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Clinical management of the Impella 5.5 pump.
No full textThe Impella 5.5 (Abiomed, USA) is a catheter-based micro-axial flow pump that has emerged as a vital tool in managing patients with cardiogenic shock (CS). Delivering up to 5.5 L/min of flow, it enables full left ventricular (LV) support with beneficial hemodynamic and metabolic effects. Its unique advantages include high-flow, antegrade circulatory support with the potential for prolonged usage, making it suitable for bridging to recovery or heart replacement therapies. This manuscript provides a comprehensive, structured guide for the clinical management of patients supported with the Impella 5.5. It outlines best practices for patient selection, surgical implantation techniques-most commonly via the axillary artery-perioperative management, anticoagulation strategies, and postoperative monitoring. Special emphasis is placed on complication management, including bleeding, hemolysis, right ventricular dysfunction, stroke, aortic valve injury, and vascular complications. Technologies like SmartAssist and Impella Connect are highlighted for their utility in real-time device monitoring and remote management. The manuscript also discusses a three-phase framework for recovery: hemodynamic stabilization, initiation of guideline-directed medical therapy (GDMT), and structured weaning protocols. Considerations for transitioning patients to heart transplantation or durable LVADs, as well as explant techniques, are detailed. The importance of multidisciplinary coordination-including a mechanical circulatory support (MCS) coordinator-is emphasized to ensure optimal patient outcomes. By synthesizing available evidence and institutional experience, this guide aims to standardize Impella 5.5 management, reduce complications, and improve outcomes in critically ill patients with advanced heart failure or CS
Systemic Inflammation and the Risks of Adverse Kidney Outcomes in Adults With Atherosclerotic Cardiovascular Disease.
No full textRATIONALE & OBJECTIVE: Inflammasome activation is involved in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD). This study investigated whether systemic inflammation, measured by C-reactive protein (CRP), is associated with adverse kidney outcomes in adults with ASCVD.
STUDY DESIGN: Retrospective cohort study.
SETTING & PARTICIPANTS: 83,928 adults with ASCVD in Stockholm, Sweden, who underwent routine CRP testing between 2007 and 2021.
EXPOSURE(S): CRP was defined as the geometric mean of serum CRP levels within a 3-month ascertainment window, excluding CRP values potentially associated with an acute inflammatory process.
OUTCOME(S): Acute kidney injury (AKI; based on diagnosis code or Kidney Disease: Improving Global Outcomes [KDIGO] serum creatinine criteria) and a composite kidney outcome defined as a sustained\u3e30% decrease in estimated glomerular filtration rate or kidney failure.
ANALYTICAL APPROACH: Cause-specific Cox proportional hazards regression.
RESULTS: 54% of the cohort was male, with a mean age of 71 years, and 59% of participants had systemic inflammation (CRP≥2mg/L). During a median follow-up of 6.4 years (IQR, 3.1-9.8 years), 8,371 kidney events, 10,757 AKI events, and 24,954 deaths were recorded. Compared with CRP\u3c 1mg/L, higher CRP categories were associated with increased risks of both outcomes. Compared with a CRP of≤1mg/L, the adjusted HRs for the composite kidney outcome were 1.16 (95% CI, 1.09-1.23) for CRP\u3e1-3mg/L, 1.24 (1.17-1.32) for CRP\u3e3-10mg/L, and 1.35 (1.25-1.46) for CRP\u3e10-20mg/L. For AKI, the HRs were 1.18 (1.12-1.25), 1.34 (1.27-1.42), and 1.37 (1.28-1.47), respectively.
LIMITATIONS: Unmeasured confounding inherent to observational studies.
CONCLUSIONS: In this large cohort of adults with ASCVD, increased CRP levels were associated with higher risks of adverse kidney outcomes.
PLAIN-LANGUAGE SUMMARY: Inconsistent evidence exists regarding the association between the circulating blood marker of inflammation C-reactive protein (CRP) and kidney outcomes. We conducted an observational study in more than 83,000 adults with atherosclerotic cardiovascular disease undergoing routine care. The study showed that CRP levels were higher in participants with lower levels of kidney function and that CRP was associated with more rapid declines in kidney function over time as well as a greater risk of acute kidney injury
Emergence and disruption of cooperativity in a denitrifying microbial community.
No full textAnthropogenic perturbations to the nitrogen cycle, primarily through use of synthetic fertilizers, is driving an unprecedented increase in the emission of nitrous oxide (N2O), a potent greenhouse gas and an ozone depleting substance, causing urgency in identifying the sources and sinks of N2O. Microbial denitrification is a primary contributor to biotic production of N2O in anoxic regions of soil, marine systems, and wastewater treatment facilities. Here, through comprehensive genome analysis, we show that pathway partitioning is a ubiquitous mechanism of complete denitrification within microbial communities. We have investigated mechanisms and consequences of process partitioning of denitrification through detailed physiological characterization and kinetic modeling of a synthetic community of Rhodanobacter thiooxydans FW510-R12 and Acidovorax sp. GW101-3H11. We have discovered that these two bacterial isolates, from a heavily nitrate (NO3-) contaminated superfund site, complete denitrification through the exchange of nitrite (NO2-) and nitric oxide (NO). The process partitioning of denitrification and other processes, including amino acid metabolism, contribute to increased cooperativity within this denitrifying community. We demonstrate that certain contexts, such as high NO3-, cause unbalanced growth of community members, due to differences in their substrate utilization kinetics. The altered growth characteristics of community members drives accumulation of toxic NO2-, which disrupts denitrification causing N2O off gassing
Heavily Pretreated Refractory Diffuse Large B-Cell Lymphoma Successfully Treated with Epcoritamab: Case Report.
No full textINTRODUCTION: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) poses considerable treatment challenges, with disheartening odds of long-term survival. Numerous strategies exist, including non-cross-resistant combination chemoimmunotherapy regimens, autologous stem cell transplantation, and chimeric antigen receptor (CAR) T-cell therapy, but some patients are not appropriate candidates or cannot sustain response to treatment. Epcoritamab, a bispecific CD20-directed CD3 T-cell engager, has been given accelerated approval by the US Food and Drug Administration for relapsed or refractory DLBCL.
CASE PRESENTATION: We present the case of a 61-year-old male diagnosed with stage 4 double-hit DLBCL with
CONCLUSION: T-cell engager therapies, such as epcoritamab, can play a role in managing patients with refractory DLBCL, including those refractory to CAR T-cell therapy
A Population-Level Real-World Analysis and Single-Center Validation of Melanoma Brain Metastasis Epidemiology following Dual-Agent Immunotherapy.
No full textPurpose: Melanoma brain metastases (MBM) are common in advanced melanoma and linked to poor prognosis. Preventing MBM can improve survival and reduce morbidity. Although dual-agent immunotherapy (dIT) improves survival, its role in MBM prevention is unclear. We compared MBM incidence, overall survival (OS), and brain metastasis-free survival (BMFS) between dIT and single-agent immunotherapies.
Experimental design: A real-world multi-institutional database identified patients with melanoma without MBM at immunotherapy initiation. Patients were stratified by anti-CTLA4, anti-PD1, and combination anti-CTLA4/anti-PD1 (dIT) treatment. MBM incidences were measured within 5 years after immunotherapy initiation and compared with risk ratios (RR). In a complementary single-institution cohort, the median OS and BMFS were compared between dIT, anti-CTLA4, and anti-PD1 via log-rank tests and multivariate Cox proportional hazards models.
Results: TriNetX identified 8,287 patients receiving anti-CTLA (3,205), anti-PD1 (3,218), and dIT (1,864). MBM incidence was significantly lower in dIT (8.6%) and anti-PD1 (7.8%) versus anti-CTLA4 (12.2%) cohorts, with RR = 0.72 [95% confidence interval (CI), 0.61-0.86] and 0.63 (95% CI, 0.57-0.70), respectively. There was no significant difference in MBM incidence between anti-PD1 (7.8%) and dIT (8.6%; RR = 1.13; 95% CI, 0.93-1.36). In the single-institution analysis (n = 119), 2-year OS probabilities were 90%, 80%, and 95%, and 2-year BMFS probabilities were 72.7%, 80%, and 95.7%, in the dIT, anti-CTLA4, and anti-PD1 cohorts, respectively. DIT and anti-PD1 showed improved early-phase protection against MBM development. The number of metastatic sites was significantly associated with MBM development (HR = 2.36; 95% CI, 1.22-4.58; P = 0.01).
Conclusions: These findings highlight dIT\u27s potential role in primary prophylaxis against MBM, with anti-PD1 as the likely workhorse agent. Prospective studies are warranted
Mind the gap in kidney care: translating what we know into what we do.
No full textHistorically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay
