Health Care Quality in CKD Subjects: A Cross-Sectional In-Hospital Evaluation.

Methods: The study was performed in a retrospective and observational manner. All adult (age 18 years or older) in-hospital subjects treated from January until December 2019 were included. CKD was diagnosed according to the KDIGO 2012 CKD Guideline. The following variables were assessed: CKD stage, quantification/analysis (yes/no) of blood pressure, proteinuria, serum phosphate, serum 25-OH-D3, ferritin and transferrin saturation, and blood gas analysis. In addition, recommendations of the following medicines were analyzed (given/not given): ACE inhibitor or sartan, phosphate binder, vitamin D3 (activated or native), iron, erythropoietin, and bicarbonate. It was also evaluated whether discharge letters contained CKD-related diagnoses or not. Results: In total, 581 individuals were included in the study. The majority of aspects related to the monitoring and therapeutic management of CKD were either considered in only a small proportion of affected individuals (e.g., quantification of PTH - 5.5%/25-OH-D3 - 6%/transferrin saturation - 13.6%) or avoided nearly at all (e.g., recommendation of erythropoietin-1%, documentation of CKD-MBD diagnosis-0.3%). A reasonable quality of care was identified concerning the blood pressure monitoring (performed in 100%) and blood gas analysis (55% of the patients received analysis). Serum phosphate was measured in 12.9%, particularly in subjects at higher CKD stages. Conclusions: The current investigation revealed poor quality of care in CKD patients treated at the Brandenburg University Hospital over the period of one year. Quality improvement must be achieved, most likely via a standardized educational program for physicians and a directer access to CKD management guidelines.

Effective treatment of electrical storm by a wearable cardioverter defibrillator in a patient with severely impaired left ventricular function after myocardial infarction: a case report.

BACKGROUND: The implantation of cardioverter defibrillators (ICDs) is an established therapy in the prevention of sudden cardiac death in patients with systolic dysfunction after myocardial infarction. To avoid immediate implantation of an ICD, wearable cardioverter defibrillator vests (WCD) can be used to protect patients against malignant rhythm disorders, while at the same time drug-based heart failure therapy has to be initiated. This drug therapy can improve left ventricular ejection fraction and primary prophylactic cardioverter defibrillator implantation may not be necessary. However, the recent Vest Prevention of Early Sudden Death Trial (VEST) questioned the regular use of the WCD in this setting. CASE PRESENTATION: A 47-year-old Caucasian man with severely impaired left ventricular function early after myocardial infarction was prescribed a WCD as primary prophylaxis to prevent sudden cardiac death. Seven days after the patient was supplied with a WCD, the patient suffered from an electrical storm with recurrent ventricular tachycardia (VT), which was successfully terminated 17 times by the WCD. On coronary angiography, the formerly infarct-related right coronary artery had TIMI (Thrombolysis in Myocardial Ischemia Trial) III flow, and a remaining stenosis in the left anterior descending artery (LAD) was stented, which did not stop recurrent VT. In the electrophysiology (EP) study, a focus was mapped in the left inferior ventricle, which was ablated. This stopped the VT. A second radio-frequency (RF) ablation in the same area was necessary after 14 days. Finally, a permanent cardioverter defibrillator was implanted. CONCLUSION: We report the case of a patient who survived recurrent episodes of VT early after myocardial infarction by effective defibrillation with a WCD. The WCD is a useful device to bridge time until a final decision for implantation of a defibrillator.

AKI Epidemiology and Outcomes: A Retrospective Cohort Study from the Prenephrology Era.

BACKGROUND: Acute kidney injury substantially worsens the prognosis of hospitalized patients. The Brandenburg Medical School was founded in 2014, and a nephrology section was opened in summer 2017. The aim of the study was to analyze AKI epidemiology and outcomes in one of two university hospitals belonging to the medical school. The period of interest dated from January to December 2015. METHODS: The investigation was designed as a single-center, retrospective cohort study at the Brandenburg Hospital of the Brandenburg Medical School. All in-hospital patients treated between January and the end of December 2015 were included. AKI was defined as specified in the 2012 published KDIGO criteria (criteria 1 and 2). Four parameters were evaluated in particular: AKI incidence, in-hospital mortality, frequency of renal replacement therapy, and renal recovery during the stay at the hospital. RESULTS: A total number of 5,300 patients were included in the analysis. AKI was diagnosed in 490 subjects (10.1%). The in-hospital mortality was 26%. The following conditions/parameters significantly differed between survivors (s) and nonsurviving (ns) subjects: duration of in-hospital treatment (s > ns), AKI onset (outpatient vs. in-hospital) (outpatient in s > ns), dialysis due to AKI (s < ns), vasopressor administration (s < ns), and invasive ventilation (s < ns). 5.6% received dialysis therapy, and renal recovery occurred in 31% of all surviving AKI subjects. CONCLUSION: Both, the AKI incidence and the frequency of dialysis were lower than reported in the literature. However, fewer subjects recovered from AKI. These discrepant findings possibly result from the lack of prehospitalization creatinine values, the lack of follow-up data, and a generally lower awareness for the need to perform renal replacement therapy in AKI.

PAC-Mediated AKI Protection Is Critically Mediated but Does Not Exclusively Depend on Cell-Derived Microvesicles.

INTRODUCTION: Acute kidney injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as a reliable option for improving AKI outcomes in experimental AKI. Our previous studies focused on the so-called proangiogenic cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production/secretion of extracellular vesicles (MV, microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and/or the secretome alone. METHODS: AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI-40 minutes). Syngeneic murine PACs were stimulated with either melatonin, angiopoietin-1 or -2, or with bone morphogenetic protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v.-injected after ischemia. Mice were analyzed 48 hours later. RESULTS: IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened after ischemic renal function even further: MV + Ang-1, MV + BMP-5, MV + melatonin, and MV + secretome + Ang-1. CONCLUSION: Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonin, BMP-5), mechanisms other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

Association of cytokine patterns and clinical/laboratory parameters, medication and periodontal burden in patients with rheumatoid arthritis (RA).

To evaluate serum levels of the following cytokines in rheumatoid arthritis subjects with periodontal disease: Interleukin-6, -10, -17, and -23. Patients with rheumatoid arthritis frequently suffer from periodontal disease. Both diseases partly result from a dysregulated immune response. The current study aimed to quantify Interleukin-6, -10, -17, and -23 levels in rheumatoid arthritis. It should be investigated if the periodontal disease would have additional modifying effects. A total of 157 patients were included. Serum levels of IL-6, -10, -17, and -23 were measured by ELISA. Serum IL-10 increased with longer duration of morning stiffness and with higher rheumatoid factor and anti-cyclic citrullinated peptide titres. IL-10 was also elevated with longer duration of prednisolone (< 5 mg daily) and leflunomide therapy. Subjects with lower erythrocyte sedimentation rate/longer leflunomide therapy displayed more missing teeth/more clinical attachment loss. IL-17 was higher in subjects with fewer missing teeth if the following criteria were fulfilled: shorter prednisolone (< 5 mg) and methotrexate therapy, more swollen joints, longer morning stiffness. IL-23 finally was increased in subjects with higher rheumatoid factor and in those with higher periodontal probing depth/clinical attachment loss in the following situations: lower rheumatoid factor and shorter leflunomide therapy. Subjects suffering from dental/periodontal burden show an aberrant systemic cytokine availability of serum IL-6, IL-10, IL-17 and IL-23 related to disease activity and medication. This examination underlines the complexity of potential interactions between disease activity and medication related to periodontal burden.

The impact of aerobic and isometric exercise on different measures of dysfunctional high-density lipoprotein in patients with hypertension.

BACKGROUND: Exercise training increases high-density lipoprotein (HDL) cholesterol, but its effect on HDL function is unclear. In hypertensives, exercise improves endothelial dysfunction, which is related to HDL function. In the present study, we assess for the first time the effects of different exercise modalities on two cell-free assays of HDL function. DESIGN: The study was conducted as a prospective randomized controlled trial in 75 hypertensive patients. METHODS: Patients were randomized in three groups: (a) handgrip isometric training five times weekly; (b) placebo-handgrip; and (c) aerobic exercise training at least three times per week. HDL function was assessed in serum samples at baseline and after 12 weeks of training by two independent assays that determine the proinflammatory phenotype (haptoglobin content) of a specific amount of HDL (Haptoglobin-HDL [HPHDL]) and oxidized HDL (HDLox) as a measure of reduced antioxidant function of HDL. HDL function measures were normalized by the measures of a pooled control of sera from healthy participants and by HDL-C levels (normalized ratio, no units). RESULTS: Aerobic exercise led to significant reduction of the HDLox from 0.99 ± 0.27 to 0.90 ± 0.29 (no units, p = 0.03). The HPHDL did not change in any training group. Changes of HDLox correlated with reduction of the systolic blood pressure only after aerobic exercise (R = 0.64, p = 0.03). CONCLUSIONS: Aerobic but not isometric exercise improves the antioxidant function of HDL in patients with hypertension. This improvement correlates positively with reductions of blood pressure.

Description of a novel RyR2 mutation in a juvenile patient with symptomatic catecholaminergic polymorphic ventricular tachycardia in sleep and during exercise: a case report.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an inherited disease presenting with arrhythmic events during physical exercise or emotional stress. If untreated, catecholaminergic polymorphic ventricular tachycardia is a highly lethal condition: About 80% of affected individuals experience recurrent syncope, and 30% experience cardiac arrest. Catecholaminergic polymorphic ventricular tachycardia is caused by mutations in genes encoding ryanodine receptor type 2 (RyR2) and cardiac calsequestrin (CASQ2). In cases of sympathoadrenergic activation, both mutations result in a spontaneous Ca2+ release in cardiac cells, facilitating ventricular arrhythmias. CASE PRESENTATION: We present a case of a 17-year-old Caucasian boy who survived sudden cardiac death caused by ventricular fibrillation while performing running exercise in a fitness center. The diagnostic workup included blood tests, coronary angiography, electrophysiological testing, and cardiac magnetic resonance imaging, but all results were normal. Because the patient's medical history included recurrent syncope during physical and emotional stress, we strongly suspected catecholaminergic polymorphic ventricular tachycardia as the underlying disease. Genetic screening was performed and confirmed the diagnosis, revealing a new heterozygous point mutation in the gene for RyR2, c.12520T>A (p.F4174 l, exon 90, RyR2 gene). The patient was discharged from our hospital after undergoing implantation of an implantable cardioverter defibrillator for secondary prevention. Shortly after implantation, the implantable cardioverter defibrillator terminated a sustaining ventricular tachycardia episode by antitachycardic pacing. This episode occurred early in the morning while the patient was asleep. CONCLUSIONS: We present a case of catecholaminergic polymorphic ventricular tachycardia associated with a novel single point mutation in the RyR2 gene, which, to the best of our knowledge, has not been described in the literature so far. Our patient experienced arrhythmic events under both resting conditions and physical activity, an uncommon finding in patients with catecholaminergic polymorphic ventricular tachycardia. This novel mutation may cause arrhythmias independent of sympathoadrenergic stimulation, but further evidence is needed to prove causality.

Contrast-Induced Nephropathy: Update on the Use of Crystalloids and Pharmacological Measures.

Contrast-induced nephropathy (CIN) is a frequent and severe complication in subjects receiving iodinated contrast media for diagnostic or therapeutic purposes. Several preventive strategies were evaluated in the past. Recent clinical studies and meta-analyses delivered some new aspects on preventive measures used in the past and present. We will discuss all pharmacological and nonpharmacological procedures. Finally, we will suggest individualized recommendations for CIN prevention.

Autophagy activation in circulating proangiogenic cells aggravates AKI in type I diabetes mellitus.

Acute kidney injury (AKI) occurs frequently in hospitals worldwide, but the therapeutic options are limited. Diabetes mellitus (DM) affects more and more people around the globe. The disease worsens the prognosis of AKI even further. In recent years, cell-based therapies have increasingly been applied in experimental AKI. The aim of the study was to utilize two established autophagy inducers for pharmacological preconditioning of so-called proangiogenic cells (PACs) in PAC treatment of diabetic AKI. Insulin-dependent DM was induced in male C57/Bl6N mice by intraperitoneal injections of streptozotocine. Six weeks later, animals underwent bilateral renal ischemia for 45 min, followed by intravenous injections of either native or zVAD (benzyloxycarbonyl-Val-Ala-Asp-fluoro-methylketone)- or Z-Leu-Leu-Leu-al (MG132)-pretreated syngeneic murine PACs. Mice were analyzed 48 h (short term) and 6 wk (long term) later, respectively. DM worsened postischemic AKI, and PAC preconditioning with zVAD and MG132 resulted in a further decline of excretory kidney function. Injection of native PACs reduced fibrosis in nondiabetic mice, but cell preconditioning promoted interstitial matrix accumulation significantly. Both substances aggravated endothelial-to-mesenchymal transition (EndoMT) under diabetic conditions; these effects occurred either exclusively in the short (zVAD) or in the short and long term (MG132). Preconditioned cells stimulated the autophagocytic flux in intrarenal endothelial cells, and all experimental groups displayed increased endothelial abundances of senescence-associated ß-galactosidase, a marker of premature cell senescence. Pharmacological autophagy activation may not serve as an effective strategy for improving PAC competence in diabetic AKI in general. On the contrary, several outcome parameters (excretory function, fibrosis, EndoMT) may even be worsened.

MR safety: fast T1 thermometry of the RF-induced heating of medical devices.

Determining the MR compatibility of medical implants and devices is becoming increasingly relevant. In most cases, the heating of conductive implants due to radiefrequency (RF) excitation pulses is measured by fluoroptic temperature sensors in relevant tests for approval. Another common method to determine these heating effects is MR thermometry using the proton resonance frequency. This method gives good results in homogeneous phantoms. However in many cases, technical shortcomings such as susceptibility artifacts prohibit exact proton resonance frequency thermometry near medical implants. Therefore, this work aimed at developing a fast T1-based method which allows controlled MR-related heating of a medical implant while simultaneously quantifying the spatial and temporal temperature distribution. To this end, an inversion recovery snapshot Fast Low-Angle Shot (FLASH) sequence was modified with additional off-resonant heating pulses. With an accelerated imaging method and a sliding-window technique, every 7.6 s a new temperature map could be generated with a spatial in-plane resolution of 2 mm. The temperature deviation from calculated temperature values to reference fluoroptic probe was found to be smaller than 1 K.

Pharmacological pre- and post-conditioning with the sphingosine-1-phosphate receptor modulator FTY720 after myocardial ischaemia-reperfusion.

BACKGROUND AND PURPOSE: Our recent experiments demonstrated that the Sphingosine-1-phosphate (S1P) receptor agonist FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride) improves recovery of function after myocardial ischaemia-reperfusion ex vivo. Therefore, we tested the hypothesis that pharmacological post-conditioning with FTY720 reduces infarct size after myocardial ischaemia-reperfusion in vivo. EXPERIMENTAL APPROACH: Myocardial ischaemia was induced in Wistar rats by ligation of the left coronary artery for 45 min. FTY720 (0.5 mg kg(-1)) was applied i.p. either once, before reperfusion, or twice, 24 h before myocardial ischaemia and before reperfusion. After 24 h reperfusion, we determined infarct size by triphenyltetrazolium chloride staining and granulocyte infiltration by immunohistochemistry. Tumour necrosis factor-alpha (TNF)-alpha concentration was determined by elisa. S1P receptor expression was studied by Western blot. Calcium transients were evaluated in Indo-1-loaded cardiomyocytes. KEY RESULTS: In both groups, FTY720 significantly reduced lymphocyte count in peripheral blood. FTY720 treatment attenuated granulocyte infiltration and TNF-alpha protein expression in reperfused myocardium. However, both treatment regimens were not able to reduce infarct size. FTY720 increased mortality due to induction of fatal ventricular tachyarrhythmias when administered once before reperfusion, but protected against reperfusion arrhythmias when given 24 h prior to ischaemia. Pretreatment selectively down-regulated S1P(1) receptor expression within the myocardium. S1P receptor agonists did not induce calcium deregulation in cardiomyocytes. CONCLUSIONS AND IMPLICATIONS: FTY720 applied during reperfusion did not reduce infarct size but increased mortality during myocardial ischaemia-reperfusion due to induction of arrhythmias. Pretreatment with FTY720 before ischaemia abrogated the deleterious pro-arrhythmic effects without reducing infarct size.

Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis.

BACKGROUND: The aim of the present study was to evaluate the accuracy of routine clinical examination (per vaginam, PV) combined with transvaginal sonography (TVS) for presurgical, non-invasive diagnosis of endometriosis. METHODS: Two-hundred women with symptoms suggestive of endometriosis were prospectively assessed by PV and TVS prior to laparoscopy and radical resection of disease and histological confirmation. RESULTS: Prevalence of endometriosis on the right/left (r/l) ovary, r/l uterosacral ligament (USL), pouch of Douglas (POD), vagina, bladder, rectovaginal space (RVS) and rectum was 12%, 13%, 12%, 22%, 15%, 11%, 2%, 4% and 24%. Sensitivities, specificities, positive and negative predictive values and positive and negative likelihood ratios for combined use of TVS and PV resulted in 96/100%, 100/99%, 100/93%, 93/100% and -;0.04/87.0;- for the r/l ovarian endometriosis; 67/84%, 97/86%, 73/62%, 96/95% and 19.56;0.35/5.97;0.19 for the r/l USL disease; 87%, 98%, 90%, 98% and 49.11;0.14 for involvement of the POD; 82%, 99%, 95%, 98% and 145.64;0.18 for vaginal endometriosis; 88%, 99%, 78%, 99% and 84.0;0.13 for endometriosis of the RVS; 75%, 98%, 50%, 99% and 49.0;0.25 for bladder involvement and 96%, 98%, 94%, 99% and 48.56;0.04 for rectal endometriosis. CONCLUSIONS: The combination of PV and TVS accurately predicts the presence of endometriosis affecting the ovaries, vagina, rectum, USL, RVS and POD in patients with suspected endometriosis. We suggest the routine combination of PV and TVS as an essential part of the standard primary assessment of pelvic pain patients with suspected endometriosis.

Hotline update of clinical trials and registries presented at the German Cardiac Society meeting 2008. (PEPCAD, LokalTax, INH, German ablation registry, German device registry, DES.DE registry, DHR, Reality, SWEETHEART registry, ADMA, GERSHWIN).

This review article summarizes results of a number of new clinical trials and registries in the field of cardiovascular medicine. Key presentations made at the 74th annual meeting of the German Cardiac Society, held in Mannheim, Germany, in March 2008 are reported. The data were presented by leading experts in the field with relevant positions in the trials and registries. These comprehensive summaries should provide the readers with the most recent data on diagnostic and therapeutic developments in cardiovascular medicine.

Fast and slow degrees of freedom coupling two different reservoirs.

We considered a Hamiltonian system that can be described by two generalized variables. One of them relaxes quickly when the system is in contact with a heat bath at fixed temperature, while the second one, the slow variable, mimics the interaction of the system with another heat bath at a lower temperature. The coupling between these variables leads to an energy flow between the heat baths. Allahverdyan and Nieuwenhuizen [Phys. Rev. E 62, 845 (2000)] proposed a formalism to deal with such problem and calculated the steady states of the system and some related properties as entropy production, energy dissipation, etc. In this work we applied the formalism to a coupled system of ideal gases and also to an ideal gas interacting with a harmonic oscillator. If the temperatures of the heat baths are not too close, the Onsager relations do not apply.

[Myocardial infarction after influenza vaccination]. / Myokardinfarkt nach Influenza-Schutzimpfung.

Influenza is a common disease in the population. Influenza vaccination is performed routinely and is usually well tolerated. Minor local or systemic side effects like fever and myalgia are described. Rarely there are more severe adverse events. Systemic vasculitis has been reported in some cases. In this case we report on a female patient with secondary vasculitis and myocardial infarction after influenza vaccination. The patient received cortisol and recovered. The literature about influenza vaccination, its side effects and recommendations about vaccination in patients with coronary artery disease is reviewed.

Expression of atrial myosin light chains but not alpha-myosin heavy chains is correlated in vivo with increased ventricular function in patients with hypertrophic obstructive cardiomyopathy.

The adult rodent heart adapts to increased work load by reexpression of its fetal genes, for example, beta-myosin heavy chain (MHC), in order to improve contractile function. However, the human ventricle regulates contractility by expression of atrial essential myosin light chain (ALC-1) rather than beta-MHC. We evaluated the impact of both mechanisms in patients with hypertrophic cardiomyopathy. MHC isoform expression was quantified at the mRNA and protein levels by reverse transcriptase polymerase chain reaction and immunoblotting, respectively. Although alpha-MHC mRNA was detected in control and hypertrophied human ventricular tissue, alpha-MHC protein was not observed. Similarly, we investigated the expression of ALC-1 by two-dimensional polyacrylamide gel electrophoresis and the clinical and hemodynamic parameters of the patients with hypertrophic cardiomyopathy. We found a significant positive correlation between ALC-1 protein expression and dP/dtmax in the hypertrophied human ventricle in vivo. Correlations between dP/dtmax and expression of protein for the ryanodine receptor and L-type Ca2+ channel were excluded. Our data suggest that reexpression of ALC-1 improves the contractile state of the adult human heart. We propose that two evolutionarily divergent compensatory mechanisms for increased work demand exist in the mammalian heart: MHC regulation in rodents and essential MLC regulation, of cardiac contractility, in humans.

Remodeling of the hypertrophied human myocardium by cardiac bHLH transcription factors.

The basic helix-loop-helix transcription factors eHAND and dHAND are involved in developmental cardiac growth and differentiation. We investigated HAND gene expression in the normal and in the hypertrophied right and left ventricle of patients with tetralogy of Fallot (ToF) and hypertrophic obstructive cardiomyopathy (HOCM). HAND mRNA was constitutively expressed in the hypertrophied heart and increased in the hypertrophic tissue of both patient groups. HAND genes had a complementary left-right cardiac asymmetry of expression with dHAND predominantly in the right and eHAND in the left ventricle. The two cardiac bHLH factors have the ability to form heterodimers with the ubiquitous bHLH protein E12, subsequently recognizing E-boxes in the promoter region of target genes like ALC-1. We found a highly significant positive correlation between HAND and ALC-1 mRNA. The total ALC-1 protein level in ToF was smaller than in HOCM, although ALC-1 mRNA as well as HAND mRNA levels were significantly higher. ToF patients expressed around four times more ALC-1 mRNA for similar amounts of ALC-1 than HOCM patients. Suggesting disturbed ALC-1 translation in ToF, we found ALC-1 antisense mRNA expression in the hypertrophied, but not in the normal, ventricles. The higher the antisense/sense ALC-1 mRNA ratio, the lower ALC-1 protein was expressed.