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Surgical site infection (SSI) is one of the most devastating complications following spinal instrumented fusion surgeries because it may lead to a significant increase in morbidity, mortality, and poor clinical outcomes. Identifying the risk factors for SSI can help in developing strategies to reduce its occurrence. However, data on the risk factors for SSI in degenerative diseases are limited. This study aimed to identify risk factors for deep SSI following posterior instrumented fusion for degenerative diseases in the thoracic and/or lumbar spine in adult patients. This was a multicenter, observational cohort study conducted at 10 study hospitals between July 2010 and June 2015. The subjects were consecutive adult patients who underwent posterior instrumented fusion surgery for degenerative diseases in the thoracic and/or lumbar spine and developed SSI. Detailed patient-specific and procedure-specific potential risk variables were prospectively recorded using a standardized data collection chart and retrospectively reviewed. Of the 2913 enrolled patients, 35 developed postoperative deep SSI (1.2%). Multivariable regression analysis identified three independent risk factors: male sex (P = 0.002) and American Society of Anesthesiologists (ASA) score of ≥ 3 (P = 0.003) as patient-specific risk factors, and operation including the thoracic spine (P = 0.018) as a procedure-specific risk factor. Thoracic spinal surgery, an ASA score of ≥ 3, and male sex were risk factors for deep SSI after routine thoracolumbar instrumented fusion surgeries for degenerative diseases. Awareness of these risk factors can enable surgeons to develop a more appropriate management plan and provide better patient counseling.

Background: Pleural mesothelioma, a devastating asbestos‐associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well‐known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K/AKT/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER‐155008, an HSP70 inhibitor, on pleural mesothelioma. Methods: Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER‐155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed. Results: In mesothelioma cell lines, VER‐155008 (5.0 μM or more) inhibited cell growth and colony formation, accompanied by G1 cell cycle arrest. According to western blot analysis, VER‐155008 reduced p‐AKT expression. However, VER‐155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX‐IP‐GFP‐LC3‐RFP‐LC3ΔG, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER‐155008 and gefitinib which is an EGFR‐tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER‐155008. Conclusions: On the basis of these results, functional HSP70 inhibition by VER‐155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma. Key points Significant findings of the study In pleural mesothelioma cells, inhibition of HSP70 function by VER‐155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR‐TKI, did not show the same synergistic effect in autophagy. What this study adds The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells., The effects of VER‐155008, gefitinib or FBS deprivation on macroautophagy in mesothelioma cells were assessed by a plasmid system (pMRX‐IP‐GFP‐LC3‐RFP‐ LC3ΔG). This plasmid produces light chain 3 (LC3) protein bound to green fluorescent protein (GFP), and LC3ΔG protein, an internal control, bound to red fluorescent protein (RFP).

Surgical site infection (SSI) is a serious complication following spine surgery and is correlated with significant morbidities, poor clinical outcomes, and increased healthcare costs. Accurately identifying risk factors can help develop strategies to reduce this devastating consequence; however, few multicentre studies have investigated risk factors for SSI following posterior cervical spine surgeries. Between July 2010 and June 2015, we performed an observational cohort study on deep SSI in adult patients who underwent posterior cervical spine surgery at 10 research hospitals. Detailed patient- and procedure-specific potential risk variables were prospectively recorded using a standardised data collection chart and were reviewed retrospectively. Among the 2184 consecutive adult patients enrolled, 28 (1.3%) developed postoperative deep SSI. Multivariable regression analysis revealed 2 statistically significant independent risk factors: occipitocervical surgery (P P = 0.024). Subgroup analysis demonstrated that occipitocervical surgery (P = 0.001) was the sole independent risk factor for deep SSI in patients with instrumented fusion. Occipitocervical surgery is a relatively rare procedure; therefore, our findings were based on a large cohort acquired using a multicentre study. To the best of our knowledge, this is the first study to identify occipitocervical procedure as an independent risk variable for deep SSI after spinal surgery.

Microsatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci lengths were calculated independently of mapping against a reference genome, and their distribution was digitized by weighted mean. Weighted mean differences between tumor and non-tumor samples with different MSI status were assessed, and cut-off values for each marker in the discovery cohort were determined. Each microsatellite maker was defined as unstable if the weighted mean difference was greater than the cut-off value. In the discovery cohort, the evaluation model demonstrated sensitivity and specificity of 100% for all markers. In the validation cohort, MSI status determined by the new model was consistent with the outcome of the conventional method in 29/30 cases (97%). The single inconsistent case was classified as low-frequency MSI by the conventional method but considered MSI-high by NGS. Genetic testing for mismatch repair genes revealed a pathogenic variant in MSH6 in the discordant case. We successfully developed a quantitative evaluation method for determining MSI status using NGS. This is a robust and sensitive method and could improve LS diagnosis.

Objective: The CHADS2 score is a stroke risk stratification scheme in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to determine whether the CHADS2 score can help to predict the risk of non-cerebral acute arterial embolism. Materials and Methods: One hundred and seventeen patients who underwent surgery for non-cerebral acute arterial embolism with NVAF between 1997 and 2009 were enrolled in the cross sectional study. The CHADS2 score of each patient was calculated at the onset of symptoms. The distribution of the CHADS2 score was compared with that of other studies analyzing patients with stroke. Results: The perioperative mortality was 11.1%. A comparison of patients with stroke revealed that our distribution curves were significantly shifted to the left, showing that the CHADS2 score did better in predicting stroke than non-cerebral embolism. On the other hand, the distribution in our series coincides with that of NVAF patients in general. These results indicated that the risk of non-cerebral embolism occurs at the same rate regardless of the CHADS2 score. Conclusions: The CHADS2 scoring system seems to be an unreliable predictor of non-cerebral embolism, and may not contribute in avoiding potentially life-threatening acute arterial occlusion of the peripheral artery.

This clinical trial reports the use of hydroxyethyl starch (HES70/0.55/4) at very high dosages during surgery. HES70/0.55/4 has the lowest molecular weight among all HES products, and thus may have the least side effects. This observational retrospective study clarified the effects of high-dose HES70/0.55/4 on coagulation and renal function up to 1 month after massive bleeding during surgery. Of 20875 patients on our surgical database, 31 patients were identified who had lost more than 5000 ml of blood during surgery and had survived for more than 1 month. The fluid balance, and pre- and postoperative laboratory data were analyzed. Patients were assessed using acute kidney injury (AKI) criteria. AKI and non-AKI groups were compared regarding volume of HES70/0.55/4 infused and serum creatinine (Cr) levels before surgery and until 1 month after surgery. The mean volumes of blood loss, total transfusions, HES70/0.55/4, and urine output during surgery were 8051 ml; 5765 ml; 3085 ml (54 ml/kg); and 1338 ml (2.7 ml/kg/h), respectively. Cr increased, and activated partial thromboplastin time, prothrombin time and international normalized ratio were prolonged postoperatively (0.77–0.9 mg/dl, 34–52 s, and 1.1–1.7, respectively). Of the 31 patients, 13 developed AKI, and 10 of the 13 had recovered at 1 month. Renal impairment due to HES70/0.55/4 was not evident, as shown by the finding that the HES70/0.55/4 amount infused in the AKI patients (53 ml/kg) did not differ from that in the nonAKI patients (55 ml/kg), and there was no relationship between the amount of HES infused and Cr changes. High-dose HES70/0.55/4 could be safely used in massive bleeding during surgery. HES70/0.55/4 may affect coagulation, but renal impairment was not evident 1 month after surgery.

The purpose of this prospective study was to evaluate the usefulness of 18F-fluorodeoxyglucose (FDG) and 11C-choline positron emission tomography (PET)/computed tomography (CT) for detecting recurrences of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy. Additionally, we surveyed the time period during which an effective negative predictive value could be maintained after the first follow-up PET/CT examination and estimated the optimal timing of a second PET/CT examination for detecting late recurrences. Fifty-three subjects (36 men and 17 women; mean age: 59.4 ± 11.5 years) with advanced head and neck squamous cell carcinoma were recruited. Post-treatment 18F-FDG PET/CT and 11C-choline examinations were performed in all patients between 8 and 12 weeks after combined intra-arterial chemotherapy and radiotherapy. The PET/CT images were evaluated using a patient-based analysis and a lesion-based analysis. All of the patients were prospectively followed for at least 9 months after the post-treatment PET/CT examination, with surveillance using conventional images (including CT and/or MRI) and a physical examination performed every 3 months. Recurrences, as determined using the patient-based analysis, were eventually confirmed in 18, 6 and 5 patients at 3, 4–6 and 7–9 months after the post-treatment PET/CT examination, respectively. The sensitivity and specificity of the 18F-FDG PET/CT and the 11C-choline PET/CT examinations to predict recurrence within 3 months were higher (FDG: 89 and 91%; choline: 83 and 80%, respectively) than for recurrence detection 6 months (FDG: 67 and 90%; choline: 62 and 76%, respectively) and 9 months later (FDG: 59 and 92%; choline: 55 and 75%, respectively). The lesion-based analysis showed that the maximum standardized uptake value of 18F-FDG and 11C-choline in the recurrent lesions were correlated with each other, compared with their relation in scar tissues (R 2 = 0.492 and 0.197, respectively). 11C-choline was not superior to 18F-FDG for the detection of recurrent head and neck cancer. Both modalities had difficulty identifying recurrences at 4–9 months after the post-treatment PET/CT examination. In patients with advanced head and neck cancer who have received combined therapy, a second post-treatment PET/CT examination to check for late recurrences should be performed within 4–6 months after the first post-treatment PET/CT examination.

It has been suggested that antihypertensive drug therapy is attributable to the lower blood pressure variability, we investigated the effects of 4 classes of antihypertensives on the blood pressure variability; in addition, we also compared the effects among 4 calcium channel blockers.We measured the 24-hour blood pressure variability in 309 patients with a history of cerebrovascular disease treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, β blocker, or calcium channel blocker.The daytime blood pressure variability treated with β blockers (14.3 ± 3.1) was higher than that treated with an angiotensin receptor blockers (11.5 ± 3.1) or calcium channel blockers (12.6 ± 3.4) in patients with cerebrovascular disease (P.05). In the analysis of the patient distribution of blood pressure variability, patients receiving β blockers occurred more frequently in the higher blood pressure variability (P = .0023). Treatment with angiotensin receptor blockers and cilnidipine, which blocks N-type calcium channels, was shown to be more frequently associated with the lower blood pressure variability (P = .0202 and .0467). The mean blood pressure of patients grouped by distribution of blood pressure variability was found to be independent to blood pressure variability, for any of the antihypertensive drugs or calcium channel blockers examined.From the results, it is suggested that angiotensin receptor blocker and calcium channel blockers rather than β blockers may be more favorable for blood pressure management in patients with cerebrovascular disease. Among the calcium channel blockers, cilnidipine may be more favorable than other calcium channel blockers.

To probe the decarboxylation process of methyl–ethyl–α pyridylacetic acid (MEPA), molecular orbital calculations on the optimized geometry, transition-state geometry, and intrinsic reaction coordinate were performed by the MNDO–PM3 method. The salient features of the optimized structure of MEPA are that the carboxyl anion is nearly on the plane of the pyridine ring (the dihedral angle of C8C7C2N1 is 14.7°) and that the interatomic distance1 of O−9 … H1′ is 1.6 A (exchange of electrons exists between their atoms). The transition-state geometry of the decarboxylation process has the following features: (1) the activation enthalpy is 6.0 kcal/mol, (2) the dihedral angle of C8C7C2N1 is −50.2°, and (3) the interatomic distance of O−9H1′ and C7C8 increase by 111 and 124%, respectively, as compared with the optimized geometry. From the extreme beginning of the intrinsic decarboxylation process, the exchange of electrons between O−9 … H1′ begins to decrease. This decrease, which is considered to be induced by the rotation of C2C7, seems to initiate the dissociation of C7C8. © 1995 John Wiley & Sons, Inc.

The PM3 and AM1 molecular orbital programs have been employed for the investigation of the preferred protonation sites in pyrrole and its N-methyl, 2,5-dimethyl, 3-methyl, 2-methyl and 1,2-dimethyl derivatives. The following are reported: the LCAO coefficients of the HOMO (2p z ) (the HOMO coefficients); the atomic centered charges, which are calculated by the subroutine 'ESP' (ESP charges); the atomic net charges, which are obtained by a Mulliken population analysis (Mulliken net atomic charges). The predictions of the preferred protonation sites made by the HOMO coefficients and ESP charges are in perfect agreement with experimental data, whereas those made by the HOMO coefficients and Mulliken net atomic charges are not in agreement. It is hence obvious that the protonation of pyrrole and its methyl derivatives is controlled by not only HOMO-LUMO interaction but also by electrostatic forces, which are estimated by ESP charges. In other words, the subroutine 'ESP' is useful for estimation of a kind of electrostatic reaction of pyrrole and its methyl derivatives, which suggests that the subroutine may be effective for the investigation of the electrostatic reactions of other compounds.

The non-selective cation channel (NSCC) in the larval bullfrog skin contributes to the short-circuit current (SCC) across the skin. The effects of amiloride and acetylcholine on the SCC were examined in the presence or absence of Cu2+ to determine whether the amiloride binding site mediating activation or that mediating inhibition of the channel is blocked by Cu2+ and whether amiloride and acetylcholine share a common binding site on the NSCC. The skin of tadpoles raised in aldosterone was examined with K-Ringer present on the apical side to potentiate the SCC. Amiloride (10(-4) M) transiently increased SCC in the absence of Cu2+. Apical application of 500 microM Cu2+ increased the SCC. In the presence of Cu2+, amiloride decreased the SCC. In contrast, acetylcholine (1 mM) transiently increased SCC whether Cu2+ was present or not. These results suggest that there are two binding sites for amiloride on the NSCC, whereby the site that activates the channel is blocked by Cu2+ while the site that inhibits it is not, and that the binding sites for acetylcholine and amiloride may be different.

There are inconsistencies between the in vitro and in vivo effects of thyroid hormone and aldosterone (Aldo) on the development of an amiloride-blockable short-circuit current (SCC) across bullfrog skin [Takada, M., H. Yai, and K. Takayama-Arita. Am. J. Physiol. 268 ( Cell Physiol. 37): C218–C226, 1995]. To address this issue, tadpoles were raised in Aldo + T3. An amiloride-blockable SCC developed across the skin before forelimbs appeared. Noise analysis of the characteristics (single-channel current, blocking and unblocking rate coefficients, and apparent dissociation constant) of this amiloride-blockable Na+channel showed that it really was of the adult type. A similar SCC developed at stage XIX in the skin of tadpoles raised with Aldo alone. These results strongly support our hypothesis that the crucial hormone in the development of this SCC is Aldo but that a suppression mechanism attenuates its effect on SCC development until it is removed by the increase in the serum concentration of thyroid hormone (which starts at stages XVIII–XIX in vivo).

We have obtained the optimized geometrical structure of 2-(1-carboxy-1-hydroxyethyl)-3,4-dimethylthiazolium dipolar ion and investigated its geometric and electric changes during decarboxylation process by the MNDO-PM3 method, a molecular orbital method. The salient features of the optimized structure are that the dihedral angle of C4-C1-C2-S3 is 5.4 degrees and the distance between thiazolium S3 and carboxyl O6 is about 1.8 A (the bond order between S3 and O6 is about 0.4). The lowest energy decarboxylation profile is the following process. First the dihedral angle of C4-C1-C2-S3 becomes about 90 degrees, then the distance between C1-C2 increases while the dihedral angle holds about 90 degrees, and finally the C1-C2 bond disappears. The most remarkable change caused by the 90 degrees rotation is the disappearance of the S3-O6 bond, and this disappearance causes electric changes that prompt the decarboxylation.

Background Although little is known, a limited number of three-dimensional computed tomography (CT) images of the pelvis present focal concavity of posterior superior acetabulum. The purpose of the present study was to investigate this morphologic deformity and its relation with dysplasia and retroversion in adults who were expected to have the original morphology of the acetabulum after growth. Methods Consecutive adult patients with hip pain who visited our hospital and had three-dimensional pelvic CT images were retrospectively analyzed after approval of the institutional review board; exclusion criterions included diseases, injuries and operations that affect the morphology of the hip including radiographic osteoarthritis Tönnis grades 2 and 3. Focal concavity of posterior superior acetabulum was evaluated by three-dimensional CT image. Acetabular dysplasia was determined by lateral center edge (LCE) angle 10°, and anterior center edge (ACE) angle 10° or ACE angle