Cpne7 deficiency induces cellular senescence and premature aging of dental pulp.

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.

Physiologic dentin regeneration: its past, present, and future perspectives.

Regenerative dentistry has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of tissue formation than on how well the newly generated tissue retains the original structure and function. Once dentin is lost, tertiary dentinogenesis can be induced by new odontoblastic differentiation or re-activation of existing odontoblasts. The characteristic morphology of odontoblasts generates the tubular nature of dentin, which is a reservoir of fluid, ions, and a number of growth factors, and protects the inner pulp tissue. Therefore, understanding the dynamic but delicate process of new dentin formation by odontoblasts, or odontoblast-like cells, following dentinal defects is crucial. In this regard, various efforts have been conducted to identify novel molecules and materials that can promote the regeneration of dentin with strength and longevity. In this review, we focus on recent progress in dentin regeneration research with biological molecules identified, and discuss its potential in future clinical applications.

Tubular dentin formation by TGF-ß/BMP signaling in dental epithelial cells.

OBJECTIVES: This study aimed to identify formation of tubular dentin induced by transforming growth factor-ß (TGF-ß) and bone morphogenic protein (BMP) signaling pathway in dental epithelial cells. METHODS: We collected conditioned medium (CM) of rTGF-ß1/rBMP-2-treated HAT-7 and treated to MDPC-23 cells. The expression levels of odontoblast differentiation markers, KLF4, DMP1, and DSP were evaluated by real-time PCR and Western blot analysis. To evaluate whether CM of rTGF-ß1/rBMP-2 induces tubular dentin formation, we made a beagle dog tooth defect model. RESULTS: Here, we show that Cpne7 is regulated by Smad4-dependent TGF-ß1/BMP2 signaling pathway in dental epithelial cells. CM of rTGF-ß1/rBMP-2 treated HAT-7 or rCPNE7 raises the expression levels of KLF4, DMP1, and DSP in MDPC-23 cells. When rTGF-ß1 or rBMP-2 is directly treated to MDPC-23 cells, however, expression levels of Cpne7-regulated genes remain unchanged. In a beagle dog defect model, application of rTGF-ß1/BMP2-treated CM resulted in tubular tertiary dentin mixed with osteodentin at cavity-prepared sites, while rTGF-ß1 group exhibited homogenous osteodentin. CONCLUSIONS: Taken together, Smad4-dependent TGF-ß1/BMP2 signaling regulates Cpne7 in dental epithelial cells, and CPNE7 protein secreted from pre-ameloblasts mediates odontoblast differentiation via epithelial-mesenchymal interaction.

The effects of medical students' self-oriented perfectionism on academic procrastination: the mediating effect of fear of failure.

PURPOSE: Based on the logic that self-oriented perfectionism (SOP) is one of the most well-established predictors of academic procrastination (AP), we predicted that fear of failure (FF) would mediate the association between SOP and AP. The purpose of this study is to investigate the mediating effect of FF on the influence of SOP on AP in medical students. METHODS: A total of 156 undergraduate medical students completed a battery of questionnaires. This study is an analysis of cross-sectional data obtained through an offline survey. The self-report questionnaires assessed demographics and psychological scales, including the Multidimensional Perfectionism Scale, Performance Failure Appraisal Inventory, and Aitken Procrastination Inventory. The data were analyzed by descriptive statistics, correlations analysis, and multiple regression analyses using IBM SPSS ver. 22.0 (IBM Corp., Armonk, USA). RESULTS: SOP had a direct negative influence on AP (ß=-0.420, p<0.001). Also, SOP had a significant indirect effect on AP through FF (ß=0.0393; 95% confidence interval, 0.040-0.0936). These results indicated that the FF partially mediates the relationship between SOP and AP. CONCLUSION: Although SOP among medical students might play an adaptive role to lessen AP, in cases FF gets higher, SOP could have opposing effects via the mediating effect of FF, leading to an actual increase in AP. Attempts to deal with the FF among medical students should be made for better academic achievements.

Development and validation of a new risk scoring system for solid tumor patients with suspected infection.

This study aimed to develop a new prognostic model for predicting 30-day mortality in solid tumor patients with suspected infection. This study is a retrospective cohort study and was conducted from August 2019 to December 2019 at a single center. Adult active solid tumor patients with suspected infection were enrolled among visitors to the emergency room (ER). Logistic regression analysis was used to identify potential predictors for a new model. A total of 899 patients were included; 450 in the development cohort and 449 in the validation cohort. Six independent variables predicted 30-day mortality: Eastern Cooperative Oncology Group (ECOG) performance status (PS), peripheral oxygen saturation (SpO2), creatinine, bilirubin, C-reactive protein (CRP), and lactate. The C-statistic of the new scoring system was 0.799 in the development cohort and 0.793 in the validation cohort. The C-statistics in the development cohort was significantly higher than those of SOFA [0.723 (95% CI: 0.663-0.783)], qSOFA [0.596 (95% CI: 0.537-0.655)], and SIRS [0.547 (95% CI: 0.483-0.612)]. The discriminative capability of the new cancer-specific risk scoring system was good in solid tumor patients with suspected infection. The new scoring model was superior to SOFA, qSOFA, and SIRS in predicting mortality.

Elevation of the D-dimer cut-off level might be applicable to rule out pulmonary embolism for active cancer patients in the emergency department.

Recent guidelines for diagnosing acute pulmonary embolism (PE) are based on clinical decision rules and D-dimer. D-dimer measurement is recommended only for patients who are 'PE-unlikely'. We aimed to assess the current guidelines for cancer patients and to determine an optimal D-dimer cut-off level. This retrospective observational study was conducted in the emergency department of Asan Medical Center (Seoul, Korea) between 02/2017 and 09/2017 for the development cohort and between 06/2018 and 02/2019 for the validation cohort. Among adult active cancer patients with suspected PE, we included those who were 'PE-unlikely' according to Wells' criteria and who underwent D-dimer testing and computed tomographic pulmonary angiography (CTPA). A total of 498 patients (227 in the development cohort and 271 in the validation cohort) were included, and PE was diagnosed in 8.8% and 18.5% of patients, respectively. The optimal D-dimer cut-off level was 2.0 µg/mL. This elevated cut-off level showed a much higher specificity of 21.3% (95% confidence interval [CI] 16.2-27.3%) and 21.7% (95% CI 16.8-7.6%) in the development and validation sets, respectively, compared with the specificity of 4.4% (95% CI 2.3-8.1%) and 4.1% (95% CI 2.2-7.6%) using the age-adjusted cut-off. The new D-dimer cut-off value identified unnecessary CTPA for 21.3% of patients (absolute difference, 16.9%, 35 of 207) in the development cohort and 21.7% (absolute difference, 17.6%, 39 of 221) of patients in the validation cohort compared to using the standard age-adjusted cut-off. The elevated D-dimer cut-off value combined with Wells' criteria might reduce unnecessary CTPA in active cancer patients with a 'PE-unlikely' classification. Further clinical trials are warranted to improve the PE diagnostic strategy in cancer patients.

Voluntary peer-mentoring program for undergraduate medical students: exploring the experiences of mentors and mentees.

PURPOSE: We aimed to examine the participants' satisfaction and evaluation of the program's appropriateness, outcomes and benefits from participants' perspectives and gather suggestions from students to improve peer mentor programs. METHODS: From 2016 to 2018, 67 mentees and mentors participated in the peer mentoring program. All program participants were asked to participate in the survey, and the respondents were invited to focus group interview (FGI). Quantitative data was collected from the survey questionnaire. Qualitative data was gathered from the open-end questions in the survey and supplemented from additional semi-structured FGIs. The interview data were analyzed using qualitative content analysis. RESULTS: Nineteen responded to the survey, and six participated in the further FGI. Qualitative data contained outcomes and mutual benefits, factors for mentoring success, negative experiences, and suggestions for improvement. Especially factors for mentoring success consisted of various methods of studying assistance, motivation, autonomy, responsibility, emotional support, and relational bonding as important topics concerning mentor-mentee experiences. The satisfaction scores about the program appropriateness, others' attitudes, program implementation, ranged from 3.5 to 3.9 (5-point Likert scores) without significant difference between mentors and mentees. The only negative experience reported by a mentee was feeling the pressure. Specific guidelines on program implementation, pre-education for mentees, appropriate matching, and mentees' clear purpose and spontaneity were suggested to improve the program. CONCLUSION: Participants were generally satisfied with the peer mentoring program, gaining academic and non-academic achievements, including emotional support and improved relationships. Furthermore, we expect that this program can be improved with participants' suggestions in the future.

CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts.

Dentin, which composes most of the tooth structure, is formed by odontoblasts, long-lived post-mitotic cells maintained throughout the entire life of the tooth. In mature odontoblasts, however, cellular activity is significantly weakened. Therefore, it is important to augment the cellular activity of mature odontoblasts to regenerate physiological dentin; however, no molecule regulating the cellular activity of mature odontoblasts has yet been identified. Here, we suggest that copine-7 (CPNE7) can reactivate the lost functions of mature odontoblasts by inducing autophagy. CPNE7 was observed to elevate the expression of microtubule-associated protein light chain 3-II (LC3-II), an autophagy marker, and autophagosome formation in the pre-odontoblast and mature odontoblast stages of human dental pulp cells. CPNE7-induced autophagy upregulated DSP and DMP-1, odontoblast differentiation and mineralization markers, and augmented dentin formation in mature odontoblasts. Furthermore, CPNE7 also upregulated NESTIN and TAU, which are expressed in the physiological odontoblast process, and stimulated the elongation of the odontoblast process by inducing autophagy. Moreover, lipofuscin, which progressively accumulates in long-lived post-mitotic cells and hinders their proper functions, was observed to be removed in recombinant CPNE7-treated mature odontoblasts. Thus, CPNE7-induced autophagy reactivated the function of mature odontoblasts and promoted the formation of physiological dentin in vivo. On the other hand, the well-known autophagy inducer, rapamycin, promoted odontoblast differentiation in pre-odontoblasts but did not properly reactivate the function of mature odontoblasts. These findings provide evidence that CPNE7 functionally reactivates mature odontoblasts and introduce its potential for dentinal loss-targeted clinical applications.

Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide.

We aim to examine the effects of a newly developed peptide derived from CPNE7 (Cpne7-DP) in tertiary dentin formation and peritubular space occlusion, and comprehensively evaluate its potential as a bioactive therapeutic agent. Human dental pulp cells (HDPCs) and a mouse pre-odontoblast cell line, MDPC-23, were chosen for in vitro studies to characterize lineage-specific cell responses after Cpne7-DP treatment. Whether Cpne7-DP reproduces the dentin regenerative potential of CPNE7 was tested using a beagle dog model by generating dentinal defects of various degrees in vivo. Peritubular space occlusion was further examined by scanning electron microscopy and microleakage test, while overall mineralization capacity of Cpne7-DP was tested ex vivo. CPNE7 promotes tubular dentin formation under both shallow and deep dentinal defects, and the functional peptide Cpne7-DP induces odontoblast-like differentiation in vitro, mineralization ex vivo, and tubular dentin formation in in vivo beagle dog dentin exposure and pulp exposure models. Moreover, Cpne7-DP leads to peritubular space occlusion and maintains stability under different conditions. We show that CPNE7 and its derivative functional peptide Cpne7-DP promotes dentin regeneration in dentinal defects of various degrees and that the regenerated hard tissue demonstrates the characteristics of true dentin. Limitations of the current dental materials including post-operative hypersensitivity make biological repair of dentin a field of growing interest. Here, we suggest that the dual functions of Cpne7-DP in tubular dentin formation and peritubular space occlusion are promising for the treatment of dentinal loss and sensitivity.

Prognostic accuracy of the sequential organ failure assessment (SOFA) and quick SOFA for mortality in cancer patients with sepsis defined by systemic inflammatory response syndrome (SIRS).

PURPOSE: We aimed to assess the prognostic accuracy of SOFA and qSOFA scores in cancer patients with sepsis, and also to determine if the addition of hyperlactatemia to qSOFA increases the accuracy in predicting the 30-day mortality. MATERIAL AND METHOD: We consecutively included adult active cancer patients (age ≥ 18 years) with sepsis defined by SIRS who visited the emergency department (ED) from May 1st to July 30th, 2017. Data were collected retrospectively through reviewing medical records. The SOFA and qSOFA scores were calculated with the initial variables at the time of ED admission. The primary endpoint was 30-day mortality. RESULT: Of 1137 screened, 301 were included. The 30-day mortality was 14.3% (43 patients). Among the total 301, the SOFA score was ≥ 2 in 168 and qSOFA ≥ 2 in 23. For those with SOFA ≥ 2 and < 2, the mortality was 23.2% and 3%, respectively (P < 0.001). For those with qSOFA ≥ 2 and < 2, the mortality was 47.8% and 11.5%, respectively (P < 0.001). The AUROC of 30-day mortality for qSOFA was lower than that for SOFA (0.66 (95% CI, 0.56-0.75) vs. 0.79 (95% CI, 0.72-0.87), P = 0.004)). However, the combination of qSOFA with lactate ≥ 2 threshold considerably enhanced a discrimination capacity for mortality with an AUROC 0.77 (95% CI, 0.69-0.85), which was similar to SOFA (P = 0.11). CONCLUSION: In cancer patients with sepsis, qSOFA was inferior to SOFA in predicting mortality. However, adding lactate to qSOFA resulted in greater prognostic accuracy for short-term mortality, comparable with SOFA.

Opioid Utilization and Perception of Pain Control in Hospitalized Patients: A Cross-Sectional Study of 11 Sites in 8 Countries.

BACKGROUND: Hospitalized patients are frequently treated with opioids for pain control, and receipt of opioids at hospital discharge may increase the risk of future chronic opioid use. OBJECTIVE: To compare inpatient analgesic prescribing patterns and patients' perception of pain control in the United States and non-US hospitals. DESIGN: Cross-sectional observational study. SETTING: Four hospitals in the US and seven in seven other countries. PARTICIPANTS: Medical inpatients reporting pain. MEASUREMENTS: Opioid analgesics dispensed during the first 24-36 hours of hospitalization and at discharge; assessments and beliefs about pain. RESULTS: We acquired completed surveys for 981 patients, 503 of 719 patients in the US and 478 of 590 patients in other countries. After adjusting for confounding factors, we found that more US patients were given opioids during their hospitalization compared with patients in other countries, regardless of whether they did or did not report taking opioids prior to admission (92% vs 70% and 71% vs 41%, respectively; P < .05), and similar trends were seen for opioids prescribed at discharge. Patient satisfaction, beliefs, and expectations about pain control differed between patients in the US and other sites. LIMITATIONS: Limited number of sites and patients/country. CONCLUSIONS: In the hospitals we sampled, our data suggest that physicians in the US may prescribe opioids more frequently during patients' hospitalizations and at discharge than their colleagues in other countries, and patients have different beliefs and expectations about pain control. Efforts to curb the opioid epidemic likely need to include addressing inpatient analgesic prescribing practices and patients' expectations regarding pain control.

High mortality from viral pneumonia in patients with cancer.

Background: With the advancement of diagnostic methods, a viral infection is increasingly recognized in adult patients with pneumonia and the outcomes can be fatal especially in high-risk patients. We aimed to examine the clinical characteristics of adults with viral pneumonia and also to determine the associated factors with short-term mortality in those patients. Methods: Adult patients who were diagnosed as viral pneumonia between January 2010 and December 2015 were consecutively included. Data were collected through reviews of electronic medical records. The primary outcome was 30-day mortality. Results: A total of 1503 patients with viral pneumonia were included with a mean age of 66.0 years and male predominance in 60%. The most common viral pathogen was rhinovirus, followed by influenza virus and parainfluenza virus (PIV). Viral-bacterial co-infection and multiple viral infections were found in 24.5% and 5.2%, respectively. The 30-day mortality was 7.1% in total patients and it was not different according to viral pathogens. However, cancer patients had higher mortality than non-cancer patients for the PIV (12.3% vs. 3.8%, p < .05) and coronavirus (24.4% vs. 3.0%, p < .01) infections. On the multivariate analysis, old age (≥65) (OR 1.66, 95% CI: 1.06-2.60), viral-bacterial co-infection (OR 1.61, 95% CI: 1.05-2.48), malignancy (OR 2.26, 95% CI: 1.50-3.40), and shock at the initial presentation (OR 2.12, 95% CI: 1.03-4.37) were significantly associated with mortality. Conclusions: The mortality from viral pneumonia was high in adult patients. Old age, viral-bacterial co-infection, underlying malignancy, and initial shock were independent predictors of mortality.

Expression of CPNE7 during mouse dentinogenesis.

Interactions between the ectodermal and mesenchymal tissues are the basis of the central mechanism regulating tooth development. Based on this epithelial-mesenchymal interaction (EMI), we demonstrated that copine-7 (CPNE7) is secreted by preameloblasts and regulates the differentiation of mesenchymal cells of dental or non-dental origin into odontoblasts. However, the precise expression patterns of CPNE7 in the stages of tooth development have not yet been elucidated. The aim of the present study was to establish the spatiotemporal expression pattern of CPNE7 during mouse tooth development. To examine the spatiotemporal expression patterns of CPNE7 during mouse tooth development, we investigate the distribution of CPNE7 in the embryonic and postnatal developing mouse tooth. Immunohistochemistry, in situ hybridization, real-time PCR, and western blot analysis are performed to investigate the CPNE7 expression pattern during tooth development of the mandibular mouse first molar. During the initiation stage (bud stage), CPNE7 protein expression is observed in the dental epithelium but not yet in the dental mesenchyme. At E18 (bell stage), expression of CPNE7 protein and mRNA is primarily observed in ectomesenchymal cells of dental papilla. At P7 (crown formation stage), CPNE7 is localized in differentiating odontoblasts but weak expression is detected in mature ameloblasts. These findings suggest that CPNE7 secreted by dental epithelium induces the differentiation of ectomesenchymal cells into preodontoblast in concert with EMI. CPNE7 is clearly expressed in differentiating odontoblasts and the odontoblast process during dentinogenesis, but is no longer expressed in fully differentiated odontoblasts. Furthermore, CPNE7 is expressed in the Hertwig's epithelial root sheath (HERS) and in the facing preodontoblasts during root dentin formation. Taken together, these results illustrate the dynamic expression of CPNE7 during tooth development and suggest its important function in entire stages of tooth development.

The effect of CPNE7 on periodontal regeneration.

Introduction: Preameloblast-conditioned medium (PA-CM), as a mixture of dental epithelium-derived factors, has been reported to regenerate dentin and periodontal tissues in vitro and in vivo. The aim of this study was to investigate the biological effect of Cpne7 on the proliferation, migration, and cementoblast differentiation of periodontal cells in vitro, and on the regeneration of periodontal tissue using periodontal defect model with canine in vivo. Materials and methods: The effect of Cpne7 on cell proliferation, migration, and cementoblast differentiation of periodontal cells were evaluated in vitro. A periodontal defect canine model was designed and the defects were divided into five groups: Group 1: No treatment (negative control), Group 2: Collagen carrier only, Group 3: PA-CM with collagen carrier (positive control), Group 4: PA-CM + CPNE7 Antibody (Ab) with collagen carrier, and Group 5: recombinant CPNE7 (rCPNE7) protein with collagen carrier. Results: Cpne7 was expressed in HERS cells and periodontal ligament (PDL) fibers. By real-time PCR, Cpne7 increased expression of Cap compared to the control. In the periodontal defect canine model, rCPNE7 or PA-CM regenerated periodontal complex, and the arrangement of the newly formed PDL-like fibers were perpendicular to the newly formed cementum and alveolar bone like Sharpey's fibers in natural teeth, while PA-CM + CPNE7 Ab showed irregular arrangement of the newly formed PDL-like fibers compared to the rCPNE7 or PA-CM group. Conclusion: These findings suggest that Cpne7 may have a functional role in periodontal regeneration by supporting periodontal cell attachment to cementum and facilitating physiological arrangement of PDL fibers.

Early Risk Score for Predicting Hypotension in Normotensive Patients with Non-Variceal Upper Gastrointestinal Bleedin.

Risk assessment for upper gastrointestinal bleeding (UGIB) is important; however, current scoring systems are insufficient. We aimed to develop and validate a prediction model for rapidly determining the occurrence of hypotension in non-variceal UGIB patients with normotension (systolic blood pressure ≥90 mmHg) at emergency department presentation. In this prospective observational cohort study, consecutive non-variceal UGIB patients between January 2012 and April 2017 were enrolled. We developed and validated a new prediction model through logistic regression, with the occurrence of hypotension <24 h as the primary outcome. Among 3363 UGIB patients, 1439 non-variceal UGIB patients were included. The risk factors for the occurrence of hypotension were lactate level, blood in nasogastric tube, and systolic blood pressure. The area under the curve (AUC) of the new scoring model (LBS-Lactate, Blood in nasogastric tube, Systolic blood pressure) in the development cohort was 0.74, higher than the value of 0.64 of the Glasgow⁻Blatchford score for predicting the occurrence of hypotension. The AUC of the LBS score in the validation cohort was 0.83. An LBS score of ≤2 had a negative predictive value of 99.5% and an LBS score of ≥7 had a specificity of 97.5% in the validation cohort. The new LBS score stratifies normotensive patients with non-variceal UGIB at risk for developing hypotension.

Serial evaluation of SOFA and APACHE II scores to predict neurologic outcomes of out-of-hospital cardiac arrest survivors with targeted temperature management.

OBJECTIVE: This study was aimed at a serial evaluation and comparison of the prognostic values of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores for neurologic outcomes in comatose, out-of-hospital cardiac arrest (OHCA) survivors, treated with targeted temperature management (TTM). METHODS: We analysed a prospective cohort of comatose OHCA patients, with TTM, admitted to an emergency intensive care unit (ICU), between January 2010 and December 2015. SOFA and APACHE II scores were calculated initially, and then at day 1, 2, 3, 5, and 7 after ICU admission. Primary and secondary outcomes were the 28-day neurologic outcome and the 28-day mortality, respectively. Prognostic value of the SOFA and APACHE II scores was analysed using the receiver operating characteristic curve. RESULTS: Of the 143 selected patients, 62 survived and 34 had good neurologic outcomes at day 28. There was no significant difference in the SOFA and extracerebral SOFA scores between the good and poor neurologic outcome groups. However, the APACHE II scores were significantly higher in the good outcome group; they displayed good discriminatory power in predicting poor outcomes, unlike the SOFA scores. The APACHE II score at day 3 had the highest prognostic value for predicting poor neurologic outcomes with an area under the cure of 0.793, and with a cut-off value of 20, the APACHE II score predicted poor neurologic outcomes with a sensitivity of 43.75%, a specificity of 94.12%, a positive predictive value of 94.59%, and a negative predictive value of 41.56%. CONCLUSIONS: Identifying APACHE II score might assist as one piece of multimodal prognostic approach for the assessment of neurologic outcomes in OHCA survivors treated with TTM.

Effect of preameloblast-conditioned medium and CPNE7 on root surfaces in dogs: a histologic and histomorphometric evaluation.

Preameloblast-conditioned medium (PACM) has been reported as a potent dentin regenerative material, but its effects as a mixture on periodontal regeneration and the role of CPNE7 in PACM are not known. The purpose of this study is to evaluate the histologic and histomorphometric effects of preameloblast-conditioned medium (PACM) and CPNE7 on periodontal tissue healing in dogs. Seventy-two mandibular premolar roots from ten dogs were extracted and randomly divided into six groups (n = 12 each): (1) positive control group; (2) negative control group; (3) cementum-removed and PACM-treated group; (4) cementum-preserved and PACM-treated group; (5) CPNE7-inactivated PACM-treated group; and (6) recombinant CPNE7-treated group. The extracted roots were replanted into extraction sockets for 4 and 8 weeks and analyzed histologically. Most of the root surfaces in the negative control group showed ankylosis; and those in the experimental groups showed newly formed PDL-like and cementum-like tissues. Histomorphometric analysis of horizontal sections showed that the mean length of the PDL on the roots of the positive controls was similar to those in cementum-removed or -preserved and PACM-treated group at 8 weeks (p = 1.08). Sagittal sections showed that the mean length of the new cementum on the roots in cementum-removed and PACM-treated group was significantly greater than that in CPNE7-inactivated PACM-treated group (p = 0.037). The mean length of the newly formed PDL on the roots in CPNE7- inactivated PACM-treated and rCPNE7-treated groups was significantly greater than that in the negative controls at 8 weeks (p = 0.037, p = 0.036). The use of PACM and CPNE7 in tooth replantation resulted in increased PDL and cementum formation, suggesting the beneficial role of PACM and CPNE7 in periodontal tissue healing.

Incidence of intracranial injury in orbital wall fracture patients not classified as traumatic brain injury.

OBJECTIVE: The detection of intracranial injury in patients with facial injury rather than traumatic brain injury (TBI) remains a challenge for emergency physicians. This study aimed to evaluate the incidence and risk factors of intracranial injury in patients with orbital wall fracture (OWF), who were classified with a chief complaint of facial injury rather than TBI. METHODS: This retrospective case-control study enrolled adult OWF patients (age ≥18 years) who presented at the hospital between January 2004 and March 2016. Patients with definite TBI were excluded because non-contrast head computed tomography (CT) is recommended for such patients. RESULTS: A total of 1220 patients with OWF were finally enrolled. CT of the head was performed on 677 patients, and the incidence of concomitant intracranial injury was found to be 9% (62/677). Patients with definite TBI were excluded. Symptoms raising a suspicion of TBI, such as loss of consciousness, alcohol intoxication, or vomiting, were present in 347 of the patients, with 44 of these patients (13%) showing a concomitant intracranial injury. Of the 330 patients without such symptoms, 18 (6%) demonstrated a concomitant intracranial injury. In OWF patients, superior wall fracture (odds ratio [OR], 4.15; 95% confidence interval [CI], 2.06-8.34; P < 0.001), associated frontal bone fracture (OR, 4.38; 95% CI, 2.08-9.23; P < 0.001), and older age (decades) (OR, 1.03; 95% CI, 1.01-1.04; P = 0.002) were independent risk factors for concomitant intracranial injury. CONCLUSIONS: Emergency physicians should maintain a high degree of suspicion of TBI, even when their primary concern is facial trauma with OWF. Head CT is recommended for OWF patients with a superior OWF, frontal bone fracture, or increased age.

Lactate Level Versus Lactate Clearance for Predicting Mortality in Patients With Septic Shock Defined by Sepsis-3.

OBJECTIVES: This study aimed to compare the prognostic value of lactate level and lactate clearance at 6 hours after septic shock recognition. And, we performed it to determine lactate kinetics in the Sepsis-3 defined septic shock. DESIGN: This retrospective study was performed from a prospective septic shock registry. SETTINGS: This study was performed at single urban tertiary center. And, all patients were treated with protocol-driven resuscitation bundle therapy between 2010 and 2016. PATIENTS: We included septic shock patients who met the Sepsis-3 definition, which involves lactate levels greater than or equal to 2 mmol/L and vasopressor use. INTERVENTIONS: Serum lactate levels were measured at initial and 6 hours from septic shock recognition. MEASUREMENTS AND MAIN RESULTS: Lactate clearance was calculated as ([initial lactate - 6-hr lactate]/initial lactate) × 100. The prognostic value of measured lactate levels and lactate clearance for 28-day mortality was analyzed and compared with that of subsequent lactate levels greater than or equal to 2 mmol/L, greater than or equal to 3 mmol/L, and greater than or equal to 4 mmol/L and less than 10%, less than 20%, and less than 30% lactate clearance. A total of 1,060 septic shock patients by Sepsis-3, 265 patients died (28-d mortality: 25%). In survivor, groups had lower median 6-hour lactate level and higher lactate clearance than nonsurvivors (2.5 vs 4.6 mmol/L and 35.4% vs 14.8%; p < 0.01). Both lactate and lactate clearance were associated with mortality after adjusting for confounders (odd ratio, 1.27 [95% CI, 1.21-1.34] and 0.992 [95% CI, 0.989-0.995]), but lactate had a significantly higher prognostic value than lactate clearance (area under the curve, 0.70 vs 0.65; p < 0.01). The prognostic value of subsequent lactate levels (≥ 2, ≥ 3, and ≥ 4 mmol/L) and lactate clearances (< 10%, < 20%, and < 30%) was not significantly differed. However, lactate levels of greater than or equal to 2 mmol/L had the greatest sensitivity (85.3%). CONCLUSIONS: Our findings indicate lactate and lactate clearance are both useful targets in patients with septic shock defined by Sepsis-3. Serum lactate level at 6-hour can be an easier and more effective tool for prognosis of septic shock patients who were treated with protocol-driven resuscitation bundle therapy.