Hospital admissions of acute cerebrovascular diseases during and after the first wave of the COVID-19 pandemic: a state-wide experience from Austria.

We investigated hospital admission rates for the entire spectrum of acute cerebrovascular diseases and of recanalization treatments for ischaemic stroke (IS) in the Austrian federal state of Styria during and also after the first coronavirus disease 2019 (COVID-19) wave. We retrospectively identified all patients with transient ischaemic attack (TIA), IS and non-traumatic intracranial haemorrhage (ICH; including intracerebral, subdural and subarachnoid bleeding types) admitted to one of the 11 public hospitals in Styria (covering > 95% of inhospital cerebrovascular events in this region). Information was extracted from the electronic medical documentation network connecting all public Styrian hospitals. We analysed two periods of interest: (1) three peak months of the first COVID-19 wave (March-May 2020), and (2) three recovery months thereafter (June-August 2020), compared to respective periods 4 years prior (2016-2019) using Poisson regression. In the three peak months of the first COVID-19 wave, there was an overall decline in hospital admissions for acute cerebrovascular diseases (RR = 0.83, 95% CI 0.78-0.89, p < 0.001), which was significant for TIA (RR = 0.61, 95% CI 0.52-0.72, p < 0.001) and ICH (0.78, 95% CI 0.67-0.91, p = 0.02), but not for IS (RR = 0.93, 95% CI 0.85-1, p = 0.08). Thrombolysis and thrombectomy numbers were not different compared to respective months 4 years prior. In the recovery period after the first COVID-19 wave, TIA (RR = 0.82, 95% CI 0.71-0.96, p = 0.011) and ICH (RR = 0.86, 95% CI 0.74-0.99, p = 0.045) hospitalizations remained lower, while the frequency of IS and recanalization treatments was unchanged. In this state-wide analysis covering all types of acute cerebrovascular diseases, hospital admissions for TIA and ICH were reduced during and also after the first wave of the COVID-19 pandemic, but hospitalizations and recanalization treatments for IS were not affected in these two periods.

A randomized controlled clinical trial of pacemaker follow-up in clinic and by telemedical interpretation of the pacemakers' magnet mode.

We assessed a two-stage follow-up procedure for cardiac pacemakers, where in-clinic follow-ups were partly replaced by telemedical follow-ups. This was compared with the standard follow-up regime (in-clinic follow-up only). The new procedure required an electronic patient record, a telemedical follow-up unit for recording ECGs while the pacemaker was temporarily set to magnet mode, an ECG processing unit, and a reviewing and reporting unit. A total of 177 (86 female) patients were randomized to the control group and 182 (98 female) patients to the telemedicine group. In the telemedicine group, 234 telemedical follow-ups were performed. Out of these, 68 required an additional in-clinic follow-up, while 166 were sufficient for assessing the pacemakers' working status. During the study, there were 19 deaths in the telemedicine group and 20 in the control group. There was no significant difference between the two groups(P = 0.40). The probability that an individual patient's pacemaker would not to be replaced over time was analysed in a similar way to the Kaplan-Meier survival function. Fewer pacemakers were replaced in the telemedicine group (14) than in the control group (18), but the difference was not significant (P = 0.26). We conclude that alternating telemedical and in-clinic follow-ups brings no additional risks for patients. The follow-up procedure is feasible and interpretation of the pacemakers' magnet effect provides an easy-to-use, manufacturer-independent method of assessing the pacemakers' working status. This should reduce the patient load on pacemaker centres and decrease the overall costs of pacemaker therapy.

Knowledge and attitude of ICU nurses, students and patients towards the Austrian organ donation law.

BACKGROUND: A survey on the knowledge and attitudes towards the Austrian organ donation legislation (an opt-out solution) of selected groups of the Austrian population taking into account factors such as age, gender, level of education, affiliation to healthcare professions and health related studies was conducted. METHODS: An online survey among 3 target groups (ICU nurses, health science students and non health science students) was performed and results were compared to the answers from transplantation patients to a paper questionnaire. A total of 8415 persons were asked to participate in the survey and 2025 (24%) persons correctly completed the questionnaire. 1945 online responses (ICU nurses n = 185; students of health sciences n = 1277; students of non-health science related courses n = 483) were analysed and data were compared to 80 manually filled-in responses from patients from a previous study. RESULTS: 84% of participants state that they know the Austrian organ donation legislation; this percentage varies significantly (p < 0.05) within the target groups and is influenced by demographic variables of the participants. 74% think that the law is good and 79% do not favour a change. Opinions and attitudes towards the legal situation are positively influenced by the affiliation to healthcare professions and health-related fields of study. Interviewed persons who were aware of the legislation before the survey had a more positive attitude towards the existing legislation (77% versus 74%, p < 0.05). CONCLUSIONS: The information level on Austrian organ donation legislation is high. ICU nurses and those who did not know the law before were most critical towards the existing legislation. Therefore education to increase knowledge in the general population and goal-oriented efforts to increase awareness in the target groups should be emphasized.

The role of CYP2C8 genotypes in dose requirement and levels of everolimus after heart transplantation.

Everolimus is an immunosuppressive drug metabolized by enzymes of the CYP family. A common variant of the CYP2C8 gene, CYP2C8*3, results in strongly decreased CYP2C8 activity, but its role for the pharmacogenetics of everolimus remains unclear. Aim of the present study was to examine the role of CYP2C8 variants in everolimus dose and drug levels after heart transplantation. The present study comprised 30 patients with everolimus based maintenance therapy after heart transplantation. CYP2C8 genotypes were determined and correlated with clinical data. In all, 21 subjects carried the CYP2C8 *1/*1 genotype and 9 subjects carried the CYP2C8 *1/*3 genotype. Neither everolimus dose nor everolimus levels were associated with CYP2C8 genotype at any point of time (p < 0.05). During follow-up, graft rejection reactions were observed in two patients and infections were observed in seven patients. In one patient, type 2 diabetes was diagnosed during follow-up. None of these adverse events were significantly associated with CYP2C8 genotypes. We conclude that in adult patients after heart transplantation, CYP2C8 genotypes are not associated with dose requirements or levels of everolimus.

Prehospital care of left ventricular assist device patients by emergency medical services.

Left ventricular assist devices (LVADs) are frequently implanted as permanent (bridge to destination [BTD]) or temporary (bridge to transplantation [BTT]) cardiac support. When LVAD patients are discharged to home, they are very likely to require emergency medical services (EMS), but there is very little literature on out-of-hospital emergency care for patients with LVADs. We present two typical cases of LVAD patients for whom EMS was called. In the first case, the patient was in an ambulance two hours distant from our university hospital when a pulsatile system malfunctioned. In the second case, EMS was called to an unconscious LVAD patient. Emergency reference cards, training programs for emergency medical staff, and a 24-hour emergency hotline for the local VAD team are advisable.

Effect of oxidative stress and endotoxin on human serum albumin in brain-dead organ donors.

Albumin, among other molecules, binds and detoxifies endotoxin in healthy people. Oxidative stress leads to protein oxidation and thus to the impaired binding properties of albumin. This property, in combination with increased gut permeability, leads to the appearance of endotoxin in the systemic circulation and to impaired organ function. We hypothesize that these processes occur in the serum of brain-dead organ donors. Endotoxin was determined with an adapted Limulus amoebocyte lysate assay. The albumin fractions and binding capacity were determined by high-performance liquid chromatography (HPLC). FlowCytomix (eBioscience, San Diego, Calif) was used to determine the cytokine levels. Carbonylated proteins (CPs) and myeloperoxidase (MPO) were measured by an enzyme-linked immunosorbent assay (ELISA). Eighty-four brain-dead organ donors were enrolled and categorized by the duration of intensive care unit (ICU) stay. The albumin-binding capacity for dansylsarcosine was reduced in brain-dead patients compared with controls. Endotoxin positivity in 16.7% of donors was associated with decreased binding capacity in donors and worse survival of recipients. The CP and MPO levels of organ donors were significantly higher than in healthy controls. The durations of ICU stay increased albumin oxidation. In addition, interleukin-6 (IL-6), IL-8, IL-10, and IL-1ß levels were increased in patients, whereas the interferon-γ (IFN-γ) levels were within the normal range. We conclude that oxidative stress and systemic endotoxemia are present in brain-dead organ donors, which might affect recipient survival. High endotoxin levels might be caused by increased gut permeability and decreased binding capacity of albumin influenced not just by higher albumin oxidation.

Ibandronate and calcitriol reduces fracture risk, reverses bone loss, and normalizes bone turnover after LTX.

BACKGROUND: Osteoporosis is a common complication in long-term survivors after liver transplantation (LTX). This study investigates the influence of a combination therapy of low dose parenteral ibandronate (IBN) and calcitriol on top of calcium and vitamin D supplementation in such patients. METHODS: For 3 years, 30 osteoporotic patients after LTX (28±6 months) were treated with quarterly 2 mg IBN intravenously and daily calcitriol (0.25-1.0 µg) on top of 1000 mg calcium and 800 IU vitamin D. Recipients with normal bone density (n=24) were enrolled as controls. Laboratory analysis and dual energy X-ray absorptiometry were performed at baseline and every 12 months. Primary endpoints were changes in bone mineral density and fracture incidence. RESULTS: IBN patients showed a significant increase of bone mineral density at the femoral neck and the trochanteric region (13% and 15%, respectively, both P=0.001) as compared with baseline whereas the control group revealed a small but significant loss of -5.0% in the trochanteric and -4.9% in the neck region (P<0.05) over the same time period. Fracture incidence was low among IBN patients (7%); however, 23% of the control patients sustained at least one vertebral fracture. The relative fracture risk was 3.21 for IBN patients (95% confidence interval, 0.6-20.9, P=0.03) resulting in an absolute risk reduction for a new vertebral fracture of 14%. CONCLUSION: In LTX recipients with osteoporosis combination therapy with low dose IBN and calcitriol on top of calcium and vitamin D supplementation is an effective treatment option.

Solid organ transplantation: technical progress meets human dignity: a review of the literature considering elderly patients' health related quality of life following transplantation.

INTRODUCTION: Many transplant studies in elderly patients focus on survival and mortality rates. It was the aim of this review to evaluate publications dealing with individual patient performance and independence. METHODS: The literature search included all articles retrievable for the hit "transplantation in elderly recipients" between 1960 and 2010. For quality search the inclusion criteria were as follows: older than 60 years and transplanted kidney, liver, heart, lung or pancreas from a deceased or living donor. We focussed on parameters concerning quality of life, frailty, nutritional status/weight loss, drugs/interactions/polypharmacy, gait/osteoporosis/fracture, delirium/dementia and geriatric assessment to address physical and psychosocial functionality of elderly recipients. RESULTS: The initial hit list contained 1427 citations from electronic databases. 249 abstracts thereof were selected for full review. A total of 60 articles met final inclusion criteria. Finally, only five studies met the qualitative inclusion criteria as listed above. CONCLUSION: The number of elderly patients placed on waiting lists has increased dramatically and will further grow. Interdisciplinary collaboration and distinct patient selection is recommended in most of the studies. However, data concerning quality of life and related parameters in elderly transplant recipients are rare.

Management of complications after varicoportal anastomosis in liver transplantation.

The presence of portal vein thrombosis is a potential limitation for liver transplantation. An intraoperative diagnosis is linked to extensive surgical treatment and massive postoperative complications and mortality. We present a surgical less risky method for the treatment of intraoperatively diagnosed portal and mesenteric vein thrombosis that served as salvage therapy for a patient who underwent liver transplantation in our centre. Postoperative complications were ascites and renal failure. Persistent ascites required repeated paracentesis during the first month after liver transplantation but medical treatment sufficed thereafter. Moderate renal failure as defined by the K/DOQI-guidelines improved gradually and dialysis was never indicated. Six months after transplantation, the patient had normal liver function and adequate renal function.

The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation.

BACKGROUND: tacrolimus and everolimus are immunosuppressive drugs metabolized by enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A5*3, results in strongly decreased CYP3A5 activity and has been shown to influence Tacrolimus blood concentrations, but its role for the pharmacogenetics of Everolimus remains unclear. Aim of the study was to examine the role of CYP3A5*3 variant in tacrolimus and everolimus dose and drug levels after heart transplantation. METHODS: The present study comprised 15 patients with Tacrolimus and 30 patients with Everolimus-based maintenance therapy after heart transplantation. CYP3A5 genotypes were determined and correlated with clinical data. RESULTS: In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared to non-expressors. Tacrolimus levels were not significantly different at any point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither Everolimus dose nor levels were significantly different between CYP3A5 expressors and non-expressors at any point of time. DISCUSSION: We conclude that in adult patients after heart transplantation, CYP3A5 genotypes have a strong influence on Tacrolimus, but not Everolimus dose requirement.

Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates.

There is in vitro proof that mTOR proteins play a role in protecting HCV infected cells from apoptosis. The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, HCV RNA and influence of donor and recipient factors on viral recurrence and survival. Viral recurrence was defined as elevated liver enzymes combined with active hepatitis diagnosed on the basis of increasing viral load and/or biopsy-proven HCV relapse in the transplanted organ. Sixty-seven HCV positive patients were included: 39 received a regimen including sirolimus; 28 patients received calcineurin inhibitors. Sirolimus patients showed a significant decrease in the HCV PCR levels (p<0.05). Survival of the sirolimus patients was significantly higher (p<0.03) than in the other patient cohort. Sirolimus has been shown to be a potent immunosuppressive agent after liver transplantation, though nothing is known about its effect on HCV. This analysis suggests that sirolimus has potential to suppress viral recurrence in HCV positive liver transplant candidates.

Serum cystatin C is an easy to obtain biomarker for the onset of renal impairment in heart transplant recipients.

OBJECTIVE: With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. Highly sensitive, early, and effective monitoring of posttransplant renal function is still being researched. This study aimed to evaluate the prognostic value of cystatin C for patients after heart transplantation. METHODS: Seventy-three long-term recipients of a heart transplant more than 5 years before the study start were included in the analysis with a follow-up of 4 years. Serum creatinine, renal glomerular filtration rate calculated by the Modification of Diet in Renal Disease formula, and serum cystatin C levels were collected, and risk factors for renal dysfunction were assessed. Statistical analysis was performed for all patients. RESULTS: Univariate analysis showed a prognostic impact of antihypertensive medication and onset of diabetes (P < .001) on renal failure after transplantation. Multivariate analysis yielded cystatin C measured at the study start as a superior prognostic parameter for all time points (area under the receiver operating characteristic 12 months: 0.963; 24 months: 0.910; 48 months: 0.949) compared with the conventionally used creatinine levels. CONCLUSIONS: Our results showed an enormous potential of serum cystatin C as an early prognostic and easy to obtain biomarker for renal dysfunction after heart transplantation.

Ibandronate prevents bone loss and reduces vertebral fracture risk in male cardiac transplant patients: a randomized double-blind, placebo-controlled trial.

Bone loss and fractures are common complications after cardiac transplantation (CTP). The aim of this study was to investigate whether intravenous ibandronate is an effective preventive option. Thirty-five male cardiac transplant recipients received either ibandronate (IBN) 2 mg intravenously every 3 mo or matching placebo (CTR) in addition to 500 mg calcium carbonate and 400 IE vitamin D(3). Sera were collected at CTP and every 3 mo thereafter. At baseline and 6 and 12 mo, standardized spinal X-rays and BMD measurements were taken. Bone biopsies were taken at CTP and after 6 mo from six patients. In the IBN group, 13% of the patients sustained a new morphometric vertebral fracture compared with 53% in the CTR group (absolute risk reduction [ARR], 40%; relative risk reduction [RRR], 75%; p = 0.04). BMD remained unchanged with IBN treatment but in the CTR group decreased at the lumbar spine by 25% and at the femoral neck by 23% (both p < 0.0001) over the 1-yr period. Serum bone resorption markers carboxy-terminal telopeptide region of type I collagen (sCTX) and TRACP 5b were significantly increased in the CTR group and decreased in the IBN group at all time points compared with baseline. In contrast, both osteocalcin and bone-specific alkaline phosphatase levels showed, after a similar decrease over the first 3 mo in both groups, a marked rise in the CTR subjects and steadily declining levels in the IBN patients throughout the remainder of the study period. Three paired biopsies were available from each group. Despite the small sample size, a difference in the relative change of eroded surface (68% in the CTR versus -23% in the IBN group, p < 0.05) could be shown. Intravenous IBN reduced fractures, preserved bone mass, and prevented uncoupling of bone formation and resorption after CTP. The favorable effects on bone turnover were also supported by histomorphometric findings.

Measurement of cardiac output and pulmonary transit time for assessment of pulmonary vascular resistance in domestic piglets.

The degree of elevated pulmonary vascular resistance (PVR) is a crucial clinical parameter. Cardiac output (CO) and pulmonary transit time (PTT) can be ascertained by a number of radiological methods. A close functional relationship between CO, PTT and PVR would facilitate non-invasive PVR measurements. One-hundred and fifty-one measurements were made in six piglets. Pressures in the pulmonary and systemic circulation were measured invasively. Cardic output was determined by the use of a Doppler flow probe around the truncus pulmonalis. Temperature sensors were placed in the pulmonary truncus and left atrium. Elevated PVR was produced by repeated air embolism. After injection of ice-cold saline, the time span between the minimal temperature in the truncus pulmonalis and the left atrium was taken as PTT. The CO and PTT were inserted into a new formula derived from the Hagen-Poiseuille law for the calculation of the PVR model. Numerical constants of the formula were calculated by the robust method of minimization. The PVR values, as calculated from invasively measured mean pulmonary artery pressure, mean left atrial pressure and CO, served as reference. In the six piglets, the PVR model and PVR reference showed a strong linear correlation with r = 0.923. The Bland-Altman plot revealed a standard deviation of -0.64/+0.67 Wood units. Cardiac output, PTT and PVR showed a close functional relationship. With a correction for blood viscosity and body size, this relationship could be used for non-invasive clinical measurements of PVR.

Myeloperoxidase as serum marker for detection of CMV infections and rejections in patients after liver or heart transplantation.

Rejection episodes and infections are common problems after organ transplantations (TX). Rejection can be diagnosed in liver-transplant (LTX) patients when liver-specific enzymes in the serum are elevated. As endomyocardial biopsy (EMB) is the gold standard for detecting heart transplant (HTX) rejection, serum parameters would permit more selective use of this invasive procedure. Cytomegalovirus (CMV) infections can have serious consequences for TX patients and so should be diagnosed and treated timely. At present, there are no suitable diagnostic methods other than CMV antigen pp65 and CMV polymerase chain reaction (PCR). Our study aimed to test the sensitivity of myeloperoxidase (MPO), an enzyme of neutrophilic granulocytes, as a new serum parameter in addition to established serum parameters and EMB for diagnosis of infection and rejection episodes after LTX and HTX. MPO in plasma from 246 blood samples (103 used for statistical analysis) from 27 patients (18 LTX and 9 HTX) was determined using ELISA; C-reactive protein (CRP), gamma-glutamyl-transpeptidase (GGT), white blood count and CMV pp65 antigen were monitored routinely. EMBs were performed at defined intervals after HTX. Results were analyzed with descriptive statistics, T-test, Wilcoxon test and Cox regression analysis, whereby a p<0.05 was viewed as significant. MPO values in TX patients with an infection (7 LTX, 2 HTX) were significantly higher than in TX patients without complications (control group) (253.9 microg/l vs. 116.6 microg/l, p=0.0194). In TX patients with rejections (6 LTX, 6 HTX), there is also a significant increase in comparison to controls (429.7 microg/l vs. 116.6 microg/l, p=0.0001). Data from individual TX patients, however, indicate that MPO levels rise distinctly earlier with infection (CMV) than with rejection, enabling earlier detection of the complication and initiation of suitable treatment. Our findings suggest that a larger and prospective study should be designed to evaluate the usefulness of MPO levels in assessing organ transplant recipients.

A simplified technique for implantation of left ventricular epicardial leads for biventricular re-synchronization using video-assisted thoracoscopy (VATS).

OBJECTIVE: Cardiac re-synchronization therapy for treatment of heart failure requires transvenous insertion of both a right ventricular and left ventricular pacing lead. Implantation of the latter by way of the coronary sinus often fails. Therefore, alternative techniques for insertion are required. We applied a simple video-assisted surgical technique (VATS) using only two ports for the insertion of left-ventricular screw-in electrodes. METHODS: Fifteen patients (M: 10; F: 5; mean age: 62.2 years; range: 46-76 years) with heart failure meeting the ACC/AHA guidelines for implantation of biventricular pacing underwent transvenous insertion of the right atrial sensor lead and the right ventricular pacing lead. In all of them transvenous implantation of the left ventricular pacing lead failed, and they were planned for VATS. In right-lateral decubitus position and under single-lung ventilation a camera port and a flexible instrumentation port were inserted in the forth intercostal space. By using routine instruments, a T-shaped incision was made lateral to the phrenic nerve and an electrode was screwed in. The lead was guided subcutaneously to the pacemaker. RESULTS: Mean skin-to-skin operating time was 55+/-16 min, no conversion to thoracotomy was necessary. All patients were extubated in the operating room and remained in the intensive care unit for less than 24h. Chest tubes were removed after a mean of 1.6+/-0.5 days and the patients were discharged after a mean of 4+/-1.3 days. Intraoperative and postoperative pacing thresholds at 1 and 7 months were satisfactory in all cases and there was no lead dislocation. All but two patients had an improvement of their NYHA function class. There was neither surgical morbidity nor mortality. CONCLUSIONS: Video-assisted thoracoscopy over two ports seems to be an excellent alternative procedure for epicardial lead implantation. It is readily available and produces good pacing results at a short intervention time and tolerable stress for the patients.