Factors Involved in Caries Experience of Dentally-fearful Patients

Background: The aim of this study was to investigate the factors that associate the decayed, missing due to caries, and filled teeth (DMFT) index of patients with dental anxiety during dental treatment discontinuation.Methods: A total of 110 patients who complained of fear and anxiety toward dental treatments and who re-visited following treatment discontinuation were enrolled in the study. Patient and dental data considered to be related to caries were digitally collected from medical and dental records. The decayed (D), missing (M), and filled (F) scores, and the DMFT index before and after discontinuation were compared using Wilcoxon signed-rank tests, and the associated factors were evaluated using the Poisson and multiple regression analyses.Results: The D score and DMFT index augmented significantly during the discontinuation period, and the F score reduced. There was no significant change in the M score. The change in the D score was associated by the pre-discontinuation D score and the number of experiences of intravenous sedation, and the change in the F score was associated by the duration of treatment discontinuation, the DMFT index before discontinuation, and the number of experiences of intravenous sedation. The upsurge in the DMFT index was associated by the experience of intravenous sedation, the D and M scores, and the DMFT index before discontinuation.Conclusion: Discontinuation of dental treatment was proven to be associated with the incidence of caries in dentally-fearful patients

Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1, 057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC. Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as disease-free survival (DFS) and overall survival (OS). Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4–113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death. Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs

Nasal high flow improves ventilation during propofol sedation: A randomized cross-over study in healthy volunteers

Objective: Hypoventilation and carbon dioxide (CO2) retention are common during sedation. The current study investigated the ventilation responses to nasal high flow (NHF) during sedation with propofol. Methods: NHF of 30 L/min and 60 L/min with room air was applied during wakefulness and sedation in 10 male volunteers. Ventilation was monitored by respiratory inductance plethysmography, transcutaneous partial pressure of CO2 (TcCO2), and SpO2. Results: During sedation, NHF of 30 L/min and 60 L/min reduced the TcCO2 by 2.9 ± 2.7 mmHg (p = 0.025) and by 3.6 ± 3.4 mmHg (p = 0.024) without affecting SpO2 and reduced the mean respiratory rate by 3 ± 3 breaths/min (p = 0.011) and by 4 ± 3 breaths/min (p = 0.003), respectively. Conclusion: During sedation with propofol, NHF without supplemental oxygen attenuated CO2 retention and reduced the respiratory rate. The findings show that NHF can improve ventilation during sedation, which may reduce the risk of complications related to hypoventilation

Characterization of the novel mutant A78T-HERG from a long QT syndrome type 2 patient: Instability of the mutant protein and stabilization by heat shock factor 1

Background:The human ether-a-go-go-related gene (HERG) encodes the α-subunit of rapidly activating delayed-rectifier potassium channels. Mutations in this gene cause long QT syndrome type 2 (LQT2). In most cases, mutations reduce the stability of the channel protein, which can be restored by heat shock (HS). Methods: We identified the novel mutant A78T-HERG in a patient with LQT2. The purpose of the current study was to characterize this mutant protein and test whether HS and heat shock factors (HSFs) could stabilize the mutant protein. A78T-HERG and wild-type HERG (WT-HERG) were expressed in HEK293 cells and analyzed by immunoblotting, immunoprecipitation, immunofluorescence, and whole-cell patch clamping. Results: When expressed in HEK293 cells, WT-HERG gave rise to immature and mature forms of the protein at 135 and 155 kDa, respectively. A78T-HERG gave rise only to the immature form, which was heavily ubiquitinated. The proteasome inhibitor MG132 increased the expression of immature A78T-HERG and increased both the immature and mature forms of WT-HERG. WT-HERG, but not A78T-HERG, was expressed on the plasma membrane. In whole-cell patch clamping experiments, depolarizing pulses evoked E4031-sensitive HERG channel currents in cells transfected with WT-HERG, but not in cells transfected with A78T-HERG. The A78V mutant, but not A78G mutant, remained in the immature form similarly to A78T. Maturation of the A78T-HERG protein was facilitated by HS, expression of HSF-1, or exposure to geranyl geranyl acetone. Conclusions: A78T-HERG was characterized by protein instability and reduced expression on the plasma membrane. The stability of the mutant was partially restored by HSF-1, indicating that HSF-1 is a target for the treatment for LQT2 caused by the A78T mutation in HERG

The effect of midazolam administration for the prevention of emergence agitation in pediatric patients with extreme fear and non-cooperation undergoing dental treatment under sevoflurane anesthesia, a double-blind, randomized study

Background: Sevoflurane is generally the preferred anesthetic agent for general anesthesia in pediatric patients, due to its rapid induction and recovery characteristics. However, it has been recognized that a major complication is emergence agitation when awakening from general anesthesia. The aim of this study was to evaluate the occurrence rate of emergence agitation in the operating room and postoperative recovery area following intraoperative administration of midazolam to pediatric patients under general anesthesia. Patients and methods: One hundred and twenty pediatric patients undergoing dental treatment under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=40 each in the 0.1 mg/kg midazolam, 0.05 mg/kg midazolam, and control with saline groups). Midazolam or saline was injected intravenously approximately 30 minutes before the end of the dental treatment. We used the Richmond Agitation and Sedation Scale (RASS) to assess the level of sedation and drowsiness at emergence phase in the operating room. We also used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level of agitation and delirium at the full recovery phase from anesthesia in the recovery area. Results:At the emergence phase, the incidence of emergence agitation in the 0.1 mg/kg midazolam group was significantly lower than in the other groups (p=0.0010). At the recovery phase, there was no significant difference among the three groups. The odds ratio between PAED score and RASS score was 4.0 using logistic regression analysis. The odds ratio between PAED score and Disability was 2.5. Conclusion: Administration of a single dose of 0.1 mg/kg midazolam dose significantly decreases the incidence of severe emergence agitation at the emergence after sevoflurane anesthesia, but not at the recovery phase. Furthermore, the evaluation of sedative and agitation condition using RASS score at emergence from anesthesia is useful to predict occurrence of agitation in the recovery phase

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset

This prespecified subanalysis of the global, randomized controlled phase Ill KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFRIALK alterations and a PD-L1 tumor proportion score of 50% or greater

First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval [CI], 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11‐0.65]; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 [95% CI, 0.17‐0.91]; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738

Management of post-hyperventilation apnea during dental treatment under monitored anesthesia care with propofol

Although hyperventilation syndrome generally carries a good prognosis, it is associated with the risk of developing severe symptoms, such as post-hyperventilation apnea with hypoxemia and loss of consciousness. We experienced a patient who suffered from post hyperventilation apnea. A 17-year-old female who suffered from hyperventilation syndrome for several years developed post-hyperventilation apnea after treatment using the paper bag rebreathing method and sedative administration during a dental procedure. We subsequently successfully provided her with monitored anesthesia care with propofol. Monitored anesthesia care with propofol may be effective for the general management of patients who have severe hyperventilation attacks and post-hyperventilation apnea. This case demonstrates that appropriate emergency treatment should be available for patients with hyperventilation attacks who are at risk of developing post-hyperventilation apnea associated with hypoxemia and loss of consciousness