The Clinical Experience of Computed Tomographic-Guided Navigation System in C1-2 Spine Instrumentation Surgery

Objective

To identify the accuracy and efficiency of the computed tomographic (CT)-based navigation system on upper cervical instrumentation, particularly C1 lateral mass and C2 pedicle screw fixation compared to previous reports.

Methods

Between May 2005 and March 2014, 25 patients underwent upper cervical instrumentation via a CT-based navigation system. Seven patients were excluded, while 18 patients were involved. There were 13 males and five females; resulting in four degenerative cervical diseases and 14 trauma cases. A CT-based navigation system and lateral fluoroscopy were used during the screw instrumentation procedure. Among the 58 screws inserted as C1-2 screws fixation, their precise positions were evaluated by postoperative CT scans and classified into three categories : in-pedicle, non-critical breach, and critical breach.

Results

Postoperatively, the precise positions of the C1-2 screws fixation were 81.1% (47/58), and 8.6% (5/58) were of non-critical breach, while 10.3% (6/58) were of critical breach. Most (5/6, 83.3%) of the critical breaches and all of non-critical breaches were observed in the C2 pedicle screws and there was only one case of a critical breach among the C1 lateral mass screws. There were three complications (two vertebral artery occlusions and a deep wound infection), but no postoperative instrument-related neurological deteriorations were seen, even in the critical breach cases.

Conclusion

Although CT-based navigation systems can result in a more precise procedure, there are still some problems at the upper cervical spine levels, where the anatomy is highly variable. Even though there were no catastrophic complications, more experience are needed for safer procedure.     

TAK1 regulates hepatic cell survival and carcinogenesis

TGF-β-activated kinase 1 (TAK1 or MAP3K7) is an intracellular hub molecule that regulates both nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that play key roles in development, cell survival, immune response, metabolism, and carcinogenesis. TAK1 activity is tightly regulated by its binding proteins, TAB1 and TAB2/TAB3, as well as by post-translational modification including ubiquitination and phosphorylation. Accumulating evidence demonstrates that TAK1 plays a role in tumor initiation, progression, and metastasis as a tumor prompter or tumor suppressor. An understanding of the role of TAK1 in liver physiology and diseases is required for the development of therapeutic agencies targeting TAK1. In this review, we highlight the activation mechanism and pathophysiological roles of TAK1 in the liver.     

JAK2V617F-positive endothelial cells contribute to clotting abnormalities in myeloproliferative neoplasms

The Janus kinase 2 (JAK2) V₆₁₇F mutation is the primary pathogenic mutation in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Although thrombohemorrhagic incidents are the most common causes of morbidity and mortality in patients with MPNs, the events causing these clotting abnormalities remain unclear. To identify the cells responsible for the dysfunctional hemostasis, we used transgenic mice expressing JAK2V₆₁₇F in specific lineages involved in thrombosis and hemostasis. When JAK2V₆₁₇F was expressed in both hematopoietic and endothelial cells (ECs), the mice developed a significant MPN, characterized by thrombocytosis, neutrophilia, and splenomegaly. However, despite having significantly higher platelet counts than controls, these mice showed severely attenuated thrombosis following injury. Interestingly, platelet activation and aggregation in response to agonists was unaltered by JAK2V₆₁₇F expression. Subsequent bone marrow transplants revealed the contribution of both endothelial and hematopoietic compartments to the attenuated thrombosis. Furthermore, we identified a potential mechanism for this phenotype through JAK2V₆₁₇F-regulated inhibition of von Willebrand factor (VWF) function and/or secretion. JAK2V₆₁₇F⁺ mice display a condition similar to acquired von Willebrand syndrome, exhibiting significantly less high molecular weight VWF and reduced agglutination to ristocetin. These findings greatly advance our understanding of thrombohemorrhagic events in MPNs and highlight the critical role of ECs in the pathology of hematopoietic malignancies.Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders, characterized by significant increases in one or more myeloid-cell lineages. Mutations in the Janus kinase 2 (JAK2) and MPL genes are common in the majority of Philadelphia chromosome-negative (Ph⁻) MPNs, which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). By far the most frequent mutation in MPNs is JAK2V₆₁₇F (1–4), which occurs in the highly conserved autoinhibitory JAK homology (JH) 2 domain, causing hyperactive kinase activity and hyperproliferation of myeloid progenitor cells, leading to overproduction of red blood cells (RBCs), platelets, and leukocytes. Although ET and PV have a relatively benign clinical course, patients’ life expectancy can be severely reduced by bleeding or thrombosis, the manifestations of which are significantly more common than other MPN-related complications such as myelofibrosis and acute leukemic transformation (5). The frequency and nature of thrombotic and hemorrhagic events vary greatly depending on disease phenotype and patient history. Data taken from a number of previous studies indicate that the probability of major thrombosis ranges between 8–29% (ET) and 11–39% (PV) whereas the incidence of bleeding at initial presentation is less frequent than thrombosis, ranging between 3–18% (ET) and 3–8% (PV) (6–8).A number of abnormalities that could potentially contribute to this prothrombotic phenotype have been identified in the blood and vascular cells of JAK2V₆₁₇F⁺ MPN patients. Much work has focused on defining platelet abnormalities, including increased expression of membrane proteins such as P-selectin and tissue factor (TF), which would prime platelets for activation and increase levels of platelet-activation markers and platelet factor 4 (PF4) in the plasma (9–12). Interestingly, however, aggregation studies show a decreased response to ADP and epinephrine in platelets isolated from patients with ET and PV compared with controls (10). Furthermore, no correlation has been made between severity of thrombocytosis in ET patients and increased risk of thrombosis (6, 13). In contrast, extreme thrombocytosis (platelets >1,500 × 10⁹/L) is thought to contribute to a hemorrhagic phenotype in ET patients, and is commonly attributed to the development of acquired von Willebrand syndrome (AVWS) (11, 12, 14), where the increased platelets bind to highly prothrombotic, ultralarge von Willebrand factor (VWF) multimers, removing them from the plasma (15).Recent studies suggest that leukocytosis is a potential thrombotic risk factor in young PV and ET patients, possibly through the interactions of leukocytes, especially neutrophils, with platelets and endothelial cells (ECs) (16, 17) or the production of prothrombotic molecules such as TF. Increased basal activation of neutrophils has been shown in PV and ET patients, including elevated expression of CD11b and levels of neutrophil proteases in the plasma, both of which are prothrombotic (9, 18, 19). Studies have also shown increased activation of vascular ECs in JAK2V₆₁₇F⁺ MPN patients. Increased P- and E-selectin levels in the plasma, coupled with decreased levels of nitric oxide (NO), could conceivably contribute to a prothrombotic phenotype. Furthermore, JAK2V₆₁₇F⁺ ECs have recently been reported in a subpopulation of MPN patients, and EC expression was coupled with an increased risk of thrombosis (20, 21). Taken together, previous studies describe physiological abnormalities in a number of cell types in JAK2V₆₁₇F⁺ MPN patients, all of which could contribute toward increased thrombosis and/or bleeding. However, these data are often contradictory and fail to definitively explain the mechanism/s responsible for the development of thrombohemorrhagic disease.Here, we used FF1 transgenic mice (22) to express human JAK2V₆₁₇F in specific lineages to determine which cells are responsible for the thrombohemorrhagic manifestations seen in patients with MPNs. FF1 mice were crossed with Pf4-Cre or Tie2-Cre mice to express JAK2V₆₁₇F specifically in platelets alone, or in hematopoietic cells and ECs, respectively (23–28). These models have provided us with an unparalleled opportunity to determine the specific role/s of JAK2V₆₁₇F in pathological thrombosis and hemostasis.     

Factors associated with complex regional pain syndrome type I in patients with surgically treated distal radius fracture

Purpose

Wrist fracture is considered a typical initiating trauma for complex regional pain syndrome type I (CRPS I). However, few studies have comprehensively evaluated factors associated with the occurrence of CRPS I after the surgical treatment of a distal radius fracture (DRF). This study evaluates the factors influencing the occurrence of CRPS I after the surgical treatment of a DRF.

Methods

A total of 477 patients with a DRF who had been treated surgically were enrolled in this prospective observational study. Patients were followed for 6 months after surgery, and CRPS I was diagnosed using the Budapest diagnostic criteria for research. The factors assessed for the development of CPRS I were age, gender, the body mass index, the type of fracture, the energy of trauma, the number of trial reductions, the type of surgery, and the duration of immobilization. A multivariate logistic regression analysis was conducted to identify independent predictors of the occurrence of CRPS I.

Results

Among the 477 patients, 42 (8.8 %) satisfied the Budapest criteria for CRPS I within 6 months of surgery. Female patients developed CRPS I more frequently, and the patients who developed CRPS I were older and more likely to sustain a high energy injury or have a comminuted fracture. According to the multivariate analysis, female patients and those with a high energy trauma or severe fracture type were significantly more likely to develop CRPS I (p = 0.02, 0.01, and 0.01, respectively).

Conclusions

High energy injuries, severe fractures, and the female gender contribute to the development of CRPS I after the surgical treatment of DRF. The results have important implications for physicians who wish to identify patients at high risk for CRPS I after operative fixation for DRF and instigate treatment accordingly.     

The Effects of Single Nucleotide Polymorphisms in Korean Patients with Early-onset Atrial Fibrillation after Catheter Ablation

BackgroundThis study evaluated the status of single nucleotide polymorphisms (SNPs) in Korean patients with early-onset (< 40 years old) atrial fibrillation (AF) and their effects on the outcome after catheter ablation.MethodsA total of 89 patients (35.7 ± 3.7 years, 81 males) with drug-refractory AF (paroxysmal 64.0%) who underwent catheter ablation were included in this study. Sixteen SNPs, including rs13376333, rs10465885, rs10033464, rs2200733, rs17042171, rs6843082, rs7193343, rs2106261, rs17570669, rs853445, rs11708996, rs6800541, rs251253, rs3807989, rs11047543, and rs3825214, were genotyped. Serial 48-hour Holter monitoring was conducted to detect AF recurrences during long-term follow up.ResultsWild-type genotypes of rs11047543 (GG; 26/69 [37.7%] vs. GA; 13/18 [72.2%] vs. AA; 0/0 [0%], P = 0.009) and rs7193343 (CC; 0/7 [0%] vs. CT; 22/40 [55.0%] vs. TT; 18/41 [43.9%], P = 0.025) and the homozygous variant of rs3825214 (AA; 16/31 [51.6%] vs. AG; 22/43 [51.2%] vs. GG; 2/13 [15.4%], P = 0.056) were significantly associated with a lower rate of late recurrence. When the patients were assigned to four groups according to the number of risk alleles (n = 0–3), there were significant differences in recurrence rate (n = 0; 0/3 vs. n = 1; 2/13 [15.4%] vs. n = 2; 24/52 [46.2%] vs. n = 3; 13/17 [76.5%], P = 0.003). When correcting for multiple variables, rs11047543 (hazard ratio [HR], 2.723; 95% confidence interval [CI], 1.358–5.461; P = 0.005) and the number of risk alleles (HR, 2.901; 95% CI, 1.612–5.219; P < 0.001) were significantly associated with recurrence of AF after catheter ablation.ConclusionPolymorphisms on rs7193343 closest to ZFHX3 (16q22), rs3825214 near to TBX5 (12q24), and rs11047543 near to SOX5 (12p12) modulate the risk for AF recurrence after catheter ablation. The number of risk alleles of these 3 SNPs was an independent predictor of recurrence during long-term follow up in Korean patients with early-onset AF.     

Influence of Apical Root Resection on the Biomechanical Response of a Single-rooted Tooth: A 3-dimensional Finite Element Analysis

Introduction

Apical root resection is a biologically essential component in endodontic microsurgery. However, because it reduces the total root length and supported root surface, it changes the biomechanical response of the tooth. The purpose of this study was to analyze the biomechanical effect of apical root resection and to compare apical root resection with periodontal bone loss from a biomechanical standpoint.

Methods

Finite element models of the maxillary central incisor were reconstructed. First, preoperative and surgically treated models were generated to assess the factors altering the biomechanical response of the tooth. Then, apically resected models with different amounts of resection (3, 4, 5, 6, 7, and 8 mm) were created to estimate the clinically applicable limit of apical root resection. Periodontally destructed models with varying degrees of bone loss (0.5, 1, 1.5, 2, and 3 mm) were also created to compare the effect of apical root resection with periodontal bone loss. Stress distribution, tooth displacement, and effective crown-to-root ratio (α) were analyzed for each condition.

Results

Apical root resection did not significantly alter the maximum von Mises stress or tooth displacement until it reached 6 mm (α = 0.67) when the tooth was supported by normal periodontium. In contrast, periodontal bone loss had a greater impact on biomechanical response change compared with apical root resection.

Conclusions

For a tooth supported by normal periodontium, 3 mm of apical root resection (α = 1.07) appeared to be mechanically acceptable. The biomechanical influence of apical root resection was weak compared with that of periodontal bone loss.     

Allergic Diseases and Multiple Chemical Sensitivity in Korean Adults

Purpose

Multiple chemical sensitivity (MCS) is a clinical syndrome representing multi-organ and psychological symptoms caused by chronic exposure to various chemicals in low concentrations. We evaluated the prevalence and related factors of MCS targeting Korean adults using the Quick Environmental Exposure and Sensitivity Inventory (QEESI©).

Methods

A total of 446 participants were recruited from Severance Hospital. Participants underwent a questionnaire interview including questions on sociodemographic factors, occupational and environmental factors, allergic diseases, and the QEESI©. Among them, 379 participants completed the questionnaire and the QEESI©. According to the QEESI© interpretation results, participants were divided into very suggestive (VS) group and less suggestive (LS) group.

Results

The estimated prevalence of MCS was higher in allergic patients than non-allergic participants (19.7% and 11.3%, respectively, P=0.04). In the multivariate logistic regression analysis, ages of 30-39 (OR, 2.94; 95% CI, 1.25-6.95) and those of 40-49 (OR, 2.51; 95% CI, 1.02-6.21) were significantly related to MCS compared to those aged less than 30 years. Female sex (OR, 2.16; 95% CI, 1.11-4.18), experience of dwelling in a new house (OR, 2.05; 95% CI, 1.04-4.03), and atopic dermatitis (OR, 1.95; 95% CI, 1.04-3.69) were also significantly related to MCS. However, only age of 30-39 in the allergic group was significant in the stratified analysis.

Conclusions

The estimated prevalence of MCS was higher among allergic patients than non-allergic participants. People with experience of dwelling in a new house and atopic dermatitis were more at risk of being intolerant to chemicals. Further studies to provide the nationally representative prevalence data and clarify risk factors and mechanisms of MCS are required.     

当归的等级化研究

中草药标准化是非常有必要的,需要用物理和化学的方法来建立标准.标准化的分级是每位草药生产的指标之-.中国当归的等级分为5级:大体、形状、颜色、香味及杂质是否存在.而韩国的生当归分为三级,分别是60 g以上,20～60 g之间,20 g以下.当归身的重量约占整个当归的30%,其表面颜色是浅黄棕色到褐色.-般没有次品.若有次品,多为腐烂、中空、表面色黑或中节呈褐色.提出了当归标准化的等级,并期待着进-步研究.此研究可以做为中药标准化研究的参考指标.