The evolution of acute stroke care in Germany from 2019 to 2021: analysis of nation-wide administrative datasets.

BACKGROUND: The treatment of ischemic stroke (IS) has changed considerably in recent years. Particularly the advent of mechanical thrombectomy (MTE) has revolutionized the available treatment options. Most patients in developed countries have access to intravenous thrombolysis (IVT). However access to MTE remains restricted in some regions despite efforts to increase its availability. We performed an evaluation of national datasets to monitor improvements made in access to revascularization therapies for IS patients in Germany. METHODS: We analyzed national datasets on German Diagnosis-Related Groups and structured quality reports by extracting information of patients admitted with stroke with and without IVT and MTE for the period of 2019-2021. Data from 2016 and limited data for 2022 were also included for comparison. RESULTS: Admissions with ischemic stroke declined during the years of the COVID 19 pandemic by 4.5% from 227,258 in 2019 to 216,923 in 2021. IVT rates were stable with 16.3% being treated with IVT in 2019 and 2021. MTE rates continued to increase from 7.1 to 8.4% and the number of MTE centers increased by 14.8% in the same period. Over 87.3% of MTEs were performed in centers with a case volume exceeding 50 cases per year in 2021. The largest increase in the relative share of MTEs was seen in large MTE centers (n ≥ 200). Patient age for MTEs surpassed the age for IVTs in 2019 and the proportion of patients ≥ 80 years receiving MTE continued to increase. The proportion of regions in Germany with poor MTE rates (≤ 4.1%) decreased significantly from 2019 (12.3%) to 2021 (5.3%) (p < 0.001). CONCLUSIONS: We found strong evidence that while IVT rates reached a temporary ceiling effect, both the absolute number of and access to MTEs continued to increase in Germany. Regional disparities have become less significant and the majority of MTEs are performed in centers with medium or high case volumes.

Real-world outcomes in non-endemic hereditary transthyretin amyloidosis with polyneuropathy: a 20-year German single-referral centre experience.

BACKGROUND: Hereditary transthyretin amyloidosis is caused by pathogenic variants in the TTR gene and typically manifests, alongside cardiac and other organ dysfunctions, with a rapidly progressive sensorimotor and autonomic polyneuropathy (ATTRv-PN) leading to severe disability. While most prospective studies have focussed on endemic ATTRv-PN, real-world data on non-endemic, mostly late-onset ATTRv-PN are limited. METHODS: This retrospective study investigated ATTRv-PN patients treated at the Amyloidosis Centre of Heidelberg University Hospital between November 1999 and July 2020. Clinical symptoms, survival, prognostic factors and efficacy of treatment with tafamidis were analysed. Neurologic outcome was assessed using the Coutinho ATTRv-PN stages, and the Peripheral Neuropathy Disability (PND) score. RESULTS: Of 346 subjects with genetic TTR variants, 168 patients had symptomatic ATTRv-PN with 32 different TTR variants identified. Of these, 81.6% had the late-onset type of ATTRv-PN. Within a mean follow-up period of 4.1 ± 2.8 years, 40.5% of patients died. Baseline plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥900 ng/l (HR 3.259 [1.421-7.476]; p = .005) was the main predictor of mortality in multivariable analysis. 64 patients were treated with tafamidis and presented for regular follow-up examinations. The therapeutic benefit of tafamidis was more pronounced when treatment was started early in ATTRv-PN stage 1 (PND scores II vs. I; HR 2.718 [1.258-5.873]; p = .011). CONCLUSIONS: In non-endemic, mostly late-onset ATTRv-PN, cardiac involvement assessed by NT-proBNP is a strong prognosticator for overall survival. Long-term treatment with tafamidis is safe and efficacious. Neurologic disease severity at the start of treatment is the main predictor for ATTRv-PN progression on tafamidis.

Factors affecting prehospital delay in rural and urban patients with stroke: a prospective survey-based study in Southwest Germany.

BACKGROUND: Reducing prehospital delay plays an important role in increasing the thrombolysis rate in patients with stroke. Several studies have identified predictors for presentation ≤4.5 h, but few compared these predictors in urban and rural communities. We aimed to identify predictors of timely presentation to the hospital and identify possible differences between the urban and rural populations. METHODS: From January to June 2017, we conducted a prospective survey of patients with stroke admitted to an urban comprehensive stroke centre (CSC) and a rural primary care centre (PCC). Predictors were identified using binary logistical regression. Predictors and patient characteristics were then compared between the CSC and PCC. RESULTS: Overall, 459 patients were included in our study. We identified hesitation before seeking help, awareness of the existence of a time-window, type of admission and having talked about stroke symptoms with friends/relatives who had previously had a stroke as the strongest predictors for presentation to the emergency room ≤4.5 h. Patients admitted to the rural PCC were more hesitant to seek help and less likely to contact emergency services, even though patients had comparable knowledge pertaining to stroke care concepts. CONCLUSIONS: Patients from rural areas were more likely to be hesitant to seek help and contacted the EMS less frequently, despite similar self-awareness of having a stroke. Educational campaigns should focus on addressing these disparities in rural populations. Affected patients should also be encouraged to talk about their symptoms and take part in educational campaigns.

[Brain Death and Treatment of (Potential) Organ Donors and Interactions with their Relatives]. / Hirntod und Umgang mit (potenziellen) Organspendern und Angehörigen.

In recent years, the diagnosis of irreversible brain function loss in severely brain-damaged patients has gained in importance. Brain death, defined as an irreversible loss of the overall function of the cerebrum, cerebellum and brain stem, is a prerequisite for organ removal in the context of organ donation. The article presents the legal and organizational framework.Brain death is determined on the basis of the latest update of the guidelines of the German Medical Chamber (Bundesärztekammer) using a three-step scheme and consists of clinical and instrumental examinations. After the final diagnosis of brain death, the phase of organ-preserving treatment for the potential organ donor begins. In the case of patients who themselves or their relatives have not agreed to organ donation, the intensive care therapy must be terminated promptly. The legal framework for the determination of brain death and for the removal of organs from potential organ donors is provided by the Transplantation Act. The German Foundation for Organ Transplantation (DSO) is responsible for the coordination of organ donations in Germany. The DSO supports hospitals in many ways during the organ donation process, but also in training courses for medical staff on organ donation. The main contact person of the DSO is the transplant officer in the hospitals. The care of the relatives of a potential organ donor is of great importance.

The KEEP SIMPLEST Study: Improving In-House Delays and Periinterventional Management in Stroke Thrombectomy-A Matched Pair Analysis.

BACKGROUND AND PURPOSE: Although the treatment window for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) has been extended in recent years, it has been proven that recanalizing treatment must be administered as soon as possible. We present a new standard operating procedure (SOP) to reduce in-house delay, standardize periinterventional management and improve patient safety during MT. METHODS: KEep Evaluating Protocol Simplification In Managing Periinterventional Light Sedation for Endovascular Stroke Treatment (KEEP SIMPLEST) was a prospective, single-center observational study aimed to compare aspects of periinterventional management in AIS patients treated according to our new SOP using a combination of esketamine and propofol with patients having been randomized into conscious sedation (CS) in the Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) trial. Primary outcome was early neurological improvement at 24h using the National Institutes of Health Stroke Scale, and secondary outcomes were door-to-recanalization, recanalization grade, conversion rate and modified Rankin Scale (mRS) at 3 months. RESULTS: Door-to-recanalization time (128.6 ± 69.47 min vs. 156.8 ± 75.91 min; p = 0.02), mean duration of MT (92.01 ± 52 min vs. 131.9 ± 64.03 min; p < 0.001), door-to-first angiographic image (51.61 ± 31.7 min vs. 64.23 ± 21.53 min; p = 0.003) and computed tomography-to-first angiographic image time (31.61 ± 20.6 min vs. 44.61 ± 19.3 min; p < 0.001) were significantly shorter in the group treated under the new SOP. There were no differences in early neurological improvement, mRS at 3 months or other secondary outcomes between the groups. Conversion rates of CS to general anesthesia were similar in both groups. CONCLUSION: An SOP using a novel sedation regimen and optimization of equipment and procedures directed at a leaner, more integrative and compact periinterventional management can reduce in-house treatment delays significantly in stroke patients receiving thrombectomy in light sedation and demonstrated the safety and feasibility of our improved approach.

Steroid-Responsive Relapsing-Remitting Neutrophilic Encephalitis: A Case Report.

We report a case of a rapidly progressing, relapsing-remitting, steroid-responsive granulocytic encephalitis without any signs of peripheral nervous system or other organ involvement. It apparently had an immune-mediated etiology that could not be attributed to any known disease entity. A 22-year-old man presented with rapidly progressive severe neurological symptoms caused by encephalitis. Examination of the cerebrospinal fluid as well as brain biopsy showed extensive accumulation of neutrophilic granulocytes with no hints of an infectious agent. Magnetic resonance imaging revealed multiple T2/FLAIR demarcated lesions. Subsequent to a steroid pulse therapy, the clinical symptoms and imaging abnormalities improved rapidly. Ten months later, the patient experienced a disease relapse, which again responded well to steroids. Forty months after the relapse, he is currently doing well on azathioprine. This case highlights that an immunosuppressive treatment should be considered in patients with extensive neutrophilic encephalitis when no infectious agent is detected. A new immune-mediated relapsing-remitting CNS disease entity might need to be considered.

Immunosuppression with tacrolimus early after orthotopic heart transplantation: a comparison of prograf and advagraf.

BACKGROUND: We compared trough levels and clinical outcomes in patients who received Prograf or Advagraf (tacrolimus) de novo following heart transplantation surgery. METHODS: Eighty-two patients were included in this follow-up study. Biopsy results were controlled for the first 3 months after orthotopic heart transplantation. Trough levels were monitored for 4 weeks: daily during the first 7 days and once every week thereafter. The lengths of stay in the hospital and in intensive care were compared. The end point of the study was the 1-year mortality rate. RESULTS: We found significant differences between the groups for both biopsy results and trough levels. Trough levels differed for the first 5 days and then converged on the sixth day. The levels remained comparable throughout the monitoring period. The 1-year mortality rates for Prograf and Advagraf were 20% and 15%, respectively. CONCLUSIONS: Trough levels were comparable after an adjustment period. There were no differences between the 2 groups in their 1-year mortality rates. These results suggest that Advagraf is a safe alternative to Prograf for patients who have undergone heart transplantation.

Surgical therapy of end-stage heart failure: understanding cell-mediated mechanisms interacting with myocardial damage.

Worldwide, cardiovascular disease results in an estimated 14.3 million deaths per year, giving rise to an increased demand for alternative and advanced treatment. Current approaches include medical management, cardiac transplantation, device therapy, and, most recently, stem cell therapy. Research into cell-based therapies has shown this option to be a promising alternative to the conventional methods. In contrast to early trials, modern approaches now attempt to isolate specific stem cells, as well as increase their numbers by means of amplifying in a culture environment. The method of delivery has also been improved to minimize the risk of micro-infarcts and embolization, which were often observed after the use of coronary catheterization. The latest approach entails direct, surgical, trans-epicardial injection of the stem cell mixture, as well as the use of tissue-engineered meshes consisting of embedded progenitor cells.

Less invasive off-pump implantation of axial flow pumps in chronic ischemic heart failure: survival effects.

BACKGROUND: Off-pump implantation of left ventricular assist device (LVAD) axial or centrifugal flow pumps in patients with low ejection fraction (EF) is of major clinical relevance. In addition, all pre-clinical, long-term implantations performed so far have been carried out in healthy animals, but this does not reflect the eventual clinical setting. In this study we established a new technique using a miniaturized axial flow pump in sheep with chronically ischemic myocardium. METHODS: Sheep (n = 15) underwent intracoronary sphere injection to create chronic ischemic heart failure. Reduced EF was assessed using transesophageal echocardiography. All animals underwent implantation of a new miniaturized axial flow pump via an extraperitoneal, subcostal surgical approach. RESULTS: Our technique allows easy exposure of the diaphragmatic surface of the heart and the descending aorta. Ten animals (range 65 to 78 kg) underwent off-pump implantation 30 (range 25 to 33) days after intracoronary sphere injection. All animals had significantly reduced EF (25 ± 4.8%) and were receiving high doses of inotropic agents to maintain cardiac function. Nine animals survived the surgical procedure. The average 12-hour blood loss was 435 ml. Cardiac index improved significantly in all animals. The procedure time was not extended by any adverse events (60 to 145 minutes). CONCLUSIONS: The extraperitoneal, subcostal surgical approach is less invasive than a median sternotomy and allows centrifugal or axial to be implanted quickly and without cardiopulmonary bypass (CPB). Avoiding CPB and an extensive mediastinal dissection can help to decrease significantly the number of complications in patients with end-stage organ failure.

Transplanted human cord blood-derived unrestricted somatic stem cells preserve high-energy reserves at the site of acute myocardial infarction.

BACKGROUND AIMS: It has been demonstrated that transplantation of human cord blood-derived unrestricted somatic stem cells (USSC) in a porcine model of acute myocardial infarction (MI) significantly improved left ventricular (LV) function and prevented scar formation as well as LV dilation. Differentiation, apoptosis and macrophage mobilization at the infarct site could be excluded as the underlying mechanisms. The paracrine effect of the cells is most likely to be observed as the cause for the USSC treatment. The aim of our study was to examine the cardiomyocyte metabolism and the role of high-energy phosphates at the marginal infarct. Methods. USSC were transplanted into the myocardium of the LV, which was supplied by a ligated circumflex artery. Forty-eight hours later, the hearts were harvested and biopsies were performed from the marginal infarct zone surrounding the site of the cell injection. The concentrations of creatinine phosphate (CP), adenosine monophosphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP) were determined by chromatography. RESULTS: The concentration of ADP, ATP and CP in the marginal zone of the infarction was significantly higher in the USSC group. The mean global left ventricular ejection fraction (LVEF) (SD) was 64% (8%) before MI; post-MI, LVEF decreased to 35% (9%). CONCLUSIONS: Preservation of high-energy phosphates in the marginal infarct zone suggests that the preservation of energy reserves of surviving cardiomyocytes is a possible mechanism of action of transplanted stem cells in acutely ischemic myocardium.