Does early intervention with a light mobilization program reduce long-term sick leave for low back pain?

STUDY DESIGN: A controlled randomized clinical trial was performed. OBJECTIVE: To investigate the effect of a light mobilization program on the duration of sick leave for patients with subacute low back pain. SUMMARY OF BACKGROUND DATA: Early intervention with information, diagnostics, and light mobilization may be a cost-effective method for returning patients quickly to normal activity. In this experiment, patients were referred to a low back pain clinic and given this simple and systematic program as an outpatient treatment. METHODS: In this study, 457 patients sick-listed 8 to 12 weeks for low back pain, as recorded by the National Insurance Offices, were randomized into two groups: an intervention group (n = 237) and a control group (n = 220). The intervention group was examined at a spine clinic and given information and advice to stay active. The control group was not examined at the clinic, but was treated with conventional primary health care. RESULTS: At 12-month follow-up assessment, 68.4% in the intervention group had returned to full-duty work, as compared with 56.4% in the control group. CONCLUSIONS: Early intervention with examination, information, and recommendations to stay active showed significant effects in reducing sick leave for patients with low back pain.     

Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance.

PURPOSE: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. PATIENTS AND METHODS: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. RESULTS: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P =.0100) and DFS (HR, 2.00; P =.0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear.     

Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis

BACKGROUND: Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG. Since the kidneys are frequently involved in WG, we studied the in situ expression of PR-3 by renal parenchymal cells. METHODS: We assessed the expression of PR-3 in kidney biopsies of 15 patients with WG by immunohistochemistry (IHC) and in situ hybridization (ISH). Normal kidney tissue served as the control. RESULTS: We detected PR-3 mRNA and PR-3 protein in distal tubular epithelial cells (TECs) and glomerular epithelial cells (GECs) in normal kidney tissue and in CGN. Furthermore, a strong glomerular PR-3mRNA expression restricted to the site of cellular crescents was detected in patients with WG. The analysis of 144 glomeruli with cellular or sclerotic crescents revealed a positive correlation of glomerular PR-3mRNA expression with the percentage of cellular crescents per glomerulus. The capability of human TECs and GECs to synthesize PR-3 was confirmed by Northern blot and ISH on cultured cells. CONCLUSION: These data provide evidence that nonhematopoetic renal parenchymal cells express PR-3 and that glomerular expression of PR-3 is associated with crescent formation in WG. Our findings suggest that renal parenchymal cells may directly be involved in the pathogenesis of CGN in WG.     

Bio-chemotherapeutic strategies and the (dis) utility of hypoxic perfusion of liver, abdomen and pelvis using balloon catheter techniques.

AIMS: To review the development and current status of balloon catheter mediated hypoxic perfusion of abdomen, pelvis and liver for treatment of locally advanced malignancies. Within this context we focus on the addition of tumour necrosis factor-alpha (TNF) to these minimal invasive perfusion procedures. METHODS: A literature search on these topics was carried out in PubMed for indexed articles and in all issues of Regional Cancer Treatment. The findings were related to our own experiences. RESULTS: Hypoxic abdominal (HAP) and hypoxic pelvic perfusion (HPP) using balloon catheters, are currently applied modalities for treatment of a wide variety of abdominal and pelvic tumours, yet scientific validation of these procedures is poor. Following the results of several Phase I-II trials, both treatments are associated with severe systemic toxicity, significant morbidity and even mortality. The degree of systemic leakage associated with these procedures prohibits addition of TNF. For leakage free liver perfusion surgery is still required, as with current balloon catheter techniques it is not possible to perform leakage free isolated hypoxic hepatic perfusion (IHHP), using either orthograde or retrograde hepatic flow. Experimental and clinical observations suggest that within any perfusion setting, the utilization of TNF is only indicated for treatment of highly vascularised tumours and not for treatment of colorectal tumours. CONCLUSION: Balloon catheter technology in its present form does not provide adequate leakage control in any of these settings and is therefore associated with considerable toxicity. It is associated with poor response rates and cannot be considered in any setting as a standard of care.     

High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions

Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all age, race, and ethnic groups, a subset of patients have suboptimal outcomes and are labeled as having high risk disease. A uniform approach to risk in NDMM remains elusive despite several validated risk stratification systems in clinical use. While we attempt to capture risk at diagnosis, the reality is that many important prognostic characteristics remain ill-defined as some patients relapse early who were defined as low risk based on their genomic profile at diagnosis. It is critical to establish a definition of high risk disease in order to move towards risk-adapted treatment approaches. Defining risk at diagnosis is important to both effectively design future clinical trials and guide which clinical data is needed in routine practice. The goal of this review paper is to summarize and compare the various established risk stratification systems, go beyond the R-ISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently. In addition, we explore the wealth of new genomic information from recent whole genome/exome sequencing as well as gene expression data and review known clinical factors affecting outcome such as disease burden and early relapse as well as patient related factors such as race. Finally, we provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations.Subject terms: Myeloma, Genetic translocation, Risk factors, Cancer genetics     

Effects of Sand-Based Plyometric-Jump Training in Combination with Endurance Running on Outdoor or Treadmill Surface on Physical Fitness in Young Adult Males

This study aimed at examining the effects of nine weeks of sand-based plyometric-jump training (PJT) combined with endurance running on either outdoor or treadmill surface on measures of physical fitness. Male participants (age, 20.1 ± 1.7 years) were randomly assigned to a sand-based PJT combined with endurance running on outdoor surface (OT, n = 25) or treadmill surface (TT, n = 25). The endurance running intervention comprised a mixed training method, i.e., long slow distance, tempo, and interval running drills. A control group was additionally included in this study (CG, n = 25). Participants in CG followed their regular physical activity as OT and TT but did not receive any specific intervention. Individuals were assessed for their 50-m linear sprint time, standing long jump (SLJ) distance, cardiorespiratory fitness (i.e., Cooper test), forced vital capacity (FVC), calf girth, and resting heart rate (RHR). A three (groups: OT, TT, CG) by two (time: pre, post) ANOVA for repeated measures was used to analyze the exercise-specific effects. In case of significant group-by-time interactions, Bonferroni adjusted paired (within-group) and independent (between-group comparisons at post) t-tests were used for post-hoc analyses. Significant group-by-time interactions were found for all dependent variables (p < 0.001 – 0.002, ɳ_p² = 0.16 – 0.78). Group-specific post-hoc tests showed improvements for all variables after OT (p < 0.001, Hedges’g effect size [g] = 0.05 – 1.94) and TT (p < 0.001, g = 0.04 – 2.73), but not in the CG (p = 0.058 – 1.000, g = 0.00 – 0.34). Compared to CG, OT showed larger SLJ (p = 0.001), cardiorespiratory fitness (p = 0.004), FVC (p = 0.008), and RHR (p < 0.001) improvements. TT showed larger improvements in SLJ (p = 0.036), cardiorespiratory fitness (p < 0.001), and RHR (p < 0.001) compared with CG. Compared to OT, TT showed larger improvements for SLJ (p = 0.018). In conclusion, sand-based PJT combined with either OT or TT similarly improved most measures of physical fitness, with greater SLJ improvement after TT. Coaches may use both concurrent exercise regimes based on preferences and logistical constrains (e.g., weather; access to treadmill equipment). Key points

• Concurrent training in the form of sand-based plyometric-jump training and endurance running exercise can enhance physical fitness in young individuals;
• Compared to treadmill running, rating of perceived exertion was higher in outdoor running sessions;
• Sand-based plyometric-jump training may induce greater standing long jump performance when combined with endurance running on treadmill surface as compared to outdoor surface.

Key words: Muscle strength, musculoskeletal and neural physiological phenomena, movement, resistance training, high-intensity interval training, exercise     

Die Gesundheitliche Jugendfürsorge der Stadt Frankfurt A. M.

Ohne Zusammenfassung     

SARS CoV-2 (Delta Variant) Infection Kinetics and Immunopathogenesis in Domestic Cats

Continued emergence of SARS-CoV-2 variants highlights the critical need for adaptable and translational animal models for acute COVID-19. Limitations to current animal models for SARS CoV-2 (e.g., transgenic mice, non-human primates, ferrets) include subclinical to mild lower respiratory disease, divergence from clinical COVID-19 disease course, and/or the need for host genetic modifications to permit infection. We therefore established a feline model to study COVID-19 disease progression and utilized this model to evaluate infection kinetics and immunopathology of the rapidly circulating Delta variant (B.1.617.2) of SARS-CoV-2. In this study, specific-pathogen-free domestic cats (n = 24) were inoculated intranasally and/or intratracheally with SARS CoV-2 (B.1.617.2). Infected cats developed severe clinical respiratory disease and pulmonary lesions at 4- and 12-days post-infection (dpi), even at 1/10 the dose of previously studied wild-type SARS-CoV-2. Infectious virus was isolated from nasal secretions of delta-variant infected cats in high amounts at multiple timepoints, and viral antigen was co-localized in ACE2-expressing cells of the lungs (pneumocytes, vascular endothelium, peribronchial glandular epithelium) and strongly associated with severe pulmonary inflammation and vasculitis that were more pronounced than in wild-type SARS-CoV-2 infection. RNA sequencing of infected feline lung tissues identified upregulation of multiple gene pathways associated with cytokine receptor interactions, chemokine signaling, and viral protein–cytokine interactions during acute infection with SARS-CoV-2. Weighted correlation network analysis (WGCNA) of differentially expressed genes identified several distinct clusters of dysregulated hub genes that are significantly correlated with both clinical signs and lesions during acute infection. Collectively, the results of these studies help to delineate the role of domestic cats in disease transmission and response to variant emergence, establish a flexible translational model to develop strategies to prevent the spread of SARS-CoV-2, and identify potential targets for downstream therapeutic development.