Risk factors for deep surgical site infection after posterior cervical spine surgery in adults: a multicentre observational cohort study.

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 < 0.001) and male sex (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.

Risk factors for deep surgical site infection following posterior instrumented fusion for degenerative diseases in the thoracic and/or lumbar spine: a multicenter, observational cohort study of 2913 consecutive cases.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Functional inhibition of heat shock protein 70 by VER-155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism.

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.

Quantitative evaluation of MSI testing using NGS detects the imperceptible microsatellite changed caused by MSH6 deficiency.

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.

Risk Factor Analysis of Deep Surgical Site Infection After Posterior Instrumented Fusion Surgery for Spinal Trauma: A Multicenter Observational Study.

BACKGROUND: Surgical site infection (SSI) is a dire complication in spinal surgeries, resulting in reoperation, prolonged hospitalization, and increased expenses. Patients with traumatized spine have been reported to have a high risk of postoperative SSI. Precise identification of risk factors associated with SSI can be helpful in its prevention. However, there are only a limited number of studies investigating risk factors of SSI after posterior instrumented fusion for traumatized spine. METHODS: From July 2010 to June 2015, we conducted an observational study on deep SSI after posterior instrumented fusion surgery for spinal trauma in adult patients at 10 research hospitals. Detailed clinical data were prospectively collected using a standardized data collection chart and were retrospectively analyzed. SSI was diagnosed based on the definition by the Centers for Disease Control and Prevention. RESULTS: A total of 623 consecutive adult patients were enrolled in this study, of which 20 (3.2%) developed deep SSI. According to multivariate regression analysis, surgery at academic hospitals (P = 0.004) and an American Society of Anesthesiologists (ASA) score ≥3 (P = 0.017) were independent predictors of deep SSI after posterior instrumented fusion surgery for spinal trauma. CONCLUSIONS: The complexity of patients and resident involvement in surgeries may be greater at academic than at nonacademic hospitals. ASA score can be considered as an accessible and comprehensive tool for surgeons to preoperatively gauge the potential risk of SSI, a complex clinical entity. The results of this study can improve clinicians' risk perception in those undergoing posterior fusion for spinal trauma.

Focal concavity of posterior superior acetabulum and its relation with acetabular dysplasia and retroversion in adults without advanced hip osteoarthritis.

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 <25°, Tönnis angle >10°, and anterior center edge (ACE) angle <25° on standing hip radiographs. Acetabular version angle was measured at the one-fourth cranial level of axial CT image. A subgroup analysis included only younger adult patients up to 50 years. RESULTS: The subjects analyzed were 46 men (92 hips) and 54 women (108 hips) with a median age of 57.5 (21-79) and 51.0 (26-77) years, respectively. Focal concavity of posterior superior acetabulum was observed in 13 hips; 7 patients had unilaterally, while 3 patients showed bilaterally. Among these hips, pain was observed in 8 hips but 4 hips (2 patients) were associated with injuries. This morphologic abnormality was not associated with acetabular dysplasia determined by LCE angle <25°, Tönnis angle >10° or ACE angle <25°. Of note, no acetabulum with the deformity plus dysplasia was retroverted. These findings were confirmed in a subgroup analysis including 22 men (44 hips) and 27 women (54 hips) with a median age of 31.0 (21-50) and 41.0 (26-50) years, respectively. CONCLUSIONS: Focal concavity of posterior superior acetabulum could be a rare morphologic abnormality of acetabular formation independent of lateral or anterior dysplasia or retroversion.

Evaluation of the Differences in the Effects of Antihypertensive Drugs on Blood Pressure Variability by 24-Hour Ambulatory Blood Pressure Monitoring in Chronic Cerebrovascular Disease.

BACKGROUND: 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. METHODS: 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, ß blocker, or calcium channel blocker. RESULTS: The daytime blood pressure variability treated with ß 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 ß 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. CONCLUSIONS: From the results, it is suggested that angiotensin receptor blocker and calcium channel blockers rather than ß 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.

CHADS2 Score is a Poor Predictor of Non-cerebral Acute Arterial Occlusion in Patients with Non-valvular Atrial Fibrillation.

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.

18F-FDG versus 11C-choline PET/CT for the imaging of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy: the time period during which PET/CT can reliably detect non-recurrence.

PURPOSE: The purpose of this prospective study was to evaluate the usefulness of (18)F-fluorodeoxyglucose (FDG) and (11)C-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. METHODS: 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 (18)F-FDG PET/CT and (11)C-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. RESULTS: 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 (18)F-FDG and (11)C-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). CONCLUSION: (11)C-choline was not superior to (18)F-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.

Fluid therapy with hydroxyethyl starch for massive blood loss during surgery.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.