastases but not in the primary tumor or lymphatic metastases compared with normal colonic mucosa (P=0.003). The present study demonstrates that the major Wnt-effector proteins, ß-catenin, APC and Wnt-1, are heterogeneously expressed in the primary tumor and corresponding hepatic as well as nodal metastases of patients with CRC. This context-sensitive diverse expression of Wnt-effector proteins may be important for future individualized targeted therapies.

Quantitative and Qualitative Changes of Bone in Psoriasis and Psoriatic Arthritis Patients.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by periarticular bone loss and new bone formation. Current data regarding systemic bone loss and bone mineral density (BMD) in PsA are conflicting. The aim of this study was to evaluate bone microstructure and volumetric BMD (vBMD) in patients with PsA and psoriasis. We performed HR-pQCT scans at the ultradistal and periarticular radius in 50 PsA patients, 30 psoriasis patients, and 70 healthy, age- and sex-related controls assessing trabecular bone volume (BV/TV), trabecular number (Tb.N), inhomogeneity of the trabecular network, cortical thickness (Ct.Th), and cortical porosity (Ct.Po), as well as vBMD. Trabecular BMD (Tb.BMD, p = 0.021, 12.0%), BV/TV (p = 0.020, -11.9%), and Tb.N (p = 0.035, 7.1%) were significantly decreased at the ultradistal radius and the periarticular radius in PsA patients compared to controls. In contrast, bone architecture of the ultradistal radius and periarticular radius was similar in patients with psoriasis and healthy controls. Duration of skin disease was associated with low BV/TV and Tb.N in patients with PsA. These data suggest that trabecular BMD and bone microstructure are decreased in PsA patients. The observation that duration of skin disease determines bone loss in PsA supports the concept of subclinical musculoskeletal disease in psoriasis patients.

Clinically staged cT2 adenocarcinomas of the gastroesophageal junction: accuracy of staging and therapeutic consequences.

BACKGROUND: Multimodality treatment options in locally advanced adenocarcinomas of the esophagogastric junction (AEGs) have been established in the last years. However, the therapeutic approach in patients with clinically staged cT2 tumors remains controversial. The most important determinant is the accuracy of clinical staging. We aimed to evaluate the association of clinical and histopathological staging in patients with cT2 tumors in respect of possible therapeutic consequences. PATIENTS AND METHODS: Between 2001 and 2011, 71 patients with AEG tumors were clinically staged as cT2 (cN0 = 48 (68%); cN+ = 23 (32%)) and underwent surgical resection. RESULTS: A primary tumor resection was performed in 59 (83%) patients while 12 (17%) patients received neoadjuvant therapy. Primarily resected patients showed the following pT/pN categories: pT1: 13 (22%), pT2: 35 (59%), pT3: 11 (19%), pN0: 23 (39%), whereas the clinical/histopathological pN category included 55% of the patients. Neoadjuvantly treated patients showed the following pT/pN categories: ypT0: 3 (25%), ypT1: 3 (25%), ypT2: 6 (50%), ypN0: 6 (50%). The overall survival of primarily resected patients compared with patients undergoing neoadjuvant therapy was not significantly different. CONCLUSIONS: The accuracy of clinical staging in patients with cT2 tumors of the gastroesophageal junction is poor. As in primarily resected patients, over- and understaging balance each other; correct pretherapeutic staging occurs in just about 60% of the patients. Moreover, our study suggests that a radical surgical resection with adequate lymphadenectomy seems to be appropriate for cT2N0 and even in cT2N+ tumors, since down-categorizing and prognosis are not improved for neoadjuvantly treated patients. However, the data have to be interpreted with caution because of the small patient numbers.

Catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis: a computed tomography study on the role of age, disease duration and bone markers.

INTRODUCTION: The aim of this study was to determine the factors, including markers of bone resorption and bone formation, which determine catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis (RA). METHODS: Forty RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of the metacarpophalangeal joints II and III of the dominantly affected hand at two sequential time points (baseline, one year follow-up). Erosion counts and scores as well as osteophyte counts and scores were recorded. Simultaneously, serum markers of bone resorption (C-terminal telopeptide of type I collagen (CTX I), tartrate-resistant acid phosphatase 5b (TRAP5b)), bone formation (bone alkaline phosphatase (BAP), osteocalcin (OC)) and calcium homeostasis (parathyroid hormone (PTH), 25-hydroxyvitamin D3 (Vit D)) were assessed. Bone biomarkers were correlated to imaging data by partial correlation adjusting for various demographic and disease-specific parameters. Additionally, imaging data were analyzed by mixed linear model regression. RESULTS: Partial correlation analysis showed that TRAP5b levels correlate significantly with bone erosions, whereas BAP levels correlate with osteophytes at both time points. In the mixed linear model with erosions as the dependent variable, disease duration (P <0.001) was the key determinant for these catabolic bone changes. In contrast, BAP (P = 0.001) as well as age (P = 0.018), but not disease duration (P = 0.762), were the main determinants for the anabolic changes (osteophytes) of the periarticular bone in patients with RA. CONCLUSIONS: This study shows that structural bone changes assessed with HR-pQCT are accompanied by alterations in systemic markers of bone resorption and bone formation. Besides, it can be shown that bone erosions in RA patients depend on disease duration, whereas osteophytes are associated with age as well as serum level of BAP. Therefore, these data not only suggest that different variables are involved in formation of bone erosions and osteophytes in RA patients, but also that periarticular bone changes correlate with alterations in systemic markers of bone metabolism, pointing out BAP as an important parameter.

Prognostic significance of EpCAM-positive disseminated tumor cells in rectal cancer patients with stage I disease.

Here we evaluated the prevalence and prognostic impact of epithelial cell adhesion molecule (EpCAM)-positive disseminated tumor cells (DTCs) in stage I rectal cancer. Further we tested the association of these single tumor cells or small tumor cell groups with the extent of peritumoral lymphangiogenesis. A total of 845 regional lymph nodes (LN) of 44 patients classified as negative on conventional histopathology were retrospectively reanalyzed with immunohistochemistry (IHC) using the monoclonal antibody Ber-Ep4 directed against EpCAM for the detection of DTCs. The degree of lymphangiogenesis in the primary tumors was assessed by IHC of the primary tumor tissue using the monoclonal antibody D2-40, which reacts with the lymphatic endothelium. The IHC results were correlated with clinico-pathologic parameters and clinical follow-up data. EpCAM-positive DTCs in LNs were detected in 8 (18.2%) of the 44 patients. During a median follow-up of 59 months, 3 (37.5%) of the 8 patients with EpCAM-positive DTCs relapsed, whereas none of the DTC-negative patients developed tumor recurrence (P=0.004). Survival analysis revealed a significant effect of the prevalence of DTCs on overall survival (P=0.0009) and on recurrence-free survival (P=0.0001). Finally, the prevalence of EpCAM-positive DTCs in perirectal LNs was significantly correlated with a high density of peritumoral lymphatic vessels (P=0.015). Our results show that DTCs may occur in stage I of rectal cancer and are associated with poor prognosis. Their occurrence seems to be linked to a high density of newly formed lymphatic vessel at the primary tumor site. According to our data, patients with DTCs in their LN might benefit from adjuvant therapy.