24-hour Recovery Research Articles

A Decalogue on Enhanced Recovery After Breast Augmentation Surgery (ERABAS).

Medical and technical advances have changed the state of postoperative surgical patient care, allowing for better and faster recovery. Since its publication, predictable 24-hour recovery in breast augmentation surgery has been controversial and has generated discussion. In this study, we present a novel, easy, and reproducible protocol for Enhanced Recovery After Breast Augmentation Surgery (ERABAS), along with a summary of the ten points to follow. We conducted a retrospective study of all primary breast augmentation surgeries performed between 2010 and 2020 by a private activity. All surgeries were performed by the same surgeon according to the same protocol, and all implants were obtained from the same company. Data were evaluated using two binary logistic regression models, taking as variables responses to recovery time and postoperative pain and as predictor or explanatory variables to the factors age, smoking, size, and location of the implant. In total, 2906 patients were included in this study. Of these, 2770 patients (95%) immediately returned to normal life within the first 24h, 129 achievednormal life in four days, and only seven needed a week to recover. In these seven patients, the main acute complications were hemorrhage and acute hematoma. The implants were always round; textured implants were used in 88.8% of patients, while smooth implants were used in 11.2%. A subfascial pocket was used in 934 patients, and a dual-plane pocket was performed for 1972 patients. The only factor that showed a significant effect on recovery time was the location of the implant (p < 0.05), with the dual-plane pocket being the intervention associated with a later recovery, specifically a probability of recovery after 24 hour, 2.86 times greater than subfascial. The ERABAS protocol allowed rapid return to daily activities with low complication rates. Further prospective comparative multicenter studies are required to confirm these results. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Abstract 210: Carcinogenic influence of e-cigarette aerosols on breast and lung cancer models

Abstract Background and Purpose: With the rising popularity of E-cigarettes among the youth, there is an urgent need to understand their long-term health implications, particularly the potential for carcinogenesis. Although tobacco smoking is established as a major cancer risk factor, the carcinogenic potential of E-cigarettes remains underexplored. Given that metastatic cancer accounts for most cancer-related deaths in the United States, elucidating the biological impacts of E-cigarette aerosols on cancer progression is critical for developing effective interventions. This study aims to address this critical gap by exploring the effects of E-cigarette aerosols on cellular models pertinent to breast and lung cancer. Methods: Mouse breast epithelial cells (HC11), triple-negative breast cancer cells (4T1), and human lung adenocarcinoma cells (Calu-3) were exposed to E-cigarette aerosol at the air-liquid interface for one hour, followed by a 24-hour recovery period. Results: Our study revealed that E-cigarette aerosols with mint flavor induce epithelial-to-mesenchymal transition (EMT) in both normal mammary epithelial and breast cancer cells. Furthermore, we also observed activation of the TGF pathway and an increased expression of stemness-related markers (OCT4, SOX2, NANOG, KLF4, and c-MYC) in 4T1 cells exposed to mint and menthol-flavored E-cigarette aerosols in both 2D and 3D cell culture environments. Microscopic examination at a 10X magnification level revealed that 4T1 and Calu-3 cells exposed to menthol-flavored E-cigarette aerosols exhibited signs of cellular disassociation and detachment whereas the control cells maintained discoidal aggregate morphology. Conclusion: The data presented here illuminate a potential link between E-cigarette use and carcinogenic processes, challenging the notion of E-cigarettes as a safe smoking alternative. This research is of paramount importance to cancer research as it unveils possible new avenues for tumor progression, emphasizing the necessity for a critical evaluation of E-cigarette products. Citation Format: Rizwana Begum, Shilpa Thota, Naveen Chintala, Biplov Sapkota, Abhishek Pandit, Joseph Francis. Carcinogenic influence of e-cigarette aerosols on breast and lung cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 210.

In Vivo Investigation of the Molluscicidal Effect of Sambong (Blumea balsamifera) on Golden Apple Snail (Pomacea canaliculata)

One of the top 100 worst invasive species in the world is the golden apple snail (Pomacea canaliculata). Golden apple snails damage rice crops in the Philippines annually for $1.2 billion. GAS also presents a major health danger to people by carrying Angiostrongylus cantonensis, Echinostoma ilocanum, and Schistosoma spp. Applying artificial "instant kill" molluscicides is the simplest way to reduce GAS, however, it poses negative impacts on the environment, non-target species, and human health. The study aims to extract phytochemicals from Blumea balsamifera that are effective in killing invasive snails. The extract was obtained through maceration and was then evaporated through open-dish evaporation, it was then allowed to stand for 3 days. Five treatments were made; 2 control groups: the negative control and positive control; 3 experimental groups: 50000 PPM, 150000 PPM, and 300000 PPM concentration of B. balsamifera extract. The treatments were then distributed through water treatment to the five aquariums with labels containing 10 snails each. The snails were observed for 48 hours; a 24-hour exposure period and a 24-hour recovery period. The commercial molluscicide (Niclosamide), the 150000 PPM, and the 300000 PPM concentration of B. balsamifera extract killed all 10 snails. The 50000 PPM concentration killed 3 snails, and 1 moribund which eventually died, and the other 6 were still alive. All snails in negative control were alive. The 150000 PPM and 300000 PPM concentration was found effective according to the LC50 and LC90 test. Thus, the B. balsamifera extract can be used as a molluscicide.

Evaluation of insecticide resistance among Malaysian Aedes albopictus Skuse larvae based on revised diagnostic doses of larvicides.

The susceptibility levels of Malaysian Aedes albopictus larvae sampled from several agricultural, fogging-free residential and dengue prone residential areas against different larvicides were evaluated using revised diagnostic doses derived from the 2xLC99 values of the reference strain. Upon 24-hour recovery period of WHO larval bioassay, incipient resistance was observed among Ae. albopictus larvae from rubber estates against fenitrothion (96.67% mortality) and permethin (97.00% mortality) while Ae. albopictus larvae from rice cultivation areas were moderately resistant to fenthion (94.33% mortality). Aedes albopictus larvae from dengue prone residential areas developed moderate to high resistance against dichlorodiphenyltrichloroethane (DDT), fenitrothion, fenthion, propoxur and permethrin (79.67% - 97.33% mortality). Moderate to high resistance were also demonstrated among all populations of Ae. albopictus larvae against temephos and chlorpyrifos (63.00% - 97.67% mortality). Except for Ae. albopictus larvae from oil palm plantations, all Ae. albopictus larval populations were also highly resistant to bendiocarb (65.67% - 89.67% mortality). Cross resistance between larvicides from similar and different insecticide classes were also revealed in this study. The use of revised diagnostic doses established from the local reference strain could reduce the possibility of underestimation or overestimation of the insecticide susceptibility status of field strain populations.

Learning and achievement characteristics of sheltered homeless population subgroups.

There is little systematic information about intelligence and academic achievement among sheltered homeless adults. This study adds descriptive data on intelligence and academic achievement, examines discrepancies across these concepts, and explores the associations among demographic and psychosocial characteristics in the context of intelligence categories and discrepancies. We studied intelligence, academic achievement, and discrepancies between IQ and academic achievement among 188 individuals experiencing homelessness who were systematically recruited from a large, urban, 24-hour homeless recovery center. Participants completed structured interviews, urine drug testing, the Wechsler Abbreviated Scale of Intelligence, and the Wide Range Achievement Test, 4th edition. Average full-scale intelligence was low average (90) but higher than scores obtained in other studies of homeless populations. Academic achievement was lower than average (82 to 88). Performance/math deficits in the higher intelligence group indicate functional difficulties that could have contributed to homeless risk. The low-normal intelligence and below-average achievement scores are not extreme enough to warrant immediate attention and intervention for most individuals. Systematic screening during entry into homeless services might identify learning strengths and weaknesses, presenting modifiable factors that could be addressed in focused educational/vocational interventions.

Expression and Clinical Significance of circRNA Changes in Stored Erythrocytes During Platelet Transfusion in Acute Lymphoblastic Leukemia.

This study was to store the expression and clinical significance of circRNA changes in red blood cells during platelet transfusion in acute lymphoblastic leukemia (ALL). Sixty patients with ALL who underwent platelet transfusion were enrolled. Post-transfusion symptoms, platelet count (PLT), 24-hour corrected platelet increase index (CCI), and 24-hour platelet recovery rate (PPR) were collected, and their correlation with age, gender, bleeding, infection, splenomegaly, antibiotic use and infusion times were analyzed. High-throughput sequencing was used to detect the expression levels of circRNAs in suspended red blood cells of the blood samples. Then, the circRNA expression profiles were constructed, the differentially expressed circRNAs were screened, and the circRNAs related to platelet transfusion in AML were mined. PLT values of 60 ALL patients after platelet transfusion were significantly increased. Thirty-five patients were effective and 25 were ineffective after platelet transfusion, and the total effective rate was 58.33%. Patients with hemorrhage and splenomegaly, or antibiotic use, or increased blood transfusion frequency will show reduced efficacy of platelet transfusion. A total of 2,358 circRNAs were obtained from all samples, most of which were distributed in 200 - 3,000 nt. circRNAs can be divided into exonic circRNAs (58.74%), sense overlapping circRNAs (21.76%), intronic circRNAs (17.60%), antisense circRNAs (0.93%), and intergenic circRNAs (0.98%). A total of 257 differentially expressed circRNAs were obtained by volcano plot analysis, of which 126 were up-regulated and 131 were down-regulated. Differentially up-regulated and down-regulated circRNAs were mainly enriched in dif-ferent cellular processes. ALL is improved after platelet transfusion. By constructing circRNA expression profiles and screening differentially expressed circRNAs, 257 circRNAs that may be related to ALL platelet transfusion were mined.

Efeitos do treinamento de força em dias consecutivos e não consecutivos nas respostas hormonal, neuromuscular e morfológica em homens treinados recreacionalmente

abstract The purpose of the present study was to investigate the effect of two recovery periods between consecutive and non-consecutive days in strength training sessions on hormonal, neuromuscular and morphological variables in recreationally trained men. Nineteen young men completed the study and were randomly divided into two groups: 24R, 24-hour recovery group (n = nine) and 72R, 72-hour recovery group (n = ten). The strength training program (RT) lasted six weeks with two serial routines, with a weekly frequency of four times. The saliva sample was collected once a week in the morning to determine salivary testosterone. The 1RM, jump against movement and body composition tests were performed in the pre- and post-training periods. As for salivary testosterone, there was no significant effect with respect to time and between groups. Both groups improved maximal strength in terms of intervention time in the barbell bench press and in the leg press 45º, not differing between groups and body composition showed significant interaction in time to body fat percentage ∆% = -14.6 ± 10.0 (24R) and -17.2 ± 10.9 (72R); p = 0.00, fat mass ∆% = -13, 7 ± 9.2 (24R) and -18.2 ± 13.0 (72R); p = 0.00 and fat-free mass ∆% = 3.5 ± 2.7 (24R) and 2.5 ± 2 .8 (72R), p = 0.00. The recovery periods 24 and 72 hours between sessions induced similar responses in the parameters investigated in recreationally strength-trained men.

421.2: One Organ Procurement Organization’s 26-Year Experience With Uncontrolled DCD Donation

Introduction: Uncontrolled DCD donation is an underutilized method of procurement in the U.S., with 44% of all uncontrolled DCD donors to date being procured by one of 57 OPOs. The purpose of this study is to demonstrate that uncontrolled DCD organ donation can lead to the successful retrieval of transplantable organs and to evaluate kidney and liver transplant outcomes for recipients of organs from uncontrolled DCD donors. Methods: This is a retrospective single OPO, multi-center study. As a standard of practice the OPO routinely pursued uncontrolled DCD donors in the setting of hemodynamic instability and/or sudden cardiac arrest. The aggressive pursuit of these types of donors required the OPO to establish the following: an organizational expectation, training, active AOC oversight, a system to rapidly deploy resources, a communication plan with care-giving team members, and 24-hour organ preservation and surgical recovery support. Donor warm ischemic time was determined by the time from patient arrest to cross-clamp with most donors receiving CPR during that interval. Graft survival was determined by the Kaplan-Meier method. WIT, age, kidney PNF and DGF were further evaluated by donor Maastricht category. Results: Between 1996 and 2021, 334 kidneys, 15 livers, 2 pancreata and 1 lung was transplanted from 262 uncontrolled DCD donors. The mean donor age was 33 years (r = 0.5 – 76, sd=15). The median warm ischemic time was 44 minutes (IQR = 22 - 83). Kidney graft survival was 84% at 6 months, 78% at 1 year and 71% at 3 years. Of the 15 livers transplanted, 9 grafts implanted prior to 2010 failed within 3 months, but all 3 of the grafts implanted in 2021 are functioning at 6 months post-transplant. Two of the liver grafts are functioning at 12 years post-transplant and one is functioning at 19 years post-transplant. The lung graft is functioning at 8 years post-transplant.Conclusions: Uncontrolled DCDs provide acceptable kidney graft survival outcomes and represent a pool of organs that should be pursued for transplantation. OPOs should develop protocols to effectively recover organs from uncontrolled DCDs, particularly in light of promising new advancements in organ preservation.

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome.

Post-exertional malaise (PEM) is a hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We monitored the evolution of 1157 plasma metabolites in 60 ME/CFS (45 female, 15 male) and 45 matched healthy control participants (30 female, 15 male) before and after 2 maximal cardiopulmonary exercise test (CPET) challenges separated by 24 hours, with the intent of provoking PEM in patients. Four time points allowed exploration of the metabolic response to maximal energy-producing capacity and the recovery pattern of participants with ME/CFS compared with the healthy control group. Baseline comparison identified several significantly different metabolites, along with an enriched percentage of yet-to-be identified compounds. Additionally, temporal measures demonstrated an increased metabolic disparity between cohorts, including unknown metabolites. The effects of exertion in the ME/CFS cohort predominantly highlighted lipid-related as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions. The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different from the controls. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component of the homeostasis of many organs in the body, including the brain.

Serum Interleukin-6 Level Raise Up In Time With Muscle Soreness at 24 Hours Recovery From Vigorous Exercise: Does It Correlate ?

Background : Muscle soreness or muscle pain occurs after long-term physical activity or after unusual exercise. Some explains it due to pro inflammatory cytokines secreted during and after exercise. Interleukin-6 and tumor necrotic factor alpha were two cytokines believed as promoting factor of muscle soreness. Until now, it was still unclear whether interleukin-6 or tumour necrotic factor alpha that correlate with the soreness found at 24 hours recovery from vigorous exercise. Purpose : This study was aimed to analyse the level of interleukin-6 and tumour necrotic factor alpha by time of 6- and 24-hour recovery from exercise. Method/Material: Correlation study research method with a cross-sectional research design. The subject of this study were twenty voluntary trained, healthy male, aged 20-30 years old with normal body mass index was randomly registered in this study. Subjects was grouped in vigorous exercised group and moderate exercised group as control. The blood was obtained from the subjects at 6 and 24 hours recovery post exercise for interleukin-6 and tumor necrotic factor alpha level measurement. Result : Was shown raised of pain intensity of muscle soreness and interleukin-6 level but not tumor necrotic alpha level. The interleukin-6 level correlated to the pain intensity of muscle soreness at 24 hours post exercise (P<0,05).

Genomic Screening of B cell differentiation by using CRIPSR/Cas9

Abstract The differentiation of naïve B cells to antibody secreting plasma cells plays a crucial role in humoral immunity. This process is regulated by multiple factors including, transcription factors and epigenetic modifiers. Type II, clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems can be used to identify genes that influence a phenotype of interest. Herein, we established this system to identify novel regulators of plasma cell differentiation. To accomplish this, we transduced hematopoietic stem cells derived from mice expressing Cas9 specifically in B cells (Rosa26-Cas9, Cd19-Cre) with lentiviral based gRNAs targeting Ptprc (CD45), Irf8 and Bach2 and transplanted the stem cells into congenically disparate hosts. Hematopoietic stem cells are enriched with lineage depletion kit and then sorted by C-kit and Sca-1, followed by culture for 24 hours and spin-infection with corresponding lentivirus. After another 24-hour recovery, these cells are transferred to radioactively immune system destroyed hosts. Following immune constitution, B cells were isolated and the deletion of CD45, IRF8 and BACH2 was confirmed. Consistent with previous findings, deletion of IRF8 and BACH2 augmented plasma cell formation in ex vivo differentiation assays. Additionally, we used a genome-wide CRISPR gRNA lentiviral library targeting 18,424 genes to screen for factors that influenced B cell differentiation to LPS, IL-2 and IL-5. In conclusion, the CRISPR/Cas9 system allows us to rapidly generate genetic deletions to explore B cell differentiation in vivo and to discover novel factors that regulate plasma cell formation.

Successful Lung Cryoablation for a Bulky Lung Carcinoma

A 49-year-old man was referred for ablation of a 6.3-cm lung tumor (Fig 1). Prior history included Hodgkin disease (1992), tobacco use, right upper lobectomy for lung adenocarcinoma (2013), and chemotherapy for a contralateral recurrence (2015), with a complete response. A recurrence occurred in 2017; he was contraindicated for additional surgery and radiotherapy because of prior radiation and compromised pulmonary function: forced expiratory volume in 1 second (FEV1) = 68% and maximal oxygen uptake (VO2max) = 41%. Lung cryoablation was planned. Using computed tomographic guidance, 7 cryoprobes (IceRoad-Cx, Galil Medical, Yokne'am Illit, Israel) (Figs 2, 3) were successfully placed and activated for 3 freeze-thaw cycles. A 24-hour intensive care unit recovery and chest tube were required due to a pneumothorax and lung consolidation. He was discharged 12 days later. Positron emission tomography-computed tomography after 2 years of follow-up showed a complete metabolic response and the shrinkage of the ablation scar (Fig 4). Figure 2Computed tomography volume rendering reformation demonstrated the 7 cryoprobes coursing through the chest wall into the mass. View Large Image Figure Viewer Download Hi-res image Figure 3Multiplanar reconstruction orthogonal to the long axis of the probes shows their distribution within the tumor in order to create an encompassing ice ball with safety margins. View Large Image Figure Viewer Download Hi-res image Figure 4Axial computed tomography with positron emission tomography fusion obtained 2 years after treatment shows the absence of metabolic activity and the shrinkage of the ablation scar. View Large Image Figure Viewer Download Hi-res image

Dose and Recovery Response of Patellofemoral Cartilage Deformations to Running.

Background:Running is a common recreational activity that provides many health benefits. However, it remains unclear how patellofemoral cartilage is affected by varied running distances and how long it takes the cartilage to recover to its baseline state after exercise.Hypothesis:We hypothesized that patellofemoral cartilage thickness would decrease immediately after exercise and return to its baseline thickness by the following morning in asymptomatic male runners. We further hypothesized that we would observe a significant distance-related dose response, with larger compressive strains (defined here as the mean change in cartilage thickness measured immediately after exercise, divided by the pre-exercise cartilage thickness) observed immediately after 10-mile runs compared with 3-mile runs.Study Design:Descriptive laboratory study.Methods:Eight asymptomatic male participants underwent magnetic resonance imaging of their dominant knee before, immediately after, and 24 hours after running 3 and 10 miles at a self-selected pace (on separate visits).Results:Mean patellar cartilage thicknesses measured before exercise and after the 24-hour recovery period were significantly greater than the thicknesses measured immediately after both the 3- and 10-mile runs (P < .001). This relationship was not observed in trochlear cartilage. Mean patellar cartilage compressive strains were significantly greater after 10-mile runs compared with 3-mile runs (8% vs 5%; P = .01).Conclusion:Patellar cartilage thickness decreased immediately after running and returned to its baseline thickness within 24 hours of running up to 10 miles. Furthermore, patellar cartilage compressive strains were dose-dependent immediately after exercise.Clinical Relevance:These findings provide critical baseline data for understanding patellofemoral cartilage biomechanics in asymptomatic male runners that may be used to optimize exercise protocols and investigations targeting those with running-induced patellofemoral pain.

The Impact of Recovery Time on Performance in Division I Collegiate Beach Volleyball Players.

Holtgeerts, RN, Gann, J, Jung, HC, and Hey, W. The impact of recovery time on performance in Division I collegiate beach volleyball players. J Strength Cond Res 36(3): 667-673, 2022-The sport of beach volleyball has recently grown significantly at the collegiate level, and collegiate beach volleyball players often practice and compete 5 or 6 days per week during the competitive season. This study examined the effects of the amount of recovery time on performance in Division 1 Collegiate beach volleyball players. Ten female NCAA Division 1 beach volleyball players, aged 20.2 ± 1.23 years, participated in the study. Subjects completed 2 trials consisting of 4 sessions of volleyball play (with a 24-hour recovery trial and 48-hour recovery trial). Trials were randomized and counter balanced. Each trial measured counter-movement jump, 5-10-5 agility time, 3 beach volleyball drills, and scores of a beach volleyball match. Perceived recovery, sleep quality, and rating of perceived exertion were also recorded. The significance level set for the study was p ≤ 0.05. Counter-movement jump showed small but significant increases following the 24-hour recovery period (p ≤ 0.05). 5-10-5 agility test showed significant improvement with the 48-hour recovery period (p ≤ 0.05). Perceived Recovery scores demonstrated significant increases in both recovery periods (p ≤ 0.05). Beach volleyball drill and match performance were not affected by the change in recovery time. These results indicate that, although some physical skills are affected by recovery time, beach volleyball performance as a whole is relatively stable over several days. It is normal for NCAA athletes to play back-to-back days and with little recovery time, and these results indicate that this practice does not negatively affect sport performance.

The Role Of Dopaminergic Synapse And D2DR In Movement Control

Exercise fatigue is a common physiological phenomenon in sports. The central nervous system (CNS) has important regulating effect on exercise fatigue. The basal ganglia are involved in motor function regulation through direct and indirect pathways. Striatum is the main input nucleus of basal ganglia and plays an important role in movement control. PURPOSE: Explore the role of dopaminergic synapse and D2 dopamine receptors (D2DR) in movement control by investigating synaptic ultrastructural change of the dorsolateral striatum (DLS) and D2DR antagonist/agonist effect on autonomic activity in exercise-induced fatigue rats. METHODS: Male Wistar rats were randomly divided into either the sham control group (SCG), 1-day fatigue group (1FG), 3-day fatigue group (3FG), 7-day fatigue group (7FG), 24-hour recovery group (24RG) or 48-hour recovery group (48RG). The synaptic ultrastructure was observed by transmission electron microscopy. Further a D2DR antagonist and agonist were used to interfere with the autonomic exercise of rats with Open Field Test. RESULTS: We found that: (1) The proportion of asymmetrical synapse of DLS (SCG: 41±2(%), 7FG: 28±4(%), p<0.05), number of presynaptic vesicles (SCG: 13.35±4.58 (number/μm2), 7FG: 5.92±2.7 (number/μm2), p<0.05), number of synaptic terminal mitochondria (SCG: 0.19±0.18 (number/μm2), 7FG: 0.15±0.1 (number/μm2), p<0.05), and the area of synaptic terminals(SCG: 123925.64±54773.42 (μm2), 7FG: 84447.16±29495.42 (μm2), p<0.05), decreased with the increase of exercise days. (2) The total exercise distance of each group decreased gradually with the increase of exercise intensity (p<0.05). Additional rat’s exhaustion time was also significantly shortened after injection of the D2DR antagonist(before: 147.33±5.63, after: 103±4.14, p<0.01). CONCLUSIONS: The activity of synapses in the dorsolateral striatum of rats decreased with the increase of exercise fatigue. Exercise fatigue reduced the autonomic activity of rats, which was further enhanced by D2DR antagonist intervention. This indicates that the regulatory role of D2DR in motion may be related to synaptic plasticity of dopaminergic in substantia nigra and striatum, suggesting that D2DR can be used as an important target to address exercise fatigue.

Effect of computed tomography perfusion post-processing algorithms on optimal threshold selection for final infarct volume prediction.

In acute ischemic stroke (AIS) patients, eligibility for endovascular intervention is commonly determined through computed tomography perfusion (CTP) analysis by quantifying ischemic tissue using perfusion parameter thresholds. However, thresholds are not uniform across all analysis methods due to dependencies on patient demographics and computational algorithms. This study aimed to investigate optimal perfusion thresholds for quantifying infarct and penumbra volumes using two post-processing CTP algorithms: Vitrea Bayesian and singular value decomposition plus (SVD+). We utilized 107 AIS patients (67 non-intervention patients and 40 successful reperfusion of thrombolysis in cerebral infarction (2b/3) patients). Infarct volumes were predicted for both post-processing algorithms through contralateral hemisphere comparisons using absolute time-to-peak (TTP) and relative regional cerebral blood volume (rCBV) thresholds ranging from +2.8 seconds to +9.3 seconds and -0.23 to -0.56 respectively. Optimal thresholds were determined by minimizing differences between predicted CTP and 24-hour fluid-attenuation inversion recovery magnetic resonance imaging infarct. Optimal thresholds were tested on 60 validation patients (30 intervention and 30 non-intervention) and compared using RAPID CTP software. Among the 67 non-intervention and 40 intervention patients, the following optimal thresholds were determined: intervention Bayesian: TTP = +4.8 seconds, rCBV = -0.29; intervention SVD+: TTP = +5.8 seconds, rCBV = -0.29; non-intervention Bayesian: TTP = +5.3 seconds, rCBV = -0.32; non-intervention SVD+: TTP = +6.3 seconds, rCBV = -0.26. When comparing SVD+ and Bayesian post-processing algorithms, optimal thresholds for TTP were significantly different for intervention and non-intervention patients. rCBV optimal thresholds were equal for intervention patients and significantly different for non-intervention patients. Comparison with commercially utilized software indicated similar performance.

Breast Cancer Cryoablation: Assessment of the Impact of Fundamental Procedural Variables in an In Vitro Human Breast Cancer Model.

Introduction:Breast cancer is the most prominent form of cancer and the second leading cause of death in women behind lung cancer. The primary modes of treatment today include surgical excision (lumpectomy, mastectomy), radiation, chemoablation, anti-HER2/neu therapy, and/or hormone therapy. The severe side effects associated with these therapies suggest a minimally invasive therapy with fewer quality of life issues would be advantageous for treatment of this pervasive disease. Cryoablation has been used in the treatment of other cancers, including prostate, skin, and cervical, for decades and has been shown to be a successful minimally invasive therapeutic option. To this end, the use of cryotherapy for the treatment of breast cancer has increased over the last several years. Although successful, one of the challenges in cryoablation is management of cancer destruction in the periphery of the ice ball as the tissue within this outer margin may not experience ablative temperatures. In breast cancer, this is of concern due to the lobular nature of the tumors. As such, in this study, we investigated the level of cell death at various temperatures associated with the margin of a cryogenic lesion as well as the impact of repetitive freezing and thawing methods on overall efficacy.Methods:Human breast cancer cells, MCF-7, were exposed to temperatures of −5°C, −10°C, −15°C, −20°C, or −25°C for 5-minute freeze intervals in a single or repeat freeze-thaw cycle. Samples were thawed with either passive or active warming for 5 or 10 minutes. Samples were assessed at 1, 2, and 3 days post-freeze to assess cell survival and recovery. In addition, the modes of cell death associated with freezing were assessed over the initial 24-hour post-thaw recovery period.Results:Exposure of MCF-7 cells to −5°C and −10°C resulted in minimal cell death regardless of the freeze/thaw conditions. Freezing to a temperature of −25°C resulted in complete cell death 1 day post-thaw with no cell recovery in all freeze/thaw scenarios evaluated. Exposure to a single freeze event resulted in a gradual increase in cell death at −15°C and −20°C. Application of a repeat freeze-thaw cycle (dual 5-minute freeze) resulted in an increase in cell death with complete destruction at −20°C and near complete death at −15°C (day 1 survival: single −15°C freeze/thaw = 20%; repeated −15°C freeze/thaw = 4%). Analysis of thaw interval time (5 vs 10 minute) demonstrated that the shorter 5-minute thaw interval between freezes resulted in increased cell destruction. Furthermore, investigation of thaw rate (active vs passive thawing) demonstrated that active thawing resulted in increased cell survival thereby less effective ablation compared with passive thawing (eg, −15°C 5/10/5 procedure survival, passive thaw: 4% vs active thaw: 29%).Conclusions:In summary, these in vitro findings suggest that freezing to temperatures of 25°C results in a high degree of breast cancer cell destruction. Furthermore, the data demonstrate that the application of a repeat freeze procedure with a passive 5-minute or 10-minute thaw interval between freeze cycles increases the minimal lethal temperature to the −15°C to −20°C range. The data also demonstrate that the use of an active thawing procedure between freezes reduces ablation efficacy at temperatures associated with the iceball periphery. These findings may be important to improving future clinical applications of cryoablation for the treatment of breast cancer.

Differential Metabolomics and Lipidomics of Hypoxic/Hypocapnic Long-Term Stored Red Cells Associate with Improved 24-Hour Recovery after Transfusion

Storage lesion accumulates during refrigerated storage of RBC, and development of novel methods and/or additive solutions are needed for more efficacious RBC with reduced burden of harmful byproducts. Autologous 24-hr post-transfusion recovery (PTR24) at the end of storage measured in healthy volunteers is the only in vivo practical metrics to evaluate consequences of RBC storage. PTR24 studies are logistically and economically demanding and as such, the identification of easier biomarkers of stored blood quality can expedite the development and testing of novel storage strategies. We performed a prospective, randomized, dual‐arm, crossover, two‐center radio labeled 24-hr PTR24 study was conducted as a part of the pivotal study to evaluate Hemanext® hypoxic/hypocapnic processing system for meeting standard FDA acceptability criteria for RBC storage. Subjects donated CP2D whole blood (500 ± 50 mL). The Test arm consisted of whole blood‐derived RBC, leukoreduced, and processed to achieve hypoxic/hypocapnic state in AS-3 additive within 12 hours of phlebotomy then stored for 42 days at 1‐6°C under hypoxic conditions (Test). Unprocessed normal atmosphere stored units (Control) were stored within 8 hours under conventional storage condition. PTR24 data was obtained from 19 test subjects and 21 control subjects (14 paired) by infusion of 51‐Cr/99‐Tc(m) radiolabeled RBCs*. At day 0, 21 and 42, in vitro metrics, including conventional quality parameters (%hemolysis, ATP, 2,3-DPG, morphology, microparticles and deformability), as well as a large panel of metabolites and lipids were analyzed for correlations with PTR24. Bioactive lipids were quantified by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring (LC-MS/MS-MRM). Pearson's correlation coefficients for PTR24 and analytes were examined; correlation pattern differed significantly between normal air Control and hypoxic Test RBCs and thus analyzed separately. Among the conventional RBC quality metrics, ATP as well as ability to rejuvenate ATP and 2,3-DPG at end of storage correlated with PTR24. RBC deformability correlated only with Control, while reduced oxidative damage in Test removed its dependency. Test showed stronger correlations with ATP and other metabolic parameters. 302 metabolites and lipids were analyzed by qualitative metabolomics workflow, and significant correlations were observed with |R| ≥ 0.5 for 37 compounds in normal air stored RBCs (15 with p ≤ 0.05), and 41 compounds in hypoxic RBCs (19 with p ≤ 0.05). The top 5 correlating and inversely correlating compounds for each condition are reported along with p-values in Table 1. For RBC stored in normal air, strong correlations were primarily seen with membrane lipids and associated fatty acids, amino acids, and the Pentose Phosphate Pathway intermediates. Hypoxic storage PTR24 values primarily correlated with alternative membrane components, amino acids, and Pentose Phosphate Pathway intermediates (Table 2). Among 67 bio-reactive lipids analyzed quantitatively, negative correlations of oxylipins (9- or 13-HODEs, 5-, 8-, 11-, 12-HETEs) to PTR24 were observed under normal conditions, but not under hypoxic condition (Table 3). In summary, RBC deformability correlated only with PTR24 of normal air stored RBC, while reduced oxidative damage in hypoxic/hypocapnic conditions removed this dependency. Although normal air and hypoxic stored RBCs show differing metabolite correlates with PTR24, significant associations tend to occur within similar overall pathways. Comparing the PTR24-metabolite correlations between normal air and hypoxic/hypocapnic RBC storage reveals that intermediates of oxidative stress management and membrane homeostasis are potential predictors of post-transfusion recovery. Detailed analysis of lipids supports that hypoxic/hypocapnic storage may reduce membrane lipid degradation and generates the hypothesis that the metabolism of bioactive lipids under hypoxia/hypocapnia may be different from the one found in RBC stored under normal air storage conditions. * Radio-labeling for 14 subjects occurred without prior RDRC approval; one site did not meet GMP standards. Disclosures Yoshida: New Health Sciences Inc.: Employment, Equity Ownership. D'Alessandro:Hemanext, Inc.: Membership on an entity's Board of Directors or advisory committees; Omix Technologies, Inc.: Other: Founder. Nemkov:Omix Technologies, Inc.: Equity Ownership, Other: Founder. Dioguardi:Hemanext: Employment. Iselin:Hemanext: Employment. Dunham:Hemanext: Employment. Cancelas:Hemanext: Consultancy, Research Funding; Fresenius-Kabi: Research Funding; Cerus Co.: Research Funding; TerumoBCT: Consultancy, Research Funding; Macopharma Inc: Research Funding; Cytosorbents: Research Funding; Cellphire: Research Funding; Velico: Consultancy, Research Funding.

Long-Term Hypoxic/Hypocapnic Storage of Red Blood Cells Results in Amelioration of Lesion Hallmarks and Increased In Vivorecovery at 24 Hours Post-Transfusion

Oxidative damage, dysmetabolism and decreased levels of 2, 3-diphosphoglycerate (2,3-DPG) affect red blood cell (RBC) survival and the affinity of Hemoglobin for oxygen are relevant hallmarks of RBC storage lesion, especially in specific clinical contexts. We hypothesized that oxygen and carbon dioxide reduction followed by hypoxic/hypocapnic storage would result in amelioration of RBC lesion assessed at the end of their shelf-life and at the shelf-life mode (21 days).To determine the relevance of hypoxic/hypocapnic storage in humans, a pivotal, prospective, randomized, two‐arm, crossover, three‐center trial was conducted to evaluate [Hemanext®] hypoxic/hypocapnic processing system and was used to assess whether this process and storage method met standard FDA acceptability criteria for long-term RBC storage. The Test arm consisted of whole blood (WB)‐derived, leukoreduced RBC in AS-3 additive processed at room temperature with the Hemanext system for 3 hours to achieve hypoxic/hypocapnic state within 12 hours of phlebotomy which was maintained hypoxic during storage for up to 43 days at 1‐6°C (Test).Unprocessed units (Control) were stored within 8 hours under conventional storage conditions. Subjects (N=100) donated CP2D WB (500 ± 50 mL) and a minimum of 93 pairs of RBC units per arm were analyzed for in vitroquality parameters. For in vivo analysis at end of storage, RBCs from 19 test subjects and 21 control subjects (14 paired) from two sites were radiolabeled with 51‐Cr/99‐Tc(m), autologously transfused, and analyzed for 24-hour recovery. Differences between the Test and Control groups were analyzed using the paired t-test (Wilcoxon test where necessary). Paired analyses of 24-hour in vivorecoveries on day 43 was 89.3±4.5% and 84.8±6.2% for the test and control, respectively; p&lt;0.01). Significantly higher levels of 2,3-DPG and adenosine 5'-triphosphate (ATP) were maintained for the Test group by days 21 and 42/43 of storage (Table 1). Percentage of hemolysis was similar in both groups. In summary, these data demonstrate that RBCs preserved in a user-friendly, self-contained hypoxic storage system are superior than the conventionally stored RBCs and may provide more viable RBCs for transfusion at 6 weeks of storage. Disclaimer: The51‐Cr/99‐Tc(m)labeling at one of the three sites occurred without prior RDRC approval and did not meet GMP standards. Disclosures Cancelas: Fresenius-Kabi: Research Funding; Cerus Co.: Research Funding; TerumoBCT: Consultancy, Research Funding; Hemanext: Consultancy, Research Funding; Macopharma Inc: Research Funding; Cytosorbents: Research Funding; Cellphire: Research Funding; Velico: Consultancy, Research Funding. Yoshida:New Health Sciences Inc.: Employment, Equity Ownership. Dioguardi:Hemanext: Employment. Iselin:Hemanext: Employment. Dunham:Hemanext: Employment.

Donor Iron Deficiency Study (DIDS): protocol of a study to test whether iron deficiency in blood donors affects red blood cell recovery after transfusion.

Despite fulfilling all requirements for blood donation, a large proportion of regular blood donors are iron deficient. Red blood cells (RBC) from iron-deficient donors may be particularly susceptible to damage induced by standard refrigerated storage. Herein, we present a study protocol for testing whether correcting iron deficiency in donors with iron-deficient erythropoiesis will improve the quality of their refrigerator-stored RBC. This is a randomised, controlled, double-blind clinical trial. Sixty healthy regular donors who meet donation standards, while exhibiting iron-deficient erythropoiesis by laboratory testing criteria, will donate a single standard RBC unit that will be leucoreduced and stored in a refrigerator under standard conditions for 40-42 days. A 51Cr-radiolabelled 24-hour RBC recovery study will be performed and then these donors will be randomised to receive, in a double-blinded fashion, either intravenous saline, as a control, or low-molecular weight iron dextran (1 g), to provide total iron repletion. Four to six months later, they will donate a second RBC unit, which will be similarly stored, and autologous 51Cr-labelled 24-hour post-transfusion RBC recovery will again be determined. The primary endpoint will be the change in 24-hour post-transfusion recovery from the first to the second donation. The primary outcome will be the group mean difference in the primary endpoints between the group receiving intravenous saline and the group receiving intravenous iron dextran. Secondary outcomes will be quality of life, fatigue, and emotional health, assessed by surveys. This study will provide definitive evidence as to whether donor iron deficiency affects the quality of the blood supply and will assess the severity of symptoms affecting iron-deficient blood donors.