Ludwig Hoy

Early Calcification of Renal Allografts Detected by Protocol Biopsies: Causes and Clinical Implications

Interstitial calcification has been described in renal allografts, however, the etiology and significance of this finding for the graft are unclear. The aim of this study was to examine calcification in serial protocol biopsies, to test the hypothesis that calcification is related to parameters of calcium homeostasis in these patients and to analyze a possible relation between calcification and graft function at 1 year. We studied 213 patients with 586 protocol biopsies obtained 6 weeks, 3 and 6 months after transplantation. Calcifications increased over time, from 6.1% at 6 weeks to 17.8% at 6 months. Out of the 213 patients, 56 had calcification in one or more biopsies. Patients age and gender, underlying renal disease, dialysis mode and duration, previous transplantations, donor type, age and gender, HLA matches and ischemia time had no influence on calcification. Calcification was not related to rejection episodes, acute tubular lesions, calcineurin inhibitor toxicity or tubulointerstitial fibrosis and tubular atrophy. Patients with calcification had significantly higher serum parathormone and calcium levels. In patients with calcification, high PTH levels correlated with an inferior outcome of graft function at 1 year after transplantation (p < 0.05). Therefore, treatment of hyperparathyroidism should be considered earlier and more often in these patients.

Hypothermic circulatory arrest with selective antegrade cerebral perfusion in ascending aortic and aortic arch surgery: A risk factor analysis for adverse outcome in 501 patients

OBJECTIVE This study was undertaken to identify preoperative and intraoperative risk factors influencing outcome after operations requiring hypothermic circulatory arrest with selective antegrade cerebral perfusion in a single center. METHODS Between November 1999 and March 2006, a total of 501 consecutive patients (median age 64 years, range 20-86 years, 320 male) underwent aortic arch surgery with moderate hypothermic circulatory arrest (25 degrees C +/- 2 degrees C) and additional selective antegrade cerebral perfusion (14 degrees C) at our institution for various indications (256 aneurysms, 153 acute and 23 chronic type A aortic dissections, 66 other). Of these, 181 were emergency operations. Statistical analysis was carried out to determine risk factors for 30-day mortality as well as for temporary and permanent neurologic dysfunction. RESULTS Overall mortality was 11.6%. Permanent neurologic dysfunction occurred in 48 patients (9.6%); temporary neurologic dysfunction was detected in 67 patients (13.4%). Multivariate analysis revealed age (P = .001, odds ratio 1.08), reoperation (P = .006, odds ratio 3.58), femoral arterial cannulation (P = .004, odds ratio 2.87), and cardiopulmonary bypass duration (P < .001, odds ratio 1.009) as risk factors for mortality. Permanent neurologic dysfunction was associated with preoperative renal insufficiency (P = .029, odds ratio 2.79) and operation time (P < .001, odds ratio 1.005), whereas temporary neurologic dysfunction occurred in patients with coronary artery disease (P = .04, odds ratio 2.29), emergency surgery (P = .001, odds ratio 4.09), and increasing hypothermic circulatory arrest duration (P = .01, odds ratio 1.015). CONCLUSION Moderate hypothermic circulatory arrest in combination with cold selective antegrade cerebral perfusion is an adequate tool for neuroprotection during aortic surgery. Nevertheless, the safety of this technique is limited for patients with long intraoperative durations, advanced age, and multiple comorbidities. This technique, which avoids profound core temperatures, has become an alternative to simple deep hypothermic circulatory arrest.

The Hannover Dialysis Outcome study: comparison of standard versus intensified extended dialysis for treatment of patients with acute kidney injury in the intensive care unit

BACKGROUND Increasing the dose of renal replacement therapy has been shown to improve survival in critically ill patients with acute kidney injury (AKI) in several smaller European trials. However, a very recent large multicentre trial in the USA could not detect an effect of dose of renal replacement therapy on mortality. Based on those studies, it is not known whether a further increase in dialysis dose above and beyond the currently employed doses would improve survival in patients with AKI. We therefore aimed to assess mortality and renal recovery of patients with AKI receiving either standard (SED) or intensified extended dialysis (IED) therapy in the intensive care unit. METHODS A prospective randomized parallel group study was conducted in seven intensive care units of a tertiary university hospital. Pre-existing chronic kidney disease was an exclusion criterion. A total of 156 patients (570 screened) with AKI requiring renal replacement therapy were randomly assigned to receive standard dialysis [dosed to maintain plasma urea levels between 120 and 150 mg/dL (20-25 mmol/L)] or intensified dialysis [dosed to maintain plasma urea levels <90 mg/dL (<15 mmol/L)]. Outcome measures were survival at Day 14 (primary) and survival and renal recovery at Day 28 (secondary) after initiation of renal replacement therapy. RESULTS Treatment intensity differed significantly (P < 0.01 for plasma urea and administered dose). No differences between intensified and standard treatment were seen for survival by Day 14 (70.4% versus 70.7%) or Day 28 (55.6% versus 61.3%), or for renal recovery amongst the survivors by Day 28 (60.0% versus 63.0%). CONCLUSIONS Although this study cannot deliver a definitive answer, it suggests that increasing the dose of extended dialysis above the currently recommended dose might neither reduce mortality nor improve renal recovery in critically ill patients, mainly septic patients, with AKI.

Auricular acupuncture for dental anxiety: a randomized controlled trial.

Auricular acupuncture can be an effective treatment for acute anxiety, but there is a lack of direct comparisons of acupuncture to proven standard drug treatments. In this study we compared the efficacy of auricular acupuncture with intranasal midazolam, placebo acupuncture, and no treatment for reducing dental anxiety. Patients having dental extractions (n = 67) were randomized to (i) auricular acupuncture, (ii) placebo acupuncture, and (iii) intranasal midazolam and compared with a no treatment group. Anxiety was assessed before the interventions, at 30 min, and after the dental extraction. Physiological variables were assessed continuously. With the no treatment group as control, the auricular acupuncture group, and the midazolam group were significantly less anxious at 30 min as compared with patients in the placebo acupuncture group (Spielberger Stait-Trait Anxiety Inventory X1, P = 0.012 and <0.001, respectively). In addition, patient compliance assessed by the dentist was significantly improved if auricular acupuncture or application of intranasal midazolam had been performed (P = 0.032 and 0.049, respectively). In conclusion, both, auricular acupuncture and intranasal midazolam were similarly effective for the treatment of dental anxiety.

Pain measurements and side effect profile of the novel cannabinoid ajulemic acid

Preclinical findings on ajulemic acid (AJA) showed analgesic and anti-allodynic effects without psychoactive properties making it an appealing substance for the treatment of pain. A recently published randomized double-blind crossover clinical trial described the pain-reducing effects and side effect profile of AJA on 21 patients with chronic neuropathic pain. In this report from this same sample the effects of AJA on the mechanical hypersensitivity, on pain, and on psychological and physical performance were further characterized. During a 5-week study period, patients were divided into two 7-day treatment groups receiving either AJA or placebo capsules first, respectively. All patients received 40 and 80 mg of AJA or placebo daily in each treatment period. Pain measurements included the determination of mechanical hypersensitivity using the von Frey hair method as well as the visual analog scale (VAS), for which the number needed to treat (NNT) was calculated. The side effect profile of the compound was evaluated using psychotropic and physical measurements as well as obtaining reports on possible subjective side effects. The results showed no significant reduction in mechanical hypersensitivity (p=0.052), although a tendency towards pain reduction could be seen. The VAS score showed significant pain reduction (p=0.021) and NNT values for 30% pain relief were 2.14 for the first treatment group and 5.29 for the second treatment group. No significant findings were observed regarding psychotropic or physical measurements. Reported subjective side effects were mainly dry mouth, tiredness and dizziness and did not increase with dose elevation. Overall, these study findings indicate that AJA shows pain-reducing effects on patients with chronic neuropathic pain without clinically relevant psychotropic or physical side effects.

Isolated surgical aortic valve replacement after previous coronary artery bypass grafting with patent grafts: is this old-fashioned technique obsolete?

AIM High-risk patients are currently being evaluated for various catheter-based aortic valve replacement (AVR) techniques. To identify an individual patients risk, scores such as the EuroSCORE or STS risk calculator (RC) are used. The aim of the present study was to evaluate the surgical results in patients who underwent isolated AVR via a median re-sternotomy after prior CABG. PATIENTS AND METHODS Between 01/96 and 01/08, 349 patients underwent AVR as a redo procedure. One hundred and thirty patients had undergone previous CABG; in 39 patients (29 male, median age 75 (60-84)) preoperative coronary angiography revealed open grafts with no need for additional revascularization (30 had LIMA grafts). These patients underwent isolated AVR. Operative mortality was calculated using the standard and logistic EuroSCORE, and the STS RC. RESULTS Operative (30-day mortality) was 5% (2 patients). Mean calculated predicted mortality rates for the cohort were: 12+/-3% for the standard, and 32+/-21% for the logistic EuroSCORE, and 10+/-4% according to the STS RC. Receiver operated characteristics (ROC) analysis revealed 100% specificity for standard EuroSCOREs up to 12.5%, logistic EuroSCOREs up to 39.7% and up to 17.45% for STS RC, with a sensitivity of 69.5%, 75% and 97.2%, respectively. The STS RC showed significant better prediction of mortality than the EuroSCOREs (p=0.006). CONCLUSIONS Conventional AVR as a redo procedure after CABG with patent grafts can be performed with excellent results and lower mortality than estimated. Results of newer catheter-based AVR approaches should not to be compared with artificial scores to justify high morbidity rates.

The role of cerebrospinal fluid S100 and lactate to predict clinically evident spinal cord ischaemia in thoraco-abdominal aortic surgery.

OBJECTIVE Detecting spinal cord ischemia early during replacement of the thoracoabdominal aorta remains a challenge. In a high risk population, we have re-evaluated the potential impact of ischaemia/damage markers (S100, lactate) in the peripheral blood and CSF for perioperative patient management. PATIENTS AND METHODS Thirteen patients undergoing replacement of the thoracoabdominal aorta (6 female, age 63 (27-71)) with continuous CSF pressure monitoring and drainage were entered into the study. A total of 485 CSF (C) and serum (S) samples were collected and analysed for S100, lactate and glucose. RESULTS Two patients suffered from spinal cord injury (SCI) (15%). During and early after surgery, there was a strong correlation between C-S100 levels (r=0.79) and C-lactate levels (r=0.77) with time in patients with SCI. In patients with SCI C-lactate levels increased soon after aortic cross-clamping, whereas C-S100 levels did not become significantly elevated until 6 hours after cross-clamping. CONCLUSION An increase of C-lactate occurs much earlier than the increase in C-S100 in patients with SCI. Both parameters may be used to adjust protective and therapeutic measures intra- and postoperatively.

Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a randomized controlled trial. Auricular acupuncture and autogenic training in rheumatoid arthritis.

Background: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. Objective: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). Methods: Patients with RA (n = 44) were randomized into EA or AT groups. EA and lessons in AT were performed once weekly for 6 weeks. Primary outcome measures were the mean weekly pain intensity and the disease activity score 28 (DAS 28); secondary outcome measures were the use of pain medication, the pain disability index (PDI), the clinical global impression (CGI) and pro-inflammatory cytokine levels, which were assessed during the study period and 3 months after the end of treatment. Results: At the end of the treatment and at 3-month follow-up a clinically meaningful and statistically significant improvement (p < 0.05) could be observed in all outcome parameters and both groups. In contrast to the AT group, the onset of these effects in the EA group could already be observed after the 2nd treatment week. In the 4th treatment week the EA group reported significantly less pain than the AT group (p = 0.040). After the end of treatment (7th week) the EA group assessed their outcome as significantly more improved than the AT group (p = 0.035). The erythrocyte sedimentation rate in the EA group was significantly reduced (p = 0.010), and the serum concentration of tumor necrosis factor-alpha was significantly increased compared to the AT group (p = 0.020). Conclusions: The adjuvant use of both EA and AT in the treatment of RA resulted in significant short- and long-term treatment effects. The treatment effects of auricular EA were more pronounced.

The impact of deep and moderate body temperatures on end-organ function during hypothermic circulatory arrest.

OBJECTIVE Hypothermic circulatory arrest (HCA) at different temperatures is a protection technique for operations involving the aortic arch. In combination with selective cerebral perfusion, higher arrest temperatures for the remaining body may be permitted. However, the ischaemic/reperfusion injury (I/R) in various organ systems, other than the brain, related to the specific HCA temperature has so far not been evaluated. METHODS Fourteen pigs were randomly assigned to 60 min of sole HCA at 20 or 30 °C temperature, weaned from cardiopulmonary bypass (CPB) and followed 4h after HCA. Besides complex haemodynamic monitoring, laser-Doppler spectrophotometry for measuring capillary blood flow, tissue oxygen saturation and post-capillary venous filling pressures of the bowel was installed. At the end of experiment, organs were perfusion fixated and harvested. RESULTS During the entire experiment, haemodynamics revealed no differences between the groups. CPB bypass times were 177 ± 12 min in the 20 °C and 158 ± 11 min in the 30 °C group, respectively (p = 0.02). During reperfusion, lactate levels were initially significantly higher in the 30 °C animals (p = 0.001) but subsequently declined. Microcirculatory blood flow and velocity in the bowel were significantly reduced during cooling and reperfusion (p < 0.05), but were independent of final HCA temperature. Histological evaluation revealed significantly more oedema formation in the bowel wall of the 30 °C animals (p = 0.05). CONCLUSIONS Higher levels of circulating lactate levels during reperfusion indicate less effective organ protection at 30 than at 20 °C after 60 min of HCA. This is further substantiated by histological evidence for a more pronounced oedema inflammatory response within the bowel wall.

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1.

BackgroundMicro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time.MethodsPulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis.ResultsWe found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed.ConclusionsTogether, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.