Subjects with mild to moderate hearing loss today often receive hearing aids (HA) with open-fitting (OF). In OF, direct sound reaches the eardrums with minimal damping. Due to the required processing ...delay in digital HA, the amplified HA sound follows some milliseconds later. This process occurs in both ears symmetrically in bilateral HA provision and is likely to have no or minor detrimental effect on binaural hearing. However, the delayed and amplified sound are only present in one ear in cases of unilateral hearing loss provided with one HA. This processing alters interaural timing differences in the resulting ear signals.
In the present study, an experiment with normal-hearing subjects to investigate speech intelligibility in noise with direct and delayed sound was performed to mimic unilateral and bilateral HA provision with OF.
The outcomes reveal that these delays affect speech reception thresholds (SRT) in the unilateral OF simulation when presenting speech and noise from different spatial directions. A significant decrease in the median SRT from -18.1 to -14.7 dB SNR is observed when typical HA processing delays are applied. On the other hand, SRT was independent of the delay between direct and delayed sound in the bilateral OF simulation.
The significant effect emphasizes the development of rapid processing algorithms for unilateral HA provision.
The aim of pharmacological conditioning is to protect the heart against myocardial ischemia-reperfusion (I/R) injury and its consequences. There is extensive literature that reports a multitude of ...different cardioprotective signaling molecules and mechanisms in diverse experimental protocols. Several pharmacological agents have been evaluated in terms of myocardial I/R injury. While results from experimental studies are immensely encouraging, translation into the clinical setting remains unsatisfactory. This narrative review wants to focus on two aspects: (1) give a comprehensive update on new developments of pharmacological conditioning in the experimental setting concentrating on recent literature of the last two years and (2) briefly summarize clinical evidence of these cardioprotective substances in the perioperative setting highlighting their clinical implications. By directly opposing each pharmacological agent regarding its recent experimental knowledge and most important available clinical data, a clear overview is given demonstrating the remaining gap between basic research and clinical practice. Finally, future perspectives are given on how we might overcome the limited translatability in the field of pharmacological conditioning.
Hemodynamic assessment is crucial after heart transplantation (HTX) or left ventricular assist device (LVAD) implantation. Gold-standard is invasive assessment via thermodilution (TD). Noninvasive ...pulse contour analysis (NPCA) is a new technology that is supposed to determine hemodynamics completely noninvasive. We aimed to validate this technology in HTX and LVAD patients and conducted a prospective single-center cohort study. In total, 28 patients were prospectively enrolled (HTX: n = 10, LVAD: n = 18). Bland-Altman analysis revealed a mean bias of +1.05 l/min (limits of agreement ± 4.09 l/min, percentage error 62.1%) for cardiac output (CO). In LVAD patients, no adequate NPCA signal could be obtained. In 5 patients (27.8%), any NPCA signal could be detected, but was considered as low signal quality. In conclusion, according to our limited data in a small cohort of HTX and LVAD patients, NPCA using the CNAP Monitor seems not to be suitable for noninvasive evaluation of the hemodynamic status.
The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of ...research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%).
Short chain fatty acids (SCFAs) are generated by the degradation and fermentation of complex carbohydrates, (i.e., dietary fiber) by the gut microbiota relevant for microbe⁻host communication. Here, ...we present a method for the quantification of SCFAs in fecal samples by liquid chromatography tandem mass spectrometry (LC-MS/MS) upon derivatization to 3-nitrophenylhydrazones (3NPH). The method includes acetate, propionate, butyrate, and isobutyrate with a run time of 4 min. The reproducible (coefficients of variation (CV) below 10%) quantification of SCFAs in human fecal samples was achieved by the application of stable isotope labelled internal standards. The specificity was demonstrated by the introduction of a quantifier and qualifier ions. The method was applied to investigate the pre-analytic stability of SCFAs in human feces. Concentrations of SCFA may change substantially within hours; the degree and kinetics of these changes revealed huge differences between the donors. The fecal SCFA level could be preserved by the addition of organic solvents like isopropanol. An analysis of the colon content of mice either treated with antibiotics or fed with a diet containing a non-degradable and -fermentable fiber source showed decreased SCFA concentrations. In summary, this fast and reproducible method for the quantification of SCFA in fecal samples provides a valuable tool for both basic research and large-scale studies.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supports patients suffering from refractory cardiogenic shock. Thromboembolic complications (TeC) are common in VA-ECMO patients and are ...associated with increased morbidity and mortality. Valid markers to predict TeC in VA-ECMO patients are lacking. The present study investigated the predictive value of baseline Fibrinogen-Albumin-Ratio (FAR) for in-hospital TeC in patients undergoing VA-ECMO. This retrospective cohort study included patients who underwent VA-ECMO therapy due to cardiogenic shock at the University Hospital Duesseldorf, Germany between 2011 and 2018. Main exposure was baseline FAR measured at initiation of VA-ECMO therapy. The primary endpoint was the in-hospital incidence of TeC. In total, 344 patients were included into analysis (74.7% male, mean age 59 ± 14 years). The in-hospital incidence of TeC was 34%. Receiver operating characteristics (ROC) curve of FAR for in-hospital TeC revealed an area under the curve of 0.67 95% confidence interval (CI) 0.61-0.74. Youden index determined a cutoff of 130 for baseline FAR. Multivariate logistic regression revealed an adjusted odds-ratio of 3.72 95% CI 2.26-6.14 for the association between FAR and TeC. Baseline FAR is independently associated with in-hospital TeC in patients undergoing VA-ECMO. Thus, FAR might contribute to the prediction of TeC in this cohort.
Abstract
Background
The number of patients treated with extracorporeal membrane oxygenation (ECMO) devices is increasing. Anticoagulation therapy is crucial to prevent thrombosis during ECMO therapy. ...Predominantly, heparin has been used as primary anticoagulant but direct thrombin inhibitors (DTI) have been established as alternatives. The aim of this systematic review and meta-analysis was to evaluate clinical outcomes in patients treated with heparin compared to different DTI during ECMO.
Methods
A systematic search was conducted. Full scientific articles were sought for inclusion if heparin anticoagulation was compared to DTI (argatroban/bivalirudin) in ECMO patients. Risk of bias was assessed by Newcastle Ottawa scale. Primary endpoint was in-hospital mortality. Bleeding events, thrombotic events, hours of ECMO support, days of hospital stay, percentage of time within therapeutic range and time to therapeutic range were extracted from full texts as secondary endpoints. Results were presented as Forrest-plots. GRADE was used for confidence assessment in outcomes.
Results
Systematic search identified 4.385 records, thereof 18 retrospective studies for a total of 1942 patients, complied with the predefined eligibility criteria:15 studies investigated bivalirudin and 3 studies investigated argatroban versus heparin. Risk of bias was high for most studies. In-hospital mortality, major bleeding events and pump-related thrombosis were less frequent in DTI group as compared to heparin mortality—OR 0.69, 95% CI 0.54–0.86; major bleeding—OR 0.48, 95% CI 0.29–0.81; pump thrombosis—OR 0.55, 95% CI 0.40–0.76. Additionally, percentage of time within therapeutic range was higher for DTI SMD 0.54, 95% CI 0.14–0.94. GRADE approach revealed a very low level of certainty for each outcome.
Conclusion
In this meta-analysis, DTI and especially bivalirudin showed beneficial effects on clinical outcomes in ECMO patients as compared to heparin
.
However, due to the lack of randomized trials, certainty of evidence is low.
Trial Registration
This systematic review and meta-analysis was prospectively registered at PROSPERO data base (reference number
CRD42021237252
).
Graphical Abstract
The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This ...study aimed to investigate Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 95% confidence interval (CI) 0.53-0.76 for NLR. The AUCs of PLR and PCT were 0.47 95%CI 0.35-0.59 and 0.54 95%CI 0.42-0.66, respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 95%CI 1.13-9.76 for NLR, 1.0 95%CI 0.998-1.002 for PLR and 1.02 95%CI 0.99-1.05 for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose.
Orthotopic heart transplantation (HTX) is the gold standard to treat end-stage heart failure. Numerous risk stratification tools have been developed in the past years. However, their clinical utility ...is limited by their poor discriminative ability. High sensitivity troponin T (hsTnT) is the most specific biomarker to detect myocardial cell injury. However, its prognostic relevance after HTX is not fully elucidated. Thus, this study evaluated the predictive value of postoperative hsTnT for 1-year survival and days alive and out of hospital (DAOH) after HTX.
This retrospective cohort study included patients who underwent HTX at the University Hospital Duesseldorf, Germany between 2011 and 2021. The main exposure was hsTnT concentration at 48 h after HTX. The primary endpoints were mortality and DAOH within 1 year after surgery. Receiver operating characteristic (ROC) curve analysis, logistic regression model and linear regression with adjustment for risk index for mortality prediction after cardiac transplantation (IMPACT) were performed.
Out of 231 patients screened, 212 were included into analysis (mean age 55 ± 11 years, 73% male). One-year mortality was 19.7% (40 patients) and median DAOH was 298 days (229-322). ROC analysis revealed strongest discrimination for mortality by hsTnT at 48 h after HTX AUC = 0.79 95% CI 0.71-0.87. According to Youden Index, the cutoff for hsTnT at 48 h and mortality was 1640 ng/l. After adjustment for IMPACT score multivariate logistic and linear regression showed independent associations between hsTnT and mortality/DAOH with odds ratio of 8.10 95%CI 2.99-21.89 and unstandardized regression coefficient of -1.54 95%CI -2.02 to -1.06, respectively.
Postoperative hsTnT might be suitable as an early prognostic marker after HTX and is independently associated with 1-year mortality and poor DAOH.
The two main surgical options to treat end-stage heart failure are heart transplantation (HTx) or left ventricular assist device (LVAD) implantation. In hemodynamically stable patients, the decision ...for HTx listing with or without LVADs is challenging. We analyzed the impact of both options on days alive and out of hospital (DAOH) and survival. This retrospective study screened all patients with HTx or LVAD implantation between 2010 and 2020. The main inclusion criterion was hemodynamic stability defined as independence of intravenous inotropic/vasoactive support at decision. Propensity score matching (PSM) was performed. The primary endpoint was DAOH within one year after the decision. Secondary endpoints included survival, duration until HTx, and hospitalizations. In total, 187 patients received HTx and 227 patients underwent LVAD implantation. There were 21 bridge-to-transplant (BTT)-LVAD patients (implantation less than a month after HTx listing or listing after implantation) and 44 HTx-waiting patients included. PSM identified 17 matched pairs. Median DAOH at one year was not significantly different between the groups (BTT-LVAD: median 281, IQR 89; HTx waiting: median 329, IQR 74;
= 0.448). Secondary endpoints did not differ significantly. Our data suggest that BTT-LVAD implantation may not be favorable in terms of DAOH within one year for hemodynamically stable patients compared to waiting for HTx. Further investigations on quality of life and long-term outcomes are warranted.
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