INTRODUCTION: Trauma-induced coagulopathy (TIC) is a form of coagulopathy unique to trauma patients and is associated with increased mortality. The complexity and incomplete understanding of TIC have resulted in controversies regarding optimum management. This review aims to summarise the pathophysiology of TIC and appraise established and emerging advances in the management of TIC. METHODS: This narrative review is based on a literature search (MEDLINE database) completed in October 2020. Search terms used were "trauma induced coagulopathy", "coagulopathy of trauma", "trauma induced coagulopathy pathophysiology", "massive transfusion trauma induced coagulopathy", "viscoelastic assay trauma induced coagulopathy", "goal directed trauma induced coagulopathy and "fibrinogen trauma induced coagulopathy'. RESULTS: TIC is not a uniform phenotype but a spectrum ranging from thrombotic to bleeding phenotypes. Evidence for the management of TIC with tranexamic acid, massive transfusion protocols, viscoelastic haemostatic assays (VHAs), and coagulation factor and fibrinogen concentrates were evaluated. Although most trauma centres utilise fixed-ratio massive transfusion protocols, the "ideal" transfusion ratio of blood to blood products is still debated. While more centres are using VHAs to guide blood product replacement, there is no agreed VHA-based transfusion strategy. The use of VHA to quantify the functional contributions of individual components of coagulation may permit targeted treatment of TIC but remains controversial. CONCLUSION A greater understanding of TIC, advances in point-of-care coagulation testing, and availability of coagulation factors and fibrinogen concentrates allows clinicians to employ a more goal-directed approach. Still, hospitals need to tailor their approaches according to available resources, provide training and establish local guidelines.
Blood Coagulation Disorders/therapy* ; Blood Transfusion ; Hemorrhage ; Hemostasis ; Hemostatics ; Humans

OBJECTIVETo investigate the feasibility of analyzing acylcarnitine in dry filter-paper blood spots by liquid chromatography-tandem mass spectrometry (LC-MS/MS) which could be applied to detect inborn errors of metabolism in neonates.

METHODSWe obtained filter-paper blood from 26 dead infants from a neonatal intensive care unit (NICU) between October 1, 2008 and September 30, 2009. Acylcarnitine and amino acid profiles were obtained with LC-MS/MS. Four infants underwent routine autopsy. The postmortem blood specimens were compared with newborn blood specimens, and with specimens obtained from older infants with metabolic disorders.

RESULTSOf all the 26 patients, 5 (19.2%) were diagnosed as having different kinds of diseases: 3 with methylmalonic acidemia (the concentration of C3, and the ratio of C3/C16, C3/C2 increased), 1 with maple syrup urine disease (the concentration of leucine and isoleucine increased), and 1 with isovaleric acidemia (the concentration of C5 increased).

CONCLUSIONSPostmortem metabolic test can explain infant deaths and provide estimates of deaths attributable to inborn errors of metabolism in NICU. LC-MS/MS is suitable for analysis of postmortem specimens and can be considered for routine application in NICU autopsy.

Amino Acid Metabolism, Inborn Errors ; blood ; diagnosis ; Autopsy ; Carnitine ; blood ; Chromatography, Liquid ; methods ; Female ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Male ; Tandem Mass Spectrometry ; methods

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of this study was to analyze and report the results of caudal epidural injections using a catheter in patients in whom conventional epidural block had failed. SUMMARY OF LITERATURE REVIEW: Epidural nerve block is often used to treat chronic back pain and radicular pain in degenerative lumbar disease, and percutaneous epidural neuroplasty or surgery may be an alternative if it fails. MATERIALS AND METHODS: In total, 146 patients who were treated with caudal epidural block using a catheter were recruited for this study from January 1, 2015 to June 30, 2019. Forty-five patients who had not undergone any epidural block in the past were excluded from the study. Among patients who did not have a fracture and were followed up for at least 1 month, the medical records of 61 patients with degenerative disc herniation, spondylosis, and stenosis were reviewed retrospectively. Visual analogue scale (VAS) scores were evaluated before and after the procedure. RESULTS: Of the 61 patients who had undergone epidural block through a transforaminal caudal approach with no pain control effect, there were 18 males and 43 females. Their mean age was 66.3 years and the average follow-up period was 2.64 months. There were 46 cases of spinal stenosis, 33 cases of spondylosis, 2 cases of spondylolisthesis, 9 cases of disc herniation and 1 case of ankylosing spondylitis. The mean number of epidural blocks was 5.85 (times) before the procedure. The mean initial VAS score was 5.34 and the final follow-up VAS score was 2.70. There was a significant difference between before and after the procedure (p<0.05). The mean duration of effect after the procedure was 1.84 months and the mean number of procedures was 2.30. After the procedure, there were 4 cases of surgical treatment, 2 cases of neuroplasty, and 3 cases of epidural block using other methods over more than 1 year of follow-up. CONCLUSIONS: The result of this clinical study suggests that caudal epidural injections using a catheter may be effective for patients with low back pain who have not responded to previous epidural blocks before surgical treatment.
Back Pain ; Catheters ; Clinical Study ; Constriction, Pathologic ; Female ; Follow-Up Studies ; Humans ; Injections, Epidural ; Low Back Pain ; Male ; Medical Records ; Nerve Block ; Retrospective Studies ; Spinal Stenosis ; Spondylitis, Ankylosing ; Spondylolisthesis ; Spondylosis

History, 20th Century ; Humans ; Neurosurgery ; history ; Singapore

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer’s disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptor-benzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with IC₅₀ of 1.19, 0.84 μg/kg, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.
Adenosine ; Animals ; Binding Sites ; Caffeine ; Electroencephalography ; Epilepsy ; Eye Movements ; Flumazenil ; Hand ; Hypnotics and Sedatives ; Luteolin ; Mice ; Receptor, Adenosine A1 ; Receptor, Adenosine A2A ; Sleep Initiation and Maintenance Disorders

OBJECTIVES: The purpose of this study was to analyze and report the results of caudal epidural injections using a catheter in patients in whom conventional epidural block had failed.SUMMARY OF LITERATURE REVIEW: Epidural nerve block is often used to treat chronic back pain and radicular pain in degenerative lumbar disease, and percutaneous epidural neuroplasty or surgery may be an alternative if it fails. MATERIALS AND METHODS: In total, 146 patients who were treated with caudal epidural block using a catheter were recruited for this study from January 1, 2015 to June 30, 2019. Forty-five patients who had not undergone any epidural block in the past were excluded from the study. Among patients who did not have a fracture and were followed up for at least 1 month, the medical records of 61 patients with degenerative disc herniation, spondylosis, and stenosis were reviewed retrospectively. Visual analogue scale (VAS) scores were evaluated before and after the procedure. RESULTS: Of the 61 patients who had undergone epidural block through a transforaminal caudal approach with no pain control effect, there were 18 males and 43 females. Their mean age was 66.3 years and the average follow-up period was 2.64 months. There were 46 cases of spinal stenosis, 33 cases of spondylosis, 2 cases of spondylolisthesis, 9 cases of disc herniation and 1 case of ankylosing spondylitis. The mean number of epidural blocks was 5.85 (times) before the procedure. The mean initial VAS score was 5.34 and the final follow-up VAS score was 2.70. There was a significant difference between before and after the procedure (p<0.05). The mean duration of effect after the procedure was 1.84 months and the mean number of procedures was 2.30. After the procedure, there were 4 cases of surgical treatment, 2 cases of neuroplasty, and 3 cases of epidural block using other methods over more than 1 year of follow-up. CONCLUSIONS The result of this clinical study suggests that caudal epidural injections using a catheter may be effective for patients with low back pain who have not responded to previous epidural blocks before surgical treatment.

Background/Aims: Nonagenarians will purportedly account for 10% of the United States population by 2050. However, no studies have assessed the outcomes of nonvariceal upper gastrointestinal bleeding (NVUGIB) in this age group. Methods: The National Inpatient Sample database between 2016 and 2020 was used to compare the clinical outcomes of NVUGIB in nonagenarians and octogenarians and evaluate predictors of mortality and the use of esophagogastroduodenoscopy (EGD). Results: Nonagenarians had higher in-hospital mortality than that of octogenarians (4% vs. 3%, p<0.001). EGD utilization (30% vs. 48%, p<0.001) and blood transfusion (27% vs. 40%, p<0.001) was significantly lower in nonagenarians. Multivariate logistic regression analysis revealed that nonagenarians with NVUGIB had higher odds of mortality (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.3–1.7) and lower odds of EGD utilization (OR, 0.86; 95% CI, 0.83–0.89) than those of octogenarians. Conclusions Nonagenarians admitted with NVUGIB have a higher mortality risk than that of octogenarians. EGD is used significantly in managing NVUGIB among nonagenarians; however, its utilization is comparatively lower than in octogenarians. More studies are needed to assess predictors of poor outcomes and the indications of EGD in this growing population.

STUDY DESIGN: In vitro and in vivo studies to determine the anabolic effects of intervertebral disc (IVD) to adenovirus-mediated therapeutic gene transfer. OBJECTIVES: To quantify the anabolic effect of human IVD cells in vitro and rabbit IVD in vivo to therapeutic gene transfer. SUMMARY OF LITERATURE REVIEW: An alternative possibility to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Contemplating to extend this approach to treatment of disc degeneration, it is necessary to demonstrate anabolic effect of human IVD cells and rabbit disc to therapeutic gene transfer. MATERIALS AND METHODS: In vitro: IVD tissue was obtained from twelve patients. IVD cells were then isolated, cultured, and transduced with Ad/TGF-beta1. Genetically modified disc cells were incorporated into alginate beads and cultured. In vivo: Fifteen skeletally mature New Zealand white rabbit were used. 15ul of saline containing Ad/TGF-beta1 were injected into the nucleus pulposus of the disc in six rabbits. All rabbits were sacrificed 6 weeks after surgery. Nucleus pulposus tissues were harvested, weighted, and cultured. Conditioned medium of alginate bead and rabbit disc tissue cultures were subjected to ELISA to detect TGF-beta1 production. Newly synthesized proteoglycan were analyzed using chromatography on Sephadex G-25 in PD-10 columns after S35-sulfate incorporation. RESULTS: Concentration of TGF-beta1 increased over time in alginate beads cultures transduced with Ad/TGF- beta1. At 6 weeks nucleus pulposus tissue from the disc injected with Ad/TGF-beta1 exhibited 200% (p<0.05) increase in TGF- beta1 production. There was statistically significant 290% increase in newly synthesized proteoglycan in alginate cultures transduced with Ad/TGF- beta1 (p<0.05) compared to control. At 6 weeks nucleus pulposus tissue from the disc injected with Ad/TGF- beta1 exhibited 85% increase in proteoglycan synthesis (p<0.05) over that of intact control. CONCLUSION: In this study, we observed the robust upregulation of proteoglycan synthesis in gene transferred disc cells in vitro and in vivo - indicating good prospects for biologic effects of therapeutic gene therapy in the disc using adenovirus-mediated approach.
Anabolic Agents ; Chromatography ; Culture Media, Conditioned ; Enzyme-Linked Immunosorbent Assay ; Genetic Therapy* ; Humans ; Intercellular Signaling Peptides and Proteins ; Intervertebral Disc ; Intervertebral Disc Degeneration ; New Zealand ; Proteoglycans ; Rabbits ; Transforming Growth Factor beta1 ; Up-Regulation

INTRODUCTIONWhile opioids are effective in carefully selected patients with chronic non-cancer pain (CNCP), they are associated with potential risks. Therefore, treatment recommendations for the safe and effective use of opioids in this patient population are needed.

MATERIALS AND METHODSA multidisciplinary expert panel was convened by the Pain Association of Singapore to develop practical evidence-based recommendations on the use of opioids in the management of CNCP in the local population. This article discusses specific recommendations for various common CNCP conditions.

RESULTSAvailable data demonstrate weak evidence for the long-term use of opioids. There is moderate evidence for the short-term benefit of opioids in certain CNCP conditions. Patients should be carefully screened and assessed prior to starting opioids. An opioid treatment agreement must be established, and urine drug testing may form part of this agreement. A trial duration of up to 2 months is necessary to determine efficacy, not only in terms of pain relief, but also to document improvement in function and quality of life. Regular reviews are essential with appropriate dose adjustments, if necessary, and routine assessment of analgesic efficacy, aberrant behaviour and adverse effects. The reasons for discontinuation of opioid therapy include side effects, lack of efficacy and aberrant drug behaviour.

CONCLUSIONDue to insufficient evidence, the task force does not recommend the use of opioids as first-line treatment for various CNCP. They can be used as secondor third-line treatment, preferably as part of a multimodal approach. Additional studies conducted over extended periods are required.

Analgesics, Opioid ; therapeutic use ; Chronic Pain ; drug therapy ; etiology ; Evidence-Based Medicine ; Humans

PURPOSE: To develop a profiling tool which accurately assigns a patient to the appropriate attitudinal cluster for the management of asthma. METHODS: Attitudinal data from an online survey of 2,467 patients with asthma from 8 Asian countries/region, aged 18-50 years, having had ≥2 prescriptions in the previous 2 years and access to social media was used in a discriminant function analysis to identify a minimal set of questions for the Profiling Tool. A split-sample procedure based on 100 sets of randomly selected estimation and validation sub-samples from the original sample was used to cross-validate the Tool and assess the robustness of its predictive accuracy. RESULTS: Our Profiling Tool contained 10 attitudinal questions for the patient and 1 GINA-based level of asthma control question for the physician. It achieved a predictive accuracy of 76.2%. The estimation and validation sub-sample accuracies of 76.7% and 75.3%, respectively, were consistent with the tool's predictive accuracy at 95% confidence level; and their 1.4 percentage-points difference set upper-bound estimate for the degree of over-fitting. CONCLUSIONS: The Profiling Tool is highly predictive (>75%) of the attitudinal clusters that best describe patients with asthma in the Asian population. By identifying the attitudinal profile of the patient, the physician can make the appropriate asthma management decisions in practice. The challenge is to integrate its use into the consultation workflow and apply to areas where Internet resources are not available or patients who are not comfortable with the use of such technology.
Asia ; Asian Continental Ancestry Group ; Asthma* ; Discriminant Analysis ; Disease Management ; Humans ; Internet ; Prescriptions ; Social Media