Diaphyseal forearm fracture management in adolescent patients from 2011 to 2020: A multicenter study of surgery and regional anesthesia trends.

BACKGROUND: Diaphyseal forearm fractures are common traumatic injuries among children. There has been much debate on the use of intramedullary nailing (IMN) or plate fixation in the adolescent population (10-16 years of age). Furthermore, as ultrasound technology has advanced, the safety and efficacy of ultrasound-guided axillary brachial plexus block for children has dramatically improved. Therefore, anesthesia options for adolescent patients have increased in recent years. This study aimed to investigate recent surgical and regional anesthesia trends of diaphyseal forearm fractures in patients 10 to 16 years of age in Japan through a multicenter epidemiological survey from 2011 to 2020. METHODS: This retrospective, multicenter study included 226 pediatric patients with diaphyseal forearm fracture aged 10-16 years treated from January 2011 to December 2020. We divided the patients into four groups according to the period in which they were treated: early (2011-2013), middle (2014-2016), late (2017-2019), and COVID-19 (2020). Information from medical records was used to investigate the number of surgeries, types of anesthesia administered, and internal fixation methods used for diaphyseal forearm fracture in adolescent patients during each period. RESULTS: The number of surgeries was generally constant in each period but decreased during the COVID-19 period. In the early, middle, late, and COVID-19 periods, the percentages of surgeries performed under regional anesthesia were 67.7, 85.5, 87.0, and 100% respectively (p = 0.003). During the same periods, the percentages of patients receiving IMN were 41.5, 49.3, 58.0, and 66.7%, respectively (p = 0.033). CONCLUSION: The use of IMN and regional anesthesia to treat diaphyseal forearm fracture in patients 10 to 16 years of age steadily increased during the study period from 2011 to 2020. These results indicate that regional anesthesia is safe, effective, and well-tolerated by adolescent patients. The treatment strategy for diaphyseal forearm fractures in adolescents using regional anesthesia in combination with IMN worked well and was effective during COVID-19. Our evidence suggests this trend will continue. We anticipate that our findings can be extrapolated for upper extremity fractures in adolescent patients beyond the Tokai region of Japan where the study was based.

An age-matched comparative study on intramedullary nailing and plate fixation of both-bone diaphyseal forearm fracture in adolescents.

OBJECTIVE: This study aimed to compare radiological and functional outcomes and complication rates between intramedullary nailing (IMN) and plate fixation for diaphyseal forearm fractures in adolescents via an age-matched analysis. METHODS: Data were collected from medical records at 11 hospitals from 2009 to 2019, and the age-matched study was conducted between IMN and plate fixation. Functional outcomes, radiographic outcomes, and postoperative complication rates were compared. RESULTS: The IMN group (Group N) and plate fixation group (Group P) each comprised 26 patients after age matching. The mean age after matching was 13.42 years old. Bone maturities at the wrist of the radius and ulna were not significantly different between the two groups (p = 0.764 and p = 1). At the last follow-up period, functional outcomes using the Price criteria were over 90% in both groups, and the rotational range of motion was comparable to that of the healthy side. Over 70% of cases in Group N were performed by closed reduction, and operation time was half that of Group P. Postoperative neurological symptoms and refractures were more common in Group P than in Group N, although not statistically significantly so. CONCLUSIONS: Treatment outcomes for age-matched adolescent diaphyseal forearm fractures were excellent with IMN, as well as with plate fixation in many cases despite fewer complications, better cosmesis, and shorter operative times with IMN. IMN for diaphyseal forearm fractures is a useful treatment option even in adolescents although the indications for the best procedure to perform should be considered depending on individual patient needs. LEVEL OF EVIDENCE IV: Multicenter retrospective study.

Soluble (Pro)Renin Receptor Level in Patients with Severe Obesity Is Associated with Visceral Adiposity and Is Involved with Insulin Resistance and Renal Injury.

INTRODUCTION: High soluble (pro)renin receptor (s[P]RR) level in circulation is reported in obese patients; however, it is unclear which body composition components are responsible for it. In this study, the authors examined blood s(P)RR levels and ATP6AP2 gene expression levels in visceral and subcutaneous adipose tissue (VAT, SAT) in severely obese patients who underwent laparoscopic sleeve gastrectomy (LSG), with the aim of clarifying the relationship with body composition and metabolic factors. METHODS: Seventy five cases who underwent LSG between 2011 and 2015 and were postoperatively followed-up for 12 months at the Toho University Sakura Medical Center were included in the analysis of the cross-sectional survey at baseline, and 33 cases were included in the analysis of the longitudinal survey during the 12 months after LSG. We evaluated body composition, glycolipid parameters, liver/renal function, as well as serum s(P)RR level and ATP6AP2 mRNA expression level in VAT and SAT. RESULTS: The mean serum s(P)RR level at baseline was 26.1 ng/mL, this value was considered higher than values in healthy subjects. There was no significant difference in the expression level of ATP6AP2 mRNA between VAT and SAT. At baseline, multiple regression analysis for the association between s(P)RR and variables identified that visceral fat area, HOMA2-IR, and UACR showed the independent relationships with s(P)RR. During the 12 months after LSG, body weight, serum s(P)RR level showed a significant decrease (from 30.0 ± 7.0 to 21.9 ± 4.3). Multiple regression analysis for the association between the change in s(P)RR and variables showed that changes in visceral fat area, and alanine transaminase were independently related to the change in s(P)RR. CONCLUSION: This study showed that blood s(P)RR level was high in severely obese patients, decreased with weight loss by LSG, and was associated with visceral fat area in both pre- and postoperative changes. The results suggest that blood s(P)RR levels in obese patients may reflect the involvement of visceral adipose (P)RR in insulin resistance and renal damage mechanisms associated with obesity.

Longer time of implantation using the buried pin technique for intramedullary nailing would decrease refracture in the diaphyseal forearm fracture in children-retrospective multicenter (TRON) study.

BACKGROUND: Intramedullary nailing using Kirschner wires in pediatric diaphyseal forearm fractures is often performed as a less invasive treatment than plate fixation, but it remains controversial whether the tips of Kirschner wires are buried or exposed. The purpose of this study was to investigate the relationship between whether the tips are buried or exposed and complications, especially of refracture. METHODS: Data of 405 patients under 16 years who underwent surgical treatment for diaphyseal forearm fractures in our 11 hospitals between 2010 and 2020 were collected. Finally, 143 patients who underwent intramedullary nailing with at least 6-month follow-up were analyzed. We investigated difference in complication rates depending on whether the Kirschner wire tips were buried (Group B: n = 79) or exposed (Group E: n = 64). Regarding refractures, we also examined time of onset and status of bone union before the refracture occurred. RESULTS: The duration before implant removal in Group B was more than 4 times longer than that in Group E (mean 187.9 vs. 41.4 days, p<0.001), although there was no significant difference in the progression of bone union between the two groups. Regarding postoperative complications, Group B had a significantly lower rate of refractures than Group E (7.9% vs. 32.8%, p<0.001), although the rate of irritation pain was significantly higher (15.2% vs. 1.6%, p = 0.006). The infection rate was also lower in Group B than Group E, but not significantly so (3.8% vs. 10.9%, p = 0.112). Refractures between 3 and 9 months after surgery accounted for 66.7% of all refractures, and those within 3 months accounted for 14.5% of all fractures. There was no significant difference in the status of bone union before the refracture occurred between patients with and without refracture. CONCLUSIONS: The present study showed that longer time of implantation using the buried pin technique for intramedullary nailing reduces refracture of pediatric diaphyseal forearm fractures. Because of the risk of refracture during remodeling, we recommend the implantation of intramedullary nailing for 6-9 months and the instruction for the patients and the parents to pay more attention to refracture at least within 9 months postoperatively. LEVEL OF EVIDENCE: Level Ⅲ, Multicenter retrospective study.

Simultaneous muscular hemorrhages in two regions three years after successfully controlling refractory ascites using transjugular intrahepatic portosystemic shunt treatment: a case report.

INTRODUCTION: Various therapies and drugs have been developed to extend the life expectancy of patients with liver cirrhosis. The prolonged prognosis of cirrhotic patients may change the final cause of death in the future. Deep bleeding into the muscle is an uncommon but potentially life-threatening complication of liver cirrhosis. CASE REPORT: A 53-year-old man had undergone transjugular intrahepatic portosystemic shunt treatment for refractory ascites, which successfully controlled it for three years. However, he had started drinking again and experienced acute-on-chronic liver failure. He also had severe back pain. Abdominal computed tomography showed hyperdensities in the retroperitoneum and right pleural cavity. Despite blood infusion, he died from acute-on-chronic liver failure. A pathological autopsy revealed bleeding from the iliopsoas and right diaphragmatic muscle simultaneously, evident from the presence of red blood cells located between the muscle sheaths. Disruption of the small vessels in the skeletal muscle fibers was inferred. CONCLUSION: This is a critical case that underscores the significance of improving available knowledge based on the cause of final death of the patients with cirrhosis, who now have a good long-term prognosis owing to the latest medical developments.

Association of Plasma Xanthine Oxidoreductase with Arterial Stiffness in Type 2 Diabetes with Liver Dysfunction.

BACKGROUND: Type 2 diabetes is a risk factor for atherosclerosis. Oxidative stress, which is a causative factor in insulin resistance, leads to atherosclerosis in patients with diabetes. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is related to oxidative stress. We aimed to examine the influence of plasma XOR activity on arterial stiffness in patients with type 2 diabetes. METHODS: In total, 458 patients with type 2 diabetes not receiving antihyperuricemic agents were enrolled and their clinical parameters including plasma XOR activity and the cardio-ankle vascular index (CAVI) were measured. Patients were divided into the liver dysfunction and absence of liver dysfunction groups. Multiple regression analysis was performed. RESULTS: The median plasma XOR activity level was 64.3 pmol/h/mL (33.3-147.3 pmol/h/mL). Plasma XOR activity was correlated significantly and positively with aspartate transaminase and alanine transaminase (ρ > 0.5). The level of plasma XOR activity in the liver dysfunction group was eight-fold higher than that in the absence of liver dysfunction group. A significant positive correlation was observed between plasma XOR activity and the CAVI only in the liver dysfunction group (ρ = 0.3968, P < 0.0043). Multiple regression models demonstrated that plasma XOR activity was an independent predictor of the CAVI in the liver dysfunction group (P = 0.0055). CONCLUSIONS: Our results suggest that plasma XOR activity is associated with arterial stiffness and may have a role in atherosclerosis development in patients with type 2 diabetes and liver dysfunction.

Fatty acid desaturase 2 is up-regulated by the treatment with statin through geranylgeranyl pyrophosphate-dependent Rho kinase pathway in HepG2 cells.

Statins have been reported to increase the plasma concentration of arachidonic acid (AA), an omega-6 long chain polyunsaturated fatty acid (LCPUFA) in several clinical studies indicating that statins affect the endogenous synthesis of LCUFAs. In the present study, we investigated the roles of the intrinsic mevalonate cascade and Rho-dependent pathway in LCPUFA synthesis, especially focusing on fatty acid desaturases (Fads) 2, using the human hepatocellular carcinoma cell line HepG2. Cell number and the activity of caspase-3 and 7 (caspase-3/7) was measured using a commercial kit. Gene expression was analyzed by quantitative real-time PCR. Protein expression was detected by Western blot analysis. Atorvastatin decreased cell viability and increased caspase-3/7 activity in a dose-dependent manner. At lower concentrations, atorvastatin stimulated both mRNA and protein expression of Fads2, and increased mRNA expression of FADS1 and ELVOL5. Both mevalonate and geranylgeranyl-pyrophosphate (GGPP), but not cholesterol, fully reversed atorvastatin-induced upregulation of Fads2, and mevalonate-effected reversal was inhibited by treatment with the Rho-associated protein kinase inhibitor Y-27632. These data clearly demonstrated that in human HepG2 cells, statins affect the endogenous synthesis of LCPUFAs by regulation of not only Fads2, but also Fads1 and Elovl5, through the GGPP-dependent Rho kinase pathway.

Hemorrhagic Gastric Metastasis from Hepatocellular Carcinoma Successfully Treated Using Coil Embolization of the Left Gastric Artery.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

[Unresectable combined hepatocellular-cholangiocellular carcinoma treated with transcatheter arterial chemoembolization and gemcitabine: a case study].

A 76-year-old female was referred to our hospital because of liver dysfunction. Abdominal contrasted computed tomography (CT) revealed a tumor of 7.5cm in the hepatic hilar area. Based on the biopsy, the tumor was diagnosed by as combined hepatocellular-cholangiocellular carcinoma (with stem-cell features). The tumor was considered unresectable;hence, the patient underwent transcatheter arterial chemoembolization (TACE). However, a CT scan revealed the treatment to be ineffective. Subsequently, systemic gemcitabine (GEM) chemotherapy was administered and tumor shrinkage was observed with reperfusion of the umbilical portion of the left portal vein. The patient's condition is currently stable 17 months after diagnosis, with no tumor regrowth on account of repeated TACE and GEM therapy. The present case of unresectable combined hepatocellular-cholangiocellular carcinoma was successfully treated using TACE and systemic GEM chemotherapy.

7-Ketocholesterol induces ROS-mediated mRNA expression of 12-lipoxygenase, cyclooxygenase-2 and pro-inflammatory cytokines in human mesangial cells: Potential role in diabetic nephropathy.

7-Ketocholesterol (7-KCHO) is a highly proinflammatory oxysterol and plays an important role in the pathophysiology of diabetic nephropathy (DN). Lipoxygenases (LOXs) and cyclooxygenases (COXs) are also involved in the development of DN. The aim of this study was to clarify the effects of 7-KCHO on mRNA expression of LOXs and COXs as well as pro-inflammatory cytokines in human mesangial cells (HMC). We evaluated cell viability by WST-8 assay and measured mRNA expression by reverse transcription-polymerase chain reaction. Intracellular reactive oxygen species (ROS) production was evaluated by flow cytometry. Although 7-KCHO did not affect cell viability of HMC, 7-KCHO stimulated significant increases in mRNA expression of 12-LOX, COX-2 and pro-inflammatory cytokines. 7-KCHO also induced an increase in ROS production, while N-acetylcysteine partially suppressed the increase. The 12-LOX and COX-2 inhibitors also suppressed mRNA expression of cytokines. These findings may contribute to the elucidation of the molecular mechanism of the pathophysiology of DN.

Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells.

Numerous clinical studies have reported that statins increase the plasma concentration of arachidonic acid, which is an ω-6 long-chain polyunsaturated fatty acid (LCPUFA), and decrease the concentrations of eicosapentaenoic acid and docosahexaenoic acid, which are ω­3 LCPUFAs. These findings indicate that statins may affect the endogenous synthesis of LCPUFAs, which is regulated by fatty acid desaturases (FADSs) and elongation of very long­chain fatty acids proteins (ELOVLs). The present study aimed to investigate the roles of the intrinsic mevalonate cascade and Rho­dependent pathway in statin­induced regulation of these desaturases and elongases, as well as cell viability using mouse 3T3­L1 cells. mRNA expression was analyzed by quantitative polymerase chain reaction. Treatment with atorvastatin decreased cell viability and increased the mRNA expression levels of Fads1, Fads2 and ELOVL fatty acid elongase 5 (Elovl5) in a dose­dependent manner. Mevalonate and geranylgeranyl pyrophosphate (GGPP), but not cholesterol, fully reversed the atorvastatin­induced downregulation of cell viability and upregulation of gene expression; however, mevalonate itself did not affect cell viability and gene expression. The Rho­associated protein kinase inhibitor Y­27632 inhibited the mevalonate­ and GGPP­mediated reversal of atorvastatin­induced upregulation of Fads1, Fads2 and Elovl5. These findings indicated that statins may affect the endogenous synthesis of LCPUFAs by regulating Fads1, Fads2 and Elovl5 gene expression via the GGPP­dependent Rho kinase pathway in mouse 3T3-L1 cells.

Resveratrol attenuates triglyceride accumulation associated with upregulation of Sirt1 and lipoprotein lipase in 3T3-L1 adipocytes.

AIM: We aimed to investigate the effect of resveratrol (Rsv) on expression of genes regulating triglyceride (TG) accumulation and consumption in differentiated 3T3-L1 preadipocytes. METHODS: 3T3-L1 preadipocytes were cultured in DMEM supplemented with 10% fetal calf serum. Upon reaching confluence, cells were induced to differentiate for 4 days, cultured for 10 days for TG accumulation, and then incubated with Rsv (0, 25 or 50 µM) for 3 days. TG accumulation was analyzed by Oil Red-O staining. To understand how Rsv regulates TG accumulation and consumption, changes in gene and protein expressions of several factors associated with free fatty acid (FFA) uptake and ß-oxidation were investigated by real-time RT-PCR and Western blot. For further elucidation of underlying mechanisms, we also investigated gene expressions using Sirtuin1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) siRNA. RESULTS: Rsv dose dependently enhanced Sirt1 expression and reduced TG accumulation. Rsv-induced reduction of TG accumulation was abolished by inhibition of Sirt1 and PGC1α. Rsv also enhanced expressions of genes involved in FFA uptake [peroxisome proliferator-activated receptor-gamma (PPARγ) and lipoprotein lipase] and in ß-oxidation regulation [PGC1-α and carnitine palmitoyl-transferase 1a (CPT1a)]. All these effects were abolished by Sirt1 inhibition. CONCLUSION: The present results suggest that Rsv may augment synthesis and oxidation of fatty acid, and possibly increases energy utilization efficiency in adipocytes through activation of Sirt1. The present study may provide meaningful evidence supporting the efficacy of Rsv in the treatment of obesity.

7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO) has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS) production and apoptotic rate, and upregulated the caspase-3/7 pathway. Furthermore, these effects of 7KCHO were abolished by pre-incubation of the cells with N-acetylcysteine (NAC), an ROS inhibitor. Also, 7KCHO enhanced the mRNA expression of two endoplasmic reticulum (ER) stress markers; CHOP and GRP78, in MC3T3-E1 cells. Pre-incubation of the cells with NAC suppressed the 7KCHO-induced upregulation of CHOP, but not GRP78. In conclusion, we demonstrated that 7KCHO induced apoptosis of MC3T3-E1 cells associated with ROS generation, ER stress, and caspase-3/7 activity, and the effects of 7KCHO were abolished by the ROS inhibitor NAC. These findings may provide new insight into the relationship between oxysterol and pathophysiology of osteoporosis seen in T2DM.

Screening of a heptamer-type sgRNA library for potential therapeutic agents against hematological malignancies.

tRNase-Z(L)-utilizing efficacious (TRUE) gene silencing is an RNA-mediated gene expression control technology that has therapeutic potential. This technology is based on the property of tRNase Z(L) that it can cleave any target RNA at any desired site under the direction of an appropriate artificial small guide RNA (sgRNA). To search for novel potential therapeutic sgRNAs for hematological malignancies, we screened a library composed of 156 sgRNAs, and found that 20 sgRNAs can efficiently induce apoptosis in leukemia and/or myeloma cells. Furthermore, we demonstrated that 4 of the 20 sgRNAs can reduce growth rates of HL60 cells in mouse xenograft models.

Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells.

Serotonin (5-HT) is a known mitogen for vascular smooth muscle cells (VSMCs). The dedifferentiation and proliferation/apoptosis of VSMCs in the arterial intima represent one of the atherosclerotic changes. LR11, a member of low-density lipoprotein receptor family, may contribute to the proliferation of VSMCs in neointimal hyperplasia. We conducted an in vitro study to investigate whether 5-HT is involved in LR11 expression in human VSMCs and apoptosis of VSMCs induced by 7-ketocholesterol (7KCHO), an oxysterol that destabilizes plaque. 5-HT enhanced the proliferation of VSMCs, and this effect was abolished by sarpogrelate, a selective 5-HT2A receptor antagonist. Sarpogrelate also inhibited the 5-HT-enhanced LR11 mRNA expression in VSMCs. Furthermore, 5-HT suppressed the 7KCHO-induced apoptosis of VSMCs via caspase-3/7-dependent pathway. These findings provide new insights on the changes in the differentiation stage of VSMCs mediated by 5-HT.

Hot flashes and blood pressure in middle-aged Japanese women.

BACKGROUND: Some Western studies have reported that hot flashes are risk factors of cardiovascular diseases. We aimed to investigate the association between hot flashes and blood pressure in middle-aged Japanese women. METHODS: Annual medical checkup data from 1,058 healthy middle-aged Japanese women were analyzed. Nonstandardized coefficients (B), which were calculated by multiple linear regression analysis, were used to evaluate differences in blood pressure resulting from hot flashes. RESULTS: The prevalence of current hot flashes was 20.2%, and the experience of hot flashes was significantly more frequent according to age (P < 0.01). Systolic blood pressure was significantly higher in women currently experiencing hot flashes and in those experiencing them within the previous month than in those without such experience (B = 6.0, P < 0.01; B = 3.7, P < 0.05, respectively). Diastolic blood pressure was significantly higher in women currently experiencing hot flashes than in those without such experience (B = 3.9; P < 0.01). Among current smokers, systolic blood pressure was 16.4mm Hg higher in those currently experiencing hot flashes (P < 0.01), but this difference was less among nonsmokers (P < 0.05). In addition, pulse pressure was 10.5mm Hg higher in current smokers currently experiencing hot flashes than in other current smokers (P < 0.01), but not among nonsmokers. CONCLUSIONS: In middle-aged Japanese women, hot flashes were associated with higher pulse pressure among smokers but not among nonsmokers.

Histopathology of the tissue adhering to the multiple tine expandable electrodes used for radiofrequency ablation of hepatocellular carcinoma predicts local recurrence.

OBJECTIVE: To assess the ability to predict the local recurrence of hepatocellular carcinoma by analyzing tissues adhering to the radiofrequency ablation probe after complete ablation. METHODS: From May 2002 to March 2011, tissue specimens adhering to the radiofrequency ablation probe from 284 radiofrequency ablation sessions performed for hepatocellular carcinomas ≤3 cm in size were analyzed. The specimens were classified as either viable tumor tissue or complete necrosis, and the local recurrence rates were calculated using the Kaplan-Meier method. RESULTS: From the tumors ≤3 cm in size, viable tissue was present in 6 (2.1%) of 284 specimens, and the local recurrence rates after 1 and 2 years of follow-up were 6.7% and 11.2%, respectively. Local recurrence developed significantly earlier in the viable tissue group. The recurrence rate was not significantly different based on whether transcatheter arterial chemoembolization was performed. CONCLUSION: The histopathology of the tissue adhering to the radiofrequency ablation probes used for hepatocellular carcinoma treatment can predict local recurrence. Additional aggressive treatment for patients with viable tissue can therefore improve the overall survival.