Alterations in intervertebral disc composition,matrix homeostasis and biomechanical behavior in the UCD‐T2DM rat model of type 2 diabetes

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end‐product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia‐inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE‐mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:738–746, 2015.     

Difference in outcomes after antibody‐mediated rejection between abo‐incompatible and positive cross‐match transplantations

Graft survival seems to be worse in positive cross‐match (HLAi) than in ABO‐incompatible (ABOi) transplantation. However, it is not entirely clear why these differences exist. Sixty‐nine ABOi, 27 HLAi and 10 combined ABOi+HLAi patients were included in this retrospective study, to determine whether the frequency, severity and the outcome of active antibody‐mediated rejection (AMR) were different. Five‐year death‐censored graft survival was better in ABOi than in HLAi and ABOi+HLAi patients (99%, 69% and 64%, respectively, P = 0.0002). Features of AMR were found in 38%, 95% and 100% of ABOi, HLAi and ABOi+HLAi patients that had a biopsy, respectively (P = 0.0001 and P = 0.001). After active AMR, a declining eGFR and graft loss were observed more frequently in HLAi and HLAi+ABOi than in ABOi patients. The poorer prognosis after AMR in HLAi and ABOi+HLAi transplantations was not explained by a higher severity of histological lesions or by a less aggressive treatment. In conclusion, ABOi transplantation offers better results than HLAi transplantation, partly because AMR occurs less frequently but also because outcome after AMR is distinctly better. HLAi and combined ABOi+HLAi transplantations appear to have the same outcome, suggesting there is no synergistic effect between anti‐A/B and anti‐HLA antibodies.     

Guidelines for empiric antimicrobial prescribing in community-acquired pneumonia

Empiric antimicrobial prescribing for community-acquired pneumonia remains a challenge, despite the availability of treatment guidelines. A number of key differences exist between North American and European guidelines, mainly in the outpatient setting. The North American approach is to use initial antimicrobial therapy, which provides coverage for Streptococcus pneumoniae plus atypical pathogens. Europeans tend to focus on providing pneumococcal coverage with less emphasis on covering for an atypical pathogen. Ambulatory patients without comorbidity are more likely to receive macrolide therapy in North America, whereas in Europe these patients would probably receive a beta-lactam agent. Major issues that are fundamental to this difference include the importance of providing therapy for atypical pathogens and the clinical significance of macrolide-resistant S pneumoniae. Prospective data are required to evaluate which of these two approaches offers clinical superiority.     

Irritable bowel syndrome in France: a common, debilitating and costly disorder

OBJECTIVE: This epidemiological investigation aims to measure the prevalence of irritable bowel syndrome (IBS) in the general population using the Rome II criteria and to evaluate the medical management including treatments and the impact of IBS on patient life. METHODS: A nationally representative sample of 20,000 French subjects, aged 18 years and over, were interviewed by SOFRES (French Public Opinion Poll Institute) in May 2001. In a second phase (June/July 2001), a 48-question self-administered questionnaire was given to the subjects who have been selected during the first phase as suffering from IBS (Rome II criteria). RESULTS: The prevalence of IBS was 4.7% (confidence interval, 4.36-5.04% with 5% risk) with a predominance in women (5.7% versus 3.7%, P < 0.01). The abdominal pain was often longstanding (> 5 years, 50%), intense (43%) and nocturnal (35%). During the most recent painful episode the levels of associated transit problems were almost equally divided between diarrhoea (36%), constipation (29%) and alternate episodes of both (31%). Apart from pain, bloating was given as the most frequent (73%) and most troublesome (24%) symptom. Since the onset, 80% of subjects with IBS had consulted a doctor (90% consulted a general physician, 57% a gastroenterologist, 50% both) and of these, 80% consulted within the previous 12 months. Sixty-seven per cent of subjects underwent additional investigations since the start of their illness (average of 3.4 examinations per patient examined: colonoscopy, 34.1%; laboratory tests, 34%; and abdominal ultrasound, 27.7%). Over the previous 12 months, 8% of the subjects had been admitted to hospital (average length of stay, 6.6 days), 11% of employed subjects had to take time off, 93% of subjects had taken prescribed medication (87%), but 43% of people thought it was ineffective. The effect on daily life was considerable (score, 6.2/10; close to the score for flu, 7/10). Two-thirds of the individuals changed their diet; 54% said it affected their social life and 29% their professional life. Seventy-four per cent of patients trusted their doctor, with a satisfaction index of 63%, but 45% of patients would like to have more information on IBS. CONCLUSION: This study confirmed that the Rome II criteria detected IBS with a prevalence of 4.7%. The recruited subjects had severe symptoms (frequency, intensity and duration) that had a considerable effect on their daily life. The high level of referrals and initial consultations in all categories and the patient's attitudes towards the illness and its treatment emphasize the relative ineffectiveness of care for patients suffering from IBS.     

Preconditioning and metabolic anti-ischaemic agents.

Preconditioning a powerful protective mechanism, is the response to transient ischemia and reperfusion. However, the best way to achieve total protection is to avoid ischemia altogether. Therefore prevention of ischemia and protection by preconditioning are differently mediated so that anti-ischemic agents may not precondition, whereas paradoxically pro-ischemic agents may precondition. Metabolically active agents such as glucose-insulin-potassium, trimetazidine and ranolazine that protect from ischemia, increase glucose metabolism relative to that of fatty acids. By promoting glycolysis they tend to close the ATP-dependent potassium channels that help to mediate preconditioning. By lessening the oxygen-wasting effects of fatty acids, they are mitochondrial protective and oxygen-sparing. These qualities should help in the therapy of myocardial ischemia and also heart failure.     

Occurrence and Genotyping of Coxiella burnetii in Ixodid Ticks in Oromia,Ethiopia

This study was conducted from September 2011 to March 2014 to address the occurrence and genotypes of Coxiella burnetii using molecular methods in ticks collected from domestic animals in Ethiopia. Ticks were tested for C. burnetii by quantitative real-time polymerase chain reaction (qPCR) targeting two different genes followed by multispacer sequence typing (MST). An overall prevalence of 6.4% (54/842) of C. burnetii was recorded. C. burnetii was detected in 28.6% (14/49) of Amblyomma gemma, 25% (31/124) of Rhipicephalus pulchellus, 7.1% (1/14) of Hyalomma marginatum rufipes, 3.2% (2/62) of Am. variegatum, 3.1% (4/128) of Am. cohaerens, 1.6% (1/63) of Rh. praetextatus, and 0.6% (1/153) of Rhipicephalus (Boophilus) decoloratus. Significantly higher overall frequencies of C. burnetii DNA were observed in Am. gemma and Rh. pulchellus than in other tick species (Mantel–Haenszel [MH], P < 0.0001). The overall frequency of C. burnetii was significantly higher (MH, P < 0.0001) in ticks from southeastern districts (Arero, Moyale, and Yabelo) than that from other districts. This study demonstrated the presence of C. burnetii genotype MST 18 in ticks in southeastern districts and genotype MST 20 in ticks in central districts. This study highlights the importance of ticks in the epidemiology of C. burnetii in Ethiopia.     

The Axillary View Typically Does Not Contribute to Decision Making in Care for Proximal Humeral Fractures

Background

Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting.

Questions/Purposes

The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF.

Patients and Methods

PHF treated between 2009 and 2011 that were ordered for an AP, scapular Y, and axillary view was identified. The types of radiographs actually obtained were recorded. The cost of obtaining three views and a single view of the shoulder with X-ray was determined. Lastly, three surgeons reviewed 42 PHF, both with and without an axillary view (AV), and treatment recommendations were compared.

Results

30% of PHF in this series had an adequate axillary view, and 14% received a complete trauma series. No factors could be identified that were associated with successfully obtaining an axillary view. Reviewers demonstrated substantial intraobserver reliability (κ = 0.759–0.808) regarding treatment recommendations for PHF with and without the axillary view. The addition of the AV had minimal influence on treatment recommendations.

Conclusion

Considering that the axillary view for PHF is painful, labor-intensive, costly, and does not appear to provide additional diagnostic value, orthopedic surgeons can consider foregoing the use of the axillary view when evaluating and treating PHF, particularly if other advanced imaging is utilized.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9445-9) contains supplementary material, which is available to authorized users.