Joachim Lotz

Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial

BACKGROUNDnEmerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infarction. In this randomised trial, we aimed to assess whether intracoronary transfer of autologous bone-marrow cells could improve global left-ventricular ejection fraction (LVEF) at 6 months follow-up.nnnMETHODSnAfter successful percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction, 60 patients were randomly assigned to either a control group (n=30) that received optimum postinfarction medical treatment, or a bone-marrow-cell group (n=30) that received optimum medical treatment and intracoronary transfer of autologous bone-marrow cells 4.8 days (SD 1.3) after PCI. Primary endpoint was global left-ventricular ejection fraction (LVEF) change from baseline to 6 months follow-up, as determined by cardiac MRI. Image analyses were done by two investigators blinded for treatment assignment. Analysis was per protocol.nnnFINDINGSnGlobal LVEF at baseline (determined 3.5 days [SD 1.5] after PCI) was 51.3 (9.3%) in controls and 50.0 (10.0%) in the bone-marrow cell group (p=0.59). After 6 months, mean global LVEF had increased by 0.7 percentage points in the control group and 6.7 percentage points in the bone-marrow-cell group (p=0.0026). Transfer of bone-marrow cells enhanced left-ventricular systolic function primarily in myocardial segments adjacent to the infarcted area. Cell transfer did not increase the risk of adverse clinical events, in-stent restenosis, or proarrhythmic effects.nnnINTERPRETATIONnIntracoronary transfer of autologous bone-marrow-cells promotes improvement of left-ventricular systolic function in patients after acute myocardial infarction.

Intracoronary Bone Marrow Cell Transfer After Myocardial Infarction Eighteen Months’ Follow-Up Data From the Randomized, Controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) Trial

Background— Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered. Methods and Results– After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8±1.3 days after PCI. Cardiac MRI was performed 3.5±1.5 days, 6±1 months, and 18±6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001). Conclusions– In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.

Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial

AIMSnWe assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27).nnnMETHODS AND RESULTSnLeft ventricular ejection fraction and clinical status were re-assessed in all surviving patients after 61 +/- 11 months. Major adverse cardiac events occurred with similar frequency in both groups. When compared with baseline, LVEF assessed by magnetic resonance imaging at 61 months decreased by 3.3 +/- 9.5% in the control group and by 2.5 +/- 11.9% in the BMC group (P = 0.30). Patients with an infarct transmurality > median appeared to benefit from BMC transfer throughout the 61-month study period (P = 0.040).nnnCONCLUSIONnA single intracoronary application of BMCs does not promote a sustained improvement of LVEF in STEMI patients with relatively preserved systolic function. It is conceivable that a subgroup of patients with more transmural infarcts may derive a sustained benefit from BMC therapy. However, this needs to be tested prospectively in a randomized trial.

In vitro validation of phase-contrast flow measurements at 3 T in comparison to 1.5 T: Precision, accuracy, and signal-to-noise ratios†

To evaluate the signal‐to‐noise ratio (SNR), precision, and accuracy of phase‐contrast flow measurements at 3 T with the help of an in vitro model and to compare the results with data from two 1.5‐T scanners.

Hepatic artery embolization for treatment of patients with hereditary hemorrhagic telangiectasia and symptomatic hepatic vascular malformations

At present there is no established therapy for treating patients with hereditary hemorrhagic telangiectasia (HHT) and symptomatic hepatic involvement. We present the results of a prospective study with 15 consecutive patients who were treated with staged hepatic artery embolization (HAE). Branches of the hepatic artery were selectively catheterized and embolized in stages using polyvinyl alcohol particles (PVA) and platinum microcoils or steel macrocoils. Prophylactic antibiotics, analgesics and anti-emetics were administered after every embolization. Clinical symptomatology and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 28 months; range 10–136 months). Five patients had abdominal pain and four patients had symptoms of portal hypertension. The cardiac output was raised in all patients, with cardiac failure being present in 11 patients. After treatment, pain resolved in all five patients, and portal hypertension improved in two of the four patients. The mean cardiac output decreased significantly (P<0.001) from 12.57±3.27xa0l/min pre-treatment to 8.36±2.60xa0l/min at the end of follow-up. Symptoms arising from cardiac failure resolved or improved markedly in all but one patient. Cholangitis and/or cholecystitis occurred in three patients of whom two required a cholecystectomy. One patient with pre-existent hepatic cirrhosis died as a complication of the procedure. Staged HAE yields long-term relief of clinical symptoms in patients with HHT and hepatic involvement. Patients with pre-existing hepatic cirrhosis may be poor candidates for HAE.

Endoluminal treatment of aortic dissection

Aortic dissection is most often a catastrophic medical emergency which, if untreated, can be potentially fatal. The intention of therapy in patients with aortic dissection is to prevent aortic rupture or aneurysm formation as well as to relieve branch vessel ischaemia. Patients with aortic dissection are often poor candidates for anaesthesia and surgery and the surgical procedure itself is challenging requiring thoracotomy, aortic cross clamping, blood transfusion as well as prolonged hospital stay in some cases. Operative mortality is especially high in patients with critical mesenteric or renal ischaemia. The past decade has experienced the emergence of a number of interventional radiological or minimally invasive techniques which have significantly improved the management of patients with aortic dissection. These include stent grafting for entry site closure to prevent aneurysmatic widening of the false lumen as well as percutaneous techniques such as balloon fenestration of the intimal flap and aortic true lumen stenting to alleviate branch vessel ischaemia. False lumen thrombosis following entry closure with stent grafts has been observed in 86–100% of patients, whereas percutaneous interventions are able to effectively relieve organ ischaemia in approximately 90% of the cases. In the years to come, it is to be expected that these endoluminal techniques will become the method of choice for treating most type-B dissections and will assist in significantly reducing the number of open surgical procedures required for type-A dissections. The intention of this article is to provide an overview of the current status of these endoluminal techniques based on our own experience as well as on a review of the relevant literature.

No mid-term difference in mosaicplasty in previously treated versus previously untreated patients with osteochondral lesions of the talus

IntroductionOsteochondral transplantations, albeit technically challenging, appear promising not only in knee joint lesions, but also in the treatment of talus lesions. We hypothesized that in patients suffering osteochondral lesions of the talus, favorable outcomes are obtained in patients undergoing primary mosaicplasty as compared to patients undergoing secondary mosaicplasty.Materials and methodsOver a 3-year period (1998–2001), 14 patients (six male, eight female, median age 22xa0years) were treated with an autologous osteochondral transplantation of the talus. Eight patients were previously untreated (group I). Six patients had previous ankle procedures, such as microfracturing (group II). The median follow-up was 24xa0months and 100% complete at 12xa0months. The functional outcome was evaluated at least at 6xa0weeks, 12xa0weeks, and 1xa0year after surgery using pain on a visual analog scale (VAS) and sports activity was recorded at 1xa0year after surgery. In ten patients, magnetic resonance imaging (MRI) of the ankle was performed at 1xa0year after surgery (group I/II: 7/3).ResultsOverall ankle pain was decreased from 6.9xa0±xa02.1 to 4.0xa0±xa02.8 postoperatively. The mean knee pain for the donor knee was 2.6xa0±xa02.4. We found no significant difference between the primary mosaicplasty group and the secondary mosaicplasty group with regard to pain. MRI scans of ten patients showed a complete incorporation of the osteochondral cylinders at 1xa0year after surgery.ConclusionFavorable outcomes were obtained in patients undergoing primary mosaicplasty as compared to patients undergoing secondary mosaicplasty. We found no significant difference among patients with previous ankle surgery in contrast to those without, with a median 24-months follow-up.

Accuracy of Pedicle Screw Placement in Thoracic Spine Fractures

Background and Purpose:Transpedicular instrumentation in the thoracic spine is technically difficult because of small pedicle diameters. There are not many studies assessing in vivo accuracy, complications, and the revision rate of transpedicular screws in the thoracic spine. In this retrospective study 278 thoracic pedicle screws of 43 patients were assessed using a scoring system and postoperative computed tomography (CT) scans.Patients and Methods:43 consecutive patients with traumatic thoracic spine fractures underwent posterior transpedicular reduction and fixation. The universal spine system was used for placement of 278 pedicle screws under fluoroscopic control. Fractures were classified according to the Magerl classification by plain radiographs and CT scans. Evaluation of pedicle screw placement was assessed by a scoring system from grade I to grade III. Revision rate of pedicle screws as well as pre- and postoperative neurologic status were analyzed.Results:In the thoracic spine, vertebral body T7 was mainly fractured followed by T6 and T5. In 37 (86.0%) of 43 patients type C fractures and in three patients each type A and B fractures were determined, respectively. Of all 278 pedicle screws, 78.1% were inserted in pedicles T4–T9. The rate of optimally placed grade I screws was 84.5%. Grade II screws were scored in 6.8% and grade III screws in 8.6%. The revision rate of all pedicle screws was 5.0%, whereas 64.3% of these were grade III. None of the patients suffered neurologic or vascular structure compromise postoperatively.Conclusion:Although most pedicle screws were placed in pedicles of the middle thoracic spine where the pedicle width is smallest, most screws were optimally placed with grade I. The revision rate of pedicle screws was acceptable and associated with the grade of pedicle screw placement.

Inflammatory pseudotumor of the lung following invasive aspergillosis in a patient with chronic graft‐vs.‐host disease

Abstract:u2002 Inflammatory myofibroblastic tumor (IMT) is an uncommon cause of solitary or multifocal lung nodules and can also be rarely found in various other extrapulmonary sites. Although this pseudotumor is benign, it can be locally very aggressive. The pathogenesis of IMT remains unclear; autoimmune or infectious origins have been hypothesized, so far. Here, we report a case of inflammatory pseudotumor of the lung secondary to invasive pulmonary aspergillosis in a patient with chronic graft‐vs.‐host disease. The 42‐year‐old patient presented with coughing and hemoptysis as major clinical signs 1u2003yr after successful HLA‐identical stem cell transplantation. Aspergillus fumigatus was cultured from the bronchoscopoic lavage, but intensive antifungal treatment could only initially improve the clinical situation. Diagnostic re‐evaluation by open‐chest biopsy surprisingly revealed an inflammatory pseudotumor responsible for clinical and radiographical deterioration. Both clinical and radiographical signs resolved under long‐term steroids and secondary antifungal prophylaxis.

Automatic postprocessing for the assessment of quantitative human myocardial perfusion using MRI

ObjectiveQuantitative determination of myocardial perfusion currently involves time-consuming postprocessing. This retrospective study presents automatic postprocessing consisting of image registration and image segmentation to obtain regional signal intensity time courses and quantitative perfusion values.MethodsThe automatic postprocessing was tested in 75 examinations in volunteers and patients, 57 at rest and 18 under adenosine-induced stress, and compared with a manual evaluation. In a substudy consisting of 10 examinations, the interobserver variability of the manual evaluation was investigated.ResultsManual evaluation resulted in perfusion values with a median of 0.70xa0ml/g/min ranging from 0.03 to 3.68xa0ml/g/min. For all 75 examinations, the variability (standard deviation of the differences) between automatic and manual evaluation was 0.34xa0ml/g/min. Interobserver variability was of a similar order, 0.35xa0ml/g/min for all measurements.ConclusionsAutomatic evaluation was successfully applied to all datasets giving results equivalent to manual evaluation. The time of user interaction for one single slice could be reduced from 25xa0min for manual evaluation to less than 1xa0min using the automatic algorithm. This reduction may allow quantitative magnetic resonance perfusion imaging to become a routine clinical procedure.