Assessment of coronary artery disease during hospitalization for cancer treatment.

BACKGROUND: With improvement of cancer-specific survival, comorbidities and treatment-related side effects, particularly cardiovascular toxicities, need close attention. The aim of the present study was to evaluate clinical characteristics and outcomes of cancer patients requiring coronary angiography during inpatient care. METHODS: We performed a retrospective analysis of patients hospitalized between 02/2011 and 02/2018 in our two university hospital cancer centers. From a cohort of 60,676 cancer patients, we identified 153 patients (65.7 ± 11.6 years, 73.2% male), who underwent coronary angiography and were eligible for analysis. These were compared to a control group of 153 non-cancer patients pair-matched with respect to age, sex, and indication for catheterization. RESULTS: Cancer patients presented in 66% with an acute coronary syndrome (ACS). The most prevalent cancer entities were lymphoma (19%) and lung cancer (18.3%). The rate of primary percutaneous coronary interventions (PCI) was significantly lower in the cancer cohort (40.5% vs. 53.6%, p = 0.029), although manifestation of coronary artery disease (CAD) and PCI results were comparable (SYNergy between PCI with TAXus and cardiac surgery (SYNTAX)-score, delta pre- and post-PCI - 9.8 vs. - 8.0, p = 0.2). Mortality was remarkably high in cancer patients (1-year mortality 46% vs. 8% in non-cancer patients, p < 0.001), particularly with troponin-positive ACS (5-year mortality 71%). CONCLUSION: Strategies to effectively control cardiovascular risks in cancer patients are needed. Additionally, suspected CAD in cancer patients should not prevent prompt diagnostic clarification and optimal revascularization as PCI results in cancer patients are comparable to non-cancer patients and occurrence of troponin-positive ACS leads to a significantly increased risk of mortality.

Clinical process optimization of transfemoral transcatheter aortic valve implantation.

Background: The avoidance of prolonged hospital stay is a major goal in the management of transcatheter aortic valve implantation (TAVI) - medically and economically. Materials & methods: We compared the time range of the preprocedural length of stay in 2014/2015 with 2016/2017, after the implementation of the TAVI coordinator in 2016. This included restructured pathways for screening and pre-interventional diagnosis, performed examinations during the inpatient stay and major outcome variables. Results: After 2016, we observed a significant reduction in preprocedural length of stay (admission to procedure) compared with 2014/2015 (11.3 ± 7.9 vs 7.5 ± 5.6 days, p = 0.001). There was no difference in other major outcome variables. Conclusion: The introduction of the TAVI coordinator caused a shortening of preprocedural length of stay.

Impact of Diabetes Mellitus on Outcomes after High-Risk Interventional Coronary Procedures.

An increasing number of patients with coronary artery disease are at high operative risk due to advanced age, severe comorbidities, complex coronary anatomy, and reduced ejection fraction. Consequently, these high-risk patients are often offered percutaneous coronary intervention (PCI) as an alternative to coronary artery bypass grafting (CABG). We aimed to investigate the outcome of patients with diabetes mellitus (DM) undergoing high-risk PCI. We analyzed consecutive patients undergoing high-risk PCI (period 01/2016-08/2018). In-hospital major adverse cardiac and cerebrovascular events (MACCEs), defined as in-hospital stroke, myocardial infarction and death, and the one-year incidence of death from any cause were assessed in patients with and without DM. There were 276 patients (age 70 years, 74% male) who underwent high-risk PCI. Eighty-six patients (31%) presented with DM (insulin-dependent DM: n = 24; non-insulin-dependent DM: n = 62). In-hospital MACCEs occurred in 9 patients (3%) with a non-significant higher rate in patients with DM (n = 5/86, 6% vs. n = 4/190 2%; p = 0.24). In patients without DM, the survival rate was insignificantly higher than in patients with DM (93.6% vs. 87.1%; p = 0.07). One-year survival was not significantly different in DM patients with more complex coronary artery disease (SYNTAX I-score ≤ 22: 89.3% vs. > 22: 84.5%; p = 0.51). In selected high-risk patients undergoing high-risk PCI, DM was not associated with an increased incidence of in-hospital MACCEs or a decreased one-year survival rate.

Safety and efficacy of a novel algorithm to guide decision-making in high-risk interventional coronary procedures.

BACKGROUND: Patients with severe coronary artery disease (CAD), comorbidities, or impaired hemodynamics are at risk during percutaneous coronary interventions. The aim of the study was to investigate the safety and efficacy of a novel risk-stratification algorithm for high-risk coronary procedures. METHODS AND RESULTS: We prospectively screened 1189 patients with CAD requiring revascularization (period 07/2017-06/2018). The algorithm was designed to select high-risk procedures. Patients with elevated risk (n = 150) were classified into 3 risk groups (high-risk intervention [HRI] I-III) and procedural management was adjusted according to HRI group. Overall, 55 patients were categorized as HRI I, 52 as HRI II, and 43 as HRI III. With increasing HRI-level, SYNTAX score increased (HRI I:15 ±â€¯5% vs. HRI II:24 ±â€¯8% vs. HRI III:34 ±â€¯7%; p < 0.001), and ejection-fraction decreased (HRI I:48 ±â€¯10% vs. HRI II:49 ±â€¯10% vs. HRI III:40 ±â€¯11%; p < 0.001). The primary endpoint (hemodynamic compromise requiring mechanical circulatory support [MCS] [HRI I/II], unsuccessful weaning from MCS in the catheterization laboratory[HRI III], or periprocedural death[HRI I-III]) occurred in no case. The secondary endpoint of hemodynamic deterioration occurred in 26% (n = 39) but did not result in hemodynamic instability due to the risk-adjusted procedural management. The composite endpoint of in-hospital major adverse cardiac and cerebrovascular events (death, new myocardial infarction, cerebrovascular accident) occurred in 4 patients (3%). CONCLUSIONS: The novel algorithm is a safe team-based stratification method for the identification and management of patients undergoing high-risk coronary interventions.

Impact of left-ventricular end-diastolic pressure as a predictor of periprocedural hemodynamic deterioration in patients undergoing Impella supported high-risk percutaneous coronary interventions.

BACKGROUND: An increasing number of high-risk percutaneous coronary interventions (PCI) are performed with mechanical circulatory support (MCS) to minimize the risk of periprocedural hemodynamic compromise. Prior studies have demonstrated that an elevated left-ventricular end-diastolic pressure (LVEDP) is associated with worse outcome after acute myocardial infarction or cardiac surgery. Although LVEDP is frequently measured, little is known about the usefulness for predicting periprocedural hemodynamic deterioration in high-risk PCI. The objective of this study is to assess the impact of preprocedural measured LVEDP in non-shock patients undergoing high-risk PCI with MCS on periprocedural hemodynamic deterioration. METHODS AND RESULTS: We reviewed the PCI protocol and the Automated Impella Controller in a consecutive series of 64 patients (mean age 73 years, 80% male), who underwent high-risk PCI with Impella MCS (period 01/2017-12/2018). LVEDP (17 ± 8 mm Hg) was measured in all cases before Impella insertion and start of PCI. Periprocedural hemodynamic deterioration was defined as: systolic blood pressure (SBP) drop (decrease ≥20 mm Hg or ≤90 mm Hg), or transient loss of arterial pressure pulsatility. Hemodynamic deterioration occurred in 33% (n = 21) of all patients but did not lead to a hemodynamic compromise due to the Impella support. Regression analysis of LVEDP for periprocedural hemodynamic deterioration or in-hospital major adverse cardiac and cerebrovascular events (MACCE) showed no significant results. CONCLUSION: LVEDP was not associated with periprocedural hemodynamic deterioration or a higher rate of in-hospital MACCE. Our data propose that LVEDP may not be used as a risk stratification variable for MCS usage in non-shock patients undergoing high-risk PCI.

Access site complications following Impella-supported high-risk percutaneous coronary interventions.

Mechanical circulatory support (MCS) devices are increasingly used to provide hemodynamic stability for patients with severe coronary artery disease, comorbidities, and/or impaired hemodynamics during high-risk percutaneous coronary interventions (PCI). Vascular access site complications, particularly those due to the use of large-bore sheaths, may limit outcomes in these patients. The aim of this study was to investigate the incidence and predictors of vascular complications in protected high-risk PCIs. Therefore, we included patients undergoing high-risk PCI with an Impella device from January 2016 to August 2018. Vascular complications were graded according to 'Valve Academic Research Consortium-2', a definition routinely used in transcatheter valve implantation procedures. In total, 61 patients (mean age 72 ± 11 years, 79% male, SYNTAX score 33 ± 7) were included, and angiographic- and fluoroscopic-guided vascular access was used for Impella implantation in all patients. Major vascular complications occurred in 5 male patients (8%). All major vascular complications were treated conservatively without the need for surgical intervention, and only one patient received a transfusion of three erythrocyte concentrates. Regression analysis revealed that patients with peripheral arterial disease of the lower extremities are at higher risk of major vascular complications. In conclusion, the utilization of Impella using a standardized protocol for angiographic- and fluoroscopic-guided vascular access was associated with a low rate of vascular complications.

MiR-34a is differentially expressed in dorsal root ganglia in a rat model of chronic neuropathic pain.

INTRODUCTION: Recent evidence shows that numerous microRNAs (miRNAs) regulate pain-related genes in chronic pain. The aim of the present study was to further explore the regulation of miRNAs and their effect on the expression of pain-associated target genes in experimental neuropathic pain. METHODS: Male Wistar rats underwent chronic constriction injury (CCI) of the sciatic nerve or Sham procedure. After assessment of mechanical allodynia, the ipsilateral dorsal root ganglia (DRG) were harvested. MiRNA expression levels were analysed with Agilent microRNA microarrays and real time quantitative PCR. An interaction between miRNAs and pain-relevant genes was confirmed by luciferase assays. Western Blot analysis and ELISA were performed to evaluate protein expression, respectively. RESULTS: Mechanical allodynia developed within 6 days after CCI. MiRNA-arrays revealed the differential expression of 49 miRNAs after 4 h, of 3 miRNAs after 1 d, of 26 miRNAs after 6 d and of 28 miRNAs after 12 d in the CCI group versus Sham. Time-dependent down regulation of miR-34a was verified by qPCR. Bioinformatic prediction revealed an interaction with several pain-relevant targets including voltage-gated sodium channel ß2 subunit (SCN2B) and vesicle-associated membrane protein 2 (VAMP-2), both of which were subsequently confirmed by luciferase assay. VAMP-2 expression was statistically significantly increased 12 d after CCI. A non-significant upregulation of SCN2B in the DRG after CCI was confirmed by ELISA. DISCUSSION: Peripheral mononeuropathic pain in rats was associated with distinct alterations of miRNA expression in the ipsilateral DRG. Notably, miR-34a was time-dependently down regulated. We validated SCN2B and VAMP-2 as new targets of miR-34a. While SCN2B expression was only marginally altered, VAMP-2 expression was increased. The present study underlines that the induction and maintenance of neuropathic pain is accompanied by expression changes of miRNAs in the peripheral nervous system, adding several previously unreported miRNAs, including miR-34a.

Sensitivity of an opiate immunoassay for detecting hydrocodone and hydromorphone in urine from a clinical population: analysis of subthreshold results.

Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former scenario, it is vital to determine whether the drug is present in the urine, even at low concentrations, because failure to detect the drug may lead to accusations of opioid abuse or diversion. Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine. Although many opiate immunoassays also detect hydrocodone (HC) and/or hydromorphone (HM), sensitivities for these analytes are often much lower, increasing the possibility of negative screening results when the drug is present in the urine. We selected 112 urine specimens from patients who had been prescribed HC or hydromorphone but were presumptive negative by the Roche Online DAT Opiate II™ urine drug screening assay, which is calibrated to 300 ng/mL morphine. Using a GC/MS confirmatory method with a detection limit of 50 ng/mL both for HC and for HM, one or both of these opiates were detected in 81 (72.3%) of the urine specimens. Examination of the raw data from these presumptive negative opiate screens revealed that, in many cases, the turbidity signal was greater than the signal obtained for the negative control, but less than the signal for the 300 ng/mL (morphine) threshold calibrator. A receiver operating characteristic curve generated for the reciprocal of the ratio of turbidity measurements in the patient specimens and negative (drug-free) controls, against the presence or absence of HC and/or HM by confirmatory analyses, produced an area under the curve of 0.910. We conclude that this opiate immunoassay has sufficient sensitivity to detect HC and/or HM in some urine specimens that screen presumptive negative for these commonly prescribed opiates at the established threshold.

Validation of a pre-existing formula to calculate the contribution of ethanol to the osmolar gap.

PURPOSE: The aim of this study was to validate the formula derived by Purssell et al. that relates blood ethanol concentration to the osmolar gap and determine the best coefficient for use in the formula. The osmolar gap is often used to help diagnose toxic alcohol poisoning when direct measurements are not available. METHODOLOGY: Part I of the study consisted of a retrospective review of 603 emergency department patients who had a concurrent ethanol, basic metabolic panel and a serum osmolality results available. Estimated osmolarity (excluding ethanol) was calculated using a standard formula. The osmolar gap was determined by subtracting estimated osmolarity from the actual osmolality measured by freezing point depression. The relationship between the osmolar gap and the measured ethanol concentration was assessed by linear regression analysis. In Part II of this study, predetermined amounts of ethanol were added to aliquots of plasma and the estimated and calculated osmolarities were subjected to linear regression analysis. RESULTS: In the cases of 603 patients included in Part I of the study, the median ethanol concentration in these patients was 166 mg/dL (Q1: 90, Q3: 254) and the range ethanol concentrations was 10-644 mg/dL. The mean serum osmolality was 338 mOsm/kg (SD: 30) and a range of 244-450 mOsm/kg. The mean osmolar gap was 47 (SD: 29) and a range of - 15 to 55. There was a significant proportional relationship between ethanol concentration and osmolar gap (r(2) = 0.9882). The slope of the linear regression line was 0.2498 (95% CI: 0.2472-0.2524). The slope of the linear regression line derived from the data in Part II of the study was 0.2445 (95% CI: 0.2410-0.2480). CONCLUSIONS: The results of our study are in fairly close agreement with previous studies that used smaller samples and suggest that an accurate conversion factor for estimating the contribution of ethanol to the osmolar gap is [Ethanol (mg/dL)]/4.0.

Failure of amoxicillin to produce false-positive urine screens for cocaine metabolite.

Amoxicillin has been causally linked in the lay and medical literature to false-positive urine drug screens for cocaine metabolites. An exhaustive search of the peer-reviewed medical literature revealed no data to support this link. We hypothesized that amoxicillin does not cause false-positive urine drug screens for cocaine metabolites. To test this hypothesis, we examined the urine of 33 subjects administered a course of amoxicillin, subjecting the specimens to four common urine screening immunoassays. Thirty-one specimens were negative for the cocaine metabolite, benzoylecgonine (BE), by all four screening methods; two were positive for BE by all four screening methods. Both positive specimens were confirmed by gas chromatography-mass spectrometry (GC-MS) for the presence of BE at > 150 ng/mL. Three specimens that screened negative, but produced absorbance values that were intermediate between negative and positive controls, were submitted for GC-MS analysis; BE was detected in all three specimens at concentrations of 54, 94, and 119 ng/mL. Twenty-eight specimens produced screening results indistinguishable from negative controls. Within the limitations of the study design, we conclude that amoxicillin is unlikely to produce false-positive urine screens for cocaine metabolites.

False-positive acetaminophen results in a hyperbilirubinemic patient.

BACKGROUND: Acetaminophen was falsely detected in the plasma of a severely jaundiced patient, and a methodologic interference from bilirubin was suspected. METHODS: Acetaminophen was measured by an enzymatic method (GDS Diagnostics). The putative bilirubin interference was investigated in 12 hyperbilirubinemic specimens and in bilirubin linearity calibrators. The analytical method was modified to correct for background absorbance at a second wavelength. Hyperbilirubinemic specimens were fortified with acetaminophen to assess the effect of the interference on acetaminophen measurements. RESULTS: Acetaminophen was detected in 12 specimens from hyperbilirubinemic patients without a history of recent acetaminophen exposure. Dilution of hyperbilirubinemic specimens produced a nonproportional decrease in apparent acetaminophen concentrations, and no acetaminophen was detected when bilirubin was <50 mg/L. Background correction at a second wavelength failed to compensate for the interference. Although erroneous acetaminophen concentrations were detected in all specimens with high bilirubin, acetaminophen measurements in fortified specimens were accurate. CONCLUSION: The data are consistent with bilirubin interference in the enzymatic and/or chromogenic reactions involved in the acetaminophen method.

False elevation of serum CA-125 level caused by human anti-mouse antibodies.

Discordant results were observed for serum CA-125 (carbohydrate antigen-125) assays in a patient who was monitored for recurrence of ovarian cancer. Serum CA-125 levels in this patient were normal when measured in one laboratory, but >5-times the upper limit of normal (35 U/mL) when measured in another laboratory. Both laboratories used dual antibody heterogeneous immunoassays, but from different manufacturers. Cross-linking heterophilic antibodies were suspected as a cause of the discrepancy, but the interference was not alleviated after 10-fold dilution. Assay of the patient's serum for human anti-mouse antibodies was positive, but only slightly above the reference range. Addition of blocking antibodies eliminated the interference, showing that human anti-mouse antibodies were the cause of the discrepant CA-125 results. These findings indicate that relatively low concentrations of human anti-mouse antibodies can cause significant interference in two-site immunoassays.