Association between Case Volumes of Extracorporeal Life Support and Clinical Outcome in Out-of-Hospital Cardiac Arrest.

AIM: Extracorporeal life support (ECLS) for out-of-hospital cardiac arrest (OHCA) is increasing. There is little evidence identifying the association between hospital ECLS case volumes and outcomes in different populations receiving ECLS or conventional cardiopulmonary resuscitation (CPR). The goal of this investigation was to identify the association between ECLS case volumes and clinical outcomes of OHCA patients. METHODS: This cross-sectional observational study used the National OHCA Registry for adult OHCA cases in Seoul, Korea between January 2015 and December 2019. If the ECLS volume during the study period was >20, the institution was defined as a high-volume ECLS center. Others were defined as low-volume ECLS centers. Outcomes were good neurologic recovery (cerebral performance category 1 or 2) and survival to discharge. We performed multivariate logistic regression and interaction analyses to assess the association between case volume and clinical outcome. RESULTS: Of the 17,248 OHCA cases, 3,731 were transported to high-volume centers. Among the patients who underwent ECLS, those at high-volume centers had a higher neurologic recovery rate than those at low-volume centers (17.0% vs. 12.0%), and the adjusted OR for good neurologic recovery was 2.22 (95% confidence interval (CI): 1.15-4.28) in high-volume centers compared to low-volume centers. For patients who received conventional CPR, high-volume centers also showed higher survival-to-discharge rates (adjusted OR of 1.16, 95%CI: 1.01-1.34). CONCLUSIONS: High-volume ECLS centers showed better neurological recovery in patients who underwent ECLS. High-volume centers also had better survival-to-discharge rates than low-volume centers for patients not receiving ECLS.

Design, synthesis, and biological evaluation of novel HSP27 inhibitors to sensitize lung cancer cells to clinically available anticancer agents.

Expression of heat shock protein (HSP) correlates with the oncogenic status of malignant cells and plays an important role in tumorigenesis. HSP27 is constitutively expressed at specific stages of cancer development, and several clinical trials have reported correlations between HSP27 expression and tumor progression, metastasis, and chemoresistance in various types of cancer cells. These findings indicate that HSP27 is a major drug target, particularly in chemo-resistant cancers. As part of our ongoing efforts to improve the previously identified J2, a HSP27 cross-linker, we, in this study, report the identification of NK16 as a novel inducer of abnormal HSP27 dimers that did not affect the expression of HSP90 in an NCI-H460 lung cancer cell model. When NCI-H460 cells were treated with NK16 in combination with the anticancer drug cisplatin or paclitaxel, cleavage of PARP and caspase-3 was increased compared to administration of cisplatin or paclitaxel alone. Similar results were obtained in an NCI-H460-xenografted mouse model, in which tumor growth was suppressed more by co-administration of NK16 and paclitaxel than by paclitaxel alone. We propose NK16 as a meaningful strategy to improve the anticancer efficacy of cisplatin and paclitaxel.

Efficacy of distance training program for cardiopulmonary resuscitation utilizing smartphone application and home delivery system.

AIM OF THE STUDY: Community cardiopulmonary resuscitation (CPR) education is important for laypersons. However, during the COVID-19 pandemic, with social distancing, conventional face-to-face CPR training was unavailable. We developed a distance learning CPR training course (HEROS-Remote) using a smartphone application that monitors real-time chest compression quality and a home delivery collection system for mannikins. This study aimed to evaluate the efficacy of the HEROS-Remote course by comparing chest compression quality with that of conventional CPR training. METHODS: We applied layperson CPR education with HEROS-Remote and conventional education in Seoul during the COVID-19 pandemic. Both groups underwent a 2-min post-training chest compression test, and we tested non-inferiority. Chest compression depth, rate, complete recoil, and composite chest compression score was measured. Trainees completed a satisfaction survey on CPR education and delivery. The primary outcome was the mean chest compression depth. RESULTS: A total of 180 trainees were enrolled, with 90 assigned to each training group. Chest compression depth of HEROS-Remote training showed non-inferiority to that of conventional training (67.4 vs. 67.8, p = 0.78), as well as composite chest compression score (92.7 vs. 95.5, p = 0.16). The proportions of adequate chest compression depth, chest compression rate, and chest compressions with complete chest recoil were similar in both training sessions. In the HEROS-Remote training, 90% of the trainees were satisfied with CPR training, and 96% were satisfied with the delivery and found it convenient. CONCLUSION: HEROS-Remote training was non-inferior to conventional CPR training in terms of chest compression quality. Distance learning CPR training using a smartphone application and mannikin delivery had high user satisfaction and was logistically feasible.

Correlates of Self-Reported Viral Suppression Among HIV-Positive, Young, Black Men Who Have Sex With Men Participating in a Randomized Controlled Trial of An Internet-Based HIV Prevention Intervention.

BACKGROUND: Young, black men who have sex with men are disproportionately impacted by the US HIV epidemic, and HIV-positive, young, black men who have sex with men face stark disparities in HIV clinical outcomes. METHODS: We performed an observational analysis of the 199 HIV-positive black men aged 18 to 30 years followed up for 12 months in healthMpowerment, a randomized controlled trial of an Internet-based HIV prevention intervention, to identify time-varying correlates of self-reported viral suppression using relative risk (RR) regression. RESULTS: Retention at the 12-month visit was 84%. One hundred five (65%) of 162 participants reported being undetectable at baseline. At 3, 6, and 12 months, 83 (72%) of 115, 84 (82%) of 103, and 101 (86%) of 117 reported an undetectable viral load, respectively. In a multivariable model, participants who reported homelessness (RR, 0.85; 95% confidence interval [CI], 0.72-0.99), who had clinically significant depressive symptoms (RR, 0.88; 95% CI, 0.79-0.98), and who used methamphetamine or crack (RR, 0.61; 95% CI, 0.38-0.96) were less likely to report an undetectable viral load. Young men who engaged in condomless insertive anal intercourse were more likely to report viral suppression (RR, 1.14; 95% CI, 1.04-1.24). CONCLUSION: HIV care for young, black men who have sex with men must be multidimensional to address medical needs in the context of mental health, substance use, and housing insecurity.

The Conjugated Double Bond of Coniferyl Aldehyde Is Essential for Heat Shock Factor 1 Mediated Cytotoprotection.

Coniferyl aldehyde (1) is previously reported as a potent inducer of heat shock factor 1 (HSF1). Here, we further examined the active pharmacophore of 1 for activation of HSF1 using the derivatives coniferyl alcohol (2), 4-hydroxy-3-methoxyphenylpropanal (3), and 4-hydroxy-3-methoxyphenylpropanol (4). Both 1 and 2 resulted in increased survival days after a lethal radiation (IR) dose. The decrease in bone marrow (BM) cellularity and Ki67-positive BM cells by IR was also significantly restored by 1 or 2 in mice. These results suggested that the vinyl moiety of 1 and 2 is necessary for inducing HSF1, which may be useful for developing small molecules for cytoprotection of normal cells against damage by cytotoxic drugs and radiation.

Human salivary gland cells express bradykinin receptors that modulate the expression of proinflammatory cytokines.

Bradykinin is an important peptide modulator that affects the function of neurons and immune cells. However, there is no evidence of the bradykinin receptors and their functions in human salivary glands. Here we have identified and characterized bradykinin receptors on human submandibular gland cells. Both bradykinin B1 and B2 receptors are expressed on human submandibular gland cells, A253 cells, and HSG cells. Bradykinin increased the intracellular Ca2+ concentration ([Ca2+ ]i ) in a concentration-dependent manner. Interestingly, a specific agonist of the B1 receptor did not have any effect on [Ca2+ ]i in HSG cells, whereas specific agonists of the B2 receptor had a Ca2+ mobilizing effect. Furthermore, application of the B1 receptor antagonist, R715, did not alter the bradykinin-mediated increase in cytosolic Ca2+ , whereas the B2 receptor antagonist, HOE140, showed a strong inhibitory effect, which implies that bradykinin B2 receptors are functional in modulating the concentration of cytosolic Ca2+ . Bradykinin did not affect a carbachol-induced rise of [Ca2+ ]i and did not modulate translocation of aquaporin-5. However, bradykinin did promote the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), implying the role of bradykinin in salivary gland inflammation. These data suggest that bradykinin receptors are involved in Ca2+ signaling in human submandibular gland cells and serve a unique role, which is separate from that of other salivary gland G protein-coupled receptors.

Spectral-converting study of Ba((9-3)(m+n)/2)Er(m)Yb(n)Y2Si6O24 (m = 0.005 - 0.2, n = 0 - 0.3) orthosilicate phosphors.

Optical materials composed of Ba((9-3)(m+n)/2)Er(m)Yb(n)Y2Si6O24 (m = 0.005-0.2, n = 0-0.3) were prepared using a solid-state reaction. The X-ray diffraction patterns of the obtained phosphors were examined to index the peak positions. The photoluminescence (PL) excitation and emission spectra of the Er(3+)-activated phosphors and the critical emission quenching as a function of Er(3+) content in the Ba(9-3m/2)Er(m)Y2Si6O24 structure were monitored. The spectral conversion properties of Er(3+) and Er(3+)-Yb(3+) ions doped in Ba9Y2Si6O24 phosphors were elucidated under diode-laser irradiation at 980 nm. Up-conversion emission spectra and the dependence of the emission intensity on pump power for the Ba8.55Er0.1Yb0.2Y2Si6O24 phosphor were investigated. The desired up-conversion of the emitted light, which passed through the green, yellow, orange and red regions of the spectrum, was achieved through the use of appropriate Er(3+) and/or Yb(3+) concentrations in the host structure and 980 nm excitation light. The up-conversion mechanism in the phosphors is described by an energy-level schematic.

Reducing Children's Susceptibility to Alcohol Use: Effects of a Home-Based Parenting Program.

This 4-year efficacy trial tested whether a home-based, self-administered parenting program could have a long-term effect on children's cognitive susceptibility to alcohol use, and it tested hypothesized moderators and mediators of any such program effect. Using a two-group randomized controlled design, 1076 children (540 treatment; 536 control; mean age of 9.2 years at baseline) completed telephone interviews prior to randomization and follow-up interviews 12, 24, 36, and 48 months post-baseline. Mothers of children randomized to treatment received a 5-month-long parenting program during year 1, followed by two 1-month-long boosters in years 2 and 3. Exposure to the program was significantly inversely associated with susceptibility to alcohol use 48 months post-baseline (b = -0.03, p = .04), with no variation in program effects by parental alcohol use or mother's race/ethnicity or education, suggesting broad public health relevance of the parenting program. Path analyses of simple indirect effects through each hypothesized mediator showed that program exposure positively influenced parental communication to counter pro-drinking influences in the family and media domains and parental rule setting 36 months post-baseline; these variables, in turn, predicted reduced susceptibility to alcohol use 48 months post-baseline. Parallel (multiple) mediation analysis showed that the program had a significant indirect effect on susceptibility through parental rule setting. Together, the findings indicate that internalization of protective alcohol-related expectancies and intentions is possible among children whose mothers provide early exposure to alcohol-specific socialization. Additional research is needed to link alcohol-specific socialization during childhood with adolescent drinking outcomes.

Epigenetic modulation of the muscarinic type 3 receptor in salivary epithelial cells.

Muscarinic receptors, particularly the type 3 subtype (M3R), have an important role in exocrine secretion. M3R normally function in HSG cells originated from human submandibular gland ducts, but not in A253 and SGT cells, derived from human submandibular carcinoma and salivary gland adenocarcinoma. However, the underlying mechanism of this suppression has remained elusive. In this study, we examined whether M3R function is suppressed by epigenetic modulation of the receptor. To this end, we investigated the mRNA transcript and protein levels of the M3R using reverse transcriptase-PCR, western blot, and confocal microscopy analyses. Global DNA methylation assays, methylation-specific PCR, and bisulfite sequencing were also performed to understand the epigenetic status of the M3R CpG island. We found that A253 cells expressed all subtypes of muscarinic receptors, except M3R, on the mRNA level. However, treatment of cells with 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA-demethylating agent, increased the expression levels of both M3R mRNA transcript and protein in proportion to the incubation period. 5-Aza-CdR completely restored the carbachol-induced calcium response, which was not observed in untreated A253 cells. In untreated A253 cells, all CG pairs from the 1st to 14th were methylated and 5-Aza-CdR treatment demethylated one of the methylated CG pairs. We also examined the methylation pattern of M3R CpG island in human cancer tissue. Interestingly, the result was very similar to those of A253 cells. All CG pairs in M3R CpG island were also methylated. Another salivary gland tumor cell line, SGT, also showed the similar methylation pattern, heavy methylation in M3R CpG island. It is concluded that CpG island in M3R is hypermethylated in cancer cell lines and human cancer. Our results further suggest that 5-Aza-CdR could potentially be used to restore the function of M3R, suppressed in some cancer cell types.

Epigenetic alteration of the purinergic type 7 receptor in salivary epithelial cells.

Purinergic receptors, particularly type 7 (P2RX7), are involved in apoptotic cell death. However, the expression and function of P2RX7 are suppressed in HSG cells. In the present study, we explored whether P2RX7 function is regulated by epigenetic alteration of the receptors in two different cell lines, HSG cells derived from human submandibular ducts, and A253 cells, originated from human submandibular carcinoma. We discovered that HSG cells expressed all subtypes of purinergic receptors, excluding P2RX7, at the mRNA level. However, treatment of the cells with 5-Aza-CdR, a DNA demethylating agent, increased the mRNA expression levels of P2RX7 in a time-dependent manner. Furthermore, 5-Aza-CdR completely rescued the calcium response induced by P2RX7 agonist BzATP, a response that was absent in untreated HSG cells. In contrast, A253 cells showed a moderate methylation pattern in the P2RX7 CpG island. Most CG pairs from the first to the 21st were methylated in untreated HSG cells, but 5-Aza-CdR-treatment partially demethylated the methylated CG pairs. We obtained similar results when investigated human tissues; the CG pairs in the P2RX7 CpG islands showed hypermethylation and hypomethylation patterns in human normal and cancer tissues, respectively. Our results suggest that the expression level and function of P2RX7 are regulated by DNA methylation in epithelial cells.

Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 µM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

Chaperone stress 70 protein (STCH) binds and regulates two acid/base transporters NBCe1-B and NHE1.

Regulation of intracellular pH is critical for the maintenance of cell homeostasis in response to stress. We used yeast two-hybrid screening to identify novel interacting partners of the pH-regulating transporter NBCe1-B. We identified Hsp70-like stress 70 protein chaperone (STCH) as interacting with NBCe1-B at the N-terminal (amino acids 96-440) region. Co-injection of STCH and NBCe1-B cRNA into Xenopus oocytes significantly increased surface expression of NBCe1-B and enhanced bicarbonate conductance compared with NBCe1-B cRNA alone. STCH siRNA decreased the rate of Na(+)-dependent pHi recovery from NH4(+) pulse-induced acidification in an HSG (human submandibular gland ductal) cell line. We observed that in addition to NBCe1-B, Na(+)/H(+) exchanger (NHE)-dependent pHi recovery was also impaired by STCH siRNA and further confirmed the interaction of STCH with NHE1 but not plasma membrane Ca(2+) ATPase. Both NBCe1-B and NHE1 interactions were dependent on a specific 45-amino acid region of STCH. In conclusion, we identify a novel role of STCH in the regulation of pHi through site-specific interactions with NBCe1-B and NHE1 and subsequent modulation of membrane transporter expression. We propose STCH may play a role in pHi regulation at times of cellular stress by enhancing the recovery from intracellular acidification.

TRPV1 in Salivary Gland Epithelial Cells Is Not Involved in Salivary Secretion via Transcellular Pathway.

Transient receptor potential vanilloid subtype 1 (TRPV1) was originally found in sensory neurons. Recently, it has been reported that TRPV1 is expressed in salivary gland epithelial cells (SGEC). However, the physiological role of TRPV1 in salivary secretion remains to be elucidated. We found that TRPV1 is expressed in mouse and human submandibular glands (SMG) and HSG cells, originated from human submandibular gland ducts at both mRNA and protein levels. However, capsaicin (CAP), TRPV1 agonist, had little effect on intracellular free calcium concentration ([Ca(2+)]i) in these cells, although carbachol consistently increased [Ca(2+)]i. Exposure of cells to high temperature (>43℃) or acidic bath solution (pH5.4) did not increase [Ca(2+)]i, either. We further examined the role of TRPV1 in salivary secretion using TRPV1 knock-out mice. There was no significant difference in the pilocarpine (PILO)-induced salivary flow rate between wild-type and TRPV1 knock-out mice. Saliva flow rate also showed insignificant change in the mice treated with PILO plus CAP compared with that in mice treated with PILO alone. Taken together, our results suggest that although TRPV1 is expressed in SGEC, it appears not to play any direct roles in saliva secretion via transcellular pathway.

Comparison of prehospital resuscitation quality during scene evacuation and early ambulance transport in out-of-hospital cardiac arrest between residential location and non-residential location.

BACKGROUND: High-quality prehospital cardiopulmonary resuscitation (CPR) is important for out-of-hospital cardiac arrest (OHCA). We aimed to evaluate prehospital CPR quality during scene evacuation and early ambulance transport in patients with OHCA according to the type of cardiac arrest location. METHODS: This retrospective observational cohort study enrolled patients with non-traumatic adult OHCA in Seoul between July 2020 and March 2022. Prehospital CPR quality data extracted from defibrillators were merged with the national OHCA database. The location of cardiac arrest was categorized into two groups (residential and non-residential). CPR quality indices including no-flow (any pause >1.5 s) fraction were compared according to the type of arrest location at each minute of EMS scene evacuation and early ambulance transport (5 min prior to 5 min after ambulance departure). RESULTS: A total of 1,222 OHCAs were enrolled in the final analysis after serial exclusion. A total of 966 OHCAs (79.1%) occurred in the residential areas. The CPR quality deteriorated during the scene evacuation in both location type. The mean no-flow fractions were significantly higher in residential places than in non-residential places. The mean proportion of adequate compression depth and rate was lower in cardiac arrests in residential places. The discrepancy in EMS CPR quality during scene evacuation was more prominent when mechanical CPR devices were not used. CONCLUSION: Deterioration of CPR quality was observed just before and during early ambulance transport, especially when the cardiac arrest location was a residential area or when only manual CPR was provided.

Estimated health and economic impact of using high-dose influenza vaccine on respiratory and circulatory plus respiratory hospitalizations of older adults in Australia.

Background: Standard dose influenza vaccine provides moderate protection from infection, but with lower effectiveness among the elderly. High dose and adjuvanted vaccines (HD-TIV and aTIV) were developed to address this. This study aims to estimate the incremental health and economic impact of using HD-TIV (high dose trivalent vaccine) instead of aTIV (adjuvanted trivalent vaccine) on respiratory and circulatory plus respiratory hospitalizations of older people (≥65 years) in Australia. Methods: This is a modelling study comparing predicted hospitalization outcomes in people receiving HD-TIV or aTIV during an average influenza season in Australia. Hospitalization records of Australian adults ≥65 years of age from 01 April to 30 November during 15 influenza seasons (2002-2017 excluding 2009, which was a pandemic) were extracted from the Australian Institute of Health and Welfare [AIHW] and used to calculate hospitalisation rates during an average season. Relative vaccine effectiveness data for aTIV and HD-TIV were used to estimate morbidity burden related to influenza. Results: Between 2002 and 2017, the average respiratory hospitalization rate among older people during influenza season (April-November) was 3,445/100,000 population-seasons, with an average cost of AU$ 7,175 per admission. The average circulatory plus respiratory hospitalization rate among older Australian people during that time was 10,393/100,000 population-seasons, with an average cost of AU$ 7829 per admission. For older Australians, HD-TIV may avert an additional 6,315-9,410 respiratory admissions each year, with an incremental healthcare cost saving of AU$ 15.9-38.2 million per year compared to aTIV. Similar results were also noted for circulatory plus respiratory hospitalizations. Conclusions: From the modelled estimations, HD-TIV was associated with less economic burden and fewer respiratory, and circulatory plus respiratory hospitalizations than aTIV for older Australians.

Activation of the HSP27-AKT axis contributes to gefitinib resistance in non-small cell lung cancer cells independent of EGFR mutations.

PURPOSE: Although epidermal growth factor receptor (EGFR)-activating mutations in non-small cell lung cancer (NSCLC) usually show sensitivity to first-generation EGFR-tyrosine kinase inhibitors (TKIs), most patients relapse because of drug resistance. Heat shock protein 27 (HSP27) has been reported to be involved in the resistance of EGFR-TKIs, although the underlying mechanism is unclear. Here, we explore the mechanisms of HSP27-mediated EGFR TKI resistance and propose novel therapeutic strategies. METHODS: To determine the mechanism of HSP27 associated gefitinib resistance, differences were assessed using gefitinib-sensitive and -resistant NSCLC cell lines. In vivo xenograft experiments were conducted to elucidate the combinatorial effects of J2, a small molecule HSP27 inhibitor, and gefitinib. Analyses of human NSCLC tissues and PDX tissues were also used for comparison of HSP27 and phosphorylated AKT expression. RESULTS: Large-scale cohort analysis of NSCLC cases revealed that HSP27 expression correlated well with the incidence of EGFR mutations and affected patient survival. Increased pAKT and HSP27 was observed in gefitinib-resistant cells compared with gefitinib-sensitive cells. Moreover, increased phosphorylation of HSP27 by gefitinib augmented its protein stability and potentiated its binding activity with pAKT, which resulted in increased gefitinib resistance. However, in gefitinib-sensitive cells, stronger binding activity between EGFR and HSP27 was observed. Moreover, these phenomena occurred regardless of EGFR mutation including secondary mutations, such as T790M. AKT knockdown switched HSP27-pAKT binding to HSP27-EGFR, which promoted gefitinib sensitivity in gefitinib-resistant cells. Functional inhibition of HSP27 yielded sensitization to gefitinib in gefitinib-resistant cells by inhibiting the interaction between HSP27 and pAKT. CONCLUSIONS: Our results indicate that combination of EGFR-TKIs with HSP27 inhibitors may represent a good strategy to overcome resistance to EGFR-TKIs, especially in cancers exhibiting AKT pathway activation.

Quality of chest compressions during prehospital resuscitation phase from scene arrival to ambulance transport in out-of-hospital cardiac arrest.

AIM: Prehospital cardiopulmonary resuscitation is performed from scene arrival to hospital arrival. The diverse prehospital resuscitation phases can affect the quality of chest compressions. This study aimed to evaluate the dynamic changes in chest compression quality during prehospital resuscitation. METHODS: Adult out-of-hospital cardiac arrest patients treated without prehospital return of spontaneous circulation were included in Seoul between July 2020 and September 2021. The chest compressions quality was assessed using a real-time chest compression feedback device. The prehospital phase was divided by key events during the prehospital resuscitation timeline (phase 1: first 2 min after initiation of chest compression, phase 2: from the end of phase 1 to 1 min prior to ambulance departure; phase 3: from 1 min before to 1 min after ambulance departure; phase 4: from the end of phase 3 to hospital arrival). The main outcome was no-flow fraction. The no-flow fraction between prehospital phases was compared using repeated-measure analysis of variance. RESULTS: In total, 788 patients were included. Mean no-flow fraction was the highest in phase 3 (phase 1: 11.3% ± 13.8, phase 2: 19.3% ± 12.3, phase 3: 33.0% ± 34.9, phase 4: 18.7% ± 23.7, p < 0.001). The mean number of total no-flow events per minute was also the highest in phase 3. The minute-by-minute analysis showed that the no-flow fraction rapidly increased before ambulance departure and decreased during ambulance transport. CONCLUSION: Dynamic changes in chest compression quality were observed during prehospital resuscitation phase. The no-flow fraction was the highest from 1 min before to 1 min after ambulance departure.

East Asian Herbal Medicine to Reduce Primary Pain and Adverse Events in Cancer Patients : A Systematic Review and Meta-Analysis With Association Rule Mining to Identify Core Herb Combination.

Objective: Cancer pain is an important factor in cancer management that affects a patient's quality of life and survival-related outcomes. The aim of this review was to systematically evaluate the efficacy and safety of oral administration of East Asian herbal medicine (EAHM) for primary cancer pain and to explore core herb patterns based on the collected data. Methods: A comprehensive literature search was conducted in 11 electronic databases, namely, PubMed, Cochrane Library, Cumulative Index to Nursing & Allied Health Literature, EMBASE, Korean Studies Information Service System, Research Information Service System, Oriental Medicine Advanced Searching Integrated System, Korea Citation Index, Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Data, and CiNii for randomized controlled trials from their inception until August 19, 2021. Statistical analysis was performed in R version 4.1.1 and R studio program using the default settings of the meta-package. When heterogeneity in studies was detected, the cause was identified through meta-regression and subgroup analysis. Methodological quality was independently assessed using the revised tool for risk of bias in randomized trials (Rob 2.0). Results: A total of 38 trials with 3,434 cancer pain patients met the selection criteria. Meta-analysis favored EAHM-combined conventional medicine on response rate (risk ratio: 1.06; 95% CI: 1.04 to 1.09, p < 0.0001), continuous pain intensity (standardized mean difference: -1.74; 95% CI: -2.17 to -1.30, p < 0.0001), duration of pain relief (standardized mean difference: 0.96, 95% CI: 0.69 to 1.22, p < 0.0001), performance status (weighted mean difference: 10.71; 95% CI: 4.89 to 16.53, p = 0.0003), and opioid usage (weighted mean difference: -20.66 mg/day; 95% CI: -30.22 to -11.10, p < 0.0001). No significant difference was observed between EAHM and conventional medicine on response rate and other outcomes. Patients treated with EAHM had significantly reduced adverse event (AE) incidence rates. In addition, based on the ingredients of herb data in this meta-analysis, four combinations of herb pairs, which were frequently used together for cancer pain, were derived. Conclusion: EAHM monotherapy can decrease adverse events associated with pain management in cancer patients. Additionally, EAHM-combined conventional medicine therapy may be beneficial for patients with cancer pain in increasing the response rate, relieving pain intensity, improving pain-related performance status, and regulating opioid usage. However, the efficacy and safety of EAHM monotherapy are difficult to conclude due to the lack of methodological quality and quantity of studies. More well-designed, multicenter, double-blind, and placebo-controlled randomized clinical trials are needed in the future. In terms of the core herb combination patterns derived from the present review, four combinations of herb pairs might be promising for cancer pain because they have been often distinctly used for cancer patients in East Asia. Thus, they are considered to be worth a follow-up study to elucidate their actions and effects. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021265804.

Association between the number of prehospital defibrillation attempts and neurologic outcomes in out-of-hospital cardiac arrest patients without on-scene return of spontaneous circulation.

OBJECTIVE: Delivery of prehospital defibrillation for shockable rhythms by emergency medical service providers is crucial for successful resuscitation in out-of-hospital cardiac arrest (OHCA) patients. The optimal range of prehospital defibrillation attempts for refractory shockable rhythms is unknown. This study evaluated the association between the number of prehospital defibrillation attempts and neurologic outcomes in OHCA patients. METHODS: A retrospective observational study was conducted using the nationwide OHCA registry. Adult OHCA patients who were treated by emergency medical service providers due to presumed cardiac origin with initial shockable rhythm were enrolled from 2013 to 2016. The final analysis was performed on patients without on-scene return of spontaneous circulation. The number of prehospital defibrillation attempts was categorized as follows: 2-3, 4-5, and ≥6 attempts. The primary outcome was a good neurologic recovery at hospital discharge. Multivariate logistic regression analysis was performed to evaluate the association between neurologic outcomes and the number of prehospital defibrillation attempts. RESULTS: A total of 4,513 patients were included in the final analysis. The numbers of patients for whom 2-3, 4-5, and ≥6 defibrillation attempts were made were 2,720 (60.3%), 1,090 (24.2%), and 703 (15.5%), respectively. Poorer outcomes were associated with ≥6 defibrillation attempts: survival to hospital discharge (adjusted odds ratio, 0.38; 95% confidence interval, 0.21-0.65) and good neurologic recovery (adjusted odds ratio, 0.42; 95% confidence interval, 0.21-0.84). CONCLUSION: Six or more prehospital defibrillation attempts were associated with poorer neurologic outcomes in OHCA patients with an initial shockable rhythm who were unresponsive to on-scene defibrillation and resuscitation.

Drug-Like Small Molecule HSP27 Functional Inhibitor Sensitizes Lung Cancer Cells to Gefitinib or Cisplatin by Inducing Altered Cross-Linked Hsp27 Dimers.

Relationships between heat shock protein 27 (HSP27) and cancer aggressiveness, metastasis, drug resistance, and poor patient outcomes in various cancer types including non-small cell lung cancer (NSCLC) were reported, and inhibition of HSP27 expression is suggested to be a possible strategy for cancer therapy. Unlike HSP90 or HSP70, HSP27 does not have an ATP-binding pocket, and no effective HSP27 inhibitors have been identified. Previously, NSCLC cancer cells were sensitized to radiation and chemotherapy when co-treated with small molecule HSP27 functional inhibitors such as zerumbone (ZER), SW15, and J2 that can induce abnormal cross-linked HSP27 dimer. In this study, cancer inhibition effects of NA49, a chromenone compound with better solubility, longer circulation time, and less toxicity than J2, were examined in combination with anticancer drugs such as cisplatin and gefitinib in NSCLC cell lines. When the cytotoxic drug cisplatin was treated in combination with NA49 in epidermal growth factor receptors (EGFRs) WT cell lines, sensitization was induced in an HSP27 expression-dependent manner. With gefitinib treatment, NA49 showed increased combination effects in both EGFR WT and Mut cell lines, also with HSP27 expression-dependent patterns. Moreover, NA49 induced sensitization in EGFR Mut cells with a secondary mutation of T790M when combined with gefitinib. Augmented tumor growth inhibition was shown with the combination of cisplatin or gefitinib and NA49 in nude mouse xenograft models. These results suggest the combination of HSP27 inhibitor NA49 and anticancer agents as a candidate for overcoming HSP27-mediated drug resistance in NSCLC patients.