Survival benefits of interventional radiology and surgical teams collaboration during primary trauma surveys: a single-centre retrospective cohort study.

BACKGROUND: A team approach is essential for effective trauma management. Close collaboration between interventional radiologists and surgeons during the initial management of trauma patients is important for prompt and accurate trauma care. This study aimed to determine whether trauma patients benefit from close collaboration between interventional radiology (IR) and surgical teams during the primary trauma survey. METHODS: A retrospective observational study was conducted between 2014 and 2021 at a single institution. Patients were assigned to an embolization group (EG), a surgery group (SG), or a combination group (CG) according to their treatment. The primary and secondary outcomes were survival at hospital discharge compared with the probability of survival (Ps) and the time course of treatment. RESULTS: The analysis included 197 patients, consisting of 135 men and 62 women, with a median age of 56 [IQR, 38-72] years and an injury severity score of 20 [10-29]. The EG, SG, and CG included 114, 48, and 35 patients, respectively. Differences in organ injury patterns were observed between the three groups. In-hospital survival rates in all three groups were higher than the Ps. In particular, the survival rate in the CG was 15.5% higher than the Ps (95% CI: 7.5-23.6%; p < 0.001). In the CG, the median time for starting the initial procedure was 53 [37-79] min and the procedure times for IR and surgery were 48 [29-72] min and 63 [35-94] min, respectively. Those times were significantly shorter among three groups. CONCLUSION: Close collaboration between IR and surgical teams, including the primary survey, improves the survival of severe trauma patients who require both IR procedures and surgeries by improving appropriate treatment selection and reducing the time process.

High-Concentration Insulin Glargine Overdose: Polyphasic Patterns of Blood Insulin Levels.

In the treatment of diabetes mellitus, there is a growing trend towards using high-concentration insulin, with Lantus XR (Bridgewater, NJ: Sanofi-Aventis U.S. LLC), which has a drug concentration three times higher than that of conventional Lantus (100 U/mL; Bridgewater, NJ: Sanofi-Aventis U.S. LLC), being a prominent example. This type of high-concentration insulin is known for its smaller injection volumes, leading to a slower absorption rate and maintenance of more consistent blood insulin levels. When administered in high doses, the pharmacological effects of insulin are generally prolonged; however, insulin glargine overdose rarely occurs, and its pharmacokinetics remain unclear. We encountered a case of an insulin overdose in a 19-year-old female patient, who had self-injected glargine (Lantus XR) 1,350 units and aspart (NovoRapid; Bagsværd, Denmark: Novo Nordisk A/S) 600 units. We measured blood glucose and insulin levels over time. Bimodal peaks in blood insulin levels were observed, and we adjusted high doses of intravenous infusion with a 50% glucose solution until the blood insulin levels returned to the normal range. Consequently, the patient was treated without inducing severe hypoglycemia. U300 glargine overdose may lead to both a multimodal elevation in blood insulin levels and prolonged hypoglycemia compared to U100 glargine. Therefore, monitoring blood insulin levels and adjusting treatment accordingly may contribute to safer patient management. This study represents the initial documentation of blood insulin levels measured in a U300 glargine overdose patient, revealing a bimodal peak.

The aminopeptidase LAP3 suppression accelerates myogenic differentiation via the AKT-TFE3 pathway in C2C12 myoblasts.

Skeletal muscle maintenance depends largely on muscle stem cells (satellite cells) that supply myoblasts required for muscle regeneration and growth. The ubiquitin-proteasome system is the major intracellular protein degradation pathway. We previously reported that proteasome dysfunction in skeletal muscle significantly impairs muscle growth and development. Furthermore, the inhibition of aminopeptidase, a proteolytic enzyme that removes amino acids from the termini of peptides derived from proteasomal proteolysis, impairs the proliferation and differentiation ability of C2C12 myoblasts. However, no evidence has been reported on the role of aminopeptidases with different substrate specificities on myogenesis. In this study, therefore, we investigated whether the knockdown of aminopeptidases in differentiating C2C12 myoblasts affects myogenesis. The knockdown of the X-prolyl aminopeptidase 1, aspartyl aminopeptidase, leucyl-cystinyl aminopeptidase, methionyl aminopeptidase 1, methionyl aminopeptidase 2, puromycine-sensitive aminopeptidase, and arginyl aminopeptidase like 1 gene in C2C12 myoblasts resulted in defective myogenic differentiation. Surprisingly, the knockdown of leucine aminopeptidase 3 (LAP3) in C2C12 myoblasts promoted myogenic differentiation. We also found that suppression of LAP3 expression in C2C12 myoblasts resulted in the inhibition of proteasomal proteolysis, decreased intracellular branched-chain amino acid levels, and enhanced mTORC2-mediated AKT phosphorylation (S473). Furthermore, phosphorylated AKT induced the translocation of TFE3 from the nucleus to the cytoplasm, promoting myogenic differentiation through increased expression of myogenin. Overall, our study highlights the association of aminopeptidases with myogenic differentiation.

Lactate promotes neuronal differentiation of SH-SY5Y cells by lactate-responsive gene sets through NDRG3-dependent and -independent manners.

Lactate serves as the major glucose alternative to an energy substrate in the brain. Lactate level is increased in the fetal brain from the middle stage of gestation, indicating the involvement of lactate in brain development and neuronal differentiation. Recent reports show that lactate functions as a signaling molecule to regulate gene expression and protein stability. However, the roles of lactate signaling in neuronal cells remain unknown. Here, we showed that lactate promotes the all stages of neuronal differentiation of SH-SY5Y and Neuro2A, human and mouse neuroblastoma cell lines, characterized by increased neuronal marker expression and the rates of neurites extension. Transcriptomics revealed many lactate-responsive genes sets such as SPARCL1 in SH-SY5Y, Neuro2A, and primary embryonic mouse neuronal cells. The effects of lactate on neuronal function were mainly mediated through monocarboxylate transporters 1 (MCT1). We found that NDRG family member 3 (NDRG3), a lactate-binding protein, was highly expressed and stabilized by lactate treatment during neuronal differentiation. Combinative RNA-seq of SH-SY5Y with lactate treatment and NDRG3 knockdown shows that the promotive effects of lactate on neural differentiation are regulated through NDRG3-dependent and independent manners. Moreover, we identified TEA domain family member 1 (TEAD1) and ETS-related transcription factor 4 (ELF4) are the specific transcription factors that are regulated by both lactate and NDRG3 in neuronal differentiation. TEAD1 and ELF4 differently affect the expression of neuronal marker genes in SH-SY5Y cells. These results highlight the biological roles of extracellular and intracellular lactate as a critical signaling molecule that modifies neuronal differentiation.

Little involvement of recycled-amino acids from proteasomal proteolysis in de novo protein synthesis.

Myoblast integrity is essential for skeletal muscle regeneration. Many intracellular proteins are degraded by the proteasome and converted to amino acids by aminopeptidases through the protein degradation pathway. Although we previously reported its importance for myoblast integrity, the involved mechanism remains unclear. In this study, we focused on the reusability of proteolytic products to elucidate the regulatory mechanism of protein synthesis mediated by the proteasome and aminopeptidases. Proteasome inhibition decreased protein synthesis, but recycled-amino acids derived from proteasomal proteolysis were not reused for de novo protein synthesis in C2C12 myoblasts. On the other hand, proteasome and aminopeptidase inhibition decreased intracellular ATP levels in C2C12 myoblasts. Therefore, it was indicated that amino acids produced by these proteolytic systems may be reutilized for ATP production through its metabolism, not for de novo protein synthesis. These findings suggested the proteasome and aminopeptidases are thought to be involved in protein synthesis through intracellular energy production by recycled-amino acid metabolism, thereby maintaining myoblast integrity.

The effect of participation of interventional radiology team in a primary trauma survey on patient outcome.

PURPOSE: The purpose of this study was to examine the survival benefits of a workflow in which an interventional radiology (IR) team participates in a primary trauma survey on patients with hemodynamically unstable trauma. MATERIALS AND METHODS: A retrospective observational study was conducted between 2012 and 2019 at a single institution. Patients who underwent an IR procedure as the initial hemostasis were assigned to the hemodynamically stable group (HSG) or hemodynamically unstable group (HUG). The primary and secondary outcomes were survival at hospital discharge compared with the probability of survival (Ps) and the time course. RESULTS: A total of 160 patients (100 men, 60 women; median age, 57.5 years [interquartile range (IQR): 31.5-72 years]) with an injury severity score of 24 (IQR: 13.75-34) were included. A total of 125 patients were included in the HSG group and 35 patients in the HUG group. The observational survival rate was significantly greater than the Ps rate by 4.9% (95% confidence interval [CI]: 1.6-8.4%; P = 0.005) in HSG and by 24.6% in HUG (95% CI: 16.9-32.3%; P < 0.001). The observational survival rate was significantly greater than Ps in HUG than in HSG (P < 0.001). The median time to initiate IR procedures and the median procedure time in HUG were 54 min [IQR: 45-66 min] and 48 min [IQR: 30-85 min], respectively; both were significantly shorter than those in the HSG. CONCLUSION: A trauma workflow utilizing an IR team in a primary survey is associated with improved survival of patients with hemodynamically unstable trauma when compared with Ps with a shorter time course.

Variability of extracorporeal cardiopulmonary resuscitation practice in patients with out-of-hospital cardiac arrest from the emergency department to intensive care unit in Japan.

AIM: A lack of known guidelines for the provision of extracorporeal cardiopulmonary resuscitation (ECPR) to patients with out-of-hospital cardiac arrest (OHCA) has led to variability in practice between hospitals even in the same country. Because variability in ECPR practice has not been completely examined, we aimed to describe the variability in ECPR practice in patients with OHCA from the emergency department (ED) to the intensive care units (ICU). METHODS: An anonymous online questionnaire to examine variability in ECPR practice was completed in January 2020 by 36 medical institutions who participated in the SAVE-J II study. Institutional demographics, inclusion and exclusion criteria, initial resuscitation management, extracorporeal membrane oxygenation (ECMO) initiation, initial ECMO management, intra-aortic balloon pumping/endotracheal intubation/management during coronary angiography, and computed tomography criteria were recorded. RESULTS: We received responses from all 36 institutions. Four institutions (11.1%) had a hybrid emergency room. Cardiovascular surgery was always involved throughout the entire ECMO process in only 14.7% of institutions; 60% of institutions had formal inclusion criteria and 50% had formal exclusion criteria. In two-thirds of institutions, emergency physicians carried out cannulation. Catheterization room was the leading location of cannulation (48.6%) followed by ED (31.4%). The presence of formal exclusion criteria significantly increased with increasing ECPR volume (P for trend <0.001). Intra-aortic balloon pumping was routinely initiated in only 25% of institutions. Computed tomography was routinely carried out before coronary angiography in 25% of institutions. CONCLUSIONS: We described the variability in ECPR practice in patients with OHCA from the ED to the ICU.

Puromycin-sensitive aminopeptidase is required for C2C12 myoblast proliferation and differentiation.

The ubiquitin-proteasome system is a major protein degradation pathway in the cell. Proteasomes produce several peptides that are rapidly degraded to free amino acids by intracellular aminopeptidases. Our previous studies reported that proteolysis via proteasomes and aminopeptidases is required for myoblast proliferation and differentiation. However, the role of intracellular aminopeptidases in myoblast proliferation and differentiation had not been clarified. In this study, we investigated the effects of puromycin-sensitive aminopeptidase (PSA) on C2C12 myoblast proliferation and differentiation by knocking down PSA. Aminopeptidase enzymatic activity was reduced in PSA-knockdown myoblasts. Knockdown of PSA induced impaired cell cycle progression in C2C12 myoblasts and accumulation of cells at the G2/M phase. Additionally, after the induction of myogenic differentiation in PSA-knockdown myoblasts, multinucleated circular-shaped myotubes with impaired cell polarity were frequently identified. Cell division cycle 42 (CDC42) knockdown in myoblasts resulted in a loss of cell polarity and the formation of multinucleated circular-shaped myotubes, which were similar to PSA-knockdown myoblasts. These data suggest that PSA is required for the proliferation of myoblasts in the growth phase and for the determination of cell polarity and elongation of myotubes in the differentiation phase.

Disseminated Varicella zoster infection with abdominal pain and periarterial fat stranding in a patient taking pomalidomide.

BACKGROUND: Disseminated Varicella zoster virus infection (DVI) is a severe infection associated with severe abdominal pain of unknown cause. We report a case in which periarterial (the celiac artery and superior mesenteric artery) fat stranding (PFS) on computed tomography (CT) was the presumed cause of abdominal pain in a patient taking pomalidomide. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital with abdominal pain. Her medical history was multiple myeloma treated with pomalidomide. Computed tomography showed no remarkable findings on admission, but 1 day later, a contrast-enhanced CT showed PFS. A skin eruption appeared on day 4 and we started acyclovir. On day 10, Varicella zoster virus antigen and antibody tests were positive, confirming the diagnosis of DVI. The abdominal pain subsequently improved, together with the PFS, and she was discharged. CONCLUSION: When patients present with severe abdominal pain and PFS, DVI and acyclovir must be considered.

Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy.

We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient's serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.