CXCR1 and CXCR2 haplotypes synergistically modulate cystic fibrosis lung disease

Cystic fibrosis (CF) lung disease severity is largely independent on the CF transmembrane conductance regulator (CFTR) genotype, indicating the contribution of genetic modifiers. The chemokine receptors CXCR1 and CXCR2 have been found to play essential roles in the pathogenesis of CF lung disease. Here, we determine whether genetic variation of CXCR1 and CXCR2 influences CF lung disease severity. Genomic DNA of CF patients in Germany (n = 442) was analysed for common variations in CXCR1 and CXCR2 using a single-nucleotide polymorphism (SNP) tagging approach. Associations of CXCR1 and CXCR2 SNPs and haplotypes with CF lung disease severity, CXCR1 and CXCR2 expression, and neutrophil effector functions were assessed. Four SNPs in CXCR1 and three in CXCR2 strongly correlated with age-adjusted lung function in CF patients. SNPs comprising haplotypes CXCR1_Ha and CXCR2_Ha were in high linkage disequilibrium and patients heterozygous for the CXCR1-2 haplotype cluster (CXCR1-2_Ha) had lower lung function compared with patients with homozygous wild-type alleles (forced expiratory volume in 1 s ≤ 70% predicted, OR 7.24; p = 2.30 × 10(-5)). CF patients carrying CXCR1-2_Ha showed decreased CXCR1 combined with increased CXCR2 mRNA and protein expression, and displayed disturbed antibacterial effector functions. CXCR1 and CXCR2 genotypes modulate lung function and antibacterial host defence in CF lung disease.     

Gesunderhaltung und Entlastung pflegender Angeh?riger von Demenzkranken durch ein ?initiales Case Management“

Background

When facing the well-known demographic development with an increasing number of people suffering from dementia, there is a need of programmes to support nursing relatives and care at home. Many support services have been established in the past few years but they are rarely used by the relatives and the patients. The purpose of the Lighthouse Project Ulm (ULTDEM Study) was to prove the effectiveness of a single advisory approach in order to provide support services after care level classification and to relieve the burden placed on relatives caring for family members suffering from dementia (“initial case management”).

Methods

The ULTDEM Study is a prospective, open, randomized, controlled, interventional study with different parallel outcome measures (burden of caring, quality of life and mood). After the randomization, the interventional group was given comprehensive, individual advice about available treatment possibilities for dementia patients. Control group participants received standard treatment. Inclusion criteria were application of a care level (0 or 1) as well as dementia diagnosis. All participants (patients/relatives) underwent an initial and a 6?month comprehensive assessment.

Results

Our results show that a single advisory approach does not lead to a significant difference in outcome measures in interventional and control groups. Those tendencies described have to be interpreted as clinically not relevant. Although utilization of support services increases, it remains similar in both study groups. A confirmatory interpretation has not been possible due to a lack of adjustment to the findings regarding multiple testing and an insufficient degree of recruitment. Possible causes will be discussed such as premature intervention during the course of the disease, a lack of intervention blinding, recruitment bias and lack of an influence on adherence with regard to the use of support services.

Implications

The study demonstrates that there is a substantial information deficit for persons affected by dementia and their relatives. Innovative ways still have to be developed to ensure that this information actually reaches the target audience.     

The Torg-Pavlov ratio for the prediction of acute spinal cord injury after a minor trauma to the cervical spine

Background contextAcute cervical spinal cord injury (SCI) has been observed in some patients after a minor trauma to the cervical spine. The discrepancy between the severity of the trauma and the clinical symptoms has been attributed to spinal canal stenosis. However, to date, there is no universally established radiological parameter for identifying critical spinal stenosis in these patients. The spinal canal–to–vertebral body ratio (Torg-Pavlov ratio) has been proposed for assessing developmental spinal canal stenosis. The relevance of the Torg-Pavlov ratio for predicting the occurrence and severity of acute cervical SCI after a minor trauma to the cervical spine has not yet been established.PurposeTo investigate the Torg-Pavlov ratio values of the cervical spine in patients suffering from acute cervical SCI after a minor trauma to the cervical spine and the use of the Torg-Pavlov ratio for identifying patients at risk of cervical SCI and predicting the severity and course of symptoms.Study design/settingRetrospective radiological study of consecutive patients.Patient sampleForty-five patients suffering from acute cervical SCI and 68 patients showing no neurologic symptoms after a minor trauma to the cervical spine.Outcome measuresMidvertebral sagittal cervical spinal canal diameter and the sagittal vertebral body diameter. Calculation of the Torg-Pavlov ratio values.MethodsConventional lateral radiographs of the cervical spine (C3–C7) were analyzed to determine the Torg-Pavlov ratio values. Receiver operating characteristic curves were calculated for evaluating the classification accuracy of the Torg-Pavlov ratio for predicting SCI.ResultsThe Torg-Pavlov ratio values in the SCI group were significantly (p<.04) smaller compared with that in the control group. A Torg-Pavlov ratio cutoff value of 0.7 yielded the greatest positive likelihood ratio for predicting the occurrence of SCI. However, there were no significant differences in the Torg-Pavlov ratio values between the different American Spinal Injury Association Impairment Score groups and between patients with complete, partial, and no recovery of symptoms.ConclusionsDevelopmental cervical spinal canal stenosis assessed by the Torg-Pavlov ratio was characteristic for patients suffering from acute cervical SCI after a minor trauma to the cervical spine. Patients at risk of SCI after a minor trauma to the cervical spine can be identified by applying a Torg-Pavlov ratio cutoff value of 0.7. Other factors in addition to the spinal canal–to–vertebral body ratio affect the severity and course of symptoms as a result of cervical SCI.     

Association between joint hypermobility and pelvic organ prolapse in women: a systematic review and meta-analysis

Introduction and hypothesis

Abnormalities of common collagen proteins have been noted in individuals affected by POP and JHM, suggesting a common aetiology. We assessed strength, consistency and potential for bias in pooled associations of the relationship between JHM and POP.

Methods

We searched MEDLINE, EMBASE and CINAHL, as well as International Continence Society (ICS) and International Urogynaecologic Association (IUGA) annual meeting abstracts, including reference lists, without language restrictions. We included case–control and cohort studies and applied strict criteria for choosing eligible studies. Methodologically trained reviewers independently screened abstracts and full texts to confirm eligibility. We extracted data on study and patient characteristics, clinical assessment tools, and methodology. We assessed comparability and representativeness of source populations, confidence in the assessment of JHM and POP and adjustment for confounding and missing data. Meta-analysis was performed using a random effects model.

Results

We retrieved 39 full texts, of which 14 were used in the meta-analysis. Overall pooled odds ratio (OR) was 2.37 [95 % confidence interval (CI) 1.54–3.64, I²?=?77.0 %]. We identified no significant factors in meta-regression, and there was no evidence of publication bias; six studies were at high risk of bias with frequent differences in sampling frames, limited validity for clinical assessments and failure to match for important prognostic variables.

Conclusions

We found a strong association between POP and JHM, with an effect size that is clinically relevant. Our findings are limited by high heterogeneity and the potential for residual confounding factors. JHM is an important early indicator for POP risk, and future longitudinal studies should explore the shared aetiology.

     

Flexing a standard hinge-powered operating table for lumbosacral three-column osteotomy (3-CO) site closure in 84 consecutive patients

Three-column osteotomy (3-CO) is a powerful technique in adult deformity surgery, and pedicle subtraction osteotomy (PSO) is the workhorse to correct severe kyphotic spinal deformities. Aging of the population, increasing cases of iatrogenic flat back deformities and understanding the importance of sagittal balance have led to a dramatic increase of this surgical technique. Surgery, however, is demanding and associated with high complication rates so that every step of the procedure requires meticulous technique. Particularly, osteotomy closure is associated with risks like secondary fracture, translation, or iatrogenic stenosis. This step is traditionally performed by compression or a cantilever maneuver with sometimes excessive forces on the screws or instrumentation. Implant loosening or abrupt subluxation resulting in construct failure and/or neurological deficits can result. The aim of this prospective registry study was to assess the efficacy and safety of our surgical PSO technique as well as the osteotomy closure by flexing a hinge-powered OR table. In a series of 84 consecutive lumbosacral 3-CO, a standardized surgical technique with special focus on closure of the osteotomy was prospectively evaluated. The surgical steps with the patients positioned prone on a soft frame are detailed. Osteotomy closure was achieved by remote controlled bending of a standard OR table without compressive or cantilever forces in all 84 cases. This technique carries a number of advantages, particularly the reversibility and the slow speed of closure with minimum force. There was not a single mechanical intraoperative complication such as vertebral body fracture, subluxation, or adjacent implant loosening during osteotomy closure, compared to external cohorts using the cantilever technique (p?=?0.130). The feasibility of controlled 3-CO closure by flexing a standard OR table is demonstrated. This technique enables a safe, gentle closure of the osteotomy site with minimal risk of implant failure or accidental neurological injury.

     

A Better Landmark for Positioning a Central Venous Catheter

Background.Improper positioning of central venous catheters (CVCs) can lead to erosion through the superior vena cava (SVC) or right atrium (RA) and pericardial tamponade. It is widely recommended that the tip of CVCs be placed above the heart or the pericardial reflection. The purpose of this study was to identify an easily recognized landmark to allow identification of the proximal extent of the pericardial reflection on a routine chest radiograph (CXR). Methods.We analyzed the computerized tomograms of the chest from 97 adults to evaluate the relationship between the pericardial reflection, SVC, carina, and right mainstem bronchus. Correlations between demographic data and length of SVC or pericardial reflection were sought. Results.The mean length of the SVC was 6.5 cm. The pericardial reflection covered an average of 3.6 cm of the distal SVC. The carina was a mean of 1.3 cm below the mid-point of the SVC and 0.7 cm below the pericardial reflection. There was no significant correlation between SVC or pericardial length and either age, height, or weight. Conclusions.The distal half of the SVC lies within the pericardial reflection, and the upper limit of the pericardial reflection is slightly above the level of the carina. These landmarks are useful for determining proper position of the tip of a CVC on CXR.