„Oxygen to see“ bei der computertomographiegesteuerten Sympathikolyse

Background

The indications for chemical sympathectomy (CS) for sympathicolytic treatment of peripheral artery occlusive disease (PAOD) are still controversially discussed. This measure is not mentioned in the current guidelines of the transatlantic inter-society consensus document on management of peripheral arterial disease (TASC II). The reason is that CS could cause an increase in arteriovenous shunts and an improvement in oxygen saturation by CS has not yet been confirmed. Additionally, it was difficult to determine ex ante which patients could benefit from CS. “Oxygen to see” (O2C) allows a non-invasive measurement of microvascular perfusion under static conditions and an estimate of endothelial integrity by functional tests. This study tested the utilization of O2C in CS.

Material and methods

Patients with PAOD Fontaine stages III and IV underwent CS using a standard clinical protocol (temporary and definitive CS). Microcirculatory parameters (e.g. tissue oxygen saturation and blood flow) were recorded in a standardized protocol including baseline and functional measurements with O2C before and after CS. A total of eight patients with chronic ischemia of the extremities and no possibility of surgical and interventional revascularization were included in the study.

Aims

This pilot study investigated the effects on microvascular perfusion before and after CS using the O2C procedure to characterize potential pathophysiological mechanisms also in patients with diabetes.

Results

A clinical response to CS was shown by seven out of the eight patients. The O2C procedure was capable of discriminating between the clinically more prominent extremity and the contralateral side (baseline and functional oxygen saturation and flow). Functional measurements with a defined high positioning of the extremity (65 cm equivalent to 50 mmHg) were more qualified than static measurements to show CS-induced changes in tissue microcirculation.

Discussion

As measurable effects of CS on the microcirculation were evident which correlated with the clinical response, this method could be used to characterize microcirculatory changes when performing prospective controlled clinical trials in patients with chronic limb ischemia. This is particularly true for patients who are difficult to assess with clinical parameters (e.g. diabetic neuropathy).     

Changes in thigh muscle volume predict bone mineral density response to lifestyle therapy in frail,obese older adults

Summary

We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD.

Introduction

Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise.

Methods

One hundred seven obese older adults were randomized to control, diet, exercise, and diet–exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay.

Results

Thigh muscle volume decreased in the diet group (?6.2?±?4.8 %) and increased in the exercise group (2.7?±?3.1 %), while it was not significantly different from the control in the diet–exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23?±?20 %; 25?±?19 %) and diet–exercise group (20?±?19 %; 20.6?±?27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD (r?=?0.55, P?=?<0.001) and were an independent predictor of changes in hip BMD (β?=?0.12, P?=?0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no correlations between BMD changes and knee strength, 1-RM, and sclerostin changes.

Conclusions

Changes in thigh muscle volume predict hip BMD changes in obese older patients undergoing lifestyle therapy. The effect of exercise in attenuating thigh muscle loss when added to diet may in part account for the reduction in weight loss-induced bone loss in the diet–exercise group.     

Pretreatment with protease is a useful experimental strategy for enhancing adenovirus-mediated cancer gene therapy

A key impediment to the development of effective virus-mediated gene therapy for cancer is the low level of gene transfer that occurs after the administration of recombinant viral vectors. Improving in vivo infection and transduction efficiency is an important goal for gene therapy. The limited distribution of gene delivery is particularly problematic when large vectors such as recombinant adenoviruses and retroviruses are used to mediate transgene delivery to solid tumors. To facilitate the spread of virus, we have investigated the potential of administering proteases prior to the intratumoral inoculation of recombinant replication deficient adenovirus. For these studies, we chose proteases that are active against collagen and the other extracellular matrix proteins found in primary brain tumor tissue, but are not widely expressed in normal brain. Various concentrations of a mixture of collagenase/dispase or trypsin were inoculated into xenografts of human glioblastoma multiforme-derived brain tumor cell lines U87, U251, and SF767. Subsequently, recombinant adenovirus encoding the beta-galactosidase gene was administered and tumor tissue was examined for evidence of virus infection. Both collagenase/dispase and trypsin enhanced virus infection, indicating that protease pretreatment may be a useful strategy for enhancing virus-mediated gene transduction for many in vivo applications.     

Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflammatory diseases of skeletal muscle. In PM, CD8+ T cells invade and destroy muscle fibers, whereas humoral effector mechanisms prevail in DM. We studied the expression of the cytotoxic mediator perforin in inflammatory cells in PM and DM muscle by semiquantitative PCR, immunohistochemistry and confocal laser microscopy. Similar levels of perforin mRNA were expressed in PM and DM, and abundant perforin-expressing CD3+CD8+ and CD3+ CD4+ T cells were observed in both diseases. However, there was a striking difference in the intracellular localization of perforin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that contacted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distribution of perforin in the cytoplasm of muscle-infiltrating T cells observed in DM reflects nonspecific activation, and (b) that the vectorial orientation observed only in PM reflects the specific recognition via the T cell receptor of an antigen on the muscle fiber surface, pointing to a perforin- and secretion-dependent mechanism of muscle fiber injury.     

Multiaxial high-modularity spinopelvis (HMSP) fixation device in neuromuscular scoliosis: a comparative study

Purpose

To compare radiological and clinical results in patients operated for neuromuscular scoliosis with pelvic fixation using high-modularity spinopelvic screw (HMSP) designed by authors.

Methods

Of 54 patients with neuromuscular scoliosis, group 1 comprised of 27 patients with conventional pelvic fixation; and group 2 comprised of 27 patients using HMSP. Results were evaluated radiologically and functionally. We compared preoperative and postoperative complications, especially the loosening or breakage of spinopelvis fixation device, failure of fixation, and the change of shadow around the spinopelvis fixation device.

Results

There was no difference of correctional power, preoperative average Cobb’s angle of each group was 79.8 and 75 to postoperative 30.2 and 28.3 (P < 0.05). Pelvic obliquity improved from average 18.3°–8.9° in group I and average 24.3°–12.5° in group II (P < 0.05). However, there was no difference between two groups (P > 0.05). Average blood loss was 2,698 ml in group 1 and 2,414.8 ml in group 2 (P > 0.05). Average operative time was 360 min in group 1 and 332 min in group 2 (P = 0.30). There was no difference found between two groups regarding gait and functional evaluation. On the all cases of group 1 and 2, the change of shadow around the spinopelvis fixation device was observed. There was one case of the fracture of spinopelvis fixation device in group I.

Conclusion

There was no difference of Cobb’s angle and correctional power between the groups using HMSP when compared with the group using standard spinopelvis fixation device. Therefore, HMSP can be used more effectively in case of neuromuscular scoliosis.     

Laparoscopic mesh-augmented hiatoplasty without fundoplication as a method to treat large hiatal hernias

Purpose

Laparoscopic hiatal hernia repair with additional fundoplication is a commonly recommended standard surgical treatment for symptomatic large hiatal hernias with paraesophageal involvement (PEH). However, due to the risk of persistent side effects, this method remains controversial. Laparoscopic mesh-augmented hiatoplasty without fundoplication (LMAH), which combines hiatal repair and mesh reinforcement, might therefore be an alternative.

Methods

In this retrospective study of 55 (25 male, 30 female) consecutive PEH patients, the perioperative course and symptomatic outcomes were analyzed after a mean follow-up of 72 months.

Results

The mean DeMeester symptom score decreased from 5.1 to 1.8 (P < 0.001) and the gas bloating value decreased from 1.2 to 0.5 (P = 0.001). The dysphagia value was 0.7 before surgery and 0.6 (P = 0.379) after surgery. The majority of the patients were able to belch and vomit (96 and 92 %, respectively). Acid-suppressive therapy on a regular basis was discontinued in 68 % of patients. In 4 % of patients, reoperation was necessary due to recurrent or persistent reflux. A mesh-related stenosis that required endoscopic dilatation occurred in 2 % of patients.

Conclusions

LMAH is feasible, safe and provides an anti-reflux effect, even without fundoplication. As operation-related side effects seem to be rare, LMAH is a potential treatment option for large hiatal hernias with paraesophageal involvement.     

Do surgeon credentials affect the rate of incidental durotomy during spine surgery

Purpose

Incidental durotomy is a potential complication of spinal surgery which can cause a number of intra-operative and post-operative complications. The purpose of this study was to determine if the primary operator’s credentials impacted on the incidence of durotomy intra-operatively.

Methods

Prospectively collected data of operator credentials in relation to the incidence of durotomy were acquired from the International Eurospine Tango database. The significance of variability and risk factors between operators was measured using the Chi-squared test.

Results

Data from a total of 3,764 patients were captured from the Tango registry. Of these 162 (4.3 %) had a durotomy. Of the total number of patients, the primary operator was neurosurgical in 1,369 (36.4 %) cases; orthopaedic in 180 (4.8 %) cases; other (pre-certification) in 236 (6.3 %) cases; specialised spine surgeon in 1,741 (46.3 %) cases; 6 cases had missing operator data. cerebrospinal fluid (CSF) leak occurred in 57 (4.16 %) of neurosurgeon-operated cases; 5 (2.78 %) orthopaedic-operated cases; 19 (4.06 %) of other surgeon-operated cases; and 81 (4.65 %) in specialised spine surgeon-operated cases. Using Chi-squared test, the significance of the variation in incidence of CSF leak between primary operator groups was not statistically significant (P = 0.1405).

Conclusion

From the data captured and analysed, the rate of durotomy ranged from 2.78 to 4.65 % between operator groups with a mean rate of 4.3 %. The primary operator credentials do not appear to significantly impact the rate of durotomy in spine surgery.     

Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture?

Summary

In an observational study population of 62,413 individuals (6,455 [10 %] with diabetes), diabetes was independently associated with major osteoporotic fractures (MOFs) but did not significantly modify the effect of FRAX^TM risk factors or prior fracture site. However, the presence of diabetes exerted a much stronger effect on hip fracture risk in younger versus older individuals.

Introduction

Diabetes mellitus increases fracture risk independent of risk factors that comprise the WHO FRAX^TM tool. We explored whether diabetes modifies the effect of FRAX clinical risk factors on MOF and hip fracture risk.

Methods

Using a registry of clinical dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified women and men aged 40 years and older undergoing baseline DXA in 1996–2011. Health services data were used to identify diabetes diagnosis, FRAX risk factors and incident fractures using previously validated algorithms. Prior fracture was stratified as clinical vertebral, hip, humerus, forearm, pelvis and ‘other’. Cox proportional hazards models were used to test for statistical interactions of diabetes with FRAX clinical risk factors and prior fracture site.

Results

During a mean follow-up of 6 years, there were 4,218 MOF and 1,108 hip fractures. Diabetes was a significant independent risk factor for MOF adjusted for FRAX risk factors including bone mineral density (BMD) (adjusted hazard ratio [aHR] 1.32 [95 % confidence interval (CI) 1.20–1.46]). No significant interactions of FRAX risk factors or prior fracture site with diabetes were identified in analyses of MOF. For predicting hip fractures, age significantly modified the effect of diabetes (aHR age <60, 4.67 [95 % CI 2.76–7.89], age 60–69, 2.68 [1.77–4.04], age 70–79, 1.57 [1.20–2.04], age >80, 1.42 [1. 10–1.99]; pinteraction <0.001).

Conclusions

Diabetes is an independent risk factor for MOFs and does not significantly modify the effect of FRAX risk factors or prior fracture site. However, diabetes exerts a much stronger effect on hip fracture risk in younger than older individuals which needs to be considered in hip fracture prediction.     

Multimorbidity in women with and without osteoporosis: results from a large US retrospective cohort study 2004–2009

Summary

To determine the incidence of comorbidities in women with and without osteoporosis, incidence rates per 1,000 person-years were calculated using electronic health records from an integrated healthcare system. The overall comorbidity burden and health service utilization were greater in women with osteoporosis than in the controls.

Introduction

This retrospective cohort study describes the incidence of an array of comorbidities in women with and without osteoporosis (OP).

Methods

Using electronic health records from an integrated healthcare system, we identified 22,414 women aged 55–89 years with OP and 22,414 age-matched controls without OP. Incidence rates (IRs) per 1,000 person-years (P-Y) were calculated and 95 % confidence intervals (CI) were estimated.

Results

Women with OP had significantly more comorbidities, medications, hospitalizations, and outpatient visits than the controls. Most cardiac comorbidity rates were 20–25 % lower in the OP cohort than in the control cohort. Hypertension had the largest rate difference; the IR was 42.0 per 1,000 P-Y (95 % CI 40.2–44.0) in the OP cohort compared to 94.0 (95 % CI 90.7–97.4) in the control cohort. Rates for cerebrovascular disease were similar for both cohorts at 26 per 1,000 P-Y. Bronchitis, sinusitis, and cystitis were each 55 per 1,000 P-Y in the OP cohort, whereas they ranged from 28 to 34 per 1,000 P-Y in the controls. The OP cohort had decreased incidence of ovarian, uterine, colorectal, and liver cancers and increased incidence of lung cancer, breast cancer, and multiple myeloma, compared to the non-OP cohort. Falls, depression, vision, and musculoskeletal issues were higher for the OP cohort than the controls.

Conclusions

This study demonstrates the high disease burden in women with OP. This knowledge may help guide the clinical management of this population and may aid in the interpretation of adverse events in randomized clinical trials of OP therapies.