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.

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.

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.

Outcomes and Role of Urgent Endoscopy in High-Risk Patients With Acute Nonvariceal Gastrointestinal Bleeding.

BACKGROUND & AIMS: We investigated clinical outcomes in high-risk patients with acute nonvariceal upper gastrointestinal bleeding (UGIB), and determined if urgent endoscopy is effective. METHODS: Consecutive patients with a Glasgow-Blatchford score greater than 7 who underwent endoscopy for acute nonvariceal UGIB at the emergency department from January 1, 2005, to December 31, 2014, were included. Urgent (<6 h) and elective (6-48 h) endoscopies were defined according to the time to endoscopy after the initial presentation. The primary outcomes were mortality and rebleeding within 28 days of admission. RESULTS: Among 961 patients, 571 patients underwent urgent endoscopy. The 28-day mortality rate was 2.5%, and the rebleeding rate was 10.4%. There were significant differences in mortality rate (1.6% vs 3.8%), the number of transfused packed red blood cells (2.6 ± 2.5 vs 2.3 ± 2.1 packs), need for intervention (69.5% vs 53.5%), and embolization (2.8% vs 0.5%), but no differences in rebleeding, intensive care unit admission, vasopressor use, and length of stay between the urgent and elective endoscopy groups. Mortality was associated with malignancy (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.33-9.62), cirrhosis (OR, 4.67; 95% CI, 1.85-11.76), urgent endoscopy (OR, 0.36; 95% CI, 0.14-0.95), failed primary endoscopic treatment (OR, 15.03; 95% CI, 4.63-48.82), and rebleeding (OR, 2.77; 95% CI, 1.03-7.45). Rebleeding was associated with Forrest I ulcers (OR, 7.67; 95% CI, 2.71-21.69), Forrest II ulcers (OR, 2.34; 95% CI, 1.51-3.60), and coagulopathy (OR, 2.34; 95% CI, 1.51-3.60). CONCLUSIONS: Urgent endoscopy was an independent predictor of lower mortality rate but was not associated with rebleeding in high-risk patients with acute nonvariceal UGIB.

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.

Predictors of septic shock in initially stable patients with pyogenic liver abscess.

OBJECTIVES: The incidence of pyogenic liver abscess (PLA), a life-threatening condition, is increasing worldwide. This study was designed to evaluate clinical features and outcomes in initially stable patients with PLA and to determine the predictors of septic shock. METHODS: The medical records of all adult patients who were hemodynamically stable and diagnosed with PLA in the emergency department from January 2010 to December 2014, inclusive, were reviewed. The primary outcome was septic shock. RESULTS: A review of medical records identified 453 patients (66.7% male), of mean age 61.4 years, diagnosed with PLA. Of these patients, 73 (16.1%) had septic shock and 10 (2.2%) died in-hospital. Of the 73 patients with septic shock, nine (12.3%) died in-hospital. The most common symptom was fever (79.5%), and the most common infectious agent was Klebsiella pneumoniae. Septic shock was significantly associated with age ≥60 years [odds ratio (OR): 2.99, 95% confidence interval (CI): 1.38-6.48], malignancy (OR: 2.11, 95% CI: 1.08-4.09), systolic blood pressure <100 mmHg (OR: 3.63, 95% CI: 1.43-9.21), respiratory rate ≥24/min (OR: 3.15, 95% CI: 1.20-8.28) and lactate concentration ≥2 mmol/L (OR: 4.92, 95% CI: 2.51-9.64). Septic shock also tended to be associated with procalcitonin concentration, but this was not statistically significant (OR: 3.42, 95% CI: 0.96-12.18). CONCLUSIONS: Septic shock was frequent in initially stable patients with PLA and was associated with older age, malignancy, low blood pressure, tachypnea and elevated lactate concentration.

Misdiagnosis of Spontaneous Intracranial Hypotension as a Risk Factor for Subdural Hematoma.

OBJECTIVE: This study aimed to evaluate the association between misdiagnosis of spontaneous intracranial hypotension (SIH) and subdural hematoma development. BACKGROUND: Although SIH is more prevalent than expected and causes potentially life-threatening complications including subdural hematoma (SDH), the association between misdiagnosis of SIH and SDH development is not yet evaluated. METHODS: Retrospective observational study was conducted between January 1, 2005, and December 31, 2014. Adult patients with spontaneous intracranial hypotension (age ≥ 18 years) were enrolled. RESULTS: Of the 128 patients with SIH, 111 (86.7%) were in no SDH group and 17 (13.3%) were in SDH group. Their clinical presentation did not show significant different between the two groups, except age, the days from symptom onset to correct diagnosis, and the number of misdiagnoses. Age (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.07-1.23) and the number of times SIH was misdiagnosed (OR, 1.82; 95% CI, 1.03-3.21) were independent risk factors for the development of SDH in SIH patients by multivariate logistic analysis. The clinical outcomes, including length of hospital stay and revisit rate, were similar in the two groups. CONCLUSIONS: The number of times SIH was misdiagnosed was associated with the later development of SDH perhaps because of delay in correct diagnosis of SIH. Clinicians would prevent the later complication of SDH in SIH patients by increasing the awareness and a high index of suspicion of SIH.

Predictive performance of the quick Sequential Organ Failure Assessment score as a screening tool for sepsis, mortality, and intensive care unit admission in patients with febrile neutropenia.

PURPOSE: In Sepsis-3, the quick Sequential Organ Failure Assessment (qSOFA) score was developed as criteria to use for recognizing patients who may have poor outcomes. This study was performed to evaluate the predictive performance of the qSOFA score as a screening tool for sepsis, mortality, and intensive care unit (ICU) admission in patients with febrile neutropenia (FN). We also tried to compare its performance with that of the systemic inflammatory response syndrome (SIRS) criteria and Multinational Association of Supportive Care in Cancer (MASCC) score for FN. METHODS: We used a prospectively collected adult FN data registry. The qSOFA and SIRS scores were calculated retrospectively using the preexisting data. The primary outcome was the development of sepsis. The secondary outcomes were ICU admission and 28-day mortality. RESULTS: Of the 615 patients, 100 developed sepsis, 20 died, and 38 were admitted to ICUs. In multivariate analysis, qSOFA was an independent factor predicting sepsis and ICU admission. However, compared to the MASCC score, the area under the receiver operating curve of qSOFA was lower. qSOFA showed a low sensitivity (0.14, 0.2, and 0.23) but high specificity (0.98, 0.97, and 0.97) in predicting sepsis, 28-day mortality, and ICU admission. CONCLUSIONS: Performance of the qSOFA score was inferior to that of the MASCC score. The preexisting risk stratification tool is more useful for predicting outcomes in patients with FN.

Contrast-induced nephropathy in patients with active cancer undergoing contrast-enhanced computed tomography.

PURPOSE: This study was performed to measure the incidence and identify potential predictors of contrast-induced nephropathy (CIN) in cancer patients without chronic kidney disease and with normal or near-normal baseline serum creatinine measures who underwent contrast-enhanced computed tomography (CECT). Severity of CIN was reported based on the RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal disease) classification of acute kidney injury. METHODS: A retrospective analysis was performed on 820 cancer patients who presented at our emergency department from October 2014 to March 2015. CIN was defined as an increase in creatinine concentration of ≥0.5 mg/dL or ≥25 % above baseline that occurred 48 to 72 h after CECT. RESULTS: The incidence of CIN was 8.0%. Serial CT examination [odds ratio (OR) 4.09; 95% confidence interval (CI) 1.34-12.56], hypotension before the CT scan (OR 3.95; 95% CI 1.77-8.83), liver cirrhosis (OR 2.82; 95% CI 1.06-7.55), BUN/creatinine >20 (OR 2.54; 95% CI 1.44-4.46), and peritoneal carcinomatosis (OR 1.75; 95% CI 1.01-3.00) were independently associated with CIN. Of 66 CIN patients, 44 met any of the severity criteria of the RIFLE classification. Five of these patients died during hospitalization but only one death was related to renal failure. CONCLUSIONS: Even when the baseline serum creatinine is ≤1.5 mg/dL, a significant portion of cancer patients are still at risk of CIN. Consecutive CECT examinations, hypotension before CT, liver cirrhosis, dehydration, and peritoneal carcinomatosis seem to predispose patients to CIN.

A new prognostic model for chemotherapy-induced febrile neutropenia.

BACKGROUND: The objective of this study was to develop and validate a new prognostic model for febrile neutropenia (FN). METHODS: This study comprised 1001 episodes of FN: 718 for the derivation set and 283 for the validation set. Multivariate logistic regression analysis was performed with unfavorable outcome as the primary endpoint and bacteremia as the secondary endpoint. RESULTS: In the derivation set, risk factors for adverse outcomes comprised age ≥ 60 years (2 points), procalcitonin ≥ 0.5 ng/mL (5 points), ECOG performance score ≥ 2 (2 points), oral mucositis grade ≥ 3 (3 points), systolic blood pressure <90 mmHg (3 points), and respiratory rate ≥ 24 breaths/min (3 points). The model stratified patients into three severity classes, with adverse event rates of 6.0 % in class I (score ≤ 2), 27.3 % in class II (score 3-8), and 67.9 % in class III (score ≥ 9). Bacteremia was present in 1.1, 11.5, and 29.8 % of patients in class I, II, and III, respectively. The outcomes of the validation set were similar in each risk class. When the derivation and validation sets were integrated, unfavorable outcomes occurred in 5.9 % of the low-risk group classified by the new prognostic model and in 12.2 % classified by the Multinational Association for Supportive Care in Cancer (MASCC) risk index. CONCLUSIONS: With the new prognostic model, we can classify patients with FN into three classes of increasing adverse outcomes and bacteremia. Early discharge would be possible for class I patients, short-term observation could safely manage class II patients, and inpatient admission is warranted for class III patients.

Predicting the Occurrence of Hypotension in Stable Patients With Nonvariceal Upper Gastrointestinal Bleeding: Point-of-Care Lactate Testing.

OBJECTIVES: It is difficult to assess risk in normotensive patients with upper gastrointestinal bleeding. The aim of this study was to evaluate whether the initial lactate value can predict the in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. DESIGN: Retrospective, observational, single-center study. SETTING: Emergency department of a tertiary-care, university-affiliated hospital during a 5-year period. PATIENTS: Medical records of 3,489 patients with acute upper gastrointestinal bleeding who were normotensive at presentation to the emergency department. We analyzed the ability of point-of-care testing of lactate at emergency department admission to predict hypotension development (defined as systolic blood pressure <90 mm Hg) within 24 hours after emergency department admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,003 patients with acute nonvariceal upper gastrointestinal bleeding, 157 patients experienced hypotension within 24 hours. Lactate was independently associated with hypotension development (odds ratio, 1.6; 95% CI, 1.4-1.7), and the risk of hypotension significantly increased as the lactate increased from 2.5-4.9 mmol/L (odds ratio, 2.2) to 5.0-7.4 mmol/L (odds ratio, 4.0) and to greater than or equal to 7.5 mmol/L (odds ratio, 39.2) (p<0.001). Lactate elevation (≥2.5 mmol/L) was associated with 90% specificity and an 84% negative predictive value for hypotension development. When the lactate levels were greater than 5.0 mmol/L, the specificity and negative predictive value increased to 98% and 87%, respectively. CONCLUSIONS: Point-of-care testing of lactate can predict in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. However, subsequently, prospective validate research will be required to clarify this.

Tumor Necrosis Factor-Alpha Gene Polymorphism Associated With Development of Hepatitis B Virus-associated Hepatocellular Carcinoma.

GOAL AND BACKGROUND: Host genetic diversity may play roles in development of HCC. This study was conducted to validate the effects of tumor necrosis factor-alpha (TNF-α) gene polymorphism on development of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV). STUDY: The study cohort comprised 224 patients with HBV-associated HCC and 206 with HBV-associated liver cirrhosis (LC). Using chromosomal DNA, TNF-α promoter gene polymorphisms were determined at 3 common single-nucleotide polymorphism (SNP) sites (TNF-α-1031 T>C, TNF-α-857 C>T, and TNF-α-308 G>A) using a single base extension method. The genotype distributions were compared between the 2 groups. All the HBV-associated LC patients were followed up regularly every 6 to 12 months for surveillance of HCC development. RESULTS: In the cross-sectional analysis, the frequency of TNF-α-857 T allele was much higher in patients with HCC compared with those with LC (42% vs. 31%, P<0.01). Of 206 HBV-associated LC patients, 12 (5.8%) developed HCC during the median follow-up period of 36 months. The cumulative occurrence rates of HCC were significantly higher in patients with TNF-α-857 T allele than those withTNF-α-857 C/C genotype (1-, 3-, and 5-y rates: 2.9%, 12.8%, and 20.7% vs. 0%, 3.1%, and 5.3%, respectively; P=0.013). However, the other genetic polymorphisms of TNF-α promoter gene did not affect the development of HCC. In multivariate analysis, TNF-α-857 T allele was a significant predictor of HCC development (hazard ratio 6.29, P=0.01). CONCLUSION: Our data suggest that TNF-α-857 T allele is closely associated with development of HCC in HBV-associated LC patients.

Biphasic reactions in patients with anaphylaxis treated with corticosteroids.

BACKGROUND: Although the incidence of anaphylaxis is rapidly increasing, the clinical characteristics and associated factors of a biphasic reaction are unclear. OBJECTIVE: To determine the incidence and clinical characteristics of biphasic reactions in patients with anaphylaxis treated with corticosteroids. METHODS: A total of 655 patients with anaphylaxis visiting the emergency department of a tertiary teaching hospital from January 2007 through December 2014 were analyzed. Patient characteristics, triggers, symptoms and signs, in-hospital management, and disposition were recorded. A biphasic reaction was defined as the development of anaphylaxis after complete resolution of the initial reaction without further exposure to the offending agent within 7 days. Univariate and multivariate analyses on the predictors of the biphasic reaction were performed. RESULTS: Of the 415 patients with anaphylaxis treated with corticosteroids, 9 patients (2.2%) developed a biphasic reaction. The mean age was 48.4 years, and 221 patients (54.4%) were women. The median time from complete resolution of initial clinical symptoms to occurrence of the biphasic reaction was 15 hours (range 1-45). History of drug anaphylaxis (odds ratio 14.3, 95% confidence interval 2.4-85.8) was a contributing factor to the development of the biphasic reaction. CONCLUSION: The incidence of biphasic reactions was 2.2% in patients treated with corticosteroids and those with a history of drug anaphylaxis were at greater risk.

Model for end-stage liver disease score as a predictor of short-term outcome in patients with drug-induced liver injury.

OBJECTIVES: The purposes of this study were to investigate the clinical presentation, cause and outcome of drug-induced liver injury (DILI) and to evaluate the predictive value of the model for end-stage liver disease (MELD) score in DILI. METHODS: Patients diagnosed with DILI between January 1, 2010 and December 31, 2012 in the Emergency Department at Asan Medical Center in Seoul, Korea were analyzed retrospectively. The primary end point was poor outcome, defined as liver transplantation or death within 30 days of the initial hospital visit. RESULTS: Of 213 patients, 13.1% had a 30-day poor outcome. Folk remedies were the most common cause of DILI in 147 patients (69%). Univariate logistic regression analysis showed that multiple drugs (odds ratio [OR] 2.30, 95% confidence interval [CI]: 1.03-5.15), concurrent alcohol consumption (OR 3.69, 95% CI: 1.03-13.18), white blood cell (WBC) count (OR 1.17, 95% CI: 1.07-1.28), hemoglobin (Hb) (OR 0.60, 95% CI: 0.49-0.74), platelet count (OR 0.993, 95% CI: 0.987-0.998), total bilirubin (OR 1.09, 95% CI: 1.06-1.13) and MELD (OR 1.23, 95% CI: 1.15-1.32) were significantly associated with 30-day poor outcomes. Multivariate analysis showed that the MELD (OR 1.21, 95% CI: 1.12-1.30) and Hb (OR 0.77, 95% CI: 0.61-0.98) were independent predictors of poor outcome. For 30-day mortality, the c-statistics for MELD alone and for combination of MELD and Hb were 0.93 (95% CI: 0.89-0.97) and 0.94 (95% CI: 0.90-0.97), respectively. CONCLUSION: The outcome of patients with DILI was poor. MELD score and Hb were reliable predictors of short-term outcome in patients with DILI.

Impact of time to antibiotics on outcomes of chemotherapy-induced febrile neutropenia.

PURPOSE: The aim of this study was to determine the relationship between the time to antibiotic administration and patients' outcomes of febrile neutropenia (FN). We also investigated the relationship between the time to antibiotics and mortality rates in a subgroup of patients with bacteremia or severe sepsis or septic shock. METHODS: From the Neutropenic Fever Registry, we analyzed 1001 consecutive FN episodes diagnosed from November 1, 2011, to August 31, 2014. Timing cutoffs for antibiotics included the following: ≤1 vs. >1 h, ≤2 vs. >2 h, ≤3 vs. >3 h, and ≤4 vs. >4 h. Multivariate logistic regression was used to adjust for potential confounders in the association between timing intervals and outcomes of FN episodes. RESULTS: The median length of time from triage to antibiotics was 140 min (interquartile range, 110-180 min). At each time cutoff, the time from triage to antibiotic administration was not significantly associated with FN outcomes after adjusting for potential confounders. Antibiotic timing was not significantly associated with complication rates in overall FN episodes. We failed to find a significant relationship between antibiotic timing and mortality in FN episodes with severe sepsis or septic shock or with bacteremia. Procalcitonin concentration and the Multinational Association for Supportive Care in Cancer (MASCC) risk index score were found to be more crucial determinants of outcomes in patients with FN. CONCLUSIONS: The time to antibiotic administration is not a major factor in FN outcomes.

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.

Blatchford score is a useful tool for predicting the need for intervention in cancer patients with upper gastrointestinal bleeding.

BACKGROUND AND AIM: The Blatchford score is based on clinical and laboratory variables to predict the need for clinical interventions in upper gastrointestinal bleeding (UGIB). The primary object was to evaluate the Blatchford score with clinical and full Rockall scores in patients with active cancer presenting to the emergency department with UGIB. The secondary object was to assess the accuracy of the Blatchford score at different source of UGIB; cancer bleeding versus non-malignant lesions. METHODS: We reviewed and extracted data from electronic medical record on patients with active cancer presenting to the emergency department from January 2009 to December 2011. Clinical interventions included blood transfusion, therapeutic endoscopy, angiographic intervention, and surgery. RESULTS: Of the 225 patients included, 197 (87.6%) received interventions. Comparing the area under receiver-operator curves, the Blatchford score (0.86, 95% confidence interval [CI] 0.77-0.95) was superior to clinical Rockall (0.67, 95% CI 0.55-0.79) and full Rockall score (0.72, 95% CI 0.61-0.83) in predicting interventions. When the score of 2 or less is counted as negative, sensitivity of 0.99 and specificity of 0.54 were calculated. When the patients were separated according to the source of UGIB, sensitivity and specificity were not changed. CONCLUSIONS: The Blatchford score outperformed both Rockall scoring system in predicting intervention in patients with active cancer. The source of bleeding was not important factor in the score performance. The Blatchford score has a very good sensitivity. However, suboptimal specificity limits its role as sole means of decision making in cancer patient with UGIB.

Validation of the clinical prediction rule for recurrent venous thromboembolism in cancer patients: the Ottawa score.

PURPOSE: Recently, a clinical prediction rule for recurrent venous thromboembolism (VTE) in cancer patients, named Ottawa score, was derived to individualize treatments with different intensities. It is composed of four variables including sex, primary tumor site, tumor stage, and prior history of VTE. The objective of this study was to validate the Ottawa score in an independent patient population in a tertiary hospital in Korea. METHODS: Medical records of consecutive adult patients (>18 years) with active malignancy and newly diagnosed VTE from January 1, 2006 to December 31, 2010 were analyzed. Using the same definition of predictor variables in the original derivation study, patients were divided into low (score ≤ 0) and high (score ≥ 1) risk groups for recurrent VTE, and their actual recurrence rate were analyzed. RESULTS: Of the 546 patients with newly diagnosed VTE, 99 (18.1 %) had recurrent VTE during the follow-up period. In the low-risk group, 34 (13.2 %) had recurrence, compared to 65 (22.4 %) in the high-risk group. Ottawa score's performance showed 66 % sensitivity, 50 % specificity, 22 % positive predictive value, and 87 % negative predictive value in our validation cohort. CONCLUSION: We were not able to accurately ascertain the relevance of the Ottawa score in our validation cohort. Future validation studies, including a more diverse patient population with different cancer predominance, are warranted.

Adding procalcitonin to the MASCC risk-index score could improve risk stratification of patients with febrile neutropenia.

PURPOSE: Infectious complication could be life-threatening in patients with chemotherapy-induced febrile neutropenia (FN). The Multinational Association of Supportive Care in Cancer (MASCC) risk-index score is used to predict the complications of these patients, and it has been focused on identifying low-risk patients who may be candidates for outpatient management. In this study, we evaluated procalcitonin (PCT) and the MASCC score in predicting bacteremia and septic shock in patients with FN. METHODS: From November 2010 to October 2011, 355 patients with FN were prospectively enrolled. Clinical and laboratory findings, including procalcitonin, and the MASCC score were analyzed and correlated with the infectious complications of FN. RESULTS: Of the 355 patients, 35 (9.9 %) had bacteremia, and 25 (7.0 %) developed septic shock. PCT ≥ 0.5 ng/mL (OR 3.96, 95 % CI 1.51-10.40), platelet count <100 × 10(3)/mm(3) (OR 2.50, 95 % CI 1.10-5.66), and MASCC score <21 (OR 2.45, 95 % CI 1.03-5.85) were independently predictive of bacteremia, and PCT ≥ 1.5 ng/mL (OR 29.78, 95 % CI 9.10-97.39) and MASCC score <21 (OR 9.46, 95 % CI 3.23-27.72) were independent factors of septic shock. In 306 patients with low-risk FN classified by the MASCC score, 52 had PCT ≥ 0.5 ng/mL and 31 had PCT ≥ 1.5 ng/mL. Of the 52 patients with PCT ≥ 0.5 ng/mL, 12 (23.1 %) had bacteremia, and of the 31 patients with PCT ≥ 1.5 ng/mL, 7 (22.6 %) developed septic shock. CONCLUSION: Implicating PCT as a routine use in clinical practice along with the MASCC score could improve risk stratification of patients with FN.