Abstract 216: Therapeutic Hypothermia Alone and in Combination With Preconditioning Improves Long Term Survival During Resuscitation of Hemorrhagic Shock

Background: We investigated the effects of hypothermia treatment alone and in combination with experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Previously we showed that RIPC alone improved survival. Methods: In the hypothermia alone study, adult Sprague Dawley rats (both genders) were randomized to hypothermia (n=16) or control group (n=15); in a combination study, rats were randomized to hypothermia plus RIPC (n=11) or control group (n=10). Rats were anesthetized with intraperitoneal ketamine/xylazine. Therapeutic hypothermia (Thermosuit) was started at 5 minutes after mean blood pressure (MBP) reached 30 mmHg. Core temperature was maintained at ~ 32 °C until blood volume was fully restored. RIPC was induced by 4 cycles of inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute deflation of the cuffs prior to hemorrhagic shock. In the control group, body temperature was maintained at 37 °C during the procedure. Hemorrhagic shock was induced by withdrawing blood from the carotid artery. Target mean blood pressure of 30 mmHg was maintained for 30 minutes followed by reinfusion of shed blood within the next 30 min. Rats were allowed recovery and the primary endpoint was survival rate at 6 weeks. Results: In the setting of hypothermia alone, 4 of 15 (26.7 %) rats in the control group and 11 of 16 (68.8 %; p = 0.032) rats in the hypothermia group survived at 6 weeks. In the combination study, 1 of 10 (10 %) rats in the control group and 7 of 11 (63.6 %; p = 0.024) rats in the hypothermia plus RIPC group survived at 6 weeks. Kaplan Meier Survival Curves are shown in Fig1. Conclusions: Hypothermia alone and combination with RIPC significantly improved long term survival in rats subjected to hemorrhagic shock. Hypothermia and RIPC did not show survival rates greater than hypothermia alone.

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Different Effects of Volatile and Nonvolatile Anesthetic Agents on Long-Term Survival in an Experimental Model of Hemorrhagic Shock

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420919221 ◽

2020 ◽

Vol 25 (4) ◽

pp. 346-353

Author(s):

Wangde Dai ◽

Jianru Shi ◽

Juan Carreno ◽

Robert A. Kloner

Keyword(s):

Blood Pressure ◽

Survival Rate ◽

Hemorrhagic Shock ◽

Blood Volume ◽

Brain Infarction ◽

Anesthetic Agent ◽

Term Survival ◽

Long Term Survival ◽

Isoflurane Group

Background: We investigated whether the cardioprotective, volatile gas anesthetic agent, isoflurane, could improve survival and organ function from hemorrhagic shock in an experimental rat model, compared to standard nonvolatile anesthetic agent ketamine/xylazine. Methods: Sprague Dawley rats (both genders) were randomized to receive either intraperitoneal ketamine/xylazine (K/X, 90 and 10 mg/kg; n = 12) or isoflurane (5% isoflurane induction and 2% maintenance in room air; n = 12) for anesthesia. Blood was withdrawn to maintain mean arterial blood pressure at 30 mm Hg for 1 hour, followed by 30 minutes of resuscitation with shed blood. Rats were allowed to recover and survive for 6 weeks. Results: During the shock phase, the total withdrawn blood volume (expressed as % of estimated total blood volume) to maintain a level of hypotension of 30 mm Hg was significantly higher in the isoflurane group (51.0% ± 1.5%) than in the K/X group (45.3% ± 1.8%; P = .023). Recovery of blood pressure during the resuscitation phase was significantly improved in the isoflurane group compared to the K/X group. The survival rate at 6 weeks was 1 (8.3%) of 12 in rats receiving K/X and 10 (83.3%) of 12 in rats receiving isoflurane ( P < .001). Histology performed at 6 weeks demonstrated brain infarction in the 1 surviving rat receiving K/X; no brain infarction occurred in the 10 surviving rats that received isoflurane. No infarction was detected in heart, lung, liver, or kidneys among the surviving rats. Conclusions: Isoflurane improved blood pressure response to resuscitation and resulted in significantly higher long-term survival rate.

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Abstract 218: Therapeutic Hypothermia Alone and Combination With Preconditioning Blunt Inflammation in Experimental Hemorrhagic Shock

Circulation ◽

10.1161/circ.140.suppl_2.218 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

Jianru Shi ◽

Wangde Dai ◽

Juan Carreno ◽

Sharon L Hale ◽

Robert A Kloner

Keyword(s):

Hemorrhagic Shock ◽

Therapeutic Hypothermia ◽

Absolute Lymphocyte Count ◽

Control Group ◽

Sprague Dawley ◽

Term Survival ◽

Shed Blood ◽

Arterial Blood ◽

The Absolute ◽

Experimental Hemorrhagic Shock

Background: Recent studies by our group indicate that preconditioning, therapeutic hypothermia (TH) and TH combined with preconditioning improved long-term survival during resuscitation of hemorrhagic shock. The neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation associated with increased mortality in patients with severe hemorrhage shock. The aim of this study is to evaluate the effects of these three therapies on NLR level in rats with acute hemorrhagic shock. Methods and Results: In the preconditioning study, Sprague Dawley rats (both genders) were randomized to preconditioning (n=26) or control group (n=27); in the hypothermia study, rats were randomized to TH (n=16) or control group (n=15); in a combination study, rats were randomized to TH plus preconditioning (n=11) or control group (n=10). Rats were anesthetized with intraperitoneal Ketamine and xylazine. After heparinizing, hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure (MBP) of 30 mmHg for 30 minutes and then shed blood was reinfused. Preconditioning was induced by 4 cycles of inflating small cuffs around the femoral arteries to 200 mmHg for 5 minutes, followed by 5-minute deflation of the cuffs prior to hemorrhagic shock. TH started at 5 minutes after MBP reached 30 mmHg. Core temperature was maintained at ~32 °C until blood volume was fully restored. In the control group, body temperature was maintained at ~ 37°C. Arterial blood samples were collected 1 hour after resuscitation. The NLR is an easily accessible biomarker, which is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The NLR was significantly lower in TH group (0.20 ± 0.02) compared with the control group (0.32 ± 0.03; p=0.003). Similarly, the NLR level was significantly decreased in TH plus preconditioning group (0.19 ± 0.02) versus the control group (0.33 ± 0.02; p= 0.001). There was no difference in NLR level between the preconditioning group (0.41 ± 0.04) and the control group (0.41 ± 0.04; p=0.984). Conclusions: NLR is widely recognized inflammation marker associated with poor prognosis in severe hemorrhagic shock. TH alone and TH combined with preconditioning blunt the inflammation by decreasing the NLR level in experimental hemorrhagic shock.

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Abstract 186: Remote Limb Ischemic Preconditioning Improves Short and Long Term Survival and Maintains Intravascular Blood Volume During Resuscitation of Hemorrhagic Shock

Circulation ◽

10.1161/circ.138.suppl_2.186 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Wangde Dai ◽

Jianru Shi ◽

Juan Carreno ◽

Sharon Hale ◽

Robert A Kloner

Keyword(s):

Blood Pressure ◽

Hemorrhagic Shock ◽

Blood Volume ◽

Ischemic Preconditioning ◽

Control Group ◽

Term Survival ◽

Shed Blood ◽

Short And Long Term ◽

And Control

Background: We further examined the protective effects of experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Methods: Sprague Dawley rats (both genders) were randomized into RIPC (n= 26) or control group (n= 27), and anesthetized with intraperitoneal ketamine/xylazine. RIPC was induced by 4 cycles of inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute deflation of the cuffs. Hemorrhagic shock was induced by withdrawing blood from the carotid artery. Target mean blood pressure of 30 mmHg was maintained for 30 minutes followed by reinfusion of shed blood within the next 30 min. Rats remained anesthetized for another 30 min before recovery; endpoints were survival at 72 hours and 6 weeks. Results: The % of estimated total blood volume withdrawn to maintain a level of 30 mmHg was similar in the RIPC group (41.7 ± 1.0 %) and control group (41.9 ± 1.0 %). Recovery of blood pressure during the early resuscitation phase was significantly improved in the RIPC group. The diastolic internal dimension of the left ventricle (echocardiogram), which indicates circulating intravascular blood volume, was significantly larger in the RIPC group at 1 hour after initiation of shed blood reinfusion (5.8 ± 0.1 mm) compared to 5.4 ± 0.1mm in the control group (p=0.04). Left ventricular fractional shortening was comparable between RIPC (50.9 ± 1.9 %) and control group (49.6 ± 1.8 %; p=0.64) at 1 hour after initiation of resuscitation. At 48 hours after shock, BUN was within normal range in the RIPC group (17.3 ± 1.2 mg/dl); but elevated in the control group (22.0 ± 1.7 mg/dl). At 72 hours after hemorrhagic shock injury, 6 of 27 (22.2 %) rats in the control group and 13 of 26 (50 %, p = 0.047) rats in the RIPC group survived. At 6 weeks, 5 of 27 (18.5 %) rats in the control group and 13 of 26 (50 %; p = 0.021) rats in the RIPC group survived. RIPC significantly increased survival rate at both 72 hours and 6 weeks. Conclusions: RIPC improved recovery of blood pressure and maintained more circulating intravascular blood volume in the early phase of resuscitation, improved BUN, and markedly and significantly improved short and long term survival in rats subjected to hemorrhagic shock.

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Therapeutic Hypothermia Improves Long-Term Survival and Blunts Inflammation in Rats During Resuscitation of Hemorrhagic Shock

Therapeutic Hypothermia and Temperature Management ◽

10.1089/ther.2020.0024 ◽

2020 ◽

Vol 10 (4) ◽

pp. 237-243

Author(s):

Jianru Shi ◽

Wangde Dai ◽

Juan Carreno ◽

Lifu Zhao ◽

Robert A. Kloner

Keyword(s):

Hemorrhagic Shock ◽

Therapeutic Hypothermia ◽

Term Survival ◽

Long Term Survival

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The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review

Cancer Control ◽

10.1177/1073274821997430 ◽

2021 ◽

Vol 28 ◽

pp. 107327482199743

Author(s):

Ke Chen ◽

Xiao Wang ◽

Liu Yang ◽

Zheling Chen

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Survival Rate ◽

Meta Analysis ◽

Response Rates ◽

Control Group ◽

Term Survival ◽

Long Term Survival ◽

And Control

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.

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Improved Long-Term Survival with Edaravone Therapy in Patients with Amyotrophic Lateral Sclerosis: A Retrospective Single-Center Study in Japan

Pharmaceuticals ◽

10.3390/ph14080705 ◽

2021 ◽

Vol 14 (8) ◽

pp. 705

Author(s):

Hideki Houzen ◽

Takahiro Kano ◽

Kazuhiro Horiuchi ◽

Masahiro Wakita ◽

Azusa Nagai ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rank Test ◽

Positive Pressure ◽

Control Group ◽

Single Center ◽

Term Survival ◽

Long Term Survival ◽

Kaplan Meier ◽

Lateral Sclerosis

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2–64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan–Meier analysis, which revealed that the median survival durations were 49 (9–88) and 25 (8–41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.

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Comparison of Long-term outcomes between Lynch sydrome and sporadic colorectal cancer: a propensity score matching analysis

10.21203/rs.3.rs-130271/v1 ◽

2020 ◽

Author(s):

Yun Xu ◽

Cong Li ◽

Charlie Zhi-Lin Zheng ◽

Yu-Qin Zhang ◽

Tian-An Guo ◽

...

Keyword(s):

Colorectal Cancer ◽

Propensity Score ◽

Propensity Score Matching ◽

Control Group ◽

Sporadic Colorectal Cancer ◽

Long Term Outcomes ◽

Term Survival ◽

Long Term Survival ◽

Tumor Stages

Abstract Background Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. Comparison of prognosis between LS and sporadic CRC (SCRC) were rare,with conflicting results. This study aimed to compare the long-term outcomes between patients with LS and SCRC. Methods Between June 2008 and September 2018, a total of 47 patients were diagnosed with LS by genetic testing at Fudan University Shanghai Cancer Center. A 1:2 propensity score matching was performed to obtain homogeneous cohorts from SCRC group. Thereafter, 94 SCRC patients were enrolled as control group. The long-term survival rates between the two groups were compared, and the prognostic factors were also analyzed. Results The 5-year OS rate of LS group was 97.6%, which was significantly higher than of 82.6% for SCRC group (p = 0.029). The 5-year PFS rate showed no significant differences between the two groups (78.0% for LS group vs. 70.6% for SCRC patients; p = 0.262). The 5-year TFS rates in LS group was 62.1% for LS patients, which were significantly lower than of 70.6% for SCRC group (p = 0.039). By multivariate analysis, we found that tumor progression of primary CRC and TNM staging were independent risk factors for OS. Conclusion LS patients have better long-term survival prognosis than SCRC patients. Strict regular follow-up monitoring, detection at earlier tumor stages, and effective treatment are key to ensuring better long-term prognosis.

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