Management of Immune Thrombotic Thrombocytopenic Purpura without Therapeutic Plasma Exchange.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP, receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the two cohorts (3 and 4 days; P = 0.31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B co-infection, an ovarian teratoma with associated anti-platelet antibodies, and multiple platelet transfusion before the correct diagnosis may have impeded immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.

Arteriovenous oscillometric plethysmography for fistula functional testing.

The aim of the presented prospective observational study was to evaluate the effect of fistula flow on peripheral wave morphology and pulse wave velocity by means of the oscillometric Vicorder®-device with the purpose of fistula surveillance. METHODS: Digitized and normalized curves of 53 haemodialysis patients at the fistula and non-fistula arm were analyzed. Slope parameters and the areas under the curve of characteristic sections of pulse waves as well as the power spectrum of the pulse waves and their first and second derivatives were computed. Furthermore, the amplitude of volumetric change (AMP) was assessed. Duplex-sonography served as a reference method. RESULTS: In the comprehensive set of novel pulse wave parameters significant inter-arm differences were demonstrated and a significant delay of the systolic maximum at the fistula arm in comparison to the non-fistula arm (204 ± 3.4 versus 162 ± 5.3 ms, p<0.001) was proven. Unexpectedly, pulse wave velocity apparently did not differ between both arms (7.85 versus 8.05 m/sec at the fistula/non-fistula side, p=0.942). The inter-arm differences of the slope parameters were more pronounced in forearm than in upper arm fistulas. Finally, we showed that the inter-arm difference of AMP correlated with volume-flow (r= 0.326 with p=0.017). CONCLUSION: Pulse waves as assessed by oscillometric pulse wave analysis have distinct features at fistula and non-fistula arms. This is due to enhanced arteriovenous flow, i.e. in both the brachial artery and the fistula vein. The analysis of those alterations has the potential to assess fistula function.

Urinary calprotectin as a diagnostic tool for detecting significant bacteriuria.

Pyuria in dipstick examination serves as the most widespread screening tool for urinary tract infections (UTI). The absence of pyuria, however, does not exclude UTI. We investigated the diagnostic value of urinary calprotectin, a mediator protein of the innate immune system, which is released by leukocytes, for the detection of UTI and compared it with dipstick pyuria. Since even low numbers of leukocytes in the urine significantly increase urinary calprotectin concentrations, calprotectin might be a more sensitive marker than pyuria detected by dipstick. All 162 patients were prospectively included and underwent a urine dipstick, urine culture, quantification of proteinuria and determination of calprotectin in the urine. Urinary calprotectin was determined using an enzyme-linked immunosorbent assay (ELISA). UTI was defined as urine cultures with detection of one or a maximum of two uropathogenic bacteria with ≥ 105 colony-forming units per millilitre (CFU/ml). Exclusion criteria were acute kidney injury, chronic renal insufficiency and tumors of the urinary tract. 71 (43.8%) patients had a UTI. Of the 91 patients without UTI, 23 had a contamination and 19 had evidence of ≥ 105 CFU/ml considered to be asymptomatic bacteriuria. The median calprotectin concentration in patients with UTI and pyuria was significantly higher than in patients with UTI and without pyuria (5510.4 vs. 544.7 ng/ml). In ROC analyses, calprotectin revealed an area under the curve (AUC) of 0.70 for the detection of significant bacteriuria. Pyuria in dipstick examinations provided an AUC of 0.71. There was no significant difference between these AUCs in the DeLong test (p = 0.9). In patients with evidence of significant bacteriuria but without pyuria, a significantly higher calprotectin concentration was measured in the urine than in patients with neither pyuria nor UTI (544.7 ng/ml vs 95.6 ng/ml, p = 0.029). Urinary calprotectin is non-inferior to dipstick pyuria in the detection of UTI.

Prevalence of masked hypertension in attended versus unattended office blood pressure measurement.

There is a controversial debate regarding whether unattended blood pressure (BP) measurement should be regarded as the new gold standard of office BP measurement. Unattended BP measurement eliminates the white-coat effect and reduces external influences on the patient. On the other hand, it might underestimate real-life BP. The present study compares the prevalence of masked hypertension using attended versus unattended office BP measurements. We performed a cross-sectional study on 213 patients in a general practitioner's outpatient clinic and compared attended and unattended office BP with 24h-ambulatory BP monitoring (24h-ABPM). Masked hypertension was defined as pressure ≥135/85 mmHg in daytime ABPM with office systolic BP < 140/90 mmHg. Median attended and unattended office BPs were 140/86 and 134/80 mmHg with a median 24h-BP of 129/79 mmHg and daytime ABP of 133/82 mmHg. The number of patients with masked hypertension was 45/213 (21.2%) using unattended and 23/213 (10.8%) using attended office BP measurements (p < .0001). Bland-Altman analysis revealed a 7.4 mmHg systolic and 6.2 mmHg diastolic bias between the attended versus unattended office BP, and two systolic and -1.7 mmHg diastolic biases between the unattended office BP and daytime ambulatory BP. In linear regression analysis, an unattended office BP of 134 mmHg corresponded to 140 mmHg in attended BP measurement. Using a cut-off of 135/85 mmHg instead of 140/90 mmHg in unattended office BP measurement, the rate of masked hypertension was 26/213 (12.2%). Thus, unattended office BP measurement results in a substantial increase in the prevalence of masked hypertension using the traditional definition of hypertension. The present findings suggest that it might be reasonable to use a definition of 135/85 mmHg.

Impact of the COVID-19 pandemic on hospital admission rates for arterial hypertension and coronary heart disease: a German database study.

Background: During the SARS-CoV-2 pandemic it was speculated that the virus might be associated with a persistent increase of cardiovascular risk. The present study compares pre- and post-pandemic hospital admission rates for hypertension and coronary artery disease. Methods: Systematic multicentric retrospective cohort analysis of 57.795 hospital admissions in an urban region in Germany during two different periods (pre-pandemic 01-06/2019 vs. post-pandemic era 01-06/2023). Information on hospital admissions for arterial hypertension, chronic coronary syndrome, unstable angina pectoris and acute myocardial infarction were extracted from the hospitals data systems. Additionally, six comorbidities and performed coronary interventions were monitored. Results: Compared to the pre-pandemic era, there was no increase in hospitalizations for arterial hypertension (516 vs. 483, -6.8%, p = 0.07) or myocardial infarction (487 vs. 349, -23.8%, p < 0.001), but the total number of patient admissions with chest pain as the presenting symptom increased (chronic coronary syndrome: 759 vs. 943, +24.2%, p < 0.001; unstable angina pectoris: 270 vs. 451, +67.0%, p < 0.001). At the same time, the number of performed coronary angiographies increased, but less patients underwent percutaneous interventions. Patients admitted with chest pain in the post-pandemic era were in general healthier with less comorbidities. Conclusion: The present multicenter cohort study found no evidence for an increase in hospitalizations for arterial hypertension or coronary artery disease after the end of the pandemic. However, further studies with larger sample sizes are needed to confirm our results.

Predictors of blood pressure response to continuous positive airway pressure treatment in patients with sleep apnea.

BACKGROUND: Sleep apnea is associated with hypertension. Metaanalyses indicate that treatment of sleep apnea by continuous positive airway pressure (CPAP) reduces blood pressure (BP) by a mean of 3 mmHg. To date, predictors of BP response to CPAP remain incompletely understood. We hypothesized that the magnitude of CPAP-induced BP reduction depends on baseline apnea-hypopnea index (AHI) and the extent of daytime sleepiness. METHODS: We performed a retrospective study on the association of BP response to CPAP with polysomnographic readings, intensity of sleepiness (measured by Epworth Sleepiness Scale, ESS), and epidemiologic parameters in 2461 patients with obstructive sleep apnea. BP response was defined as the difference between office BP at polysomonography examinations before and after initiation of CPAP. RESULTS: Five hundred and fifty-five patients fulfilled all inclusion and exclusion criteria and were included in the analysis. Median monthly CPAP usage was 143.7 h (85.4-204.1 h). BP was significantly higher at baseline than at follow-up (129.9 ±â€Š15.5 vs. 128.3 ±â€Š15.2, P  = 0.021) resulting in mean reduction of BP of -1.5 ±â€Š19.2 mmHg. patients with a higher than median baseline AHI (median 21) showed a more pronounced reduction of BP than those with lower AHI (AHI ≥21: 130.5 ±â€Š15.3 vs. 128.6 ±â€Š14.6, P  = 0.06; AHI <21: 129.5 ±â€Š15.8 vs. 127.9 ±â€Š15.8, P  = 0.18). CPAP therapy led to a significant reduction in sleepiness (8.3 ±â€Š4.8 vs. 6.6 ±â€Š4.5, P  < 0.0001). Those subjects with higher than median sleepiness score (ESS ≥8), however, did not show a significant difference in BP response compared with those with a lower sleepiness score. Receiver-operating characteristic (ROC) curve analyses investigating the accuracy of AHI and ESS to predict a BP reduction at least 5 mmHg revealed an AUC of 0.51 and 0.52, respectively. CONCLUSION: The study confirms that CPAP therapy for sleep apnea has a mild BP lowering effect. Although this effect is slightly higher in patients with above-average AHI, neither AHI nor ESS can be used to define threshold values predicting a BP decrease at least 5 mmHg.

Oxidized high-density lipoprotein associates with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia and considered to be a progressive chronic disease associated with increased morbidity and mortality. Recent data suggest a link between inflammation, oxidative stress, and AF, although the underlying mechanisms are not fully understood. Because oxidized lipoproteins cause structural damage and electrophysiologic changes in cardiomyocytes, it is feasible that the transformation of atheroprotective high-density lipoprotein (HDL) into dysfunctional HDL contributes to the development of AF. OBJECTIVE: The purpose of this study was to determine whether a reduced antioxidant function of HDL is associated with the presence of AF. METHODS: In this multicenter cross-sectional cohort study, we assessed HDL function in sera of 1206 participants. Patients were divided into groups according to the presence of AF (n = 233) or no AF (n = 973). A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased normalized HDL lipid peroxide content (nHDLox). RESULTS: Participants with AF had a 9% higher mean relative nHDLox compared to persons without AF (P = .025). nHDLox was strongly associated with AF in all models of logistic regression, including the analysis adjusted for age, sex, and risk factors for AF (all P ≤.01). CONCLUSION: Reduced antioxidant HDL function is associated with the presence of AF, which supports growing evidence that impaired lipoprotein function is linked to electrophysiological changes in cardiomyocytes. nHDLox is one of several contributors to the initiation and perpetuation of AF.

Severity of neurological Long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors.

BACKGROUND: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting. METHODS: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies specific for the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires. RESULTS: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10-9) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in the Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ -0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087). CONCLUSIONS: Concentrations of autoantibodies correlates to the intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.

Dysfunctional high-density lipoprotein in chronic inflammatory rheumatic diseases.

Background: The mechanism explaining low cholesterol concentrations in chronic inflammatory rheumatic disease (CIRD) is incompletely understood. We hypothesized that chronic inflammation impairs the functionality of high-density lipoprotein (HDL), for example, by oxidative processes. Objectives: Assessment of oxidized HDL (HDLox), a marker of dysfunctional HDL, in newly diagnosed patients with CIRD before and after initiation of immunosuppressive therapy and comparison of HDLox values of patients with CIRD to non-CIRD controls. Design: Prospective observational trial. Methods: The study was conducted on 44 newly diagnosed CIRD patients, who were initiated on immunosuppressive therapy (baseline). A total of 136 patients without CIRD served as control. Lipid profiles including HDLox levels and C-reactive protein (CRP) were measured in both groups at baseline. In CIRD patients, measurements were repeated 12 weeks after baseline. Validated outcome tools for disease activity and function were assessed at baseline and 12 weeks. Results: A total of 33 (75%) patients with rheumatoid arthritis, 7(16%) with axial spondyloarthritis, and 4 (9%) with systemic lupus erythematosus were included. Groups were comparable for age and BMI. CIRD patients had higher HDLox concentrations (1.57 versus 0.78, p = 0.02) and tended to have lower low-density lipoprotein cholesterol, HDL cholesterol, and cholesterol concentrations compared to controls. HDLox (1.57 versus 1.4, p = 0.26) and CRP levels (2.1 versus 0.7 mg/dl, p < 0.01) decreased in CIRD patients from baseline to follow-up. Conclusion: CIRD is associated with an impairment of the anti-inflammatory properties of HDL as reflected by an increase in HDLox concentrations. This effect may contribute to the increased cardiovascular risk in chronic inflammatory diseases.

Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019.

It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.

Oscillometric pulse wave analysis for detecting low flow arteriovenous fistula.

BACKGROUND: Pulse wave analysis may be useful to assess fistula function. We aimed to prospectively evaluate if convenient oscillometric devices are applicable to detect flow below 500 ml/min in a real life clinical setting. METHODS: Pulse waves were recorded ambilaterally with the vicorder® device at the brachial artery in 53 patients on haemodialysis with native fistula. Primary variables consisted of the mean slope between the systolic maximum and the diacrotic notch (Slope2), the sum of the mean slopes in the four characteristic sections of pulse waves (Slope∑) and the amplitude of relative volumetric change in the measuring cuff at the upper arm (AMP). Fistula flow was measured with the use of duplex sonography using a standardized approach. RESULTS: Parameter values above or below the median indicated measurement at the non-fistula side, with sensitivities/specificities of 0.79/0.79 (p < 0.001) for Slope 2, 0.64/0.64 (p = 0.003) for Slope∑ and 0.81/0.81 (p < 0.001) for AMP if measurements at the fistula and non-fistula arm were considered. ROC-analyses of parameter values measured at the fistula to detect low flow demonstrated AUCs (with CI) of 0.652 (0.437-0.866, p = 0.167) for Slope2, 0.732 (0.566-0.899, p = 0.006) for Slope∑ and 0.775 (0.56-0.991, p = 0.012) for AMP. The point with maximal youden's index was regarded as optimal cut-off, which corresponded to sensitivities and specificities of 0.8/0.56 for slope2, 0.86/ 0.56 for Slope∑ and 0.93/0.78 for AMP. CONCLUSION: Functional surveillance with oscillometry is a promising clinical application to detect a low fistula flow. Among all investigated pulse wave parameters AMP revealed the highest diagnostic accuracy.

Germline C1GALT1C1 mutation causes a multisystem chaperonopathy.

Mutations in genes encoding molecular chaperones can lead to chaperonopathies, but none have so far been identified causing congenital disorders of glycosylation. Here we identified two maternal half-brothers with a novel chaperonopathy, causing impaired protein O-glycosylation. The patients have a decreased activity of T-synthase (C1GALT1), an enzyme that exclusively synthesizes the T-antigen, a ubiquitous O-glycan core structure and precursor for all extended O-glycans. The T-synthase function is dependent on its specific molecular chaperone Cosmc, which is encoded by X-chromosomal C1GALT1C1. Both patients carry the hemizygous variant c.59C>A (p.Ala20Asp; A20D-Cosmc) in C1GALT1C1. They exhibit developmental delay, immunodeficiency, short stature, thrombocytopenia, and acute kidney injury (AKI) resembling atypical hemolytic uremic syndrome. Their heterozygous mother and maternal grandmother show an attenuated phenotype with skewed X-inactivation in blood. AKI in the male patients proved fully responsive to treatment with the complement inhibitor Eculizumab. This germline variant occurs within the transmembrane domain of Cosmc, resulting in dramatically reduced expression of the Cosmc protein. Although A20D-Cosmc is functional, its decreased expression, though in a cell or tissue-specific manner, causes a large reduction of T-synthase protein and activity, which accordingly leads to expression of varied amounts of pathological Tn-antigen (GalNAcα1-O-Ser/Thr/Tyr) on multiple glycoproteins. Transient transfection of patient lymphoblastoid cells with wild-type C1GALT1C1 partially rescued the T-synthase and glycosylation defect. Interestingly, all four affected individuals have high levels of galactose-deficient IgA1 in sera. These results demonstrate that the A20D-Cosmc mutation defines a novel O-glycan chaperonopathy and causes the altered O-glycosylation status in these patients.

Association of plasma propionate concentration with coronary artery disease in a large cross-sectional study.

Background: Microbiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD. Methods: We performed a cross-sectional study enrolling patients admitted for invasive coronary angiography in two university hospitals in Germany. Patients with known or suspected CAD and risk factors for cardiovascular disease were prospectively recruited. Blood sampling was performed after overnight fasting and before invasive procedures. Measurement of propionate was performed by liquid chromatography. Results: The study included 1,253 patients (median [IQR], 67 [58-76] years; 799 men [64%]). A total of 739 had invasively confirmed CAD with at least one coronary artery stenosis ≥50% and 514 had exclusion of CAD. CAD patients had significant lower levels of propionate (median 5.75 µM, IQR, 4.1-7.6) compared to the non-CAD groups 6.53 µM (4.6-8.6, p < 0.001). Multivariate linear regression analysis revealed an odds ratio of 0.94 (CI 0.90-0.98, p = 0.002) for propionate as predictor of CAD. The odds ratio was further decreased to 0.45 (CI 0.31-0.65, p < 0.001) when comparing patients in the lowest quartile of propionate with those with higher levels of propionate. Conclusion: The study provides large-scale in vivo data for the association of propionate to manifest coronary artery disease, independent of other traditional cardiovascular risk factors.

Urinary biomarkers to predict acute kidney damage and mortality in COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is a frequent condition in patients hospitalized for COVID-19. There are only a few reports on the use of urinary biomarkers in COVID-19 and no data so far comparing the prognostic use of individual biomarkers in the prediction of adverse outcomes. MATERIALS AND METHODS: We performed a prospective mono-centric study on the value of urinary biomarkers in predicting the composite endpoint of a transfer to the intensive care unit, the need for renal replacement therapy, mechanical ventilation, and in-hospital mortality. 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and vascular non-inflammatory molecule-1 (vanin-1). RESULTS: We identified calprotectin as a predictor of a severe course of the disease requiring intensive care treatment (AUC 0.728, p = 0.016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19-associated AKI without reaching statistical significance (AUC 0.669, p = 0.053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, p = 0.077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. CONCLUSION: While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, the present study shows that urinary calprotectin is moderately predictive of the need for intensive care unit (ICU) admission, and NGAL may be modestly predictive of AKI in COVID-19. Calprotectin and NGAL show promise as potential helpful adjuncts in the identification of patients at increased risk of poor outcomes or complications in COVID-19.

Effect of Nephrectomy After Allograft Failure on Inflammation, Erythropoiesis, Donor-Specific Antibodies, and Outcome of Re-Transplantation.

BACKGROUND Morbidity and mortality rates are high for patients returning to dialysis after renal graft failure. Keeping failed kidney transplants in situ with concomitant minimization or withdrawal of immunosuppression is standard of care in many transplant centers. It is unclear, however, whether the resulting allospecific immune response can cause a microinflammatory milieu. The present work investigated the impact of allograft nephrectomy on systemic inflammation, erythropoiesis, and donor-specific antibodies (DSA). MATERIAL AND METHODS We performed a retrospective analysis evaluating C-reactive protein (CRP), hemoglobin concentration (Hb), ferritin, iron substitution dosages, erythropoietin dosages, and DSA in 92 transplant recipients with allograft failure, of whom 49 did not (Group A) and 43 did undergo transplant nephrectomy (Group B). Blood samples and clinical data were obtained 3-6 months after returning to dialysis. We additionally assessed outcome of kidney re-transplantation in a 10-year follow-up. RESULTS There was no significant difference in Hb concentrations, ferritin concentrations, CRP concentrations, iron, and EPO substitution dosages between the 2 groups. Patients undergoing nephrectomy had a significantly higher prevalence of DSA (65.1% vs 38.8%, P<0.0001). In the 10-year follow-up, 3 patients (12%) of Group B and none in Group A had allograft failure after primary successful re-transplantation. CONCLUSIONS Keeping a kidney graft in situ after returning to dialysis did not lead to an increase in microinflammation. Although DSA develops in more than 50% of patients after an allograft nephrectomy, the outcome of a renal re-transplantation seems to be unaffected. Thus, both strategies are feasible options in kidney transplant recipients after return to dialysis.

Impact of weather changes on hospital admissions for hypertension.

Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency.

Predictors of impaired SARS-CoV-2 immunity in healthcare workers after vaccination with BNT162b2.

Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.

The impact of treatment of periodic limb movements in sleep on blood pressure in patients with and without sleep apnea.

Improving sleep quality in patients with obstructive sleep apnea (OSA) by positive airway pressure therapy is associated with a decrease of blood pressure (BP). It remains elusive, whether treatment of sleep disturbances due to restless legs syndrome with symptomatic periodic limb movements in sleep (PLMS) affects BP as well. The present study provides first data on this issue. Retrospective study on patients undergoing polysomnography in a German University Hospital. Inclusion criteria were first diagnosis of restless legs syndrome with PLMS (PLM index ≥ 15/h and PLM arousal index ≥ 5/h) with subsequent initiation of levodopa/benserazide or dopamine agonists. Exclusion criterion was an initiation or change of preexisting positive airway pressure therapy between baseline and follow-up. BP and Epworth sleepiness scale were assessed at two consecutive polysomnographies. After screening of 953 PLMS data sets, 114 patients (mean age 62.1 ± 12.1 years) were included. 100 patients (87.7%) were started on levodopa/benserazide, 14 patients (12.2%) on dopamine agonists. Treatment was associated with significant reductions of PLM index (81.2 ± 65.0 vs. 39.8 ± 51.2, p < 0.001) and ESS (6 [interquartile range, IQR, 3-10.5] vs. 5 [IQR 3-10], p = 0.013). Systolic BP decreased from 132.9 ± 17.1 to 128.0 ± 15.8 mmHg (p = 0.006), whereas there was no significant change of diastolic BP (76.7 ± 10.9 vs. 75.1 ± 9.2 mmHg, p = 0.15) and heart rate (71.5 ± 11.9 vs. 71.3 ± 12.7, p = 0.84). The number of antihypertensive drugs remained unchanged with a median of 2 (IQR 1-3, p = 0.27). Dopaminergic treatment of PLMS is associated with an improvement of sleep quality and a decrease of systolic BP comparable to treatment OSA.