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Kidney dysfunction in LVAD recipients is common and harmful. Precise mechanistic characterization of kidney health states in LVAD recipients is important to improving prognostication and outcomes. Current assessments provide limited and confounded information about kidney parenchymal health before or after LVAD implantation. Urine exosomes may offer a non-invasive window into kidney health. We performed an exploratory study assessing kidney health in LVAD recipients using urine exosome isolation and protein biomarkers. Urine was collected and exosomes were isolated from 16 patients received LVAD (HeartMate III) from 1/2022-9/2022, immediately pre-implantation and on post operative day 7. Protein markers (AQP1, NGAL, NHE3, ATF3, and fetuin A) previously found to be associated with kidney health, were studied on urine exosomes. Relationships of exosome protein levels and important baseline clinical characteristics (presence of kidney dysfunction, defined as eGFR<60 ml/min/1.73m2, and hemodynamic instability, defined as INTERMACS 1 or 2) were assessed. Biomarker levels were normalized, and median levels were used for group comparisons. For the 16 LVAD recipients (median age 61 yrs., 81% male), 8 had baseline eGFR below 60, and 8 were INTERMACS 1 or 2. Persons with baseline low kidney function had higher levels of NHE3, Fetuin A, and NGAL (fig.1A). Persons with hemodynamic instability had higher levels of AQP1, Fetuin A, and ATF3 (fig.1B). In comparing biomarker changes with changes in creatinine level (from pre-op to POD 7), NGAL had the highest correlation (Spearman's ρ=0.84, p<0.001, Fig.1C). This pilot study is the first to study urine exosomes in LVAD recipients. The results showed biomarker level changes that are generally in accordance with prior studies assessing urine exosomes in other acute and chronic kidney disease situations. Thus, we have demonstrated the feasibility of studying urine exosomes as a non-invasive way to investigate kidney health in LVAD recipients. [ABSTRACT FROM AUTHOR]

Stroke continues to be a major adverse event in advanced congestive heart failure (CHF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. Abnormalities in mitochondrial oxidative phosphorylation (OxPhos) have been critically implicated in the pathogenesis of neurodegenerative diseases and cerebral ischemia. We hypothesize that prior stroke may be associated with systemic mitochondrial OxPhos abnormalities, and impaired more in post-CF-LVAD patients with risk of developing new stroke. We studied 50 CF-LVAD patients (25 with prior stroke, 25 without); OxPhos complex proteins (complex I [C.I]-complex V [C.V]) were measured in blood leukocytes. Both at baseline (pre-CF-LVAD) and postoperatively (post-CF-LVAD), the prior-stroke group had significantly lower C.I, complex II (C.II), complex IV (C.IV), and C.V proteins when compared to the no-prior-stroke group. Oxidative phosphorylation proteins were significantly decreased in prior-stroke group at post-CF-LVAD compared to pre-CF-LVAD. Machine learning Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest modeling identified six prognostic factors that predicted postoperative stroke with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93. Oxidative phosphorylation protein reduction appeared to be associated with the new stroke after implantation. Our study found for the first time the existence of mitochondrial dysfunction at the peripheral level in CHF patients with prior ischemic stroke even before CF-LVAD implantation. The changes in OxPhos protein expression could serve as biomarkers in predicting new post-CF-LVAD strokes., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Introduction: High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft., Material and Methods: All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m 2 ). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS)., Results: Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant ( p 0.5). The EFS was also similar in both groups ( p 0.5)., Conclusion: HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells.

There is data suggesting that the clinical behavior of multiple myeloma (MM) may be different in Latin Americans than in Caucasian or African-Americans, consistent with a less aggressive course of MM in Latinos. We analyzed the overall survival (OS) of 139 persons with MM in a single institution in México, as well the variables which were associated with long-term OS. Of all patients, the median OS was 11 years whereas the 5-year and 10-year OS were 75% and 55% respectively. The analysis of variables showed that the variable related with five-year survival was having hematopoietic stem cell transplantation (HSCT), whereas the variables related with 10-year survival were HSCT, age at diagnosis (patients younger than 50 survived longer), light chain type (kappa survived longer) and ISS stage (stage I patients survived longer). The only variable associated with both 5 and 10-year survival was HSCT. A plateau in the OS was reached after 10 years, both in grafted and non-grafted patients. We have confirmed the critical role of HSCT in the prognosis of persons with MM, independent of the induction treatment or the maintenance post-transplant, and we have identified a better prognosis in this cohort, as compared with African-Americans or Caucasians, since the proportion of long-term survivors in our group is seemingly better than those in other populations.