The effectiveness of the paclitaxel-coated Luminor® balloon catheter versus an uncoated balloon catheter in superficial femoral and popliteal arteries in preventing vessel restenosis or reocclusion: study protocol for a randomized controlled trial.

BACKGROUND: The aim of this investigator-initiated trial is to evaluate the safety and efficacy of the novel Luminor® paclitaxel-coated drug-eluting balloon (DEB) catheter (iVascular, S.L.U., Barcelona, Spain) in inhibiting restenosis and in ensuring long-term vascular patency. METHODS/DESIGN: This is a multicenter randomized controlled trial to evaluate the Luminor® paclitaxel-coated DEB catheter for stenotic or occlusive lesions (length ≤15 cm) in the superficial femoral artery (SFA) and the popliteal artery (PA) up to the P1 segment compared to the noncoated, plain old balloon angioplasty (POBA) catheter. In total 172 subjects will be treated with either the DEB catheter or the POBA catheter in 11 German study centers in a 1:1 randomization study design. The primary endpoint is late lumen loss (LLL) at 6 months. Secondary endpoints are patency rate, target lesion/vessel revascularization, quality of life (assessed with the Walking Impairment Questionnaire (WIQ) and the EQ-5D), change of Rutherford stage and ankle-brachial index, major and minor amputation rate at the index limb, number of dropouts and all-cause mortality. DISCUSSION: EffPac represents a randomized controlled trial that will provide evidence on the effectiveness of the Luminor® paclitaxel-coated DEB catheter for the reduction of restenosis compared to the POBA catheter for the SFA and the PA. The results of EffPac will allow direct comparison to other already-completed RCTs applying paclitaxel-coated DEBs from different manufacturers with different coating technologies in the same target vessel. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540018 , registered on 17 August 2015. Protocol version: CIP Version Final04, 11 February 2016. EUDAMED No: CIV-15-03-013204.

Ischemic Left Ventricular Perforation Covered by a Thrombus in a Patient Presenting with Cerebral Ischemia: Importance of Time-Sensitive Performance and Adequate Interpretation of Bedside Transthoracic Echography.

If myocardial infarction remains silent, only clinical signs of complications may unveil its presence. Life-threatening complications include myocardial rupture, thrombus formation, or arterial embolization. In the presented case, a 76-year-old patient was admitted with left-sided hemiparesis. In duplex sonography, a critical stenosis of the right internal carotid artery was identified and initially but retrospectively incorrectly judged as the potential cause for ischemia. During operative thromboendarterectomy, arterial embolism of the right leg occurred coincidentally, more likely pointing towards a cardioembolic origin. Percutaneous interventions remained unsuccessful and local fibrinolysis was applied. Delayed bedside echocardiography by an experienced cardiologist demonstrated a discontinuity of the normal myocardial texture of the left ventricular apex together with an echodense, partly floating structure merely attached by a thin bridge not completely sealing the myocardial defect, accompanied by pericardial effusion. The patient was immediately transferred to emergency cardiac surgery with extirpation of the thrombus, aortocoronary bypass graft placement, and aneurysmectomy. This didactic case reveals decisive structural shortcomings in patient's admission and triage processes and underlines, if performed timely and correctly, the value of transthoracic echocardiography as a noninvasive and cost-effective tool allowing immediate decision-making, which, in this case, led to the correct but almost fatally delayed diagnosis.

Guideline-conforming timing of invasive management in troponin-positive or high-risk ACS without persistent ST-segment elevation in German chest pain units. Urban university maximum care vs. rural regional primary care.

AIM: This study aimed to analyze guideline adherence in the timing of invasive management for myocardial infarction without persistent ST-segment elevation (NSTEMI) in two exemplary German centers, comparing an urban university maximum care facility and a rural regional primary care facility. METHODS: All patients diagnosed as having NSTEMI during 2013 were retrospectively enrolled in two centers: (1) site I, a maximum care center in an urban university setting, and (b) site II, a primary care center in a rural regional care setting. Data acquisition included time intervals from admission to invasive management, risk criteria, rate of intervention, and medical therapy. RESULTS: The median time from admission to coronary angiography was 12.0 h (site I) or 17.5 h (site II; p = 0.17). Guideline-adherent timing was achieved in 88.1 % (site I) or 82.9 % (site II; p = 0.18) of cases. Intervention rates were high in both sites (site I-75.5 % vs. site II-75.3 %; p = 0.85). Adherence to recommendations of medical therapy was high and comparable between the two sites. CONCLUSION: In NSTEMI or high-risk acute coronary syndromes without persistent ST-segment elevation, guideline-adherent timing of invasive management was achieved in about 85 % of cases, and was comparable between urban maximum and rural primary care settings. Validation by the German Chest Pain Unit Registry including outcome analysis is required.

Pitfalls in suspected acute aortic syndrome: impact of appropriate and if required repeated imaging.

The incidence of acute aortic syndrome is low, but the spontaneous course is often life-threatening. Adequate ECG-gated imaging is fundamental within the diagnostic workup. We here report a case of a 53-year-old man presenting with atypical chest pain, slight increase of D dimers at admission, and extended diameter of the ascending aorta accompanied by mild aortic regurgitation. Interpretation of an initial contrast-enhanced computed tomography was false negative due to inadequate gating and motion artifacts, thereby judging a tiny contrast signal in the left anterior quadrant of the ascending aorta as a pseudointimal flap. By hazard, cardiac magnetic resonance imaging demonstrated an ulcer-like lesion superior to the aortic root, leading to aortic surgery at the last moment. As sensitivity of imaging is not 100%, this example underlines that second imaging studies might be necessary if the first imaging is negative, but the clinical suspicion still remains high.

Combination of rotational atherothrombectomy and Paclitaxel-coated angioplasty for femoropopliteal occlusion.

OBJECTIVE: The rotational atherothrombectomy with Straub Rotarex(®) is a safe and efficient treatment of acute/subactute vascular occlusions. The purpose of this study was to evaluate the benefit of paclitaxel-coated angioplasty after rotational atherothrombectomy over an observation period of six months. MATERIALS AND METHODS: Overall, 29 patients were treated with the Rotarex catheter in combination with paclitaxel-coated angioplasty. All patients had acute/subacute and chronic occlusions of the superficial femoral artery (SFA) and/or popliteal arteries. The ankle-brachial index (ABI) was detected before the intervention, after the procedure, and after six months. Also clinical examination and ultrasound scans were done in the observation period. RESULTS: There were no technical failures. The ABI shows a significant increase from 0.52 ± 0.17 to 0.91 ± 0.25 in the follow-up. By ultrasound examination, there were found two (6.9%) restenoses during the follow-up. There was one dissection during the intervention (3.5%). CONCLUSION: The rotational atherothrombectomy in combination with paclitaxel-coated angioplasty might be an effective and safe method with a promising low rate of restenosis at six months.

Superficial femoral artery TASC D Registry: twelve-month effectiveness analysis of the Pulsar-18 SE nitinol stent in patients with critical limb ischemia.

AIM: Single center observational study analyzing the primary patency rate and freedom from target lesions revascularization rate of the Pulsar-18 nitinol stent after recanalization of long superficial femoral artery (SFA) occlusions (TASC D) in 22 patients with critical limb ischemia (CLI). METHODS: Between 1/2011 and 7/2011, 22 consecutive patients (9 male, 13 female) with chronic total occlusions (CTO) of the femoro-popliteal arteries presenting with CLI (17 patients with Rutherford 4 score, and 5 patients with Rutherford 5 score) were enrolled and successfully recanalized using the Pulsar-18 self-expanding (SE) nitinol stent (BIOTRONIK AG, Buelach, Switzerland). Primary patency at 12 months was defined as no binary restenosis (>50%) on Duplex ultrasound (PSVR<2.5) and respectively no target lesion revascularization performed within 12 months. The average lesion length of the treated femoro-popliteal segment was 315 mm. Performing spot stenting average stent length in all patients was 245 mm (minimal 215 mm, maximal 315 mm). RESULTS: Technical success, with establishing an antegrade straight line flow to the foot through a reopened SFA, was achieved in all 22 patients. Subintimal and intraluminal recanalization techniques were used. Two patients with Rutherford 5 score had a minor amputation shortly after the recanalization procedure. All other patients had a complete wound healing of their lesions during a 6 month follow-up. After 12 month follow-up the primary patency rate of the Pulsar-18 SE nitinol stent was 77% with a per protocol restenosis in 5 of 22 patients. Seventeen patients showed a walking capacity on treadmill test >300 meters (Rutherford II). Two patients with a documented restenosis were Rutherford, these patients were treated conservatively. Three patients with restenosis and a Rutherford III score were scheduled for an endovascular target lesion revascularization leading to a freedom from target lesion revascularization rate of 86%. CONCLUSION: Endovascular intervention of long SFA occlusions using subintimal or intraluminal recanalization technique with implantation of the Pulsar-18 SE nitinol stent in CLI patients is safe and clinically effective with a primary patency rate after 12 months of 77% and a freedom from target lesion revascularization rate of 86%.

The Parkinson's disease protein LRRK2 impairs proteasome substrate clearance without affecting proteasome catalytic activity.

Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common known cause of Parkinson's disease (PD). The clinical features of LRRK2 PD are indistinguishable from idiopathic PD, with accumulation of α-synuclein and/or tau and/or ubiquitin in intraneuronal aggregates. This suggests that LRRK2 is a key to understanding the aetiology of the disorder. Although loss-of-function does not appear to be the mechanism causing PD in LRRK2 patients, it is not clear how this protein mediates toxicity. In this study, we report that LRRK2 overexpression in cells and in vivo impairs the activity of the ubiquitin-proteasome pathway, and that this accounts for the accumulation of diverse substrates with LRRK2 overexpression. We show that this is not mediated by large LRRK2 aggregates or sequestration of ubiquitin to the aggregates. Importantly, such abnormalities are not seen with overexpression of the related protein LRRK1. Our data suggest that LRRK2 inhibits the clearance of proteasome substrates upstream of proteasome catalytic activity, favouring the accumulation of proteins and aggregate formation. Thus, we provide a molecular link between LRRK2, the most common known cause of PD, and its previously described phenotype of protein accumulation.

[Use of the OUTBACK Re-entry Catheter for recanalization of a joint-transversing extensive occlusion of the femoral and popliteal arteries]. / Einsatz des Outback-Reentry-Katheters zur Rekanalisation eines gelenküberschreitenden langstreckigen Verschlusses der A. femoralis und A. poplitea.

Application of modern techniques for recanalization can now serve to reopen extensive chronic occlusions of the femoral artery with good results. A guide catheter and stiff J Terumo wires are used to perform subintimal recanalization. Once the occlusion site has been traversed in the subintimal plane the challenge lies in the re-entry maneuver to restore the true vessel lumen. Use of the OUTBACK catheter has proven to be particularly well suited for this purpose during which a biopsy of the true vessel lumen is obtained by advancing a needle.

Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues.

The requirement for cholesterol is greater in developing tissues (fetus, placenta, and yolk sac) as compared to adult tissues. Here, we compared cholesterol-induced suppression of sterol synthesis rates in the adult liver to the fetal liver, fetal body, placenta, and yolk sac of the Golden Syrian hamster. Sterol synthesis rates were suppressed maximally in non-pregnant adult livers when cholesterol concentrations were increased. In contrast, sterol synthesis rates were suppressed only marginally in fetal livers, fetal bodies, placentas, and yolk sacs when cholesterol concentrations were increased. To begin to elucidate the mechanism responsible for the blunted response of sterol synthesis rates in fetal tissues to exogenous cholesterol, the ratio of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) to Insig-1 was measured in these same tissues since the ratio of SCAP to the Insigs can impact SREBP processing. The fetal tissues had anywhere from a 2- to 6-fold greater ratio of SCAP to Insig-1 than did the adult liver, suggesting constitutive processing of the SREBPs. As expected, the level of mature, nuclear SREBP-2 was not different in the fetal tissues with different levels of cholesterol whereas it was different in adult livers. These findings indicate that the suppression of sterol synthesis to exogenous sterol is blunted in developing tissues and the lack of response appears to be mediated at least partly through relative levels of Insigs and SCAP.

Yolk sac cholesteryl ester secretion rates can be manipulated in the Golden Syrian hamster: effect of yolk sac cholesterol concentrations.

The yolk sac is one of two extra-embryonic fetal tissues that separates the fetal and maternal circulations. The yolk sac can secrete lipoprotein particles to the vitelline vessels, which supply yolk sac-derived nutrients to the embryo. The amount and composition of lipoproteins secreted from the rat yolk sac can be manipulated by fatty acid content and gestational age. The goals of the current studies were to determine, first, if tissue cholesterol concentration could mediate cholesterol secretion rate from the yolk sac and, second, if some of the secreted cholesterol could be derived from the maternal circulation. Golden Syrian hamsters were fed 2% added cholesterol to increase the yolk sac cholesterol concentration. Yolk sac explants secreted similar amounts of triglyceride and apolipoproteins B and E into the media regardless of yolk sac cholesterol concentration. In contrast, yolk sacs with greater cholesterol concentrations secreted 2.3-fold more cholesterol into the media as compared to control yolk sacs; the increase was found mostly as cholesteryl ester. At least part of the secreted cholesterol was maternally derived. These data demonstrate that yolk sac cholesterol concentration influences cholesterol secretion rates, and that at least some of the cholesterol secreted originates from the maternal circulation.

[New antithrombotic therapy approaches in coronary heart disease--prospects for gene therapy]. / Neue antithrombotische Therapieansätze bei koronarer Herzerkrankung--Perspektiven einer Gentherapie.

Despite considerable progress, pharmacological therapies have not provided a complete solution for common cardiovascular problems, including recurrent thrombosis, restenosis, and vein graft deterioration. Optimal drug dosage, reproducing plasma concentrations achieved in animal studies establishing proof-of-principle, would often be too toxic to administer. Local gene therapy aims at overexpressing proteins that regulate the cell cycle of vascular smooth muscle cells, inhibit vascular smooth muscle cell migration, endow the endothelium with enhanced vasoprotective properties. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote vascular smooth muscle cell proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, where it can extend the presence of this agent to weeks and, with some gene vectors, to many months. This review summarizes and discusses antithrombotic gene therapy approaches for the prevention of restenosis and late thrombosis after catheter-based revascularizations.

Results of radiotherapy on ureteric obstruction in muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer. PATIENTS AND METHODS: Retrospective evaluation of the records of 574 patients with muscle-invasive bladder cancer revealed 90 patients (16%) with ureteric obstruction; the obstruction was bilateral in 24%. The effect of radiotherapy was assessed in 55 patients with 68 obstructed kidneys. Six patients with eight obstructed kidneys required percutaneous nephrostomy or ureteric catheters in addition to radiotherapy. RESULTS: Drainage improved in 20% of kidneys and the diverting catheter was withdrawn permanently in one (17%) of the diverted patients. The median survival was 11 months. Irradiation was followed by significant complications in 37 patients (67%). CONCLUSION: The results of this study raise doubts about the assumed beneficial effect of irradiation on ureteric obstruction due to muscle-invasive bladder cancer. The short median survival of 11 months confirms that ureteric obstruction is a poor prognostic factor in muscle-invasive bladder cancer.

Removal of internal fixation--the effect on patients' complaints: a study of 66 cases of removal of internal fixation after malleolar fractures.

To estimate the effect of removal of internal fixation after treatment of malleolar fractures on postoperatively presented complaints, we retrospectively evaluated 66 patients by their records and by personal questionnaires. Of all the patients, 89.4% had one or more complaints. These were typically soreness over implant and cicatrix, reduced movement of the ankle joint, and strain-related pain. About 75% of these patients reported improvement after removal. The AO mode of fixation, i.e., typically by lateral semitubular plating and transsyndesmotic screw and a medial screw or pins, and the Wiberg-Cedell mode, i.e., typically consisting of lateral single or double cerclage and staple and medial pinning, constituted the principal groupings of the patients. The two groups were comparable. In this series, we found significantly more complaints associated with the AO mode in the postoperative period. We conclude that removal of internal fixation after malleolar fractures is indicated when common types of complaints are presented.

Hormonal treatment of obstructed kidneys in patients with prostatic cancer.

A review of 1288 patients with previously untreated prostatic cancer revealed 209 patients (16%) with ureteric obstruction; the obstruction was bilateral in 36%. The effect of hormonal treatment was assessed in 88 patients with 120 obstructed kidneys: 77 patients had androgen deprivation or hormonal medication alone and 11 patients needed percutaneous nephrostomy or ureteric catheters in addition. Drainage improved in 58% of the kidneys. The diverting catheter was withdrawn in 9 of the 11 patients after a median of 4 weeks. In all, 95% of patients were discharged. The patients with hormonal therapy alone survived for a median of 26 months (range 1-111), while the patients who also needed diversion survived for a median of 13 months (range 1-28). The median time spent at home was 24 months (0-102) and 10 months (0-23) respectively, presumably reflecting the worse general condition of the patients who required diversion.

[Hyperemesis gravidarum]. / Hyperemesis gravidarum.

On the basis of the literature available, no certain proof can be found that human chorion gonadotropin, progesterone, oestradiol, ACTH, thyreoid patrameters or vitamin B6 are of causal significance for hyperemesis gravidarum (HG). Hyperemesis gravidarum has undoubtedly a considerable psychological basis. The frequency is greatest in industrialized societies and change of environment, in itself, is frequently adequate treatment. There does not appear to be any definite increase in the incidence of malformations in infants of mothers with hyperemesis gravidarum and, similarly, the remainder of the pregnancy usually runs a normal course. All of the forms of treatment are dominated by the tendency to spontaneous remission and great placebo effect. Antihistamines, antiemetics, ginger, change of environment, hypnotherapy and psychotherapy appear to be the best forms of treatment.

Adenocarcinoma of the prostate and metastatic medullary compression. A retrospective study of 22 patients.

A retrospective study of 709 patients with prostatic cancer was carried out. Twenty-two developed medullary cord compression (an incidence of 3%). All but two of the 22 patients were treated by radiation and 10 had additional hormonal treatment. Ten had some benefit from the treatment, but only 2 of 19 regained their ability to walk. The need for immediate diagnosis and treatment is stressed.

Local anesthesia for extracorporeal shock wave lithotripsy: a study comparing eutetic mixture of local anesthetics cream and lidocaine infiltration.

A study of the anesthetic efficacy of a eutetic mixture of local anesthetics (EMLA cream) versus lidocaine infiltration in extracorporeal shock wave lithotripsy (ESWL) was done. A total of 46 patients had 30 gm. of EMLA cream applied to the skin over the kidney and 45 had subcutaneous infiltration anesthesia with 20 ml. 1% lidocaine with epinephrine. All patients received an intravenous dose of morphine just before ESWL. The patients were comparable with regard to age, sex, weight, morphine dosage, number of shock waves given and duration of treatment. Median pain score and the amount of supplementary analgesics were not significantly different between the 2 groups. There were no significant differences between the groups with regard to post-ESWL skin changes. Therefore, EMLA cream can be recommended for ESWL provided it is applied correctly.

Topical anesthesia with eutetic mixture of local anesthetics cream in vasectomy: 2 randomized trials.

Two paired randomized trials testing topical anesthesia with a eutetic mixture of local anesthetics (EMLA cream*) in vasectomy were performed. In 1 trial EMLA cream was applied on 1 side of the scrotum, while infiltration anesthesia into the skin and subcutaneous tissue with mepivacaine was used on the contralateral side. All but 1 of the 13 patients (p less than 0.05) preferred infiltration anesthesia because of pain as the incision reached the subcutaneous tissue. In the other trial 29 patients received EMLA cream on 1 side of the scrotum before bilateral mepivacaine infiltration. There was significantly less pain on the sides with the anesthetic cream (p less than 0.001). Many patients would pay the price of the cream. In conclusion, EMLA cream cannot replace but it can supplement infiltration anesthesia during vasectomy.

PIP: 2 types of randomized trials of a topical melting cream containing a mixture of local anesthetics (EMLA cream) alone or with infiltration with mepivacaine are reported in men having vasectomy. A sequential trial design was used so that the trial could be stopped when statistical significance was reached. EMLA cream was applied to a 20 square cm area and covered with occlusive tape for 30 minutes preoperatively. In the 1st trial 13 men received EMLA cream on one side and mepivacaine on the other. 12 of 13 preferred infiltration because they experienced pain when the incision reached the subcutaneous tissue. Subjects rated the procedure with EMLA cream as more painful than the one on the contralateral side, and 4 stated that they would have preferred the cream before infiltration. The procedure took on average 2 minutes longer to allow for another mepivacaine injection. In the 2nd trial 29 men had either infiltration anesthesia or both. All 15 men who had both anesthetics preferred the combined anesthesia, and 14 of the 15 stated that they would be willing to pay out-of pocket for the cream.

Long-term results of carbon dioxide laser treatment of meatal condylomata acuminata.

A group of 74 men who underwent carbon dioxide laser treatment of meatal condylomata were observed for an average of 18 months. The cure rate after 1 treatment of isolated meatal lesions was 78%; the presence of external lesions lowered the rate to 32% and additional external and urethral warts to 25%. Following multiple treatments all but 6 patients were cured; 83% of the recurrences developed within 3 months. One urethral and 6 meatal strictures occurred more than 3 months after treatment; 9 patients had a spraying stream many years after treatment and 2 complained of frequency.