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Normothermic Machine Perfusion Is Associated With Improvement in Mortality and Graft Failure in Donation After Cardiac Death Liver Transplant Recipients in the United States
No full textBackground. Use of normothermic machine perfusion (NMP) may help to expand the liver transplantation (LT) donor pool by potentially increasing the utilization of donation after circulatory death (DCD) organs. The aim of this study was to assess the impact of NMP on LT from DCD organs. Methods. Data among DCD adult LT recipients in the United Network for Organ Sharing between January 2016 and December 2022 were analyzed. Outcomes were compared between 2 groups: NMP versus non-MP using propensity score matching. Results. During the study period, 4217 DCD LT recipients (NMP: 257 and non-MP: 3960) were identified. compared with non-MP, DCD LT recipients in NMP group were older (median recipient age: 61 versus 59 y, P = 0.013), had lower model for the end-stage liver disease score, longer wait time (126 versus 107 d, P = 0.028), and received organs from older donors (median age: 42 versus 38 y, P \u3c 0.01) with longer preservation time (9.9 versus 5.3 h, P \u3c 0.001). Two-year overall survival (NMP 94.4% versus non-MP 89.7%, P = 0.040) and 2-y graft survival (NMP 91.3% versus non-MP 84.6%, P = 0.017) were better in the NMP group. After propensity score matching, 2-y overall survival (NMP 94.2% versus non-MP 88.0%, P = 0.023) and graft survival (NMP 91.3% versus non-MP 81.6%, P = 0.004) were better in the NMP group. On multivariable cox regression analysis, NMP was an independent factor of protection against mortality (hazard ratio, 0.43; 95% confidence interval: 0.20-0.91; P = 0.029) and against graft failure (hazard ratio, 0.26; 95% confidence interval: 0.11-0.61; P = 0.002). Conclusions. Use of NMP for LT from DCD donors was associated with improved posttransplant patient and graft survival
The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States
No full textBackground: New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Methods: Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N = 2770) and post-AC (Feb-2020 to Dec-2021, N = 2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Results: Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P \u3c 0.001), and less percentage of MELD exception (4.6% vs 7.7%, P = 0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P \u3c 0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P \u3c 0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56–1.16, P = 0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41–1.99, P \u3c 0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. Conclusions: The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival
Decreasing Trends of Traumatic Brain Injury Despite a Surge in Anticoagulant Use in the Elderly
No full textBackground: In recent years, with the introduction of new anticoagulants there has been a rise in their usage among elderly population who are at risk for traumatic brain injury (TBI) at the same time. We assessed the change in use of anticoagulant in elderly trauma patients and its association with TBI outcomes. Material and Methods: We performed a 5-y retrospective analysis of Trauma Quality Improvement Program (2017-2021) of trauma patients ≥65 y. Patient who had TBI were identified. We queried the preexisting comorbid conditions for anticoagulant use. The primary outcome was mortality, and the secondary outcome was TBI admissions during study period. We conducted a linear regression analysis to assess for trends in data. We also utilized a propensity score matching in 1:1 ratio to compare patients on prehospital anticoagulant versus nonreceivers. Results: A total of 1,688,157 patients were included. The trend of TBI admission over the study period has been decreasing significantly (P \u3c 0.001). Prehospital anticoagulant use has been increasing over the study period with the slope of 0.078 (P = 0.043). After propensity score matching, patients with TBI who used anticoagulants before hospitalization had a higher mortality rate compared to nonreceivers (9.1% versus 6.8%, P \u3c 0.001). The mortality rate in patients with anticoagulant use decreased from 2017 to 2019 and increased from 2019 to 2021. However this change was not significant in a linear fashion. Conclusions: Despite increasing trends of anticoagulant usage, which is associated with a higher mortality risk after TBI in elderly, the rate of TBI admissions has been decreasing over the years. Meanwhile, the trend of mortality in patients with anticoagulant use appears to remain unchanged
Phenylephrine Alters Phase Synchronization Between Cerebral Blood Velocity and Blood Pressure in ME/CFS With Orthostatic Intolerance
No full textMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60_ head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P \u3c 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P \u3c 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P \u3c 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P \u3c 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS PE= 0.69 ± 0.04, P \u3c 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV
BK Polyomavirus Microrna in Kidney Transplant Recipient
No full textBK polyomavirus-associated nephropathy (PyVAN) remains a serious threat for renal dysfunction and graft loss in kidney transplant recipients on immunosuppressive medication. In this study, a pilot cohort of 16 kidney transplant recipients were recruited of which eight were with significant BKPV viremia (sBKPV) and the rest were controls matched to age, gender, and time since transplant. We used next-generation sequencing to characterize the miRNA expression profile in urine samples. In total, the expression of 8 miRNAs (miR-16-5p,miR-200c-3p,bkv-miR-B1-3p,let-7b-3p,miR-1269b,bkv-miR-B1-5p,miR-193a-3p,miR-944) were upregulated whereas 21miRNAs (miR-134-5p,miR-4724-5p,miR-127-3p,miR-6500-3p,miR-507,miR-378b,miR-3911,miR-211-5p,miR-486-5p,miR-143-3p,miR-3195,miR-1307-5p,miR-29a-5p,miR-378f,miR-12136,miR-378g,miR-144-3p,miR-378a-3p,let-7i-5p,miR-204-5p,miR-146a-5p) were downregulated with fold change \u3e 2. We found that bkv-miR-B1-5p and bkv-miR-B1-3p have 19-fold and 5-fold higher expression values in BKPV viremia patient samples, respectively. A few earlier studies have reported BKV miRNA in urine and serum samples using the RT- PCR from PyVAN patients. Our results corroborated findings from earlier studies and highlighted the need for additional evaluation of the role of sequencing approaches for monitoring BKPV specific and host miRNAs to better understand the viral reactivation and disease pathogenesis
Shock Index Is a Stronger Predictor of Outcomes in Older Compared to Younger Patients
No full textIntroduction: The shock index (SI) is a known predictor of unfavorable outcomes in trauma. This study seeks to examine and compare the SI values between geriatric patients and younger adults. Methods: We conducted a retrospective study of the Trauma Quality Improvement Program database from 2017 to 2019. All patients≥ 25 y with injury severity score ≥ 16 were included. Age groups were defined as 25-44 y (group A), 45-64 y (group B), and ≥65 y (group C). SI was calculated for all patients. The primary outcome was mortality and secondary outcomes were need for blood transfusion and need for major surgical intervention (consisting angiography, exploratory laparotomy, and thoracotomy). Results: A total of 244,943 patients were studied. The SI was highest in group A (0.82 ± 0.33) and lowest in group C (0.62 ± 0.30) (P \u3c 0.001). Mortality rate of group C (17%) was significantly higher than group A (9.7%) and B (11.3%) (P \u3c 0.001). In group A, each 0.1 increase in SI was associated with mortality (odds ratio [OR] = 1.079), need for blood transfusion (OR = 1.225) and need for major surgical intervention (OR = 1.347) (P \u3c 0.001 for all). In group C, each 0.1 increase in SI was associated with mortality (OR = 1.126), need for blood transfusion (OR = 1.318), and need for major surgical intervention (OR = 1.648) (P \u3c 0.001 for all). The area under the curve of SI was significantly higher in group C compared to other groups for needing a major surgical intervention and need for blood transfusion (P \u3c 0.05 for both). Conclusions: These results highlight the significance of the SI as a valuable indicator in geriatric patients with severe trauma. The findings show that SI predicts outcomes in geriatrics more strongly than in younger counterparts
Correction To: Speech Language Pathology in the Neurocritical Care Unit (Current Treatment Options in Neurology, (2023), 25, 11, (499-516), 10.1007/S11940-023-00772-5)
No full textThe author noticed a typo name in the recently published review—Julie Zhang, BA. It should be Julia Zhang, MSc. The original article has been corrected
High Area Deprivation Index Is Associated With Discharge to Foster Care in Pediatric Patients With Non-Accidental Trauma
No full textBackground: Outcomes after non-accidental trauma (NAT) have been shown to be impacted by social determinants of health. Our study aims to investigate the association between NAT, patient demographics, neighborhood disadvantage as measured by the Area Deprivation Index (ADI), and patient disposition. Methods: An 8-year retrospective chart review was conducted in pediatric patients presenting to our level I trauma center with suspected NAT. Patient demographics, ADI, injury severity score (ISS), Glasgow coma scale (GCS), length of stay, and discharge disposition were analyzed using univariate and multivariate techniques to evaluate associations between patient demographics, injury severity, and patient outcomes. Results: A total of 84 patients were admitted with suspected NAT. Of our study population, 45% of patients were White and 26% were Black. Black children were overrepresented in this cohort compared to general population means, while White children were underrepresented (p \u3c 0.05). Median ADI was 6.5 (IQR 4.0–8.0). Of our cohort, 65 patients were discharged home, and 18 patients to foster care. One patient in our cohort died. An ADI \u3e6 was the only factor significantly associated with discharge to foster care. This association held on both univariate (OR 1.4; 95% CI 1.07–1.84, p = 0.02) and multivariate (OR 1.4; 95% CI 1.05–1.86, p = 0.02) analyses. Conclusion: Our study found that neighborhood disadvantage, as measured by ADI, is an independent predictor of discharge to foster care. Additionally, Black children remain over-represented in the NAT population referred to our institution, including those discharged to foster care. Efforts to address healthcare disparities and community-based NAT prevention and reunification programs are necessary. Type of Study: Prognosis Study (Retrospective Case-Control Study). Level of Evidence: Level III
Anesthetic Oxygen Use and Sex Are Critical Factors in the FLASH Sparing Effect
No full textPurpose: Ultra High Dose-Rate (UHDR) radiation has been reported to spare normal tissue, compared with Conventional Dose-Rate (CDR) radiation. However, important work remains to be done to improve the reproducibility of the FLASH effect. A better understanding of the biologic factors that modulate the FLASH effect may shed light on the mechanism of FLASH sparing. Here, we evaluated whether sex and/or the use of 100% oxygen as a carrier gas during irradiation contribute to the variability of the FLASH effect. Methods and Materials: C57BL/6 mice (24 male, 24 female) were anesthetized using isoflurane mixed with either room air or 100% oxygen. Subsequently, the mice received 27 Gy of either 9 MeV electron UHDR or CDR to a 1.6 cm2 diameter area of the right leg skin using the Mobetron linear accelerator. The primary postradiation endpoint was time to full thickness skin ulceration. In a separate cohort of mice (4 male, 4 female), skin oxygenation was measured using PdG4 Oxyphor under identical anesthesia conditions. Results: Neither supplemental oxygen nor sex affected time to ulceration in CDR irradiated mice. In the UHDR group, skin damage occured earlier in male and female mice that received 100% oxygen compared room air and female mice ulcerated sooner than male mice. However, there was no significant difference in time to ulceration between male and female UHDR mice that received room air. Oxygen measurements showed that tissue oxygenation was significantly higher when using 100% oxygen as the anesthesia carrier gas than when using room air, and female mice showed higher levels of tissue oxygenation than male mice under 100% oxygen. Conclusions: The skin FLASH sparing effect is significantly reduced when using oxygen during anesthesia rather than room air. FLASH sparing was also reduced in female mice compared to male mice. Both tissue oxygenation and sex are likely sources of variability in UHDR studies. These results suggest an oxygen-based mechanism for FLASH, as well as a key role for sex in the FLASH skin sparing effect
First Monte Carlo Beam Model for Ultra-High Dose Rate Radiotherapy With a Compact Electron LINAC
No full textBackground: FLASH radiotherapy based on ultra-high dose rate (UHDR) is actively being studied by the radiotherapy community. Dedicated UHDR electron devices are currently a mainstay for FLASH studies. Purpose: To present the first Monte Carlo (MC) electron beam model for the UHDR capable Mobetron (FLASH-IQ) as a dose calculation and treatment planning platform for preclinical research and FLASH-radiotherapy (RT) clinical trials. Methods: The initial beamline geometry of the Mobetron was provided by the manufacturer, with the first-principal implementation realized in the Geant4-based GAMOS MC toolkit. The geometry and electron source characteristics, such as energy spectrum and beamline parameters, were tuned to match the central-axis percentage depth dose (PDD) and lateral profiles for the pristine beam measured during machine commissioning. The thickness of the small foil in secondary scatter affected the beam model dominantly and was fine tuned to achieve the best agreement with commissioning data. Validation of the MC beam modeling was performed by comparing the calculated PDDs and profiles with EBT-XD radiochromic film measurements for various combinations of applicators and inserts. Results: The nominal 9 MeV electron FLASH beams were best represented by a Gaussian energy spectrum with mean energy of 9.9 MeV and variance (σ) of 0.2 MeV. Good agreement between the MC beam model and commissioning data were demonstrated with maximal discrepancy \u3c 3% for PDDs and profiles. Hundred percent gamma pass rate was achieved for all PDDs and profiles with the criteria of 2 mm/3%. With the criteria of 2 mm/2%, maximum, minimum and mean gamma pass rates were (100.0%, 93.8%, 98.7%) for PDDs and (100.0%, 96.7%, 99.4%) for profiles, respectively. Conclusions: A validated MC beam model for the UHDR capable Mobetron is presented for the first time. The MC model can be utilized for direct dose calculation or to generate beam modeling input required for treatment planning systems for FLASH-RT planning. The beam model presented in this work should facilitate translational and clinical FLASH-RT for trials conducted on the Mobetron FLASH-IQ platform