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.

[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.

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.

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.

Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones.

Bile was obtained from patients with and without cholesterol gallstones at surgery. Biliary vesicles were separated from micelles by gel filtration. The cholesterol/phospholipid ratio in vesicles was much higher than in micelles. Cholesterol crystals nucleated from vesicular fractions, but nucleation from the micellar fractions was slow or did not occur at all. Cholesterol nucleated from vesicles obtained from bile of control patients as rapidly (2.4 days +/- 0.7) as from patients with stones (2.4 days +/- 0.9) and there was no difference in the vesicular cholesterol/phospholipid ratio. The effect of alteration of the bile salt environment was studied by changing the concentration of sodium cholate in the eluting buffer. At low concentrations (5 mM) only vesicles were eluted from the column. These vesicles had a relatively low cholesterol/phospholipid ratio and cholesterol nucleated slowly from these vesicles. At higher concentrations the proportion of micelles increased. The proportion of vesicles decreased progressively but their cholesterol/phospholipid ratio increased and the nucleation time fell. These studies demonstrate that cholesterol nucleates from vesicles in the absence of micelles, that control vesicles are not protected by tightly bound antinucleating substances and that exposure of vesicles to micelles strips relatively more phospholipid than cholesterol from the vesicular fraction, resulting in vesicles with higher cholesterol/phospholipid ratios and shorter nucleation times.

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.

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.

[Results of surgical treatment of dislocation fractures of the ankle joint]. / Výsledky operacního lécení luxacních zlomenin hlezna.

The authors have made evaluation of the surgical treatment of luxation fractures of the ankle in the period 1979-1987 in 105 patients (60 female, 45 male patients) in the age range from seventeen to eighty-one years, with the most frequent representation of the age group ranging from thirty-five to forty-five years. The group comprised 2,70 percent of fractures of type Weber A, 31.53 percent of fractures of type Weber B and 65.77 percent of fractures of type Weber C. 53 percent of patients were operated on the day of injury, 24.8 percent of patients were transferred with a delay from other clinics and in the rest of the patients the timely operation was contraindicated because of the poor local or general condition. The results were processed according to a uniform worksheet by the computer. On the basis of the evaluation there were found out 87.62 percent of successful and 12.38 percent of poor results. 93.3 percent of patients resumed their original jobs and there was no patient eligible for a full disability pension. The main cause of failure was the osteoarthritis of the ankle joint found out in connection with the inaffestable factors (such as defects of cartilage, nature of the bone lesion, luxation of talus, age and sex of the patient) and affectable factors (infection, failure of osteosynthesis, pseudoarthrosis of medial malleolus, non-anatomical position in the area of tibiofibular syndesmosis). The incidence of these negative factors may be reduced by a timely operation, precise surgical strategy and technique and proper post-operative treatment.

[Urethral stricture]. / Urethrastriktur.

The incidence of urethral stricture has increased since the introduction of gonorrhoea to Europe in the 15th century. Nowadays, transurethral instrumentations and catheterisations are responsible for the majority of the urethral strictures. The mechanism is inflammatory or traumatic lesion of the urethral epithelium causing extravasation of urine and fibrosis. The symptoms often suggest to infravesical obstruction. The diagnosis is made from the patient's history in combination with flowmetry, ante- and/or retrograde urethrography, external ultrasound examination or urethral calibration and is verified at urethroscopy. Dilatation is relatively simple but seldom curative and carries a considerable morbidity. Urethrotomy is very common but also hampered with a high rate of recurrence. A technique where urethrotomy is followed by intermittent self-catheterisation or implantation of a selfexpanding wire netting seems promising but needs further investigation. Reconstructive operations in form of a free or pedicled skin island patch, skin tube graft, endourethral free split skin graft, multistaged urethroplasty, meatoplasty and excision of prostatomebraneous stricture are followed by cure in 50-95% of the cases.

[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.

[EMLA cream (lidocaine/prilocaine) versus infiltration analgesia with carbocaine (mepivacaine) in vasectomy]. / Emla-creme (lidocain/prilocain) over for infiltrationsanalgesi med Carbocain (mepivacain) ved vasektomi. En randomiseret undersøgelse.

The analgesic efficacy of EMLA cream was compared with infiltration with 1% carbocaine in 13 bilateral vasectomies. Twelve patients preferred infiltration analgesia. EMLA analgesia was only effective in the skin, and had to be supplemented as the incision reached subcutaneous tissue.

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.

Transurethral incision of urethral diverticulum in the female.

A new technique of transurethral incision of urethral diverticulum was successfully used in two women. The method described is safe, simple and shortens operating time.

Transurethral, transprostatic incision of a seminal vesicle cyst. Case report.

Cystic lesions of the seminal vesicle are rare. We report on a new technique of transprostatic incision of a seminal vesicle cyst, which was used successfully in a patient with recurrent cyst 7 years after transrectal aspiration.