Decommission of a Heartmate 3 LVAD in a patient with left ventricular recovery.

BACKGROUND: Left ventricular assist devices (LVADs) have been a significant development in the treatment of patients with advanced heart failure supporting circulation as a bridge to transplant, recovery, or long-term destination therapy. When ventricular recovery occurs, there are multiple described ways of proceeding. HM2 decommissions are well described with varying degrees of explant operations, less so in HM3 due to the novelty of the device. In certain situations, invasive surgery can carry high risk and so a minimally invasive decommission, leaving the LVAD essentially intact in situ can be considered. CASE REPORT: In this report, we describe the case of a 35-year-old male diagnosed with an idiopathic dilated cardiomyopathy requiring an LVAD with subsequent identification of cardiac recovery with the asymptomatic thrombosis of the second HM3 device. Investigations demonstrated absent flow through the pump whilst the patient-reported NYHA I functional class symptoms. The Driveline was cut with the remaining internal pump components decommissioned and left in situ. At 1 year, the patient continues to do well with continued features of cardiac recovery with an LVEF of over 40%. CONCLUSION: LV recovery is well recognized with typical management being LVAD explant surgeries performed. Each case should be analyzed for risks and benefits to the patient and future research showed be directed towards levels of decommissioning surgery and management post-LVAD decommission patient care.

[Effectiveness of abdominal minimal incision sacrocolpopexy for advanced pelvic organ prolapse].

Objective: To evaluate the indications, surgical skills and clinic outcomes of abdominal minimal incision sacrocolpopexy (AMISC) for treatment of advanced pelvic organ prolapse (POP). Methods: The retrospective study analyzed 30 women with advanced POP who underwent AMISC between June 2016 and October 2019, including 9 cases of recurrent prolapse and 10 cases of vault prolapse. AMISC was especially applicable to: (1) patients with several medical complications who was unable to tolerate general anesthesia or laparoscopic surgery, but able to tolerate combined spinal-epidural anesthesia and open surgery; (2) other abdominal procedures were indicated to perform with AMISC simultaneously, such as myomectomy, subtotal hysterectomy etc, the specimens were easy to get out of the abdominal cavity and morcellation was avoided; (3) surgeons preferring open surgery to laparoscopic surgery or skilled in open surgery; (4) patients with prior pelvic operations, presenting severe abdominal and pelvic adhesions. Objective outcomes were assessed by pelvic organ prolapse quantification (POP-Q) system. Subjective outcome were assessed by pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form (PFIQ-7) and patient global impression of improvement (PGI-I). Results: All patients with 1-3 medical complications were successfully performed with AMISC without stopping procedure, enlarging the incision or changing to other procedure, the operation duration was (110±19) minutes. The mean time of follow-up was (33.5±12.4) months (range: 8-49 months). The postoperative points of Aa, Ba, C, Ap, Bp reduced significantly and point C improved from (2.33±2.50) cm to (-7.54±1.18) cm after AMISC (P<0.01). The objective cure rates were both 100% (30/30) in apex and posterior compartment, while 97% (29/30) in anterior compartment. Postoperative scores of PFDI-20 and PFIQ-7 were all significant decreased (all P<0.01). About PGI-I, 29 patients chose "significant improvement", subjective satisfaction was 97% (29/30). Anterior sacral plexus hemorrhage occurred in 2 cases (7%, 2/30). There was no intestinal obstruction or injury of bladder, bowel and ureter intra- and postoperation. Two cases (7%, 2/30) had mesh exposure. Conclusion: AMISC is a safety, convenient, minimal traumatic and durable procedure for apical prolapse with short learning curve in the most of cases.

Atomic clock performance enabling geodesy below the centimetre level.

The passage of time is tracked by counting oscillations of a frequency reference, such as Earth's revolutions or swings of a pendulum. By referencing atomic transitions, frequency (and thus time) can be measured more precisely than any other physical quantity, with the current generation of optical atomic clocks reporting fractional performance below the 10-17 level1-5. However, the theory of relativity prescribes that the passage of time is not absolute, but is affected by an observer's reference frame. Consequently, clock measurements exhibit sensitivity to relative velocity, acceleration and gravity potential. Here we demonstrate local optical clock measurements that surpass the current ability to account for the gravitational distortion of space-time across the surface of Earth. In two independent ytterbium optical lattice clocks, we demonstrate unprecedented values of three fundamental benchmarks of clock performance. In units of the clock frequency, we report systematic uncertainty of 1.4 × 10-18, measurement instability of 3.2 × 10-19 and reproducibility characterized by ten blinded frequency comparisons, yielding a frequency difference of [-7 ± (5)stat ± (8)sys] × 10-19, where 'stat' and 'sys' indicate statistical and systematic uncertainty, respectively. Although sensitivity to differences in gravity potential could degrade the performance of the clocks as terrestrial standards of time, this same sensitivity can be used as a very sensitive probe of geopotential5-9. Near the surface of Earth, clock comparisons at the 1 × 10-18 level provide a resolution of one centimetre along the direction of gravity, so the performance of these clocks should enable geodesy beyond the state-of-the-art level. These optical clocks could further be used to explore geophysical phenomena10, detect gravitational waves11, test general relativity12 and search for dark matter13-17.

[Pathogenesis of systemic lupus erythematosus]. / Pathogenese des systemischen Lupus erythematodes.

The causes of diseases and disorders of the immune system, which lead to the development of systemic lupus erythematosus (SLE), are not yet completely understood; however, it is known that there are various mechanisms, which can lead to SLE. The development of the disease is based on an underlying genetic disposition but is first triggered by exposure to environmental factors, such as sunburn, viral infections or vitamin D deficiency. Disease flares can also be triggered by environmental factors. Many disease manifestations are caused by pathogenic autoantibodies; hence, B­cells and plasma cells play a critical role in the pathogenesis of SLE. This review provides an overview of the most frequent factors leading to the development of SLE and describes the key mechanisms of its pathogenesis.

Faraday-Shielded dc Stark-Shift-Free Optical Lattice Clock.

We demonstrate the absence of a dc Stark shift in an ytterbium optical lattice clock. Stray electric fields are suppressed through the introduction of an in-vacuum Faraday shield. Still, the effectiveness of the shielding must be experimentally assessed. Such diagnostics are accomplished by applying high voltage to six electrodes, which are grounded in normal operation to form part of the Faraday shield. Our measurements place a constraint on the dc Stark shift at the 10^{-20} level, in units of the clock frequency. Moreover, we discuss a potential source of error in strategies to precisely measure or cancel nonzero dc Stark shifts, attributed to field gradients coupled with the finite spatial extent of the lattice-trapped atoms. With this consideration, we find that Faraday shielding, complemented with experimental validation, provides both a practically appealing and effective solution to the problem of dc Stark shifts in optical lattice clocks.

[10 Years of Quality Management: Perception and Importance from GPs' Point of View]. / Zehn Jahre Qualitätsmanagement: Wahrnehmung und Stellenwert aus Sicht von Hausärzten in einem Ärztenetz.

BACKGROUND: Quality management (QM) became mandatory for the ambulatory sector of the German health care system 10 years ago. OBJECTIVES: The aim of this study was to find out how general practitioners (GPs) perceived the introduction of this measure, how they see it today and what they expect of the future concerning QM. MATERIALS AND METHODS: In a qualitative study, interviews following a semi-structured guideline with GPs were conducted. Following transcription, interviews were coded in triangulation, first inductively, then deductively until saturation was reached. Main topics and code families were agreed on after discussion. RESULTS: There was consensus on the necessity of standardization of basic processes like hygiene. However, the application of QM to an activity that emphasizes personal relationships and communication was seen as barely possible. GPs stated that they reduced QM to a tolerable and for them reasonable minimum. GPs mostly refused certification. The next 10 years were seen with pessimism in terms of more bureaucratic guidelines. CONCLUSION: The statutory introduction of QM was an attack on medical professionalism. Instead of passive resistance and reduction of QM to a minimum, engaged independent quality work might help to regain the trust of society we seem to have lost and restore the professional autonomy we need for our work.

AEGIS autonomous targeting for ChemCam on Mars Science Laboratory: Deployment and results of initial science team use.

Limitations on interplanetary communications create operations latencies and slow progress in planetary surface missions, with particular challenges to narrow-field-of-view science instruments requiring precise targeting. The AEGIS (Autonomous Exploration for Gathering Increased Science) autonomous targeting system has been in routine use on NASA's Curiosity Mars rover since May 2016, selecting targets for the ChemCam remote geochemical spectrometer instrument. AEGIS operates in two modes; in autonomous target selection, it identifies geological targets in images from the rover's navigation cameras, choosing for itself targets that match the parameters specified by mission scientists the most, and immediately measures them with ChemCam, without Earth in the loop. In autonomous pointing refinement, the system corrects small pointing errors on the order of a few milliradians in observations targeted by operators on Earth, allowing very small features to be observed reliably on the first attempt. AEGIS consistently recognizes and selects the geological materials requested of it, parsing and interpreting geological scenes in tens to hundreds of seconds with very limited computing resources. Performance in autonomously selecting the most desired target material over the last 2.5 kilometers of driving into previously unexplored terrain exceeds 93% (where ~24% is expected without intelligent targeting), and all observations resulted in a successful geochemical observation. The system has substantially reduced lost time on the mission and markedly increased the pace of data collection with ChemCam. AEGIS autonomy has rapidly been adopted as an exploration tool by the mission scientists and has influenced their strategy for exploring the rover's environment.

[Local health study : Outreach medical services for female sex workers in Bochum]. / Local Health Study : Aufsuchende medizinische Angebote für Sexarbeiterinnen in Bochum.

BACKGROUND: Inadequate access to prevention and medical treatment for female sex workers (SW) represents a challenge for the German health system. Accessibility and care for SW in Bochum (Germany) through a cooperation between the Interdisciplinary Immunology Outpatient Clinic, Center for Sexual Health and Medicine of St. Josef's Hospital, the Bochum health department and the Madonna e.V. was the focus of this work. PATIENTS AND METHODS: Medical outreach services were provided for the diagnosis of sexually transmitted infections (STI) in SW in brothels in Bochum between August 2013 and January 2014. After clarification and verbal consent from the SW, free HIV, syphilis, chlamydia, gonorrhea and trichomoniasis tests were offered and carried out using pseudonyms for the SW. RESULTS: A total of 112 SW were reached (up to 55.4 % within the framework of the STI Outreach Study). Of the SW, 94.6 % had an immigrant background. The majority (61.3 %) of SW were between 20 und 29 years old. Only 19.0 % of the collective had health insurance. The following STIs were diagnosed: 12.5 % chlamydia, 6.2 % syphilis, 3.6 % gonorrhea, 3.6 % trichomoniasis, and 0.9 % HIV. These results were compared with results from STI studies in SW in Germany. Treatment was performed in accordance with the standards of the German STI Society. CONCLUSION: The offer improved the accessibility and the utilization of medical services by SW in Bochum. A further improvement of services is urgently needed.

Embolus from probable Takotsubo cardiomyopathy: a bedside diagnosis.

A 59-year-old woman with stroke and thromboembolic aortoiliac disease in the setting of profound stress was found to have severe left ventricular (LV) systolic dysfunction and large mobile clot on focused cardiac ultrasonography (FCU). Marked recovery of LV function and thrombus resolution within 4 days suggested resolving Takotsubo cardiomyopathy. The role of FCU in early diagnosis and treatment is outlined here.

Central sleep apnea interfering with adequate left ventricular filling in a patient with left ventricular assist device.

Central sleep apnea is common in patients with advanced heart failure. Apneic episodes are associated with hypoxemia, hypercapnia, and neurohumoral activation resulting in a rise in pulmonary vascular resistance. This case report describes a patient with a left ventricular assist device implanted for severe heart failure in whom unrecognized central sleep apnea resulted in under-filling of the left ventricle and a reduction in left ventricular assist device inflow.

T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct.

Patients with acute myelogenous leukemia (AML) are in high need of novel targeted therapies. Here we explored the ex vivo activity of AMG330, a novel T-cell-engaging BiTE (bi-specific T-cell engagers) antibody (Ab) construct, that is bispecific for the myeloid differentiation antigen, CD33 and CD3, in primary samples from AML patients (N=23) and AML cell lines. KG-1 and U937 cells were lysed in co-culture with healthy donor T-cells at AMG330 concentrations as low as 0.1 ng/ml (1.8 pM). T-cells derived from AML patient samples were found to be as active in redirected lysis by AMG330 as T-cells from healthy donors. In an autologous setting, AMG330 could activate and expand T-cells in primary AML patient samples, and effectively mediated the redirected lysis of AML blasts and normal myeloid cells. A deficiency in target-cell lysis was only observed in samples with very low initial effector-to-target (E:T) ratio. However, this could be overcome if previously stimulated autologous T-cells were tested in patient samples at a higher E:T ratio. In vivo experiments in immunodeficient mice demonstrated significant inhibition of tumor growth by AMG330 and an inducible infiltration of human T-cells into subcutaneous HL60 tumors. The activities of the CD33/CD3-bispecific BiTE Ab construct AMG330 warrant further development for the treatment of AML.

Impact of adjuvanted H1N1 vaccine on cell-mediated rejection in heart transplant recipients.

During the H1N1 influenza virus pandemic, vaccination of high risk groups including solid-organ transplant recipients was advised. A retrospective case control study of 60 heart transplant patients, 15 having received the H1N1 virus antigen and ASO3 adjuvant vaccine (GlaxoSmithKline, Mississauga, ON, Canada) within 21 days and 45 having not been vaccinated, all undergoing routine surveillance endmyocardial biopsies, was performed. The overall rate of cellular rejection (all grades) was not statistically different between groups; however, acute cellular rejection, ≥grade 2 (1990 ISHLT criteria), was more frequent among those having recently vaccinated (control: 1/45 vs. 6/15, p = 0.001). On multivariate analysis, the only risk factor found to be associated with acute cellular rejection was recent H1N1 viral antigen and adjuvant vaccination (OR 26.5: 95% CI 02.59-270.5). Vaccine adjuvants increase host response to vaccine antigens by immune upregulation potentially increasing risk of rejection in solid-organ transplant recipients. The potential hazard of vaccination this study raises must be weighed with the clear benefit vaccination has proven to be.

The effect of dichloroacetate on health- and lifespan in C. elegans.

Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate. Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan. In parallel, we addressed the potential problem of operator bias by running both unblinded and blinded lifespan studies. We found that DCA treatment (1) increased ATP levels without elevating oxidative protein damage and (2) reduced ROS production in adult C. elegans. DCA treatment also significantly prolonged nematode health- and lifespan, but did not strongly impact mortality doubling time. Operator blinding resulted in considerably smaller lifespan-extending effects of DCA. Our data illustrate the promise of a "metabolic tuning" intervention strategy, emphasize the importance of mitochondria in nematode aging and highlight operator bias as a potential confounder in lifespan studies.

Everolimus: efficacy and safety in cardiac transplantation.

IMPORTANCE OF THE FIELD: Prognosis after cardiac transplantation continues to improve with long-term outcomes limited by malignancy and coronary allograft vasculopathy (CAV). Everolimus may potentially reduce these late term complications, while maintaining the low cellular rejection rates seen with standard therapy. AREAS COVERED IN THIS REVIEW: Multiple studies have demonstrated the efficacy of everolimus in reducing acute rejection in heart transplant patients, progression and development of CAV, and the prevention and treatment of common malignancies, including skin cancer and Kaposi sarcoma. This review re-examines these studies with a focus on patient tolerability and safety. WHAT THE READER WILL GAIN: Tolerability and safety of everolimus remain a concern with pneumonitis, effusions, mouth ulcers, edema and impaired wound healing associated with morbidity and mortality. Studies have repeatedly demonstrated renal function deterioration with concomitant everolimus and a standard dose calcineurin inhibitor (CNI). This impact can be partly reduced with CNI dose reduction without an increase in the rate of rejection. TAKE HOME MESSAGE: If future studies confirm reduced CAV and malignancy rates, everolimus will become an important agent in de novo and maintenance immunotherapy in cardiac transplantation. Patient centered immunotherapy is preferred to protocol-based immunotherapy as it allows tailoring of immune therapy to each individual patient's rejection risk and side profile.

Status of high current ion source operation at the GSI accelerator facility.

Vacuum arc ion sources, Penning ion sources, and filament driven multicusp ion sources are used for the production of high current ion beams of a variety of metallic and gaseous ions at the GSI accelerator facility. For accelerator operation, the ion sources have to provide a stable beam over a long period of time with an energy of 2.2 keV/u and a maximum mass over charge ratio of 65. The status of beam time operation at the high current injector is presented here giving an outline on important ion source data, such as ion beam current, ion beam spectrum, transversal emittance, life time, duty factor, and transmission along the low energy beam transport section.

Frequency of very low HCV viremia detected by a highly sensitive HCV-RNA assay.

BACKGROUND: Only limited data is available on the frequency and clinical significance of very low hepatitis C viremia (<600 IU/ml) determined by novel sensitive methods for HCV quantification. STUDY DESIGN: We evaluated the new Abbott m2000 RealTime PCR assay in 3213 consecutive anti-HCV-positive sera as well as in 50 HCV-recovered patients with sustained virological response to standard antiviral therapy. RESULTS: The assay showed a linear range between 10(1) IU/ml and 10(7) IU/ml for HCV genotypes 1-6. An HCV viremia below 600 IU/ml was detected more often with the m2000 RealTime PCR assay than with the Cobas Amplicor assay in viremic sera (7.1% versus 1.8%). Seventy-seven cases with HCV levels below 100 IU/ml not related to ongoing antiviral therapy were identified. An HCV-RNA of less than 12 IU/ml was found in nine of the 50 SVR patients. Two patients had a viral load of 34 IU/ml and 84 IU/ml, respectively, one of those showed persistently elevated ALT levels over a period of 5 years after the end of antiviral treatment. CONCLUSION: An HCV viremia below 600 IU/ml can be detected in almost every 40th anti-HCV-positive sera using real-time PCR based assays. Low persisting HCV-RNA in patients after antiviral therapy may be associated with mild liver inflammation in single cases.

Plant foods and brain aging: a critical appraisal.

In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.

Accelerated NaCl-induced hypertension in taurine-deficient rat: role of renal function.

Taurine modulates blood pressure and renal function. As the kidney plays a pivotal role in long-term control of arterial pressure, we tested the hypothesis that taurine-deficient rats display maladaptive renal and blood pressure responses to uninephrectomy. Control and taurine-deficient (i.e., beta-alanine-treated) rats with either one or two remaining kidneys were fed diets containing basal or high (8%) NaCl diet. Urine osmolality was greater in the taurine-deficient than controls fed a normal NaCl diet; proteinuria and blood pressure were unaffected by uninephrectomy. Following 6 weeks on an 8% NaCl diet, the uninephrectomized (UNX) animals developed significant hypertension, which was more severe in the taurine-deficient group; baroreflex function was unaffected. However, the UNX taurine-deficient rats displayed impaired ability to dispose of an acute isotonic saline volume load before a switchover to a high NaCl diet. Nonetheless, a more protracted exposure (i.e., 14 weeks) to dietary NaCl excess eliminated the blood pressure differential between the two groups; at this stage, renal excretory responses to an acute saline volume load or to atrial natriuretic peptide were similar in the two groups. Nonetheless, hypertensive taurine-deficient rats displayed greater proteinuria, although both groups excreted proteins of similar molecular weights ( approximately 15-66 kDa). Further, taurine-deficient kidney specimens displayed periarterial mononuclear cell infiltrates with strong immunoreactivity to the histiocyte marker CD68, suggestive of increased phagocytic activity. In conclusion, taurine deficiency modulates renal adaptation to combined uninephrectomy and dietary NaCl excess, resulting in an accelerated development of hypertension.