[Clinical features and prognostic factors of severe hemophagocytic syndrome in children].

Objective: To explore the clinical characteristics, prognostic risk factors and effective treatment of severe hemophagocytic syndrome (HPS) in children, so as to provide reference for the clinical diagnosis and treatment of the disease. Methods: The clinical data of 83 children with severe HPS admitted in Affiliated Hospital of Zunyi Medical University from January 2014 to April 2021 were collected, and their clinical characteristics, prognosis and prognostic risk factors were analyzed. The children were divided into central nervous system (CNS) dysfunction group and non-CNS dysfunction group according to whether they were accompanied with CNS dysfunction, and were divided into blood purification group and non-blood purification group according to whether they received blood purification, then the survival differences were compared. Results: Among the 83 children, there were 43 males and 40 females, aged[M(Q1,Q3)] 36(15,27)months. A total of 51 children were induced by infection, among which 41 children (80.4%) were infected with EB virus. All the children were accompanied by multiple organ dysfunction (MODS), and dysfunction of the blood system (72.3%), liver (71.1%), respiratory system (53.0%) and CNS (37.3%) were common. By the end of follow-up, 40 cases (48.2%) survived, 38 cases (45.8%) died, and 5 cases (6.0%) were lost to follow-up. CNS dysfunction was a risk factor (HR=3.358, 95%CI: 1.445-7.803, P=0.005) and blood purification was a protective factor (HR=0.362, 95%CI: 0.179-0.730, P=0.005) affecting the prognosis of children. The mortality of CNS dysfunction group was statistically higher than that of non-CNS dysfunction group (74.2% vs 28.8%) (P<0.001); The mortality of blood purification group was statistically lower than that of non-blood purification group (31.0% vs 61.0%) (P=0.010). Conclusions: Severe HPS in children was dangerous and had a poor overall prognosis. CNS dysfunction was a risk factor for death. Blood purification could significantly improve the prognosis and improve the survival rate of children.

Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study.

BACKGROUND: High-risk triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage and onset of resistance to chemotherapy, thus representing an area in need of new therapeutic approaches. Programmed death-ligand 1 (PD-L1) expression is an adaptive mechanism of tumour resistance to tumour-infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, available data support the concept that blockade of PD-L1/programmed cell death protein 1 checkpoint may improve efficacy of classical chemotherapy. PATIENTS AND METHODS: Two hundred and eighty patients with TNBC were enrolled in this multicentre study (NCT002620280) and randomized to neoadjuvant carboplatin area under the curve 2 and nab-paclitaxel 125 mg/m2 intravenously (i.v.) on days 1 and 8, without (n = 142) or with (n = 138) atezolizumab 1200 mg i.v. on day 1. Both regimens were given q3 weeks for eight cycles before surgery followed by four cycles of an adjuvant anthracycline regimen. The primary aim of the study was to compare event-free survival (EFS), and an important secondary aim was the rate of pathological complete response (pCR defined as the absence of invasive cells in breast and lymph nodes). The primary population for all efficacy endpoints is the intention-to-treat (ITT) population. RESULTS: The ITT analysis revealed that pCR rate after treatment with atezolizumab (48.6%) did not reach statistical significance compared to no atezolizumab [44.4%: odds ratio (OR) 1.18; 95% confidence interval 0.74-1.89; P = 0.48]. Treatment-related adverse events were similar with either regimen except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab. CONCLUSIONS: The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis, the presence of PD-L1 expression was the most significant factor influencing the rate of pCR (OR 2.08). Continuing follow-up for the EFS is ongoing, and molecular studies are under way.

Penetration of inferior alveolar nerve canal increased by bicortical fixation after bilateral sagittal split osteotomy in mandibular prognathism.

The purpose of this three-dimensional cone beam computed tomography (CBCT) study was to identify the difference between monocortical fixation (MCF) and bicortical fixation (BCF) in mandibular canal penetration after bilateral sagittal split osteotomy (BSSO) to correct mandibular prognathism, where interosseous fixation was done by BCF or MCF. CBCT was performed 1 week postoperatively and Dolphin 3D software was used to assess direct penetration of the mandibular canal by either type of screw. The primary outcome variable was the presence or absence of mandibular canal penetration and was categorized as a binary coded variable. The BCF and MCF groups were compared by χ2 test, and the odds ratio for canal penetration was estimated. Multiple logistic regression was performed to identify factors related to canal penetration. A total of 118 patients were included. The MCF group had only 6% canal penetrations (3/50 patients) and the BCF group had 58.8% canal penetrations (40/68 patients). The regression model showed that BCF was the only factor causing mandibular canal penetration, with an adjusted odds ratio of 52.5. Awareness of the increased risk of canal penetration with BCF and potential nerve injury might influence case selection.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. PATIENTS AND METHODS: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. RESULTS: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. CONCLUSION: Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

[A multicenter prospective randomized controlled clinical study of 5-fluorouracil in different mass concentrations combined with triamcinolone in the treatment of keloids].

Objective: To evaluate the clinical effects of 5-fluorouracil in different mass concentrations combined with triamcinolone in the treatment of keloids. Methods: From March 2018 to March 2019, 29 patients with 31 keloids receipted in the Department of Plastic Surgery of Fujian Medical University Union Hospital, 11 patients with 20 keloids receipted in the Department of Dermatology of Pingtan Comprehensive Experimental Area Hospital, and 9 patients with 9 keloids receipted in the Fuzhou Heisey-Dea Aesthetic Clinic were included in this prospectively randomized control study, with 27 males and 22 females, aged (30±9) years. According to the random number table, the keloids were divided into low mass concentration group (19 keloids, 17 patients), medium mass concentration group (21 keloids, 19 patients), and high mass concentration group (20 keloids, 17 patients). Then 5-fluorouracil at mass concentrations of 0.5, 5.0, and 12.5 mg/mL combined with triamcinolone acetonide were injected respectively, once every 4 weeks, for a total of 3 times. Before the first treatment and in 3 months after the last treatment, the appearance of keloids was evaluated by Vancouver Scar Scale (VSS) and pain and pruritus of keloids were evaluated by Visual Analogue Scale (VAS). Then the score differences before and after the treatment were calculated. In 6 months after the last treatment, the patients' efficacy satisfaction was evaluated by efficacy satisfaction rating scale. Adverse reactions during the treatment were recorded. In the follow-up of one year after the last treatment, the recurrence rates of keloids were counted. Data were statistically analyzed with chi-square test, one-way analysis of variance, paired sample t test, least significant difference t test, Wilcoxon rank sum test, Kruskal-Wallis rank sum test, or Fisher's exact probability test. Results: Before the first treatment, the appearance VSS scores of appearance of keloids in the three groups were similar (F=0.039, P>0.05). In 3 months after the last treatment, the appearance VSS scores of keloids in low mass concentration group were significantly higher than those in medium mass concentration group and high mass concentration group (t=2.267, 4.086, P<0.05 or P<0.01). In 3 months after the last treatment, the appearance VSS scores of keloids in low mass concentration group, medium mass concentration group, and high mass concentration group were significantly decreased compared with those before the first treatment (t=18.222, 44.272, 22.523, P<0.01). The differences of appearance VSS scores of keloids in low mass concentration group before and after treatment were significantly lower than those in medium mass concentration group and high mass concentration group (t=-4.096, -6.357, P<0.01), and the differences of appearance VSS scores of keloids in medium mass concentration group before and after treatment were significantly lower than those in high mass concentration group (t=-2.368, P<0.05). Before the first treatment, the pain and pruritus VAS scores of keloids in the three groups were similar (χ2=0.149, P>0.05). In 3 months after the last treatment, the pain and pruritus VAS scores of keloids in low mass concentration group were significantly higher than those in medium mass concentration group and high mass concentration group (Z=2.191, 4.386, P<0.05 or P<0.01), and the pain and pruritus VAS scores of keloids in medium mass concentration group were significantly higher than those in high mass concentration group (Z=2.276, P<0.05). In 3 months after the last treatment, the pain and pruritus VAS scores of keloids in medium mass concentration group and high mass concentration group were significantly decreased compared with those before the first treatment (Z=-3.904, -3.844, P<0.01). The differences of pain and pruritus VAS scores of keloids in low mass concentration group before and after treatment were significantly lower than those in medium mass concentration group and high mass concentration group (Z=-4.265, -6.104, P<0.01). In 6 months after the last treatment, the efficacy satisfaction scores of the corresponding patients of keloids were (88±8) points in high mass concentration group, which were significantly higher than (76±8) points in medium mass concentration group and (60±8) points in low mass concentration group (t=-3.820, -6.675, P<0.01), and the efficacy satisfaction scores of the corresponding patients of keloids in medium mass concentration group were significantly higher than those in high mass concentration group (t=-2.984, P<0.05). There was only statistically significant difference in pain within the 3 groups (P<0.01). In the follow-up of one year after the last treatment, the recurrence rate of keloids in high mass concentration group was significantly lower than that in low mass concentration group (χ2=8.313, P<0.01), and the recurrence rate of keloids in medium mass concentration group was similar to the recurrence rates in low mass concentration group and high mass concentration group (P>0.05). Conclusions: After treating keloids with high mass concentration of 5-fluorouracil combined with triamcinolone acetonide, the symptoms were significantly improved, the efficacy satisfaction of patients was increased, with no obvious adverse reactions but long lasting efficacy. Their overall effects are better than treatment using medium and low mass concentrations of 5-fluorouracil, which is worthy of clinical promotion.

Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.

BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

The impact of a surgery-first approach on oral health-related quality of life.

Orthognathic surgery using a surgery-first approach (SFA) has been shown to result in better quality of life (QoL) throughout the treatment duration; however, the effects of gender, age and type of dentofacial deformity on SFA-related QoL remain unknown. In total, 228 consecutive patients underwent SFA for correction of dentofacial deformities (skeletal class III, bimaxillary protrusion and facial asymmetry). We assessed their QoL before surgery and at 1, 6 and 12 months after surgery using the Orthognathic Quality of Life Questionnaire (OQLQ). The results indicated a significant decrease in the total OQLQ, facial aesthetics and social aspect domain scores 1, 6 and 12 months after surgery. Among all domains, the greatest improvement was noted in the facial aesthetics domain. The oral function scores declined significantly immediately after surgery, but improved significantly 6 and 12 months after surgery; however, the awareness scores remained relatively stable. At each time point, women and the bimaxillary protrusion group exhibited a significantly higher total and specific domain scores. Patients aged 18-22 years exhibited lower total and four specific domain scores than older patients. Thus, QoL improves in all aspects, except awareness domain, by 12 months after SFA, but gender, age, and type of dentofacial deformity affect this improvement.

Pharyngeal airway changes following maxillary expansion or protraction: A meta-analysis.

The aim of this meta-analysis was to investigate the changes in airway dimensions after rapid maxillary expansion (RME) and facemask (FM) protraction. Using PubMed, Medline, ScienceDirect and Web of Science, only controlled clinical trials, published up to November 2016, with RME and/or FM as keywords that had ≥6 months follow-up period were included in this meta-analysis. The changes in pharyngeal airway dimension in both two-dimensional and three-dimensional images were included in the analysis. Nine studies met the criteria. There are statically significant changes in upper airway and nasal passage airway in the intervention groups as compared to the control groups, assessed in two-dimensional and three-dimensional images. However , in the lower airway and the airway below the palatal plane, no statistically significant changes are seen in 2D and 3D images. RME/FM treatments might increase the upper airway space in children and young adolescents. However, more RCTs and long-term cohort studies are needed to further clarify the effects on pharyngeal airway changes.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Toxicity profile differences of adjuvant docetaxel/cyclophosphamide (TC) between Asian and Caucasian breast cancer patients.

AIM: For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. METHODS: Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. RESULTS: From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P <0.001) and significantly more grade ≥3 neutropenia events were documented (respectively 30.7% vs 4.0%, P <0.001). The prophylactic use of G-CSF was similar; 26.0% in Asians and 28.0% in Caucasian (P = 0.764). There were no differences in nonhematological toxicities. No significant difference in disease-free survival was observed between Asians and Caucasians (log-rank P = 0.910). CONCLUSIONS: Ethnic differences in toxicity profile exist between Asian and Caucasian patients given adjuvant TC. Over 30% Asians but less than 5% Caucasians experienced grade ≥3 neutropenia.

Patterns of recurrence after oesophagectomy and postoperative chemoradiotherapy versus surgery alone for oesophageal squamous cell carcinoma.

BACKGROUND: Patterns of recurrence after surgery with postoperative chemoradiotherapy (S-CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might influence the nature and timing of subsequent management strategies. METHODS: Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease-free survival. RESULTS: A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S-CCRT. Propensity score matching yielded 213 well balanced pairs. The 3-year overall survival rate and median survival time in the S-CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery-alone group (P = 0·006). The 3-year disease-free survival rate and median disease-free survival time in the S-CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery-alone group (P = 0·006). The 2-year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S-CCRT and surgery-alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease-free survival included age over 56 years, pT3-4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001). CONCLUSION: Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone.

Nephrolithiasis among male patients with newly diagnosed gout.

INTRODUCTION: An elevated serum urate level is recognised as a cause of gouty arthritis and uric acid stone. The level of serum uric acid that accelerates kidney stone formation, however, has not yet been clarified. This study aimed to find out if a high serum urate level is associated with nephrolithiasis. METHODS: Patients were recruited from the rheumatology clinic of Taipei City Hospital (Renai and Zhongxing branches) in Taiwan from March 2015 to February 2016. A total of 120 Chinese male patients with newly diagnosed gout and serum urate concentration of >7 mg/dL and no history of kidney stones were divided into two groups according to their serum urate level: <10 mg/dL (group 1, n=80) and ≥10 mg/dL (group 2, n=40). The mean body mass index, blood urea nitrogen level, creatinine level, urinary pH, and kidney ultrasonography were compared between the two groups. RESULTS: There were no significant differences in blood urea nitrogen or creatinine level between the two groups. The urine pH in both groups was similar and not statistically significant. Kidney stone formation was detected via ultrasonography in 6.3% (5/80) and 82.5% (33/40) of patients in groups 1 and 2, respectively (P<0.05). CONCLUSION: A serum urate level of ≥10 mg/dL may precipitate nephrolithiasis. Further studies are warranted to substantiate the relationship between serum urate level and kidney stone formation.

The lipid profile in obese asthmatic children compared to non-obese asthmatic children.

BACKGROUND: A relationship between asthma and obesity has been documented in children and adolescents. An alternate day calorie restriction diet has been reported to improve asthma symptoms by decreasing levels of serum cholesterol and triglycerides, reducing markers of oxidative stress and increasing levels of the antioxidant uric acid. Therefore, to investigate the lipid profile in asthmatic children may be important in asthma control treatment. MATERIALS AND METHODS: One hundred and sixty newly diagnosed persistent asthmatic children were selected to participate in the study. They were divided into four groups based on their body mass index (BMI): Group I normal weight (BMI=20-24.9kg/m(2), n=30); Group II under-weight (BMI<20kg/m(2), n=30); Group III overweight (BMI=25-30kg/m(2), n=25); and Group IV obese (BMI>30kg/m(2), n=25). Fasting blood sugar, fasting insulin, and HbA1c were measured to exclude the possibility of pre-diabetes. Lipid profile measurements included total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apo-A1, apo-B and triglycerides. RESULTS: There were no significant differences in the levels of apo-A1, apo-B, triglycerides, cholesterol and LDL in all four groups. Only the level of HDL was higher in GIV>GIII>GII>GI (75.84±13.95, 68.56±15.28, 64.17±13.93, 63.17±14.34mg/dl, respectively). There were no cases of pre-diabetes in any of the four groups. CONCLUSION: Hypercholesterolaemia and hypertriglyceridaemia were not found in any of the persistent asthmatic children, and thus they are not high risk factors for asthma. Similarly, there were no differences in apo-A1 and apo-B between any of the BMI groups. No differences were found in LDL levels, however HDL levels were increased in all four groups, indicating that allergic sensitisation may have occurred. Controlling body weight and restricting calorie intake may be as important as appropriate pharmacological management in controlling asthma.

Swimming exercise ameliorates neurocognitive impairment induced by neonatal exposure to isoflurane and enhances hippocampal histone acetylation in mice.

Isoflurane-induced neurocognitive impairment in the developing rodent brain is well documented, and regular physical exercise has been demonstrated to be a viable intervention for some types of neurocognitive impairment. This study was designed to investigate the potential protective effect of swimming exercise on both neurocognitive impairment caused by repeated neonatal exposure to isoflurane and the underlying molecular mechanism. Mice received 0.75% isoflurane exposures for 4h on postnatal days 7, 8, and 9. From the third month after anesthesia, the mice were subjected to regular swimming exercise for 4weeks, followed by a contextual fear condition (CFC) trial. We found that repeated neonatal exposure to isoflurane reduced freezing behavior during CFC testing and deregulated hippocampal histone H4K12 acetylation. Conversely, mice subjected to regular swimming exercise showed enhanced hippocampal H3K9, H4K5, and H4K12 acetylation levels, increased numbers of c-Fos-positive cells 1h after CFC training, and less isoflurane-induced memory impairment. We also observed increases in histone acetylation and of cAMP-response element-binding protein (CREB)-binding protein (CBP) during the swimming exercise program. The results suggest that neonatal isoflurane exposure-induced memory impairment was associated with dysregulation of H4K12 acetylation, which may lead to less hippocampal activation following learning tasks. Swimming exercise was associated with enhanced hippocampal histone acetylation and CBP expression. Exercise most likely ameliorated isoflurane-induced memory impairment by enhancing hippocampal histone acetylation and activating more neuron cells during memory formation.

Orthodontic principles and guidelines for the surgery-first approach to orthognathic surgery.

The surgery-first approach has become a new paradigm in orthognathic surgery. With the surgery-first approach, most of the patient's teeth are in their original positions and have not undergone orthodontic treatment prior to the patient undergoing orthognathic surgery. A 'treatable' malocclusion should be attained following orthognathic surgery. Orthodontists must ensure that they can manage the 'treatable' malocclusion by actively participating in the patient's surgical plan. Therefore, orthodontic principles and guidelines must be established. Three-dimensional computed tomography should be used to construct the midfacial plane and then to assess discrepancies in the midfacial structures as well as yaw and roll of the bilateral facial structures. Orthognathic surgery should be performed to improve the alignment of such discrepancies to attain a skeletal class I relationship and to attain an aesthetically pleasing face. The surgery-first approach uses osteotomy to solve most of the skeletal and dental problems and to simplify postoperative orthodontic treatment by providing a treatable malocclusion for which mostly only anteroposterior orthodontic movement is required, with minimal transverse or vertical orthodontic movements. Numerous studies have documented the efficacy and long-term stability. Patients undergoing the surgery-first approach benefit from an immediate improvement in facial aesthetics, oral function, and self-confidence, with a shorter total treatment period.