Renal function-adapted D-dimer cutoffs in combination with a clinical prediction rule to exclude pulmonary embolism in patients presenting to the emergency department.

D-dimer levels significantly increase with declining renal function and hence, renal function-adjusted D-dimer cutoffs to rule out pulmonary embolism were suggested. Aim of this study was to "post hoc" validate previously defined renal function-adjusted D-dimer levels to safely rule out pulmonary embolism in patients presenting to the emergency department. In this retrospective, observational analysis, all patients with low to intermediate pre-test probability receiving D-dimer measurement and computed tomography angiography (CTA) to rule out pulmonary embolism between January 2017 and December 2020 were included. Previously defined renal function-adjusted D-dimer cutoffs (1306 µg/l for moderate and 1663 µg/l for severe renal function impairment) were applied to determine sensitivity, specificity, negative and positive predictive values. One thousand, three hundred sixty-nine patients were included of which 229 (17%) were diagnosed with pulmonary embolism. The estimated glomerular filtration rate (eGFR) was ≥ 60 ml/min in 1079 (79%), 30-59 ml/min in 266 (19%) and < 30 ml/min in 24 (2%) patients. Only three patients (1.1%) with an eGFR < 60 ml/min had a D-dimer level < 500 µg/l. There was a significant correlation between D-dimer and eGFR (R = - 0.159, p < 0.001). Calculated on the standard D-dimer cutoff value of 500 µg/l, sensitivity of D-dimer testing was 97% for patients with an eGFR ≥ 60 ml/min and 100% for those with 30-60 ml/min, while specificity decreased in patients with renal function impairment. A negative predictive value of 0.99 as a premise to safely rule out pulmonary embolism was achieved by applying a D-dimer cutoff of 1480 µg/l for eGFR 30-59 ml/min and 1351 µg/l for eGFR < 30 ml/min. The findings of this study underline that application of renal function-adapted D-dimer levels in combination with a clinical prediction rule appears feasible to rule out pulmonary embolism. Out of the current dataset, renal function-adjusted D-dimer cutoffs to rule out pulmonary embolism were slightly different compared to previously defined cutoffs. Further studies on a larger scale are needed to validate possible renal function-adjusted D-dimer cutoffs.

Characteristics and outcome of severe hypercalcemia on admission to the emergency department: a retrospective cohort study.

AIMS OF THE STUDY: To investigate the prevalence of hypercalcemia (>2.60 mmol/l) and severe hypercalcemia (≥2.80 mmol/l) on admission. Symptoms, causes, course of serum calcium, treatment and outcome of severe hypercalcemia were evaluated and compared to historical data from previous studies. METHODS: In this retrospective cohort study, all patients presenting to the interdisciplinary emergency department of the Buergerspital Solothurn between 01 January 2017 and 31 December 2020 with measurements of serum calcium were included. Chart reviews were performed for patients with calcium ≥2.80 mmol/l to assess clinical presentation, course of disease and treatment for severe hypercalcemia. RESULTS: Of 31,963 tested patients, 869 patients (2.7%) had hypercalcemia on the admission, of which 161 had severe hypercalcemia. Non-albumin corrected calcium was 3.07 (0.32) while albumin corrected calcium was 3.34 (0.44). Calcium was higher in patients with malignancy-related hypercalcemia (3.18 [0.34] versus 3.00 [0.3], p <0.001). Neuropsychiatric (35%) and gastrointestinal (24%) were the leading symptoms. Malignancy was the most common identifiable cause of hypercalcemia (40%), with lung cancer (20%), multiple myeloma (14%) and renal cell carcinoma (11%) being the main cancer types. 36% of patients with severe hypercalcemia took calcium supplements. Bisphosphonate treatment was an independent predictor of a fall in calcium until day 5 (regression coefficient: -0.404, standard error 0.11, p <0.001). Hypercalcemia was not mentioned in the final discharge report in 38% of cases. CONCLUSION: Severe hypercalcemia is common and malignancy-related in almost half of the cases. Neuropsychiatric and gastrointestinal symptoms were most prevalent. Awareness of hypercalcemia, particularly in cancer patients and those with known triggering factors, should be raised in order to identify and treat this harmful disorder early.

Gender Equality in National Cardiology Societies: A Cross-Sectional Study.

BACKGROUND: Higher productivity and team stability have been shown for gender-diverse teams. However, there is a relevant and well-known gender gap in clinical and academic cardiovascular medicine. So far, no data concerning gender distribution in presidents and executive boards of national cardiology societies exist. METHODS: In this cross-sectional analysis, gender equality in presidents and representatives of all national cardiology societies, which were members of, or affiliated with, the European Society of Cardiology (ESC) in 2022, was analyzed. In addition, representatives of the American Heart Association (AHA) were evaluated. RESULTS: A total of 106 national societies were screened, of which 104 were included in the final analysis. Overall, 90 of 106 (85%) presidents were men, while 14 (13%) were women. In the analysis of board members and executives, a total of 1128 individuals were included. Overall, 809 (72%) board members were men, 258 (23%) women, and 61 (5%) of unknown gender. Except for society presidents in Australia, women were relevantly outnumbered by men in all world regions. CONCLUSION: Women were underrepresented in leading positions of national cardiology societies in all world regions. As national societies are important regional stakeholders, improving gender equality in executive boards might create women role models, help foster careers, and narrow the global cardiology gender gap.

Emergency medicine in Switzerland: an analysis of physician workforce, gender equality and academics.

BACKGROUND: Globally, emergency medicine is continuously evolving and in numerous countries, societies and colleges help develop the specialty on a professional and academic level. However, there are countries, including Switzerland, where emergency medicine is not a fully recognised specialty and there is a historical gender gap. AIMS OF THE STUDY: It was the aim of this study to investigate the trends and developments in Swiss emergency medicine in terms of physician workforce, gender equality and academic posts over time. METHODS: In this observational longitudinal analysis, the number and gender distribution of Swiss Society of Emergency and Rescue Medicine (SSERM) members as well as SSERM-certified physicians were analysed in 2011, 2016 and 2021. Additionally, head and leading physicians of SSERM-certified emergency departments of category 1 and 2 were analysed in 2021 with special regard to gender distribution. Finally, an analysis of Swiss academic emergency medicine including Swiss academic tracks, professors in emergency medicine as well as committees, chairs and speakers of the annual SSERM conference was performed. RESULTS: From 2011 to 2021, there was an increase in SSERM members of 52% and a growing proportion of women from 26% to 35%. Similarly, there was a rise of 66% in physicians certified in in-hospital and 79% certified in prehospital emergency medicine. The proportion of women increased by 153% and 131%, respectively. In the analysed emergency departments, 69% of all head physicians were men whereas 50% of senior consultants and consultants with extended responsibility were women in 2021. Concerning academics, emergency medicine was a mandatory subject at all Swiss universities offering a master's degree in medical studies in 2021. However, 11 Swiss universities reported only six full professors, of whom only one was a woman, and three associate professors in emergency medicine in 2021. The analysis of the annual SSERM conferences from 2016 to 2019 revealed that men outnumbered women at every conference in terms of committees, chairs and speakers. CONCLUSIONS: The number of SSERM members and board-certified emergency physicians, women in particular, remarkably increased in 10 years. Equality appears to be within reach for clinical emergency physicians, but women continue to be underrepresented in academic positions, at scientific conferences and among professors. In Switzerland, academic emergency medicine appears to be lagging behind in view of the growing emergency physician and women workforce, which might complicate further progress in and development of Swiss emergency medicine on a scientific and professional level..

Hyponatremia in the emergency department.

Hyponatremia, defined as a serum sodium <135 mmol/L, is frequently encountered in patients presenting to the emergency department. Symptoms are often unspecific and include a recent history of falls, weakness and vertigo. Common causes of hyponatremia include diuretics, heart failure as well as Syndrome of Inappropriate Antidiuresis (SIAD) and correct diagnosis can be challenging. Emergency treatment of hyponatremia should be guided by presence of symptoms and focus on distinguishing between acute and chronic hyponatremia.

A randomized controlled trial-based algorithm for insulin-pump therapy in hyperglycemic patients early after kidney transplantation.

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52-60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane.

When it rains, it pours: Peripartum cardiomyopathy with features of left-ventricular noncompaction in a hemodialysis patient.

Pregnancy and associated pre-eclampsia carry a high maternal risk in hemodialysis patients, yet no guidelines on how to monitor these patients' cardiovascular function exist. A 34-year-old hemodialysis patient presented with peripartum cardiomyopathy after a late second trimester miscarriage. On cardiac magnetic resonance imaging, diagnostic features of left ventricular noncompaction were apparent. Yet, histological and gene panel analyses remained negative. Upon stringent dry weight control and pharmacological heart failure therapy, the pathological changes showed complete regression. As pregnant hemodialysis patients have an excessively increased risk for pre-eclampsia-related cardiac disease, thorough screening appears valuable in these patients.

Comparison of glycemic control and variability in patients with type 2 and posttransplantation diabetes mellitus.

AIM: Posttransplantation diabetes mellitus (PTDM) is a common complication after renal transplantation leading to increased cardiovascular morbidity and mortality. In subjects with type 2 diabetes (T2DM) increased glycemic variability and poor glycemic control have been associated with cardiovascular complications. We therefore aimed at determining glycemic variability and glycemic control in subjects with PTDM in comparison to T2DM subjects. METHODS: In this observational study we analyzed 10 transplanted subjects without diabetes (Control), 10 transplanted subjects with PTDM, and 8 non-transplanted T2DM subjects using Continuous Glucose Monitoring (CGM). Several indices of glycemic control quality and variability were computed. RESULTS: Many indices of both glycemic control quality and variability were different between control and PTDM subjects, with worse values in PTDM. The indices of glycemic control, such as glucose mean, GRADE and M-value, were similar in PTDM and T2DM, but some indices of glycemic variability, that is CONGA, lability index and shape index, showed a markedly higher (i.e., worse) value in T2DM than in PTDM (P value range: 0.001-0.035). CONCLUSIONS: Although PTDM and T2DM subjects showed similar glycemic control quality, glycemic variability was significantly higher in T2DM. These data underscore potential important pathophysiological differences between T2DM and PTDM indicating that increased glycemic variability may not be a key factor for the excess cardiovascular mortality in patients with PTDM.

Histopathology and prognosis of de novo bladder tumors following solid organ transplantation.

BACKGROUND: Patients following solid organ transplantation have an increased risk of developing de novo bladder tumors, but their biology is poorly characterized. METHODS: We studied 1743 patients who underwent a transurethral resection of a newly diagnosed bladder tumor at a single institution. The histopathology, treatment, recurrence-free survival and overall survival were evaluated and compared between transplant and non-transplant patients. RESULTS: We identified 74 transplant patients who developed a de novo bladder tumor after a median post-transplantation interval of 62 months. The tumor was malignant in 29 patients (39 %). The most common benign lesion was nephrogenic adenoma (84 %), which neither coexisted with nor developed into malignant tumors during follow-up. Compared with non-transplant patients (n = 1669), transplant patients were significantly younger (median 55 vs 69 years, P < 0.001) and had a 9.0-fold higher odds of benign tumors (P < 0.001), while there were no differences in pathology among patients with urothelial carcinoma of the bladder (UCB). In a multivariable analysis for non-muscle-invasive UCB that was adjusted for the risk group, patients with a transplant had a 1.8-fold increased risk of recurrence (P = 0.048). Four of five transplant patients did not respond to Bacillus Calmette-Guérin instillations. There were no differences in overall survival after radical cystectomy (P = 0.87). CONCLUSIONS: The majority of bladder tumors in transplant patients are benign, and they neither coexist with nor develop into malignant tumors. Transplant patients with non-muscle-invasive UCB show an increased risk of disease recurrence, while those treated with radical cystectomy have similar outcomes to patients without a transplant.

Antidiabetic therapy in post kidney transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) is a common complication after kidney transplantation that affects up to 40% of kidney transplant recipients. By pathogenesis, PTDM is a diabetes form of its own, and may be characterised by a sudden, drug-induced deficiency in insulin secretion rather than worsening of insulin resistance over time. In the context of deteriorating allograft function leading to a re-occurrence of chronic kidney disease after transplantation, pharmacological interventions in PTDM patients deserve special attention. In the present review, we aim at presenting the current evidence regarding efficacy and safety of the modern antidiabetic armamentarium. Specifically, we focus on incretin-based therapies and insulin treatment, besides metformin and glitazones, and discuss their respective advantages and pitfalls. Although recent pilot trials are available in both prediabetes and PTDM, further studies are warranted to elucidate the ideal timing of various antidiabetics as well as its long-term impact on safety, glucose metabolism and cardiovascular outcomes in kidney transplant recipients.

Molecular regulation of the renin-angiotensin system in haemodialysis patients.

BACKGROUND: Blockade of the renin-angiotensin system (RAS) exerts beneficial effects in patients with mild-to-moderate chronic kidney disease, yet evidence suggesting a similar benefit in haemodialysis (HD) patients is not available. Furthermore, knowledge of the effects of RAS blockade on systemic RAS components in HD patients is limited. Analysis of the quantity and dynamics of all known peripheral constituents of the RAS may yield important pathomechanistic information of a widespread therapeutic measure in HD patients. METHODS: Fifty-two HD patients from the following groups were analysed cross-sectionally: patients without RAS blockade (n = 16), angiotensin-converting enzyme inhibitor (ACEi) users (n = 8), angiotensin receptor blocker (ARB) users (n = 11), patients on ACEi plus ARB (dual blockade, n = 8) and anephric patients (n = 9). Ten healthy volunteers served as controls. Angiotensin metabolites were quantified by mass spectrometry. RESULTS: In general, HD patients showed a broad variability of RAS activity. Patients without RAS blockade displayed angiotensin metabolite patterns similar to healthy controls. ACEi therapy increased plasma Ang 1-10 and Ang 1-7 concentrations, whereas ARB treatment increased both Ang 1-8 and Ang 1-5, while suppressing Ang 1-7 to minimal levels. Dual RAS blockade resulted in high levels of Ang 1-10 and suppressed levels of other angiotensins. Anephric patients were completely devoid of detectable levels of circulating angiotensins. CONCLUSION: In HD patients, the activity status of the systemic RAS is highly distorted with the emergence of crucial angiotensin metabolites upon distinct RAS blockade. The characterization of molecular RAS patterns associated with specific RAS interfering therapies may help to individualize future clinical studies and therapies.

Restoration of renal function does not correct impairment of uremic HDL properties.

Cardiovascular disease remains the leading cause of death in renal transplant recipients, but the underlying causative mechanisms for this important problem remain elusive. Recent work has indicated that qualitative alterations of HDL affect its functional and compositional properties in ESRD. Here, we systematically analyzed HDL from stable renal transplant recipients, according to graft function, and from patients with ESRD to determine whether structural and functional properties of HDL remain dysfunctional after renal transplantation. Cholesterol acceptor capacity and antioxidative activity, representing two key cardioprotective mechanisms of HDL, were profoundly suppressed in kidney transplant recipients independent of graft function and were comparable with levels in patients with ESRD. Using a mass spectroscopy approach, we identified specific remodeling of transplant HDL with highly enriched proteins, including α-1 microglobulin/bikunin precursor, pigment epithelium-derived factor, surfactant protein B, and serum amyloid A. In conclusion, this study demonstrates that HDL from kidney recipients is uniquely altered at the molecular and functional levels, indicating a direct pathologic role of HDL that could contribute to the substantial cardiovascular risk in the transplant population.

Fluid overload in hemodialysis patients: a cross-sectional study to determine its association with cardiac biomarkers and nutritional status.

BACKGROUND: Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status. METHODS: We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna (Austria) and determined associations with volume measurements using the body composition monitor (Fresenius/Germany). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters. RESULTS: We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters. CONCLUSIONS: Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease.

Glucose metabolism after renal transplantation.

OBJECTIVE: We determined prevalence, risk factors, phenotype, and pathophysiological mechanism of new-onset diabetes after transplantation (NODAT) to generate strategies for optimal pharmacological management of hyperglycemia in NODAT patients. RESEARCH DESIGN AND METHODS: Retrospective cohort study comparing demographics, laboratory data, and oral glucose tolerance test (OGTT)-derived metabolic parameters from kidney transplant recipients versus subjects not receiving transplants. RESULTS: Among 1,064 stable kidney transplant recipients (≥ 6 months posttransplantation), 113 (11%) had a history of NODAT and 132 (12%) had pretransplant diabetes. In the remaining patients, randomly assigned OGTTs showed a high prevalence of abnormal glucose metabolism (11% diabetes; 32% impaired fasting glucose, impaired glucose tolerance, or both), predominantly in older patients who received tacrolimus as the primary immunosuppressant. Compared with 1,357 nontransplant subjects, stable kidney transplant recipients had lower basal glucose, higher glycated hemoglobin, lower insulin secretion, and greater insulin sensitivity in each of the three subgroups, defined by OGTT 2-h glucose (<140, 140-199, ≥ 200 mg/dL). These findings were reinforced in linear spline interpolation models of insulin secretion and sensitivity (all P < 0.001) and in another regression model in which the estimated oral glucose insulin sensitivity index was substantially higher (by 79-112 mL/min m(2)) for transplant versus nontransplant subjects despite adjustments for age, sex, and BMI (all P < 0.001). CONCLUSIONS: Glucose metabolism differs substantially between kidney transplant recipients and nontransplant controls. Because impaired insulin secretion appears to be the predominant pathophysiological feature after renal transplantation, early therapeutic interventions that preserve, maintain, or improve ß-cell function are potentially beneficial in this population.