Use of Reverse Shock Index Multiplied by Simplified Motor Score in a Five-Level Triage System: Identifying Trauma in Adult Patients at a High Risk of Mortality.

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.

A Ten-Year Retrospective Cohort Study on Neck Collar Immobilization in Trauma Patients with Head and Neck Injuries.

Background and Objectives: In the context of prehospital care, spinal immobilization is commonly employed to maintain cervical stability in head and neck injury patients. However, its use in cases of unclear consciousness or major trauma patients is often precautionary, pending the exclusion of unstable spinal injuries through appropriate diagnostic imaging. The impact of prehospital C-spinal immobilization in these specific patient populations remains uncertain. Materials and Methods: We conducted a retrospective cohort study at Taipei Tzu Chi Hospital from January 2009 to May 2019, focusing on trauma patients suspected of head and neck injuries. The primary outcome assessed was in-hospital mortality. We employed multivariable logistic regression to investigate the relationship between prehospital C-spine immobilization and outcomes, while adjusting for various factors such as age, gender, type of traumatic brain injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and activation of trauma team. Results: Our analysis encompassed 2733 patients. Among these, patients in the unclear consciousness group (GCS ≤ 8) who underwent C-spine immobilization exhibited a higher mortality rate than those without immobilization. However, there was no statistically significant difference in mortality among patients with alert consciousness (GCS > 8). Multivariable logistic regression analysis revealed that advanced age (age ≥ 65), unclear consciousness (GCS ≤ 8), major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and the use of neck collars for immobilization (adjusted OR: 1.850, 95% CI: 1.240-2.760, p = 0.003) were significantly associated with an increased risk of mortality. Subgroup analysis indicated that C-spine immobilization was significantly linked to an elevated risk of mortality in older adults (age ≥ 65), patients with unclear consciousness (GCS ≤ 8), those with major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and individuals in shock (shock index > 1). Conclusions: While our findings do not advocate for the complete abandonment of neck collars in all suspected head and neck injury patients, our study suggests that prehospital cervical and spinal immobilization should be applied more selectively in certain head and neck injury populations. This approach is particularly relevant for older individuals (age ≥ 65), those with unclear consciousness (GCS ≤ 8), individuals experiencing major traumatic injuries (ISS ≥ 16 or RTS ≤ 7), and patients in a state of shock (shock index ≥ 1). Our study employs a retrospective cohort design, which may introduce selection bias. Therefore, in the future, there is a need for confirmation of our results through a two-arm randomized controlled trial (RCT) arises, as this design is considered ideal for addressing this issue.

The impact of holiday season and weekend effect on traumatic injury mortality: Evidence from a 10-year analysis.

Objectives: Trauma is one of the leading causes of death and its incidence increases annually. The "weekend effect" and "holiday season effect" on traumatic injury mortality remain controversial, whereby traumatic injury patients admitted during weekends and/or holiday season have a higher risk of in-hospital death. The present study is aimed to explore the association between "weekend effect" and "holiday season effect" and mortality in traumatic injury population. Materials and Methods: This retrospective descriptive study included patients from the Taipei Tzu Chi Hospital Trauma Database between January 2009 and June 2019. The exclusion criterion was age of < 20 years. The primary outcome was the in-hospital mortality rate. The secondary outcomes included intensive care unit (ICU) admission, ICU re-admission, length of stay (LOS) in the ICU, ICU admission duration ≥ 14 days, total hospital LOS, total hospital LOS ≥ 14 days, need for surgery, and re-operation rate. Results: In this study, 11,946 patients were included in the analysis, and 8143 (68.2%) patients were admitted on weekdays, 3050 (25.5%) on weekends, and 753 (6.3%) on holidays. Multivariable logistic regression revealed that the admission day was not associated with an increased risk of in-hospital mortality. In other clinical outcome analyses, we found no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups. The subgroup analysis showed that the association between holiday season admission and in-hospital mortality was noted only in the elderly and shock condition populations. The holiday season duration did not differ in terms of in-hospital mortality. Longer holiday season duration was also not associated with an increased risk of in-hospital mortality, ICU LOS ≥14 days, and total LOS ≥14 days. Conclusion: In this study, we did not find any evidence that weekend and holiday season admissions in the traumatic injury population were associated with an increased risk of mortality. In other clinical outcome analyses, there was no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups.

PREHOSPITAL SHOCK INDEX MULTIPLIED BY AVPU SCALE AS A PREDICTOR OF CLINICAL OUTCOMES IN TRAUMATIC INJURY.

ABSTRACT: Objectives: Many prehospital trauma triage scores have been proposed, but none has emerged as a criterion standard. Therefore, a rapid and accurate tool is necessary for field triage. The shock index (SI) multiplied by the AVPU (Alert, responds to Voice, responds to Pain, Unresponsive) score (SIAVPU) reflected the hemodynamic and neurological conditions through a combination of the SI and AVPU. This study aimed to investigate the prediction performance of SI multiplied by the AVPU and to compare the prediction performance of other prehospital trauma triage scores in a population with traumatic injury. Patients and Methods: This study included 6,156 patients with trauma injury from the Taipei Tzu Chi trauma database. We investigated the accuracy of four scoring systems in predicting mortality, intensive care unit (ICU) admission, and prolonged hospital stay (defined as a duration of hospitalization >14 days). In the subgroup analysis, we also analyzed the effects of age, injury mechanism and severity, underlying diseases, and traumatic brain injury. Results: The predictive accuracy of SIAVPU for mortality, ICU admission, and prolonged hospital stay was significantly higher than that of SI, modified SI, and SI multiplied by age in the traumatic injury population, with an area under the receiver operating characteristic curve of 0.738 for mortality, 0.641 for ICU admission, and 0.606 for prolonged hospital stay. In the subgroup analysis, the prediction accuracy of mortality, ICU admission, and prolonged hospital stay of SIAVPU was also better in patients with younger age, older age, major trauma (Injury Severity Score ≥16), motor vehicle collisions, fall injury, healthy, cardiovascular disease, mixed traumatic brain injury, and isolated traumatic brain injury. The best cutoff levels of SIAVPU score to predict mortality, ICU admission, and total length of stay ≥14 days in trauma injury patients were 0.90, 0.82, and 0.80, with accuracies of 88.56%, 79.84%, and 78.62%, respectively. Conclusions: In conclusion, SIAVPU is a rapid and accurate field triage score with better prediction accuracy for mortality, ICU admission, and prolonged hospital stay than SI, modified SI, and SI multiplied by age in patients with trauma. Patients with SIAVPU ≥0.9 should be considered for the highest-level trauma center available within the geographic constraints of regional trauma systems.

Shock index, modified shock index, age shock index score, and reverse shock index multiplied by Glasgow Coma Scale predicting clinical outcomes in traumatic brain injury: Evidence from a 10-year analysis in a single center.

Objectives: Early identification of traumatic brain injury (TBI) patients at a high risk of mortality is very important. This study aimed to compare the predictive accuracy of four scoring systems in TBI, including shock index (SI), modified shock index (MSI), age-adjusted shock index (ASI), and reverse shock index multiplied by the Glasgow Coma Scale (rSIG). Patients and methods: This is a retrospective analysis of a registry from the Taipei Tzu Chi trauma database. Totally, 1,791 patients with TBI were included. We investigated the accuracy of four major shock indices for TBI mortality. In the subgroup analysis, we also analyzed the effects of age, injury mechanism, underlying diseases, TBI severity, and injury severity. Results: The predictive accuracy of rSIG was significantly higher than those of SI, MSI, and ASI in all the patients [area under the receiver operating characteristic curve (AUROC), 0.710 vs. 0.495 vs. 0.527 vs. 0.598], especially in the moderate/severe TBI (AUROC, 0.625 vs. 0.450 vs. 0.476 vs. 0.529) and isolated head injury populations (AUROC 0.689 vs. 0.472 vs. 0.504 vs. 0.587). In the subgroup analysis, the prediction accuracy of mortality of rSIG was better in TBI with major trauma [Injury Severity Score (ISS) ≥ 16], motor vehicle collisions, fall injury, and healthy and cardiovascular disease population. rSIG also had a better prediction effect, as compared to SI, MSI, and ASI, both in the non-geriatric (age < 65 years) and geriatric (age ≥ 65 years). Conclusion: rSIG had a better prediction accuracy for mortality in the overall TBI population than SI, MSI, and ASI. Although rSIG have better accuracy than other indices (ROC values indicate poor to moderate accuracy), the further clinical studies are necessary to validate our results.

Association of In-Hospital Mortality and Trauma Team Activation: A 10-Year Study.

Background: Early trauma team activation (TTA) may improve clinical outcomes through early diagnosis and timely intervention by a dedicated multidisciplinary team. Controversy seems to exist about the effect of establishing trauma team systems in traumatic injury populations. Our aim was to identify factors that may be associated with clinical outcomes in trauma injury and to investigate the effect of trauma team activation. Method: This retrospective descriptive study included all traumatic patients from the Taipei Tzu Chi Hospital Trauma Database. All prehospital vital signs, management, injury type, injury mechanisms, hospitalization history, and clinical outcomes were analyzed, and multivariable logistic regression was used to investigate the association between trauma team activation and clinical outcomes. Subgroups of TTA in minor injury and non-TTA in major injury were also analyzed. Result: In this study, a total of 11,946 patients were included, of which 10,831 (90.7%) patients were minor injury (ISS < 16), and 1115 (9.3%) patients were major injury (ISS ≥ 16). In the minor injury population, TTA had a higher intensive care unit (ICU) admission rate, operation rate, re-operation rate, and prolonged total length of stay (LOS). In the major injury population, TTA had a higher mortality rate, prolonged total LOS, and prolonged ICU LOS. After adjusting for mechanism of injury and injury severity, there was no association between in-hospital mortality and TTA, compared with the non-TTA group. However, the TTA group had a higher risk of ICU admission, prolonged ICU LOS, and prolonged total LOS. The subgroup analysis showed trauma team activation had a higher risk of mortality in the 60- to 80-year-old population, major injury (ISS ≥ 16), consciousness clear population, and non-head injury group. Conclusions: We found there was no significant association between in-hospital mortality and TTA. However, in the TTA group, there was a higher risk of ICU admission, prolonged total, LOS, and prolonged ICU LOS. In the subgroup analysis, TTA had a higher risk of mortality in the 60- to 80-year-old population, major injury (ISS ≥ 16), consciousness clear population, and non-head injury group. Our results reflect TTA-criteria-selected patients with greater ISS and a high risk of mortality.

The association between blood pressure and in-hospital mortality in traumatic brain injury: Evidence from a 10-year analysis in a single-center.

OBJECTIVE: Blood pressure in patients with traumatic brain injury (TBI) is associated with clinical outcome. However, evidence of blood pressure (BP) range is scarce and the association between BP and clinical outcome is mostly controversial. We aimed to investigate the association between blood pressure and clinical outcome in TBI. METHODS: This is a retrospective cohort study using the Taipei Tzu Chi Hospital trauma database from January 2009 to June 2019; totally, 13,114 patients were examined. The primary outcome of this investigation was in-hospital mortality and the secondary outcomes were intensive care unit (ICU) admission rate and prolong ICU stay (defined as stay in ICU ≥ 14 days). Subgroups analysis of Glasgow Coma Scale (GCS) and Triage SBP was also conducted. RESULTS: A total of 1782 traumatic adult patients with TBI (AIS score < 3) were finally included. The cut-off points are 130 mmHg to 149 mmHg in all TBI patients with lower odds ratio of mortality. In different TBI severity, U-shape relationship also presented and we also found that cut-off points of 130 to 149 mmHg in mild TBI and 110 to 129 mmHg in moderate TBI have lower odds ratio of mortality. The mortality is significantly increased in BP below 90 mmHg and above 190 mmHg in TBI patients. CONCLUSIONS: Traumatic brain injury population presented a U-shape relationship between triage SBP and in-hospital mortality. Early resuscitation and correct hypotension/hypertension in TBI population with BP below 90 mmHg and above 190 mmHg may prevent from increased mortality.

A novel HDAC1/2 inhibitor suppresses colorectal cancer through apoptosis induction and cell cycle regulation.

Colorectal cancer (CRC) is one of the leading causes of death around the world, and synthetic chemicals targeting specific proteins or various molecular pathways for tumor suppression, such as histone deacetylases (HADC) inhibitors, are under intensively studied. The target of HDAC involves in regulating critical cellular mechanisms and underpins the progression of anticancer therapy. However, little is known about the antitumor mechanisms of class I specific HDAC inhibitors in CRC. We structurally designed and synthesized benzamide-based compounds, examined their anticancer activity in several solid tumors, and identified compound 9 with high potential. Results from the in vitro enzyme and cell-based studies demonstrated that compound 9 as a selective HDAC1/2 inhibitor that possessed short-term and long-term suppression capacities against colorectal cancer cells. Investigation of molecular regulatory mechanisms of 9 in colorectal cancer cells by biological functional assays evidenced that treatment of compound 9 could activate apoptosis, induce cell cycle arrest, facilitate DNA damage process, and suppress cancer migration. A non-cancerous cell line and the in vivo zebrafish model were applied for safety evaluation. In summary, our results demonstrate that compound 9 is a promising lead drug worth further investigation for development of future cancer therapeutic agents.

Design, synthesis and biological evaluation of bisindole derivatives as anticancer agents against Tousled-like kinases.

This study presents the design, synthesis, and characterization of bisindole molecules as anti-cancer agents against Tousled-like kinases (TLKs). We show that compound 2 composed of an indirubin-3'-oxime group linked with a (N-methylpiperidin-2-yl)ethyl moiety possessed inhibitory activity toward both TLK1 and TLK2 in vitro and diminished the phosphorylation level of the downstream substrate anti-silencing function 1 (ASF1) in replicating cells. The treatment of compound 2 impaired DNA replication, slowed S-phase progression, and triggered DNA damage response in replicating cells. Structure optimization further discovered six derivatives exhibiting potent TLK inhibitory activity and revealed the importance of the tertiary amine-containing moiety of the side chain. Moreover, the derivatives 6, 17, 19, and 20 strongly suppressed the growth of triple-negative breast cancer MDA-MB-231 cells, non-small cell lung cancer A549 cells, and colorectal cancer HCT-116 cells, while normal lung fibroblast MRC5 and IMR90 cells showed a lower response to these compounds. Taken together, this study identifies tertiary amine-linked indirubin-3'-oximes as potent anticancer agents that inhibit TLK activity.

Analysis of Clinical Outcome and Predictors of Mortality in Pediatric Trauma Population: Evidence from a 10 Year Analysis in a Single Center.

The shock index (SI) is a useful tool for predicting the injury severity and mortality in patients with trauma. However, pediatric physiology differs from that of adults. In the pediatric trauma population, the shock status may be obscured within the normal range of vital signs. Pediatric age-adjusted SI (SIPA) is reported more accurately compared to SI. In our study, we conducted a 10 year retrospective cohort study of pediatric trauma population to evaluate the SI and SIPA in predicting mortality, intensive care unit (ICU) admission, and the need for surgery. This retrospective cohort study included 1265 pediatric trauma patients from January 2009 to June 2019 at the Taipei Tzu Chi Hospital, who had a history of hospitalization. The primary outcome of this investigation was in-hospital mortality, and the secondary outcomes were the length of hospital and ICU stay, operation times, and ICU admission times. The SIPA group can detect changes in vital signs early to reflect shock progression. In the elevated SIPA group, more severe traumatic injuries were identified, including high injury severity score (ISS), revised trauma score (RTS), and new injury severity score (NISS) scores than SI > 0.9. The odds ratio of elevated SIPA and SI (>0.9) to predict ISS ≥ 16 was 3.593 (95% Confidence interval [CI]: 2.175-5.935, p < 0.001) and 2.329 (95% CI: 1.454-3.730, p < 0.001). SI and SIPA are useful for identifying the compensatory phase of shock in prehospital and hospital settings, especially in corresponding normal to low-normal blood pressure. SIPA is effective in predicting the mortality and severity of traumatic injuries in the pediatric population. However, SI and SIPA were not significant predictors of ICU admission and the need for surgery analysis.

Ring size changes in the development of class I HDAC inhibitors.

Five pathways involving different ring structures led to generation of fourteen thienylbenzamides (7-20) which display the structure-activity relationships of class I HDAC inhibitors. All the synthesised compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound. Compounds 8 and 16 inhibit HCT116 cells by activation of the apoptosis pathway.

Ultrasonography-Guided Minimally Invasive Surgery for Achilles Sleeve Avulsions.

BACKGROUND: Achilles sleeve avulsion, a relatively rare disorder, is characterized by sleeve-shaped injury extending from the calcaneus, located near the tendon insertion site. Unlike midsubstance tears of the Achilles tendon, end-to-end repair is difficult because less soft tissue is preserved distally. Open repair with transosseous sutures or suture anchors is currently favored. The purpose of this study was to evaluate the technical feasibility and functional outcomes of ultrasonography-guided Achilles sleeve avulsion repair. METHODS: From November 2009 to April 2018, 21 patients with Achilles sleeve avulsions (mean age, 57.8 years; range, 25-82 years) who underwent repair by the same surgeon were retrospectively reviewed. The repair was achieved through a stab wound under ultrasonographic guidance. Two parallel Bunnell-type sutures were crossed over the proximal stump and tied with sutures from suture anchors fixed in the calcaneal tuberosity. RESULTS: The mean operative time was 44 minutes, and the mean wound size was 1.5 cm. The patients were allowed to walk freely on postoperative week 6 with using high-ankle shoes. At postoperative 2 years' follow-up, the American Orthopaedic Foot & Ankle Society score significantly improved from 70.9 to 97.1 (P < .05); similarly, their 12-item Short Form Health Survey scores improved significantly (P < .05). Only 2 patients had superficial wound infections, which resolved with wound care and oral antibiotics. CONCLUSION: Our ultrasonography-guided surgical technique for Achilles sleeve avulsions provided excellent soft tissue visualization and availability as well as minimized the wound length to achieve good postsurgical outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.