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Background: Gastroesophageal reflux disease is a prevalent condition with significant clinical variability, complicating its evaluation and treatment. The gastroesophageal flap valve is a fundamental evaluation method, but have shown limitations in specificity and reliance on subjective endoscopists’ experience. Recent insights suggest that gastroesophageal junction laxity may offer an objective and quantifiable measurement for the presence of gastroesophageal reflux disease. Methods: This retrospective study analyzed data from 401 patients who underwent comprehensive evaluations, including a symptom questionnaire, endoscopy, pH-impedance monitoring, high-resolution manometry, and treatment directions, between January 1, 2022 and October 31, 2023. Gastroesophageal junction laxity was assessed using a modified approach based on endoscopic image analysis, with the diameter of endoscope as reference to estimate the long diameter of the laxity ring. The independent association of gastroesophageal junction laxity with pathologic acid exposure, esophagitis, and hiatal hernia were assessed by adjusting with age and sex. Results: The mean age was 44.5 ± 5.5 years old, and 49.9% (200/401) were male. The most common symptoms (≥ 1 point) were acid regurgitation (333/401, 83.0%), heartburn (315/401, 78.6%), belching (278/401, 69.3%), bloating (241/401, 60.1%), and globus sensation (241/401, 60.1%). The gastroesophageal junction laxity was significantly associated with pathologic acid exposure, esophagitis, hiatal hernia, and lower esophageal sphincter resting pressure. Notably, with the increase in gastroesophageal junction laxity, the rates of pathologic acid exposure, esophagitis, and hiatal hernia increased gradually, the lower esophageal sphincter resting pressure decreased gradually. The gastroesophageal junction laxity was independent associated with pathologic acid exposure (OR = 2.33, 95%CI 1.77–3.07, p< 0.001), esophagitis (OR = 2.10, 95%CI 1.62–2.73, p< 0.001), and hiatal hernia (high-resolution manometry: OR = 3.39, 95%CI: 2.46–4.67, p< 0.001) (endoscopy: OR = 21.65, 95%CI 11.70–40.06, p< 0.001). Conclusion: The gastroesophageal junction laxity was significantly associated with the indicators of pathophysiology in gastroesophageal reflux disease.

Young adult (YA) aged cancer patients have unique psychosocial needs with studies indicating more symptoms and emotional distress compared to older patients. Our study aimed to compare clinical characteristics and symptom distress between YAs and older adults. We retrospectively studied 896 randomly selected patients across 3 age groups: 18–39 YAs (n= 297), 40–64 (n= 300), and 65 and older (n= 299). We compared medical, psychosocial history, Morphine Equivalent Daily Dose (MEDD), Edmonton Symptom Assessment Scale (ESAS) scores, and Eastern Cooperative Oncology Group (ECOG) scores at the time of initial inpatient consultation with supportive care. YAs were more frequently female and white, with higher ECOG scores, had more self-reported psychiatric history and worse ESAS sleep scores compared to the other age cohort groups. YAs had higher pain expression than those of 65 years and older. YAs were more likely to have children younger than 18 years old, which was associated with worse pain, sleep, and financial distress. In general, YAs did not report higher symptoms distress, with the exception of insomnia and self-reported psychiatric history. Importantly, YAs with children was associated with higher ratings of pain, sleep difficulties, and financial distress. Overall, results suggest YAs may benefit from specialized services to address their unique psychosocial needs.

Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18), however, the process of inflammation cascades has not been fully illustrated. The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation. With bioinformatics analysis, galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation. The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain. In the heart of mice treated with β-AR agonist isoproterenol (ISO, 5 mg kg−1), galectin-3 expression was upregulated markedly later than IL-18 activation, and Nlrp3−/−and Il18−/−mice did not show ISO-induced galectin-3 upregulation. It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment. Moreover, galectin-3 deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase. Treatment with a galectin-3 inhibitor, but not a β-blocker, one day after ISO treatment effectively attenuated cardiac inflammation and injury. In conclusion, galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation, a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.

ABSTRACTHypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. This study aims to investigate the mechanism of sevoflurane (SF) post-treatment in alleviating HIE in rats. The HIE rat model and oxygen-glucose deprivation (OGD) cell model were established, and adeno-associated virus (AAV)-histone-lysine N-methyltransferase EHMT2 (G9a) was transfected after SF treatment. The learning and memory ability and the levels of nerve growth factor (NGF)/brain-derived neurotrophic factor (BDNF) were evaluated and determined. The levels of G9a/histone H3 lysine 9 dimethylation (H3K9me2) and the enrichment level of H3K9me2 in the promoter region of BDNF gene were analyzed. After SF post-treatment, the neurons in cerebral cortex, the learning and memory skills and the contents of NGF/BDNF were increased, while the apoptosis and G9a/H3K9me2 levels were reduced. After overexpression of G9a in vitro/vivo, the enrichment levels of H3K9me2 in the promoter region of BDNF were increased, the levels of BDNF were decreased, the neurons were damaged and the learning and memory abilities of HIE rats were impaired. The conclusion is that SF post-treatment can promote the expression of BDNF by inhibiting H3K9me2 on the BDNF gene promoter and inhibiting G9a, thus alleviating HIE in rats.

2,2-Difluoroethanol (DFE) is an important aliphatic fluorine-containing chemical intermediate. During its preparation, an azeotropic mixture of DFE and water is formed. To recover DFE from its aqueous solution, liquid–liquid extraction was applied in this work with isopropyl acetate (IPAc) and ethyl acetate (EtAc) as the extractants. The liquid–liquid equilibrium (LLE) experimental data for these ternary mixtures (EtAc/IPAc + DFE + water) was determined at 298.15 and 308.15 K under 101.3 kPa. To access the extraction performance of extractants EtAc and IPAc, the selectivity (S) and distribution coefficient (D) were calculated from the measured data. The results showed that the Sand Dvalues of IPAc were higher than those of EtAc, implying that IPAc is a suitable extractant. The Othmer–Tobias, Bachman, and Hand methods were applied to examine the reliability of the LLE experimental values. The UNIQUAC and NRTL models were adopted to fit the measured LLE data, and the calculated values of the root-mean-square deviation for the two models were less than 0.003.

IMPORTANCE: One of the main aims of research on nonmedical opioid use (NMOU) is to reduce the frequency of NMOU behaviors through interventions such as universal screening, reduced opioid exposure, and more intense follow-up of patients with elevated risk. The absence of data on the frequency of NMOU behavior is the major barrier to conducting research on NMOU. OBJECTIVE: To determine the overall frequency of and the independent predictors for NMOU behavior. DESIGN, SETTING, AND PARTICIPANTS: In this prognostic study, 3615 patients with cancer were referred to the supportive care center at MD Anderson Cancer Center from March 18, 2016, to June 6, 2018. Patients were eligible for inclusion if they had cancer and were taking opioids for cancer pain for at least 1 week. Patients were excluded if they had no follow-up within 3 months of initial consultation, did not complete the appropriate questionnaire, or did not have scheduled opioid treatments. After exclusion, a total of 1554 consecutive patients were assessed for NMOU behavior using established diagnostic criteria. All patients were assessed using the Edmonton Symptom Assessment Scale, the Screener and Opioid Assessment for Patients with Pain (SOAPP), and the Cut Down, Annoyed, Guilty, Eye Opener–Adapted to Include Drugs (CAGE-AID) survey. Data were analyzed from January 6 to September 25, 2020. RESULTS: A total of 1554 patients (median [interquartile range (IQR)] age, 61 [IQR, 52-69] years; 816 women [52.5%]; 1124 White patients [72.3%]) were evaluable for the study, and 299 patients (19.2%) had 1 or more NMOU behaviors. The median (IQR) number of NMOU behaviors per patient was 1 (IQR, 1-3). A total of 576 of 745 NMOU behaviors (77%) occurred by the first 2 follow-up visits. The most frequent NMOU behavior was unscheduled clinic visits for inappropriate refills (218 of 745 [29%]). Eighty-eight of 299 patients (29.4%) scored 7 or higher on SOAPP, and 48 (16.6%) scored at least 2 out of 4 points on the CAGE-AID survey. Results from the multivariate model suggest that marital status (single, hazard ratio [HR], 1.58; 95% CI, 1.15-2.18; P = .005; divorced, HR, 1.43; 95% CI, 1.01-2.03; P = .04), SOAPP score (positive vs negative, HR, 1.35; 95% CI, 1.04-1.74; P = .02), morphine equivalent daily dose (MEDD) (HR, 1.003; 95% CI, 1.002-1.004; P < .001), and Edmonton Symptom Assessment Scale pain level (HR, 1.11; 95% CI, 1.06-1.16; P < .001) were independently associated with the presence of NMOU behavior. In recursive partition analysis, single marital status, MEDD greater than 50 mg, and SOAPP scores greater than 7 were associated with a higher risk (56%) for the presence of NMOU behavior. CONCLUSIONS AND RELEVANCE: This prognostic study of patients with cancer taking opioids for cancer pain found that 19% of patients developed NMOU behavior within a median duration of 8 weeks after initial supportive care clinic consultation. Marital status (single or divorced), SOAPP score greater than 7, higher levels of pain severity, and MEDD level were independently associated with NMOU behavior. This information will assist clinicians and investigators designing clinical and research programs in this important field.

Background:Subtypes of pediatric oncology patients and childhood cancer survivors who are overweight or obese have worse prognosis than their healthy-weighted peers. Several studies have examined weight status in either pediatric patients or survivors with acute leukemia, but few have compared these data across various diagnoses.Objectives:We examined BMI from oncology diagnosis or presentation, through treatment, and into survivorship across the most common cancer types seen in pediatric oncology.Methods:Patients were categorized into three oncologic diagnoses: leukemia and lymphoma (n= 69), neural tumors (n= 80), and non-neural solid tumors (n= 80) at yearly intervals over the course of 11 years. To allow for comparisons across age groups, BMI percentiles were calculated with <5th percentile classified as underweight (n= 11), the 5th–84th percentile classified as a healthy weight (n= 129), and above the 85th percentile classified as overweight and obese (n= 87).Results:At presentation, 45.6% of leukemia and lymphoma patients were overweight or obese, and 44.3% of neural tumor patients were overweight or obese. These high obesity rates persisted into survivorship. Compared to the non-neural tumor group, the leukemia and lymphoma group had a significant increase in BMI percentile over time, while the neural tumor group did not.Conclusions:Pediatric patients with leukemia, lymphoma, and neural tumors and who are overweight or obese at presentation continue this trend into survivorship, indicating a need for management of overweight and obesity through lifestyle interventions concurrent with therapy.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine. It is elevated early in the blood of acute myocardial infarction patients. However, it is unclear whether and how MIF is released. This study investigated the cellular source and mechanism of MIF release from hearts. An ischemia-mimic treatment induced the secretion of MIF from neonatal rat cardiomyocytes but not from fibroblasts. The treatment did not cause significant leakage of lactate dehydrogenase, suggesting that ischemia induced the MIF secretion without causing severe cell damage. Plasma samples from patients with acute chest pain at the emergency department were collected for the detection of MIF. MIF levels in patients with acute coronary syndrome (ACS) increased early, when cardiac injury markers were not yet elevated, suggesting that ischemia can induce MIF secretion before the occurrence of severe myocardial damage. Serum-starvation caused MIF secretion from rat cardiomyocytes and Langendorff-perfused rat hearts. The secretion was suppressed by the inhibition of autophagy by inhibitors or by silencing of Atg5. In conclusion, serum-starvation induces the secretion of MIF from cardiomyocytes via autophagy dependent pathway. Clarifying the mechanism of MIF secretion will be helpful for its application in the early diagnosis and treatment of ACS.

IMPORTANCE: The recent parenteral opioid shortage (POS) has potential implications for cancer-related pain management in hospitalized patients. OBJECTIVE: This study compared changes in opioid prescriptions and clinically improved pain (CIP) among patients treated by an inpatient palliative care (PC) team before and after our institution first reported the POS. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of 386 eligible patients with cancer treated at a comprehensive cancer center 1 month before and after the announcement of the POS. We reviewed data from electronic health records, including patient demographics, opioid type, route of administration, and dose. Board-certified palliative care specialists assessed CIP at follow-up day 1. EXPOSURES: The announcement of the POS by the institution’s pharmacy and therapeutics committee on February 8, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome was to measure the change in opioid prescription patterns of physicians, and the secondary outcome was to measure the proportion of patients who achieved CIP before and after announcement of the POS. RESULTS: Of 386 eligible patients, 196 were men (51%), 270 were white (70%), and the median age was 58 years (interquartile range, 46-67 years). Parenteral opioids were prescribed less frequently by the referring oncology teams after the POS (56 of 314 [18%]) vs before the POS (109 of 311 [35%]) (P &lt; .001). The PC team also prescribed fewer parenteral opioids after the POS (96 of 336 [29%]) vs before the POS (159 of 338 [47%]) (P &lt; .001). After the POS (vs before the POS), significantly fewer patients achieved CIP on follow-up day 1 (119 [62%] vs 144 [75%] of 193; P = .01). Multivariate analysis showed that before the POS, patients had an 89% higher chance of achieving CIP on follow-up day 1 (odds ratio, 1.89; 95% CI, 1.22-2.94; P = .005). CONCLUSIONS AND RELEVANCE: There was a significant change in opioid prescription patterns associated with the POS. Furthermore, after the POS, fewer patients achieved CIP. These factors have potential implications for patient satisfaction and hospital length of stay.

N-Alkylated chitosan (NACS) may improve the blood clotting efficiency of chitosan (CS). To study its blood coagulation capability, a series of NACSs with various carbon chain lengths and degrees of substitution (DS) of alkyl groups were synthesized and characterized by FTIR, NMR, elemental analysis, and X-ray diffraction (XRD). The corresponding NACS nanofiber membranes (NACS-NM) were subsequently fabricated by electronic spinning technique. SEM, XRD, DSC, surface area, porosity, contact angle, blood absorption, and mechanical properties were used to characterize the CS-NM/NACS-NM. Moreover, cytotoxicity, coagulation, activated partial thromboplastin time, plasma prothrombin time, thrombin time, and platelet aggregation tests were performed to evaluate the biocompatibility and blood coagulation properties of NACS-NM. The results showed that NACS-NM was not cytotoxic. NACS-NM with DS of 19.25% for N-hexane CS (CS6b), 17.87% for N-dodecane CS (CS12b), and 8.97% for N-octadecane CS (CS18a) exhibited good blood clotting performance. Moreover, NACS-NMs favored the activation of coagulation factors and platelets. In addition, intracellular Ca2+was not related to platelet activation. The above results suggested that NACS-NM would be an effective hemostatic agent.

We report parallel-trained deep neural networks for automated endoscopic OCT image segmentation feasible even with a limited training data set. These U-Net-based deep neural networks were trained using a modified dice loss function and manual segmentations of ultrahigh-resolution cross-sectional images collected by an 800 nm OCT endoscopic system. The method was tested on in vivo guinea pig esophagus images. Results showed its robust layer segmentation capability with a boundary error of 1.4 µm insensitive to lay topology disorders. To further illustrate its clinical potential, the method was applied to differentiating in vivo OCT esophagus images from an eosinophilic esophagitis (EOE) model and its control group, and the results clearly demonstrated quantitative changes in the top esophageal layers’ thickness in the EOE model.

Objective This study was performed to evaluate the effect of a homemade autotransfusion pressure-control system on the regulation of negative pressure and to clarify the influence of different negative pressures on the recovered erythrocytes.Methods Fifty patients were randomly divided into five groups, and five different suction-generated negative pressures were applied. Before suction, 6 mL of blood was collected from the surgical field; after suction, 6 mL of blood was collected from the blood storage tank. The hemoglobin, hematocrit, mean corpuscular volume, newly generated standardized plasma free hemoglobin, and change in the hemolysis rate of erythrocytes before and after suction were compared. Additionally, the erythrocyte morphology was observed.Results The hemoglobin and hematocrit were significantly different before and after suction in all five groups. As the suction pressure increased, gradual increases were noted in the number of abnormal erythrocytes in the field of view, the newly generated standardized plasma free hemoglobin, and the change in the hemolysis rate.Conclusions The destruction rate of erythrocytes increased as the suction-generated negative pressure increased. When using a pressure-control system, a negative pressure of <200 mmHg should be applied to reduce the damage to the autotransfused blood.

In this study, we report the design and fabrication of a novel biocompatible sponge with excellent antibacterial property, making it a promising material for wound dressings. The sponge is formed by grafting amoxicillin onto regenerated bacterial cellulose (RBC). It was observed that the grafted RBC could enhance the antibacterial activity against fungus, Gram-negative, and Gram-positive bacteria. The morphology of strains treated with the grafted RBC and fluorescent stain results further demonstrated the antibacterial ability of the fabricated sponge. Moreover, a cytocompatibility test evaluated in vitro and in vivo illustrates the nontoxicity of the prepared sponge. More importantly, the wound infection model reveals that this sponge can accelerate the wound healing in vivo. This work indicates the novel sponge has the huge potential in wound dressing application for clinical use.

Stimulation of G protein-coupled receptors (GPCRs) can lead to the transactivation of the epidermal growth factor receptors (EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach. We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor (β2-AR) by isoproterenol (ISO). We further proved that β2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.

Hypoxia-inducible factor-1 (HIF-1), a transcription factor composed of HIF-1α and HIF-1β protein subunits, has been implicated in cellular protection and cell death in cerebral ischemia. The extent to which HIF-1 plays a role in brain pathology during intracerebral hemorrhage (ICH) is unknown. This study determined whether HIF-1α is upregulated at different time points in a rat model of ICH and the role of thrombin and red blood cell lysis in upregulation. Recently, thrombin has been implicated as a nonhypoxic regulator of HIF-1α in cultured smooth-muscle cells. Male Sprague-Dawley rats received intracerebral infusions of saline, autologous whole blood, blood plus hirudin, thrombin, thrombin plus hirudin, or lysed erythrocytes. Rats were killed at different time points for Western blot analysis, immunohistochemistry, immunofluorescent double staining, and reverse transcription polymerase chain reaction measurements of HIF-1α. HIF-1α protein levels increased without changing HIF-1α messenger RNA levels after intracerebral infusions of blood, thrombin, and lysed erythrocytes. HIF-1α positive cells, which proved to be neurons, were found in the brain after ICH. Hirudin, a specific thrombin inhibitor, reduced HIF-1α upregulation in response to both thrombin and blood. This study demonstrates that perihematomal HIF-1α protein is upregulated after ICH. This phenomenon is an early response of brain parenchyma to the clot. Thrombin and erythrocyte lysate are involved in HIF-1α upregulation through reducing HIF-1α degradation.

The authors previously found that pretreatment with a low dose of thrombin attenuates the brain edema induced by a large dose of thrombin or an intracerebral hemorrhage, and reduces infarct volume after focal cerebral ischemia (i.e., thrombin preconditioning). This study investigated whether thrombin preconditioning is caused by activation of the thrombin receptor, also called protease-activated receptor. In the in vivostudies, thrombin-induced brain tolerance was eliminated by RPPGF (Arg-Pro-Pro-Gly-Phe), a thrombin-receptor antagonist. Pretreatment with a thrombin-receptor agonist reduced the amount of edema induced by a large dose of thrombin infused into the ipsilateral basal ganglia 7 days later (81.3 ± 0.7% vs. 82.6 ± 0.8% in the control, P< 0.05). In the in vitrostudy, low doses of thrombin (1 or 2 U/mL) did not induce cell death. However, doses greater than 5 U/mL resulted in dose-dependent lactate dehydrogenase release (P< 0.01). Thrombin and thrombin receptor-activating peptide preconditioning reduced lactate dehydrogenase release induced by a high dose of thrombin (10 and 20 U/mL), whereas RPPGF blocked the effect of thrombin preconditioning in vitro.Western blots indicated that p44/42 mitogen-activated protein kinases were activated after thrombin preconditioning. Finally, inhibition of p44/42 mitogen-activated protein kinases activation by PD98059 abolished the thrombin-preconditioning effect. Results indicate that thrombin-induced brain tolerance is in part achieved through activation of the thrombin receptor. Activation of the thrombin receptor in the brain may be neuroprotective. The protective effect of thrombin preconditioning is achieved through the p44/42 mitogen-activated protein kinase signal-transduction pathway.

Serine proteases, such as thrombin and tissue-type plasminogen activator, play an important role in brain injury after intracerebral hemorrhage and other neurologic disorders. Plasminogen activator inhibitor-1 is one of the serine protease inhibitors, or serpins. The balance between serine proteases and serpins may affect the outcome of intracerebral hemorrhage. The purpose of this study was to determine whether plasminogen activator inhibitor-1 and tissue-type plasminogen activator are upregulated after intracerebral hemorrhage and the role that thrombin plays in that induction. Plasminogen activator inhibitor-1 protein levels were upregulated after intracerebral hemorrhage. Brain plasminogen activator inhibitor-1 content also increased after thrombin infusion in a dose-dependent manner. Hirudin, a specific thrombin inhibitor, blocked the upregulation of plasminogen activator inhibitor-1 after intracerebral hemorrhage. Time courses showed that plasminogen activator inhibitor-1 levels around the hematoma peaked at the first day. Plasminogen activator inhibitor-1–positive cells were detected in the perihematomal area and the ipsilateral basal ganglia after thrombin infusion, but not in the contralateral hemisphere. Plasminogen activator inhibitor-1 messenger RNA levels were increased at 24 hours after intracerebral hemorrhage and after thrombin infusion. However, tissue-type plasminogen activator protein levels were the same in the control, whole-blood, and thrombin-infusion groups. In conclusion, intracerebral hemorrhage and thrombin infusion stimulate plasminogen activator inhibitor-1 but not tissue-type plasminogen activator production in the brain. The upregulation of plasminogen activator inhibitor-1 may be neuroprotective by limiting thrombin or other serine protease-induced toxicity.

Intracerebral infusion of lysed erythrocytes causes brain edema without inducing ischemic cerebral blood flow. Reports have indicated that oxidative damage contributes to secondary brain injury in stroke. In the present study, we investigated whether erythrocyte lysis after intracerebral hemorrhage (ICH) might result in oxidative brain damage. This study had four parts. Male Sprague-Dawley rats received an infusion of autologous lysed erythrocytes into the right striatum. Control rats only had a needle insertion. Neurological deficits, brain water and ion contents were determined in the first part. In the second part, hemoxygenase-1 (HO-1), manganese superoxide dismutase (Mn-SOD), copper/zinc SOD (CuZn-SOD) and protein carbonyl levels were determined by Western blot analysis. In the third part, immunohistochemistry was performed for HO-1. DNA damage was examined using DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) in the fourth part. Infusion of lysed RBCs induced marked edema in the ipsilateral striatum and profound neurological deficits. Western blot analysis and immunohistochemistry indicated that HO-1 was upregulated 24 h after infusion of lysed red blood cells. Both Mn-SOD and CuZn-SOD contents decreased, protein carbonyl levels increased in the ipsilateral striatum, and there was the appearance of PANT- and TUNEL-positive cells suggesting oxidative mechanisms in the erythrocyte-induced brain injury. In conclusion, oxidative stress caused by components of the lysed erythrocytes contributes to the brain injury after ICH.

Leptomeningeal metastasis (LM) creates symptoms related to both the disease within the nervous system and treatment toxicities. Biologic processes, such as inflammation and behavioral processes, such as the meaning ascribed to illness (Meaning of Illness: MoI), can impact physical and psychosocial symptoms. The aim of this study was to understand the relationships among MoI, physical and psychosocial symptoms, and inflammation in patients with LM.

Alousi: Therakos, Inc: Research Funding.

Introduction- Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment for patients with myelofibrosis (MF). MF is stratified into various risk groups based on Dynamic International Prognostic scoring system (DIPSS plus), which determines the eventual prognosis of the disease at any time. Previous studies and expert opinion indicate that for patients with Intermediate-2 risk (INT-2) and High risk (HR) disease, HCT is a reasonable option. How applicable is this to all patients with MF and what are the barriers to doing a transplant are not known. We therefore reviewed medical records of all patients who were referred for HCT. The main purpose of this study was to determine the proportion of patients who underwent transplantation as well as to ascertain the major reasons why patients referred for transplantation did not receive it despite its reported benefit.

Absolute lymphocyte count (ALC) during early therapy has been established as an independent prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Importantly, ALC can refine minimal residual disease (MRD)-based risk stratification, particularly for MRD-positive patients. However age-dependent effects on ALC, the lymphocyte subtype (T, NK, B) which underlies this finding, and the role of ALC at relapse are not yet known.Patients with de novo pediatric B-cell ALL had blood samples drawn biweekly during induction chemotherapy and lymphocyte subsets analyzed at different time points by flow cytometry. In addition, ALC was recorded at time points throughout induction and early consolidation chemotherapy, in maintenance therapy, and at time of relapse. Demographic, NCI risk, and treatment characteristics were also collected. Continuous variables were analyzed with Pearson’s coefficient, and categorical variables were analyzed with two-sided Barnard’s test. Survival statistics were measured with Kaplan-Meier curves and accelerated failure time analysis.A total of 21 children and young adults with B-cell ALL were identified with a median age of 17 years (range 0.5-35 years). Although not unexpectedly, T cells comprise the majority of lymphocytes that make up the ALC in nearly all cases. Interestingly, absolute CD3+ T cell count at diagnosis (ATC-0) correlates with ALC-15 (p=0.0008) and ALC during maintenance chemotherapy (p=0.01), revealing that T cell numbers at diagnosis predict total lymphocyte count recovery during early treatment as well as 8+ months later. The averages of ATC-0= 828 cells/ul and ALC-maintenance= 940 cells/ul were significant cutoffs as 89% of patients with low ATC-0 had low ALC during maintenance, and 75% of patients with high ATC-0 at diagnosis had high ALC during maintenance (p=0.03). In addition, age was inversely correlated with both ATC-0 and ALC-15 (p=0.035 and 0.006 respectively), linking that older patients have lower ALCs, which correlate to poor outcome. Indeed, 80% of patients with ALC-15 over 500 were < 10 years of age, while 87% of patients with ALC-15 under 500 cells/ul were >/= 10 years at diagnosis (p=0.007). Interestingly, patients with high ATC-0 had 100% 5 year OS while patients with low ATC-0 had 52% 5 year OS (p=0.1), a trend toward significance on Kaplan-Meier curves due to the low number of ATC-0 high patients (n=4) we had in this high risk patient population. However, ALC-15, ALC in maintenance, and age at diagnosis all independently had a significant correlation with RFS in accelerated failure time analysis (p=0.01, 0.0001, and 0.03 respectively). And importantly, ALC at relapse significantly correlated with OS in accelerated failure time analysis (p=0.0001).In this study, we demonstrate that ALC in ALL patients is inversely correlated with age, reflecting the normal decrease in ALC seen in healthy children, adolescents, and young adults. We also identified T cells as the predominant lymphocyte subtype comprising the ALC, which may reflect an immune reservoir in these patients. Importantly, T cell numbers at diagnosis (ATC-0) predict lymphocyte counts throughout treatment and also inversely correlate with age. This suggests that patients with low T cell numbers at diagnosis continue to have low T cell numbers late into treatment. As ALC and ATC decline with age, this could provide one potential mechanism for why older patients have worse outcomes from ALL. Clinically, ATC at diagnosis may identify patients at risk for relapse and help determine appropriate induction and post-induction therapy. In the future, patients with low ATC/ALC may benefit from immune-modulating therapy, which may overcome a limited immune reservoir.St. Baldrick’s Foundation Fellow AwardKimberly Patterson Leukemia Research FellowshipNo relevant conflicts of interest to declare.

Absolute lymphocyte count (ALC) during early therapy has been established as an independent prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Importantly, ALC can refine minimal residual disease (MRD)-based risk stratification, particularly for MRD-positive patients. However age-dependent effects on ALC, the lymphocyte subtype (T, NK, B) which underlies this finding, and the role of ALC at relapse are not yet known.