Hemodiafiltration: a synergy yet to be convincing / Hemodiafiltração: uma sinergia ainda não convincente

ABSTRACT The desperate attempt to improve mortality, morbidity, quality of life and patient-reported outcomes in patients on hemodialysis has led to multiple attempts to improve the different modes, frequencies, and durations of dialysis sessions in the last few decades. Nothing has been more appealing than the combination of diffusion and convection in the form of hemodiafiltration. Despite the concrete evidence of better clearance of middle weight molecules and better hemodynamic stability, tangible evidence to support the universal adoption is still at a distance. Survival benefits seen in selected groups who are likely to tolerate hemodiafiltration with better vascular access and with lower comorbid burden, need to be extended to real life dialysis patients who are older than the population studied and have significantly higher comorbid burden. Technical demands of initiation hemodiafiltration, the associated costs, and the incremental benefits targeted, along with patient-reported outcomes, need to be explored further before recommending hemodiafiltration as the mode of choice.

RESUMO A tentativa desesperada de melhorar a mortalidade, morbidade, qualidade de vida e desfechos relatados pelos pacientes em indivíduos em hemodiálise levou a diversas tentativas de aprimorar os diferentes modos, frequências e durações das sessões de diálise nas últimas décadas. Nada foi mais atrativo do que a combinação de difusão e convecção na forma de hemodiafiltração. Apesar das evidências concretas de melhor depuração de moléculas de peso médio e melhor estabilidade hemodinâmica, evidências tangíveis para apoiar a adoção universal ainda estão distantes. Os benefícios de sobrevida observados em grupos selecionados que provavelmente toleram a hemodiafiltração com melhor acesso vascular e com menor carga de comorbidades precisam ser estendidos aos pacientes reais em diálise, que são mais velhos do que a população estudada e apresentam uma carga de comorbidades significativamente maior. As exigências técnicas do início da hemodiafiltração, os custos associados e os benefícios incrementais almejados, juntamente com os desfechos relatados pelos pacientes, precisam ser melhor explorados antes de se recomendar a hemodiafiltração como o modo de escolha.

Fish swim bladders as valve leaflets enhance the durability of transcatheter aortic valve replacement devices.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for inoperable patients with severe aortic stenosis (AS). However, calcification-induced limited durability restricts its application. Fish swim bladders (FSB), which are resistant to calcific degeneration, offer a viable solution to this challenge. In this study, we developed a new TAVR device using FSB as the valve leaflet. Furthermore, the in vitro durability, in vivo performance, and size selection of this TAVR device were assessed by an experimental study and finite element analysis. A self-expandable TAVR device was fabricated by suturing the FSB films into a 23 mm nitinol alloy frame. Further, hemodynamic performance, such as effective orifice area, transvalvular pressure difference and regurgitant fraction, the durability was tested by the pulsatile flow test and accelerated fatigue test, according to the ISO 5840-3. The effect of release size on hydrodynamic performance was also investigated. Finally, the in vivo performance of the TAVR device were examined using a porcine implantation model. The results showed that the strength of the FSB films satisfied the requirements for valve leaflets. The hemodynamic performance of the FSB TAVR device met the requirements of ISO 5840-3 standards. After 400 million cycles, the FSB showed no fiber loss, torn, perforation, or other valve failure phenomena. In porcine models, the devices were well-positioned, functioned well with no stenosis immediately after the operation. Collectively, we successfully developed a TAVR device with FSB as valve leaflets that exhibited good fatigue resistance. STATEMENT OF SIGNIFICANCE: The source of material for the leaflets of commercialized biological heart valves (BHVs) is mainly bovine pericardium, but this material suffers the following problems: large and uneven thickness of the material, the presence of a-Gal and Ne5Gc antigens, and the susceptibility to structural valve degradation (SVD). New material for BHVs leaflets is rarely reported. In this study, we prepared a transcatheter aortic valve (TAV) and performed long-term in vitro and short-term in vivo studies using fish swim bladder (FSB) as the leaflets. The study confirmed that FSB TAV device can complete 400 million fatigue tests and maintain the good morphology of the leaflets, and that it still maintains good functionality after a certain amount of compression, indicating that FSB is a promising material for leaflets.

Derivation of Stroke Volume from Pulmonary Artery Pressures.

INTRODUCTION: Intermittent cardiac output (CO) studies using thermodilution are considered the gold standard. We have developed a stroke volume (SV) calculator from pulmonary pulse pressure (PP) to allow continuous monitoring of SV and CO from PP. METHODS: Hemodynamic data on 169 patients following orthotopic heart transplantation were used to compare our calculator-derived SV (and SV index, or SVi) against thermodilution-derived SV on admission into intensive care unit immediately following heart transplantation (T0) and 6 h after admission (T6). RESULTS: The calculated SV correlated with thermodilution-derived SV T0 (r = 0.920, p < 0.001, coefficient of 0.539 and the constant of 2.06). The median calculator SV, adjusted for coefficient and constant, was 48.4 ml (37.7, 60.7), comparable to the median thermodilution-derived SV 47.9 ml (37.5, 61.0), p = 0.737 with acceptable agreement on Bland-Altman plots. The thermodilution-derived SVi was 28.1 ml (19.7, 38.7) and adjusted calculator-derived SVi 28.9 ml (19.7, 39.9), p = 0.781. At T6, median thermodilution-derived SVi was 27.7 ml (19.5, 35.9) compared to the calculator-derived SVi median of 26.1 ml (17.7, 37.7), p = 0.203. CONCLUSIONS: Changes in PP can be used to track changes in SV using this calculator. Changes in PP may be used to assess response to treatment in the early post-operative period.

Contact pressure-guided wearable dual-channel bioimpedance device for continuous hemodynamic monitoring.

Wearable devices for continuous monitoring of arterial pulse waves have the potential to improve the diagnosis, prognosis, and management of cardiovascular diseases. These pulse wave signals are often affected by the contact pressure between the wearable device and the skin, limiting the accuracy and reliability of hemodynamic parameter quantification. Here, we report a continuous hemodynamic monitoring device that enables the simultaneous recording of dual-channel bioimpedance and quantification of pulse wave velocity (PWV) used to calculate blood pressure (BP). Our investigations demonstrate the effect of contact pressure on bioimpedance and PWV. The pulsatile bioimpedance magnitude reached its maximum when the contact pressure approximated the mean arterial pressure of the subject. We employed PWV to continuously quantify BP while maintaining comfortable contact pressure for prolonged wear. The mean absolute error and standard deviation of the error compared to the reference value were determined to be 0.1 ± 3.3 mmHg for systolic BP, 1.3 ± 3.7 mmHg for diastolic BP, and -0.4 ± 3.0 mmHg for mean arterial pressure when measurements were conducted in the lying down position. This research demonstrates the potential of wearable dual-bioimpedance sensors with contact pressure guidance for reliable and continuous hemodynamic monitoring.

Cerebral Aneurysm Characteristics and Surgical Outcomes: An In-Depth Analysis of 346 Cases Operated Using Microsurgical Clipping.

This comprehensive study analyzes 346 surgically treated intracranial aneurysms, emphasizing the importance of understanding risk factors and prevalent characteristics in patients. Intracranial aneurysms, primarily of the saccular or berry type, significantly contribute to nontraumatic subarachnoid hemorrhages and demonstrate a rising incidence due to advances in imaging techniques. The study highlights a gender discrepancy in aneurysm occurrence and a higher prevalence in individuals over 30 years old. The research delves into various aspects, including aneurysm localization, diameter, neck dimensions, and rupture status, with a focus on the anterior communicating artery and middle communicating artery as predominant locations. Significant findings include the prevalence of ruptured aneurysms and the impact of arterial hypertension, atherosclerosis, obesity, and diabetes on aneurysm epidemiology. The study also investigates the occurrence of vasospasm, a significant factor in delayed morbidity and mortality in aneurysmal subarachnoid hemorrhage. The utilization of the Glasgow Outcome Scale and other quantification scales aids in understanding the severity and postoperative outcomes of intracranial aneurysms. Challenges such as the incidence of reopenings and postoperative osteomyelitis are addressed, underlining the need for refined protocols and multidisciplinary approaches in treatment. The study's results contribute to the existing knowledge base on intracranial aneurysms, emphasizing the importance of ongoing research and tailored treatment strategies. The comprehensive nature of this analysis, covering preoperative, intraoperative, and postoperative factors, provides valuable insights into the complex interplay of risk factors and clinical outcomes in patients with intracranial aneurysms.

The association between different anesthetic techniques and outcomes in patients undergoing transfemoral aortic valve replacement.

Background: There is an increasing number of patients undergoing transfemoral aortic valve replacement (TAVR) with sedation. There is limited data assessing the efficacy and safety of the different types of sedative drugs. The objective was to compare two sedation techniques with regard to the need for vasoactive support, respiratory support, rate of conversion to general anesthesia (GA), common perioperative morbidities, intensive care unit (ICU) stay, and in-hospital mortality. Methods: A retrospective chart review study conducted among patients who underwent TAVR at a specialized cardiac center between January 2016 and December 2019. Data collection included patient diagnosis, preoperative comorbidities, intraoperative outcomes, and postoperative outcomes. Results: A total of 289 patients received local anesthesia; 210 received propofol infusion and 79 received a mixed propofol-ketamine infusion (Ketofol). The average age was 75.5 ± 8.9 years and 58.1% of the patients were females. Comparing propofol and ketofol groups, 31.2% and 34.2% of the patients required drug support, 7.6% and 6.3% required conversion to GA, 46.7% and 59.5% required respiratory support, respectively. These intraoperative outcomes were not significantly different between groups, P = 0.540, P = 0.707, and P = 0.105, respectively. In-hospital 30-day mortality in propofol and ketofol groups were 1.9% and 3.8%, respectively, P = 0.396. In both groups, the median post-procedure coronary care unit stay was 26 hours while post-procedure hospital stay was 3 days. Conclusions: There were no significant differences in perioperative or postoperative outcomes in TAVR patients receiving either propofol or ketofol. Propofol infusion, either alone or with ketamine, is reliable and safe, with minimal side effects.

CardioMEMS monitoring device migration: A rare complication.

We present a rare case of CardioMEMS device migration six years post-implantation. Much is still being learned about endothelization of pulmonary vasculature and this case highlights the importance of device surveillance and device-related complications.

Comparison of Acute Effects of E-cigarettes With and Without Nicotine and Tobacco Cigarettes on Hemodynamic and Endothelial Parameters: A Systematic Review and Meta-analysis.

INTRODUCTION: Smoke from traditional cigarettes and e-cigarette aerosols have distinct chemical compositions that may impact blood pressure (BP) and heart rate (HR) differently. AIMS: This study compared the impact of nicotine-containing e-cigarettes (EC+) versus nicotine-free (EC-) on BP, HR and endothelial markers, and assessed if EC+ posed fewer risks than tobacco cigarettes (TC). METHODS: Electronic databases were searched from inception until November 2023 for studies reporting changes in systolic and diastolic BP (SBP, DBP) and HR and endothelial parameters before and after the use of EC+, EC- and TC. Data were analyzed using weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Fifteen studies (n = 752) were included in our meta-analysis. We demonstrate that EC+ significantly increased systolic BP (WMD = 3.41, 95% CI [0.1,6.73], p = 0.04], diastolic BP (WMD = 3.42, 95% CI [1.75, 5.09]; p < 0.01], and HR (WMD = 5.36 BPM, 95% CI [1.87, 8.85]; p < 0.01) compared to EC-. However, EC+ was observed to cause less detrimental effect on SBP (WMD = - 4.72 mmHg, 95% CI [- 6.58, - 2.86], p < 0.01), and HR (WMD = - 3.11 BPM, 95% CI [- 4.54, - 1.68]; p < 0.01) as compared to TC with no difference on DBP (WMD = - 1.14 mmHg, 95% CI [- 2.38, 0.1]; p = 0.07). EC+ also led to greater deterioration of endothelial parameters as compared to EC- but to a lesser degree as compared to TC. CONCLUSION: EC+ shows greater impairment in hemodynamic and endothelial parameters than EC- but less than TC. Additional studies are needed to evaluate prolonged effects of EC use.

Sacubitril/valsartan reversal of left ventricular remodeling is associated with improved hemodynamics in resistant hypertension.

BACKGROUND: Sacubitril/valsartan (S/V) has been shown to be an effective antihypertensive drug combination. However, its therapeutic effects on blood pressure (BP), hemodynamics, and left ventricular (LV) remodeling in resistant hypertension (RHTN) remain unclear. METHODS: Eighty-six patients completed this self-control study, during which olmesartan was administered within the first 8 weeks (phase 1), followed by S/V within the second 8 weeks (phase 2), with nifedipine and hydrochlorothiazide taken as background medications. Office BP, echocardiography, and hemodynamics assessment using impedance cardiography were performed at baseline and at the eighth and sixteenth weeks. RESULTS: The reduction in office BP was larger in phase 2 than in phase 1 (19.59/11.66 mmHg vs. 2.88/1.15 mmHg). Furthermore, the treatment in phase 2 provided greater reductions in systemic vascular resistance index (SVRI) and thoracic blood saturation ratio (TBR), with differences between the two phases of -226.59 (-1212.80 to 509.55) dyn·s/cm5/m2 and -0.02 (-0.04 to 0.02). Switching from olmesartan to S/V also significantly reduced E/E', LV mass index, LV end-diastolic volume index, and LV end-systolic volume index (all P < 0.05). Decreases in arterial stiffness, SVRI, and TBR were correlated with changes in indicators of LV remodeling (all P < 0.05). This correlation persisted even after adjusting for confounders including changes in BP. CONCLUSIONS: Switching from olmesartan to S/V effectively lowered BP and reversed ventricular remodeling in RHTN. In addition, hemodynamic improvement was also observed. Changes in hemodynamics played an important role in reversing LV remodeling of S/V, and were independent of its antihypertensive effect.

Technical challenges during emergent endovascular aneurysm repair with the ALTO system.

INTRODUCTION: Ruptured abdominal aortic aneurysms (AAAs) pose an immediate threat for patient's life and endovascular repair (EVAR) is currently the preferred treatment modality in the presence of suitable anatomy. This is determined based on the requirements of each endograft as described in the instructions for use (IFU). The new ALTO system (Endologix, Irvin, CA, U.S.A.), can accommodate a great range of anatomies such as short necks and/or narrow access, but its unique design requires specific technical modifications during treatment of ruptured AAAs. AREAS COVERED: The standard double balloon technique has long been described and it is used to provide circulatory support during EVAR for ruptured AAA. While this technique is straightforward with the use of endografts with a traditional design, this would not be the case if one uses the ALTO system. In that case specific maneuvers would be required to treat AAA patients in an acute setting. EXPERT OPINION: The ALTO system although being able to treat AAAs with adverse anatomy, it may not be appropriate during treatment of ruptured AAA patients with profound hemodynamic instability. A careful evaluation of the individual's patient anatomy and hemodynamic condition is mandatory in order to decide the best endograft for each case.

Review of the Association Between Long-Term and Current Systemic Steroid Use With Electromechanical Complications and Inpatient Mortality After ST-Elevation Myocardial Infarction.

Background The impact of long-term systemic steroid use on electrical and mechanical complications following ST-segment elevation myocardial infarction (STEMI) has not been extensively studied. Methods In a retrospective cohort study of the National Inpatient Sample (NIS) from 2018 to 2020, adults admitted with STEMI were dichotomized based on the presence of long-term (current) systemic steroid (LTCSS) use. The primary outcome was all-cause mortality. Secondary outcomes included a composite of mechanical complications, electrical, hemodynamic, and thrombotic complications, as well as revascularization complexity, length of stay (LOS), and total charge. Multivariate linear and logistic regressions were used to adjust for confounders. Results Out of 608,210 admissions for STEMI, 5,310 (0.9%) had LTCSS use. There was no significant difference in the odds of all-cause mortality (aOR: 0.89, 95%CI: 0.74-1.08, p-value: 0.245) and the composite of mechanical complications (aOR: 0.74, 95%CI: 0.25-2.30, p-value: 0.599). LTCSS use was associated with lower odds of ventricular tachycardia, atrioventricular blocks, new permanent-pacemaker insertion, cardiogenic shock, the need for mechanical circulatory support, mechanical ventilation, cardioversion, a reduced LOS by 1 day, and a reduced total charge by 34,512 USD (all p-values: <0.05). There were no significant differences in the revascularization strategy (coronary artery bypass graft (CABG) vs. percutaneous coronary interventions (PCI)) or in the incidence of composite thrombotic events. Conclusion LTCSS use among patients admitted with STEMI was associated with lower odds of electrical dysfunction and hemodynamic instability but no difference in the odds of mechanical complications, CABG rate, all-cause mortality, cardiac arrest, or thrombotic complications. Further prospective studies are needed to evaluate these findings further.

Continuous or interrupted pledgeted suture technique in stented bioprosthetic aortic valve replacement: a comparison of in-hospital outcomes.

BACKGROUND: There is ambiguity in the literature regarding the continuous suture technique (CST) for aortic valve replacement (AVR). At our center, there has been a gradual shift towards CST over the interrupted pledgeted technique (IPT). This study aims at comparing outcomes for both techniques. METHODS: We performed a retrospective analysis of a single-center study of patients undergoing AVR between January 2011 and July 2020. Patients were divided into two groups: Continuous suture technique and interrupted pledget-reinforced sutures. The pre-operative and In-hospital clinical characteristics and echocardiographic hemodynamics (i.e. transvalvular gradients and paravalvular leakage) were compared between CST and IPT. RESULTS: We compared 791 patients with CST to 568 patients with IPT (median age: 73 and 74 years, respectively, p = 0.02). In CST there were 35% concomitant procedure vs. 31% in IPT (p = 0.16). Early mortality was 3.2% in CST versus 4.8% in IPT (p = 0.15), and a second cross-clamp due to a paravalvular-leak in 0.5% vs. 1.2%, respectively (p = 0.22). The CST was not associated with new-onset conduction-blocks mandating pacemaker implants(OR 1.07, 95% CI 0.54-2.14; P = 0.85). The postoperative gradients on echocardiography were lower in CST compared to IPT, especially in smaller annuli (peak gradients: 15.7mmHg vs. 20.5mmHg, in valve size < 23 mm, p < 0.001). CONCLUSIONS: The continuous suture technique was associated with lower postoperative gradients and shorter cross-clamp time compared to interrupted pledgeted technique. Differences in paravalvular leaks were non-significant, although slightly less in the continuous suture technique. There were no further differences in valve-related complications. Hence, continues suture technique is safe, with better hemodynamics compared to the interrupted pledgeted technique. This may be of clinical importance, especially in smaller size annular size.

Lateralization of cortical activity, networks, and hemodynamic lag after stroke: A resting-state fNIRS study.

Focal damage due to stroke causes widespread abnormal changes in brain function and hemispheric asymmetry. In this study, functional near-infrared spectroscopy (fNIRS) was used to collect resting-state hemoglobin data from 85 patients with subacute stroke and 26 healthy controls, to comparatively analyze the characteristics of lateralization after stroke in terms of cortical activity, functional networks, and hemodynamic lags. Higher intensity of motor cortical activity, lower hemispheric autonomy, and more abnormal hemodynamic leads or lags were found in the affected hemisphere. Lateralization metrics of the three aspects were all associated with the Fugl-Meyer score. The results of this study prove that three lateralization metrics may provide clinical reference for stroke rehabilitation. Meanwhile, the present study piloted the use of resting-state fNIRS for analyzing hemodynamic lag, demonstrating the potential of fNIRS to assess hemodynamic abnormalities in addition to the study of cortical neurological function after stroke.

Pathophysiology of Hepatorenal Syndrome.

Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion. A state of increased intrahepatic vascular resistance characteristic of advanced cirrhosis and portal hypertension is accompanied by maladaptive peripheral arterial vasodilation and reduction in systemic vascular resistance and mean arterial pressure. As a result of a fall in effective arterial blood volume, there is a compensatory activation of the sympathetic nervous system and the renin-angiotensin system, local renal vasoconstriction, loss of renal autoregulation, decrease in renal blood flow, and ultimately a fall in glomerular filtration rate. Systemic release of nitric oxide stimulated by the fibrotic liver, bacterial translocation, and inflammation constitute key components of the pathogenesis. While angiotensin II and noradrenaline remain the critical mediators of renal arterial and arteriolar vasoconstriction, other novel molecules have been recently implicated. Although the above-described mechanistic pathway remains the backbone of the pathogenesis of HRS-1, other noxious elements may be present in advanced cirrhosis and likely contribute to the renal impairment. Direct liver-kidney crosstalk via the hepatorenal sympathetic reflex can further reduce renal blood flow independently of the systemic derangements. Tense ascites may lead to intraabdominal hypertension and abdominal compartment syndrome. Cardio-hemodynamic processes have also been increasingly recognized. Porto-pulmonary hypertension, cirrhotic cardiomyopathy, and abdominal compartment syndrome may lead to renal congestion and complicate the course of HRS-1. In addition, a degree of ischemic or toxic (cholemic) tubular injury may overlap with the underlying circulatory dysfunction and further exacerbate the course of acute kidney injury. Improving our understanding of the pathogenesis of HRS-1 may lead to improvements in therapeutic options for this seriously ill population.

Therapeutic potential of conduction system pacing as a method for improving cardiac output during ventricular tachycardia.

BACKGROUND: Ventricular tachycardia (VT) reduces cardiac output through high heart rates, loss of atrioventricular synchrony, and loss of ventricular synchrony. We studied the contribution of each mechanism and explored the potential therapeutic utility of His bundle pacing to improve cardiac output during VT. METHODS: Study 1 aimed to improve the understanding of mechanisms of harm during VT (using pacing simulated VT). In 23 patients with left ventricular impairment, we recorded continuous ECG and beat-by-beat blood pressure measurements. We assessed the hemodynamic impact of heart rate and restoration of atrial and biventricular synchrony. Study 2 investigated novel pacing interventions during clinical VT by evaluating the hemodynamic effects of His bundle pacing at 5 bpm above the VT rate in 10 patients. RESULTS: In Study 1, at progressively higher rates of simulated VT, systolic blood pressure declined: at rates of 125, 160, and 190 bpm, -22.2%, -42.0%, and -58.7%, respectively (ANOVA p < 0.0001). Restoring atrial synchrony alone had only a modest beneficial effect on systolic blood pressure (+ 3.6% at 160 bpm, p = 0.2117), restoring biventricular synchrony alone had a greater effect (+ 9.1% at 160 bpm, p = 0.242), and simultaneously restoring both significantly increased systolic blood pressure (+ 31.6% at 160 bpm, p = 0.0003). In Study 2, the mean rate of clinical VT was 143 ± 21 bpm. His bundle pacing increased systolic blood pressure by + 14.2% (p = 0.0023). In 6 of 10 patients, VT terminated with His bundle pacing. CONCLUSIONS: Restoring atrial and biventricular synchrony improved hemodynamic function in simulated and clinical VT. Conduction system pacing could improve VT tolerability and treatment.

A parametric study on pulse duplicator design and valve hemodynamics.

BACKGROUND: In vitro assessment is mandatory for artificial heart valve development. This study aims to investigate the effects of pulse duplicator features on valve responsiveness, conduct a sensitivity analysis across valve prosthesis types, and contribute on the development of versatile pulse duplicator systems able to perform reliable prosthetic aortic valve assessment under physiologic hemodynamic conditions. METHODS: A reference pulse duplicator was established based on literature. Further optimization process led to new designs that underwent a parametric study, also involving different aortic valve prostheses. These designs were evaluated on criteria such as mean pressure differential and pulse pressure (assessed from high-fidelity pressure measurements), valve opening and closing behavior, flow, and regurgitation. Finally, the resulting optimized setup was tested under five different hemodynamic settings simulating a range of physiologic and pathologic conditions. RESULTS: The results show that both, pulse duplicator design and valve type significantly influence aortic and ventricular pressure, flow, and valve kinematic response. The optimal design comprised key features such as a compliance chamber and restrictor for diastolic pressure maintenance and narrow pulse pressure. Additionally, an atrial reservoir was included to prevent atrial-aortic interference, and a bioprosthetic valve was used in mitral position to avoid delayed valve closing effects. CONCLUSION: This study showed that individual pulse duplicator features can have a significant effect on valve's responsiveness. The optimized versatile pulse duplicator replicated physiologic and pathologic aortic valve hemodynamic conditions, serving as a reliable characterization tool for assessing and optimizing aortic valve performance.

Hemodynamic goals in sepsis and septic shock resuscitation: An umbrella review of systematic reviews and meta-analyses with trial sequential analysis.

OBJECTIVE: The objective of this study was to verify whether any parameter among those used as the target for haemodynamic optimisation (e.g., mean arterial pressure, central venous oxygen saturation, systolic or diastolic dysfunction, CO2 gap, lactates, right ventricular dysfunction, and PvaCO2/CavO2 ratio) is correlated with mortality in an undifferentiated population with sepsis or septic shock. METHODS: An umbrella review, searching MEDLINE, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, and the JBI Database of Systematic Reviews and Implementation Reports, was performed. We included systematic reviews and meta-analyses enrolling a population of unselected patients with sepsis or septic shock. The main outcome was mortality. Two authors conducted data extraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarised estimates of effect using equivalent odds ratios (eORs). We used the ROBIS tool to assess risk of bias and the assessment of multiple systematic reviews 2 score to assess global quality. DATA SYNTHESIS: 17 systematic reviews and meta-analyses (15 828 patients) were included in the quantitative analysis. Diastolic dysfunction (eOR: 1.42; 95% confidence interval [CI]: 1.14-1.76), PvaCO2/CavO2 ratio (eOR: 2.15; 95% CI: 1.37-3.37), and CO2 gap (eOR: 1.86; 95% CI: 1.07-3.25) showed a significant correlation with mortality. Lactates were the parameter with highest inconsistency (I2 = 92%). Central venous oxygen saturation and right ventricle dysfunction showed significant statistical excess test of significance (p-value = 0.009 and 0.005, respectively). None of the considered parameters showed statistically significant publication bias. CONCLUSIONS: According to this umbrella review, diastolic dysfunction is the haemodynamic variable that is most closely linked to the prognosis of septic patients. The PvaCO2/CavO2 ratio and the CO2gap are significantly related to the mortality of septic patients, but the poor quality of evidence or the low number of cases, studied so far, limit their clinical applicability. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2023, CRD42023432813 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432813).

Coronary Microvascular Disease Registry (CMDR): Study design and rationale.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD. DESIGN: CMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment. SUMMARY: CMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT05960474.

Functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS and fUS revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We saw a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with the brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV response with peak CBV, activated area, and correlation coefficient increasing with ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalizes and linearly correlates with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths and the evoked hemodynamic responses colocalized and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as an understanding of how FUS displaces brain tissue and affects cerebral hemodynamics.