The Effect of Prehospital Blood Transfusion on Patient Body Temperature from the Time of Emergency Medical Services Transfusion to Arrival at the Emergency Department.

BACKGROUND: Transfusion of blood products is life-saving and time-sensitive in the setting of acute blood-loss anemia, and is increasingly common in the emergency medical services (EMS) setting. Prehospital blood products are generally "cold-stored" at 4°C, then warmed with a portable fluid-warming system for the purpose of preventing the "lethal triad" of hypothermia, acidosis, and coagulopathy. This study aims to evaluate body temperature changes of EMS patients receiving packed red blood cells (PRBC) and/or fresh frozen plasma (FFP) when using the LifeWarmer Quantum Blood & Fluid Warming System (LifeWarmer, https://www.lifewarmer.com/). METHODS: From 1 January 2020 to 31 August 2021, patients who qualified for and received PRBC and/or FFP were retrospectively reviewed. Body-temperature homeostasis pre- and post-transfusion were evaluated with attention given to those who arrived to the emergency department (ED) hypothermic (<36°C). RESULTS: For all 69 patients analyzed, the mean initial prehospital temperature (°C) was 36.5 ± 1.0, and the mean initial ED temperature was 36.7 ± 0.6, demonstrating no statically significant change in value pre- or post-transfusion (0.2 ± 0.8, p = .09). Shock index showed a statistically significant decrease following transfusion: 1.5 ± 0.5 to 0.9 ± 0.4 (p < .001). CONCLUSION: Use of the Quantum prevents the previously identified risk of hypothermia with respect to unwarmed prehospital transfusions. The data is favorable in that body temperature did not decrease in critically ill patients receiving cold-stored blood warmed during administration with the Quantum.

The COVID-19 Army Rapid Assessment Tool (CARAT) for Management of COVID-19 in the Deployed Setting.

The COVID-19 pandemic poses unique challenges within the austere clinical setting, and the time between patient presentation and deterioration is a critical opportunity for intervention. In some cases, this may be a life-saving transfer to a higher level of care. US Central Command (CENTCOM) has provided valuable guidance for COVID-19 management in the operational environment,1 and has proposed the National Early Warning System 2 (NEWS2) scoring tool as a useful adjunct to gauging illness severity. NEWS2, however, does not consider co-morbidities, such as diabetes or chronic cardiac disease, which could worsen the clinical course of SARS-CoV-2 patients. Thus, NEWS2 fails to address such factors during the risk stratification of patients to a higher level of care. To address this concern, June 2020, 3rd Medical Brigade, Operation Spartan Shield (OSS) developed the COVID-19 Army Rapid Assessment Tool (CARAT) with inputs from clinicians and researchers (The Team). The CARAT is a clinical scoring system, modified from the NEWS2, which combines the effects of co-morbid disease with the current physiological condition of a COVID-19 patient. The Team obtained clinical data for 105 patients from the CENTCOM area of responsibility (AOR), who presented to a military treatment facility (MTF) symptomatic for, and testing positive for SARS-CoV-2, during the time period of June to mid-August 2020. Each patient was retrospectively assigned a CARAT score based on his or her initial presentation. Preliminary review of data suggested a CARAT value of 4 or greater was an indicator for risk of further deterioration. Patients were then grouped into two categories: patients who received transfer to a higher level of care, versus "stay-in-place" supportive care. Results showed that 100% of patients with a score ≥4 had been transferred to a higher echelon of care, compared to 2% of patients with scores less than 4. A Fisher's exact test demonstrated a statistically significant difference between these two groups (p is less than 0.001). Interestingly, when compared with the NEWS2 score, the CARAT identified 9 individuals for transfer to a higher level of care, of whom only one patient was identified by the NEWS2, clearly underscoring the significance of CARAT despite small sample size. We therefore recommend that CARAT be further validated in predicting disease severity and need for emergent evacuation in larger patient settings.

Metabolic Imaging Detects Resistance to PI3Kα Inhibition Mediated by Persistent FOXM1 Expression in ER+ Breast Cancer.

PIK3CA, encoding the PI3Kα isoform, is the most frequently mutated oncogene in estrogen receptor (ER)-positive breast cancer. Isoform-selective PI3K inhibitors are used clinically but intrinsic and acquired resistance limits their utility. Improved selection of patients that will benefit from these drugs requires predictive biomarkers. We show here that persistent FOXM1 expression following drug treatment is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer. FOXM1 drives expression of lactate dehydrogenase (LDH) but not hexokinase 2 (HK-II). The downstream metabolic changes can therefore be detected using MRI of LDH-catalyzed hyperpolarized 13C label exchange between pyruvate and lactate but not by positron emission tomography measurements of HK-II-mediated trapping of the glucose analog 2-deoxy-2-[18F]fluorodeoxyglucose. Rapid assessment of treatment response in breast cancer using this imaging method could help identify patients that benefit from PI3Kα inhibition and design drug combinations to counteract the emergence of resistance.

NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.

Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. We have recently identified that NOTCH1 can drive 'lateral induction' of a unique senescence phenotype in adjacent cells by specifically upregulating the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells exhibit a massive increase in chromatin accessibility. NOTCH signalling suppresses SAHF and increased chromatin accessibility in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, drive similar chromatin architectural changes in adjacent cells through cell-cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in multiple human cancers. Thus, HMGA1 is involved not only in SAHFs but also in RIS-driven chromatin accessibility. In conclusion, this study identifies that the JAG1-NOTCH-HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.

MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter.

Non-invasive imaging of gene expression can be used to track implanted cells in vivo but often requires the addition of an exogenous contrast agent that may have limited tissue access. We show that the urea transporter (UT-B) can be used as a gene reporter, where reporter expression is detected using 1H MRI measurements of UT-B-mediated increases in plasma membrane water exchange. HEK cells transfected with the reporter showed an increased apparent water exchange rate (AXR), which increased in line with UT-B expression. AXR values measured in vivo, in UT-B-expressing HEK cell xenografts, were significantly higher (about twofold, P < 0.0001), compared with non-expressing controls. Fluorescence imaging of a red fluorescent protein (mStrawberry), co-expressed with UT-B showed that UT-B expression correlated in a linear fashion with AXR. Transduction of rat brain cells in situ with a lentiviral vector expressing UT-B resulted in about a twofold increase in AXR at the site of virus injection.

(13) C magnetic resonance spectroscopy measurements with hyperpolarized [1-(13) C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo.

PURPOSE: Dissolution dynamic nuclear polarization can increase the sensitivity of the (13) C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize (13) C-labeled tracers. We describe here a gene reporter based on the enzyme pyruvate decarboxylase (EC 4.1.1.1), which catalyzes the decarboxylation of pyruvate to produce acetaldehyde and carbon dioxide. METHODS: Pyruvate decarboxylase from Zymomonas mobilis (zmPDC) and a mutant that lacked enzyme activity were expressed using an inducible promoter in human embryonic kidney (HEK293T) cells. Enzyme activity was measured in the cells and in xenografts derived from the cells using (13) C MRS measurements of the conversion of hyperpolarized [1-(13) C] pyruvate to H(13) CO3-. RESULTS: Induction of zmPDC expression in the cells and in the xenografts derived from them resulted in an approximately two-fold increase in the H(13) CO3-/[1-(13) C] pyruvate signal ratio following intravenous injection of hyperpolarized [1-(13) C] pyruvate. CONCLUSION: We have demonstrated the feasibility of using zmPDC as an in vivo reporter gene for use with hyperpolarized (13) C MRS. Magn Reson Med 76:391-401, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Hemodialysis Access in the Elderly: Outcomes among Patients Older than Seventy.

BACKGROUND: Arteriovenous fistulae (AVF) are the preferred access for hemodialysis, however, there continues to be limited data guiding the surgical management of primary dialysis access creation in elderly end-stage renal disease patients. METHODS: This is an 8-year retrospective institutional study evaluating the operative and clinical characteristics of patients 70 years or above who underwent primary, first-ever, AVF or arteriovenous graft (AVG) creation. RESULTS: There was no overall significant difference in AVF and AVG primary (P = 0.127) and secondary (P = 0.870) patency. AVG had higher graft loss secondary to infection (P = 0.0002) and thrombosis (P = 0.0213). Survival was less than 50% at 2 years for AVF and AVG patients. An equal number of AVF and AVG patients who died had functional access at the time of death (P = 1.0000) with more AVG patients using their graft (initiating dialysis) before death (P = 0.0118). CONCLUSIONS: Elderly patient patency rates for AVF and AVG are satisfactory and support surgical access creation; however, overall 2-year survival is low. An equal number of AVF and AVG patients died with functioning surgical access, however, more AVG patients initiated dialysis and successfully used their access. Accordingly, special consideration needs to be given with regard to estimated timing until dialysis and predicted patient longevity. Delaying access creation until dialysis is needed and proceeding with AVG creation appears to be justified.

Current outcomes and indications for cryopreserved vein allografts in hemodialysis access surgery.

INTRODUCTION: Cryopreserved vein allografts (cadaveric vein) have emerged as an option for arteriovenous graft reconstruction; however, indications for their use in hemodialysis access remains to be clearly defined. Observations from our own experience have suggested that cadaveric vein grafts (CVGs) provide good outcomes, particularly in patients with a history of infection, recurrent access failure and advanced age. METHODS: This is a 10-year retrospective study. Primary outcomes were (1) to identify characteristics specific to this patient population and (2) to better define indications for use of cadaveric vein in hemodialysis access creation. RESULTS: Indications for creation of CVGs included patient history of either active or recent infection (41.5%), recurrent access failure (43.4%) or surgeon preference secondary to patients' advanced age (9.4%). Observed primary patency rates were 84.9% (30 days), 22.6% (1 year) and 16.0% (2 years). Secondary patency was 93.4% (30 days), 66.0% (1 year) and 52.8% (2 years). Patient death was the highest cause of graft abandonment (52.9%) followed by thrombosis (19.1%), infection (11.7%) and rupture (11.7%). CVG patency at the time of patient death was 83.7%. CONCLUSIONS: The rates of both primary and secondary patency in CVGs are highly comparable to the reported patency rates of polytetrafluoroethylene (PTFE) grafts and allow for lifelong maintenance of dialysis access. Our observed outcome suggests that CVGs should be considered for patients needing vascular access in the presence of infection. CVGs may likewise be viable alternatives to PTFE grafts in the elderly and patients with limited access options.

An Outcomes Comparison of Native Arteriovenous Fistulae, Polytetrafluorethylene Grafts, and Cryopreserved Vein Allografts.

BACKGROUND: Despite almost 2 decades of experience with cadaveric vein, there remains a paucity of available data regarding the role of cadaveric vein in hemodialysis, specifically with regard to outcomes and patency. Observations from our own experience have suggested that cadaveric vein grafts (CVGs) provide good outcomes, particularly in patients with recurrent access failure. Accordingly, this study aims to comparatively examine patency, access-related outcomes, and survival in patients undergoing placement of arteriovenous fistulae (AVF), polytetrafluorethylene (PTFE) grafts, and CVGs. METHODS: This is a single institution 11-year retrospective case series evaluating the outcomes of 210 patients who underwent creation of AVF, PTFE grafts, and CVGs for hemodialysis access. Patients in the AVF (n = 70) and arteriovenous graft (AVG; n = 70) groups were matched to the CVG (n = 70) group by age, gender, and access location. Postoperative end points for all groups included primary and assisted patency, cause of access abandonment, and survival. RESULTS: Patients were matched for age (P = 0.8707), gender (P = 0.6958), and access location and no significant differences existed between groups. AVF showed superior primary patency at 30 days, 1 year (64.3%, P < 0.0001) and 2 years (54.3%, P = 0.0091) in comparison to both AVG and CVG. AVG had reduced patency at 30 days (84.3%, P = 0.0009), 1 year (50.0%, P < 0.0001), and 2 years (32.9%, P = 0.0001) in comparison to AVF and CVG groups. Overall, AVF had the highest patency at all-time points followed, respectively by CVG and AVG. No significant difference existed between AVF and CVG groups with regard to secondary patency at 30 days (98.6% vs. 97.1%, P = 1.0000), 1 year (81.4% vs. 78.6%, P = 0.6749), and 2 years (68.6% vs. 51.4%, P = 0.0573). AVG patients had decreased survival (years) after access creation in comparison to AVF and CVG groups (P = 0.0003). CONCLUSIONS: Our findings lend further support to the use of cadaveric vein for hemodialysis access surgery. As demonstrated through this comparative study, CVGs are capable of providing favorable results with regard to patency, access longevity, and patient survival. These current outcomes indicate that cadaveric vein is a sustainable alternative to PTFE for hemodialysis access surgery and should be accordingly considered for difficult access patients.

Evolution of technique in performance of minimally invasive colectomies.

BACKGROUND: Hand-assisted laparoscopic surgery is commonly used in colorectal surgery and provides benefit in complex cases. OBJECTIVE: This study examined the minimally invasive surgical trends, patient characteristics, and operative variables unique to patients undergoing hand-assisted laparoscopic surgery. DESIGN: This was a retrospective medical chart review. SETTINGS: The study was conducted in a tertiary care medical center. PATIENTS: Patients included in the study were those who underwent pure laparoscopic colectomies, hand-assisted laparoscopic colectomies, and traditional open surgery for elective treatment of diverticular disease, colorectal cancer, IBD, and benign polyp disease. MAIN OUTCOME MEASURES: Primary outcomes included patient characteristics and operative variables unique to patients undergoing hand-assisted laparoscopic surgery and documentation of operative technique trends within an experienced colorectal group. RESULTS: Diverticular disease characteristics specific to hand-assisted laparoscopic surgery included the presence of dense inflammatory adhesions (p < 0.0001), diverticular fistulas (p < 0.0001), and unresolved phlegmon (p = 0.0003). Characteristics specific for colorectal cancer included intraoperative tumor bulk (p < 0.0001) and the inability to achieve appropriate surgical resection margins (p < 0.001). Similarly, variables identified for benign polyp disease included adhesions (p < 0.0001) and the ability to gain adequate exposure (p < 0.0001). Limited use of hand-assisted laparoscopic surgery was observed in patients with IBD. LIMITATIONS: This was a retrospective, observational study from a single center. CONCLUSIONS: Conversion to hand-assisted laparoscopic surgery provides benefit in surgical scenarios where dense inflammatory adhesions, diverticular fistulas, and intra-abdominal postdiverticulitis phlegmon are present. In addition, benefit is observed in patients with colorectal cancer where laparoscopic dissection of bulky tumor proves to be difficult and where the technical ability to obtain margins using pure laparoscopy is compromised. Although our practice has changed to favor pure laparoscopy, hand-assisted laparoscopic surgery continues to play an important role in complex colorectal cases that otherwise would require open surgery (see video, Supplemental Digital Content 1, http://links.lww.com/DCR/A146).