[Phase â ¡ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma].

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Socioeconomic characteristics of those with peripheral artery disease in the chronic renal insufficiency cohort.

BACKGROUND: The association between socioeconomic factors and peripheral arterial disease (PAD) has not been as well characterized as other cardiovascular conditions. We sought to define how annual income and education level are associated with PAD in a well-characterized diverse set of adults with chronic kidney disease (CKD). METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multi-center, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic, income, and education-level data, as well as clinical data including ankle-brachial index (ABI) were collected at baseline. Annual income was categorized as < $25,000, $25,000-50,000, $50,000-100,000, or above $100,000; educational level was categorized as some high school, high school graduate, some college, or college graduate. Participants with missing income data or incompressible ABI (>1.4) were excluded from initial analysis. Logistic regression was used to estimate the association of income and/or education level with PAD, defined as an enrollment ABI of <0.90, history of PAD, or history of PAD intervention. RESULTS: A total of 4122 were included, mean age of participants was 59.5 years, 56% were male, and 44% were Black. There were 763 CRIC participants with PAD at study enrollment (18.5%). In the final multivariable logistic regression model, Black race (OR = 1.3, 95% CI 1.1-1.6, p = 0.004) and level of annual household income remained independently associated with PAD at the time of enrollment (income <$25,000 OR = 1.9, 95% CI 1.3-2.8, p < 0.001; income $25,000-50,000 OR = 1.6, 95% CI 1.1-2.3, p = 0.011; income $50,000-100,000 OR = 1.2, 95% CI 0.9-1.8, p = 0.246), relative to a baseline annual income of >$100,000 (overall p-value <0.001). Decreasing level of educational attainment was not independently associated with increased PAD at enrollment, but lower level of educational attainment was associated with increased PAD when income data was not adjusted for (p = 0.001). Interestingly, Black race (OR = 0.7, 95% CI 0.6-0.8, p < 0.001), female gender (OR = 0.8, 95% CI 0.7-0.9, p = 0.007), and income <$25,000 (OR = 0.7, 95% CI 0.5-0.9, p = 0.008) were significantly associated with decreased statin use even after controlling for cardiovascular conditions. CONCLUSIONS: In this prospectively followed CKD cohort, lower annual household income and Black race were significantly associated with increased PAD at study enrollment. In contrast, educational level was not associated with PAD when adjusted for patient income data. Black race, female gender, and low income were independently associated with decreased statin use, populations which could be targets of future public health programs.

[A multicenter retrospective study on the efficacy of different anti-reflux reconstruction methods after proximal gastrectomy for gastric cancer].

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ2 test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ2 test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ2=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m2, P<0.01; mean difference=2.429 kg/m2, P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m2, P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ2=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ2=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.

The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease's molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45-65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.

A novel risk prediction model of pyroptosis-related genes for the prognosis and immunotherapy response of endometrial cancer.

OBJECTIVE: This study aims to develop a risk prediction model of pyroptosis-related genes based on its impact on immunotherapy sensitivity of uterine corpus endometrial carcinoma (UCEC), one of the most common and threatening gynecological malignancies. PATIENTS AND METHODS: Through multiple bioinformatics analysis, we obtained raw counts of RNA-sequencing data and corresponding clinical information related to UCEC from The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) to investigate the potential mechanisms of differentially expressed pyroptosis-related genes (DEPRGs), including the correlation between DEPRGs and prognosis, tumor immune microenvironment and the immunotherapy sensitivity of UCEC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis were used to figure out the functional differences. Furthermore, a mRNA-miRNA-lncRNA network was constructed to identify potential impact of pyroptosis on tumor progression. RESULTS: In this study, we achieved six DEPRGs (CASP3, GPX4, GSDMD, NOD2, PYCARD and TIRAP) and constructed a 6-gene signature which classified UCEC patients in the TCGA cohort into a low-risk group or a high-risk group. Patients in the low-risk group showed significantly longer survival time (p=0.000373). The risk score was also confirmed as an independent prognostic factor combining with the clinical characteristics. GO and KEGG functional analysis revealed the possible molecular mechanisms by which six DEPRGs influence anti-tumor immunity in UCEC patients. In addition, we found that two DEPRGs (GPX4, TIRAP) were not only significantly associated with tumor mutational burden (TMB) or microsatellite Instability (MSI), but also involved in regulating the number and function of CD8+ cells. CONCLUSIONS: Upon comprehensive bioinformatics analysis, it was concluded that pyroptosis-related genes (PRGs) could predict the prognosis of EC patients and be affected in modulating the anti-tumor immune responses for patients with EC.

The Association Between Socioeconomic Factors and Incident Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort (CRIC).

BACKGROUND: The association between socioeconomic factors and development of peripheral artery disease (PAD) has not been as well characterized compared to other cardiovascular diseases. We sought to define how annual income, sex, race, and education level are associated with newly diagnosed PAD in a well-characterized, diverse set of adults with CKD. METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multicenter, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic and clinical data including ankle brachial index (ABI) and interventions were collected at baseline, as well as yearly during follow-up visits. Annual income was categorized as: <$25,000, $25,000-50,000, $50,000-100,000, or above $100,000. We excluded those with pre-existing PAD, defined as enrollment ABI of <0.9 or >1.4, or missing income data. Cox proportional hazards regression was used to estimate the risk for incident PAD during CRIC enrollment, defined as a drop in ABI to <0.90 or a confirmed PAD intervention, including revascularization or amputation. RESULTS: A total of 3,313 patients met inclusion criteria, the mean age was 58.7 years, 56% were male, and 42% were Black. Over a median follow-up of 10.1 years, 639 participants (19%) were newly diagnosed with PAD. After adjusting for cardiovascular risk factors, all lower levels of annual household income were associated with increased incidence of PAD (income <$25,000 HR 1.7, 95% CI 1.1-2.4, P = 0.008; income $25,000-50,000 HR 1.5, 95% CI 1.1-2.3, P = 0.009; income $50,000-100,000 HR 1.6, 95% CI 1.2-2.4, P = 0.004), relative to a baseline annual income of >$100,000 (overall P-value = 0.02). In the multivariable model, there was no association between education level and PAD incidence (P = 0.80). Black race (HR 1.2, 95% CI 1.0-1.5, P = 0.023) and female sex (HR 1.7, 95% CI 1.4-2.0, P < 0.001) were independently associated with PAD incidence. Multiple imputation analysis provided similar results. CONCLUSIONS: In the CRIC, a multi-center cohort of prospectively followed CKD patients undergoing yearly CVD surveillance, lower annual household income, female sex, and Black race were significantly associated with the PAD incidence. In contrast, level of education was not independently associated with incident PAD.

International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials.

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

Cut-offs for defining uterine prolapse using transperineal ultrasound in Chinese women: prospective multicenter study.

OBJECTIVE: Transperineal ultrasound is a simple and highly repeatable method that has been used increasingly in the quantification of pelvic organ prolapse, but abnormal uterine descent on ultrasound in Chinese women is still poorly defined. We aimed to determine the optimal cut-off to define abnormal uterine descent on transperineal ultrasound in Chinese women. METHODS: This prospective multicenter study recruited women who were examined in tertiary-level gynecological centers, due to symptoms of lower urinary tract and/or pelvic floor dysfunction, between February 2017 and September 2018. All recruited women underwent a standardized interview, pelvic organ prolapse quantification (POP-Q) examination, and four-dimensional transperineal ultrasound examination. On ultrasound, uterine descent was measured relative to the posteroinferior margin of the symphysis pubis during maximum Valsalva maneuver. The optimal cut-off value for definition of abnormal uterine descent was selected as the value with the highest Youden index and the diagnostic performance of this cut-off for the prediction of prolapse symptoms and POP-Q stage was assessed and compared by means of the area under the receiver-operating-characteristics curve (AUC). RESULTS: In total, 538 Chinese women, with a mean age of 39.4 (range, 18-81) years, were enrolled into the study. Both uterine descent on transperineal ultrasound (P < 0.001) and POP-Q stage (P < 0.001) were associated strongly with presence of prolapse symptoms. Uterine descent on ultrasound was associated significantly with POP-Q stage for apical compartment prolapse (P < 0.001). The optimal cut-off value for the definition of abnormal uterine descent on transperineal ultrasound during maximum Valsalva maneuver in the prediction of prolapse symptoms was 4.79 mm above the symphysis pubis (AUC, 0.75 (95% CI, 0.71-0.78)), while the optimal cut-off values in the prediction of prolapse of POP-Q Stage ≥ 1 and POP-Q Stage ≥ 2 were 6.63 mm above the symphysis pubis (AUC, 0.83 (95% CI, 0.80-0.86)) and 8.42 mm below the symphysis pubis (AUC, 0.85 (95% CI, 0.82-0.88)), respectively. CONCLUSIONS: The optimal cut-off value to define abnormal uterine descent on transperineal ultrasound during maximum Valsalva maneuver for the prediction of prolapse symptoms in this population of Chinese women was 4.79 mm above the symphysis pubis, close to that for predicting apical compartment prolapse of POP-Q Stage ≥ 1 (6.63 mm above the symphysis pubis). These are somewhat different from values described previously in mainly Caucasian populations. Ethnic differences should be taken into account in the evaluation of pelvic organ prolapse using transperineal ultrasound. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Structural difference analysis of adult's intestinal flora basing on the 16S rDNA gene sequencing technology.

OBJECTIVE: Through 16S rDNA technology, we aimed at separating adults aging 20-50 years old into a few groups and processing the high-throughput sequencing analysis, in order to explore the features and differences of intestinal flora in each age group in a microcosmic perspective. PATIENTS AND METHODS: 120 stool specimens were collected strictly in accordance with acceptance criteria and exclusion criteria. 49 subjects aging 20-29 years old (Group AGE1), 51 subjects aging 30-39 years old (Group AGE2), and 20 subjects aging 40-49 years old (Group AGE3) were divided into 3 groups. Bacteria DNA from fresh stool specimens of 3 groups were abstracted. Illumina MiSeq high-throughput sequencing platform was applied to process 16S rDNA sequencing in Area 338F_806R for intestinal flora detection. I-Sanger Bio-cloud platform was applied for the analysis of intestinal flora structure changes in phylum level and genus level. RESULTS: Among the age of 20-50, with older age, the abundance of intestinal flora decreased among healthy adults more than 40 years old. In addition, the diversity and sample dispersion of intestinal flora is significantly different from people among 20-40 years old. The decrease ratio of Firmicutes/Bacteroidetes indicated that as the age grows, glucose tolerance might decrease. Comparing with people among 20-40 years old, the amount of Bifidobacterium and Eubacterium in people over 40 years old have significantly decreased. The decrease of Bifidobacterium and Eubacterium may increase the risks of cognitive impairment and lower the anti-inflammation and anti-cancer efficacy in human body, respectively. Subdoligranulum relates to poor metabolism and chronic inflammation and it happens more in people aged over 40 than young people who are among 20-40 years old. CONCLUSIONS: There are differences in the intestinal flora of healthy adults aged 20-50. Effective intervention of the intestinal flora may play a role in delaying aging and preventing diseases.

[A multicentric study on clinical characteristics and antibiotic sensitivity in children with methicillin-resistant Staphylococcus aureus infection].

Objective: To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods: The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children's hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children's general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results: Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (ß-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ(2)=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ(2)=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ(2)=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10(9)/L vs. (13±7)×10(9)/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions: The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.

Could symptom burden predict subsequent healthcare use in patients with end stage kidney disease on hemodialysis care? A prospective, preliminary study.

Context: Patients treated with maintenance hemodialysis experience significant symptom burden resulting in impaired quality of life. However, the association of patient reported symptom burden and the risk of healthcare use for patients with end stage kidney disease on hemodialysis has not been fully explored.Objectives: To investigate if higher symptom burden, assessed by the Edmonton Symptom Assessment System-revised (ESASr), is associated with increased healthcare use in patients with end stage kidney disease on hemodialysis.Methods: Prospective, single-center, study of adult patients on HD. Participants completed the ESASr questionnaire at enrollment. Baseline demographic, clinical information as well as healthcare use events during the 12-month following enrollment were extracted from medical records. The association between symptom burden and healthcare use was examined with a multivariable adjusted negative binomial model.Results: Mean (SD) age of the 80 participants was 71 (13) years, 56% diabetic, and 70% male. The median (IQR) dialysis vintage was 2 (1-4) years. In multivariable adjusted models, higher global [incident rate ratio (IRR) 1.02, 95% confidence interval (CI) 1.00-1.04, p = .025] and physical symptom burden score [IRR 1.03, CI 1.00-1.05, p = .034], but not emotional symptom burden score [IRR 1.05, CI 1.00-1.10, p = .052] predicted higher subsequent healthcare use.Conclusions: Our preliminary evidence suggests that higher symptom burden, assessed by ESASr may predict higher risk of healthcare use amongst patients with end stage kidney disease on hemodialysis. Future studies need to confirm the findings of this preliminary study and to assess the utility of ESASr for systematic symptom screening.

[Safety evaluation on different ventilation strategies set for neonatal respiratory distress syndrome: a network Meta-analysis].

Objective: To evaluate the relative safety of different ventilation methods regarding mortality and rates of complication, on neonatal respiratory distress syndrome (NRDS). Methods: Network Meta-analysis was used to collect data on randomized controlled trials of pulmonary ventilation strategies in preterm infants with a mean gestational age of less than 32 weeks. Diagnostic criteria on NRDS were published in the PubMed, Cochrane, Web of Science, EBSCO, and Springer Link databases from January 1986 to June 2018. Revman 5.3 software was used to evaluate the quality of studies, based on the Cochrane quality assessment tool. Data were analyzed by Bayesian and frequency methods, using both Win BUGS 1.4.3 and STATA 13.0 software. Safety of different ventilation strategies for NRDS mortality and complications would include intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA) and retinopathy of prematurity (ROP) and were evaluated. Counted data was displayed by OR and 95%CI. Results: A total of 31 RCTs were included in this paper, including 5 827 preterm infants and 11 ventilation strategies. There were no statistically significant differences appearing in 11 ventilation strategies on mortality, PDA or ROP. IVH results were reported in 28 studies. Compared with nasal intermittent positive pressure ventilation (NIPPV), both high- frequency oscillation ventilation (HFOV) (OR=3.33, 95%CI: 1.08-16.67, P<0.05) and synchronized intermittent mechanical ventilation (SIMV) (OR=8.22, 95%CI: 1.25-29.44, P<0.05) schemes seemed to have increased the risk of IVH in preterm infants with NRDS. NIPPV appeared the optimal ventilation strategy in the rankings of cumulative probability. Results on clustering showed that NIPPV was probably the best ventilation strategy for children with NRDS after considering the orders of IVH, PDA and ROP on mortality, respectively. However, HFOV, IMV, and SIMV did not seem to be the ideal ventilated strategies. Conclusions: Most of the clinical decision makers might prefer using NIPPV in the treatment of children with NRDS through mechanical ventilation systems to reduce both the incidence and death caused by IVH, PDA and ROP. It was not recommended to use HFOV, SIMV and IMV in treating NRDS with gestational less than 32 weeks. We suggested that larger numbers of multi-center RCTs ba carried out to make the above conclusions more convincing.

Dietary sodium and potassium and risk of diabetes: A prospective study using data from the China Health and Nutrition Survey.

AIMS: Dietary sodium and potassium intakes are well-known risk factors for cardiovascular outcomes. However, the associations between dietary sodium and potassium and diabetes are still controversial. Our study aimed to examine whether dietary sodium, potassium and the sodium-potassium ratio are associated with the risk of diabetes, based on a large sample of Chinese adults. METHODS: The study data were from the 2004-2009 China Health and Nutrition Survey (CHNS), and 5867 participants were eligible for analysis. Sodium and potassium intakes were estimated based on three consecutive 24-h recalls at an individual level combined with a food inventory at a household level performed over the same 3-day period. Diabetes was defined as fasting glucose ≥7.0mmol/L (≥126mg/dL), HbA1c ≥6.5% or use of antidiabetic drugs. RESULTS: Over a mean follow-up of 4.7 years, there were 611 (10.4%) incident cases of diabetes. Participants in the higher quartiles (Q3 and Q4) of sodium intake had significantly higher risks of diabetes than those with the lowest sodium intake [Q3, RR: 1.41, 95% CI: 1.06-1.86 and Q4, RR: 1.35, 95% CI: 1.02-1.80; P<0.001 for trend]. In addition, high sodium intakes were significantly associated with levels of fasting glucose and HbA1c (P<0.05 for trend), with similar associations also found with sodium-potassium ratios (P<0.05 for trend), but not for potassium intakes. CONCLUSION: This study found that higher sodium intakes and sodium-potassium ratios were significantly associated with a higher risk of diabetes. Further clinical research is now necessary to confirm these results.

[Efficacy of exercise rehabilitation in patients with knee osteoarthritis].

Objective: To explore whether exercise could influence outcomes and improve life quality of patients with knee osteoarthritis. Methods: This study included 210 patients diagnosed with knee osteoarthritis from October to December 2018 in Shijiazhuang Derui Exercise Rehabilitation Medical Center. These patients were divided into two groups with random number table: experiment and control group. Patients in experimental group got exercise rehabilitation training and routine therapy,but patients in control group got routine treatment only that included physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs). We applied different kinds of measure to follow-up these patients,which included Lysholm scale, the Western Ontario and McMaster Osteoarthritis Index (WOMAC), SF-36 life quality questionnaire, and knee range of motion.The degree of pain and symptoms and the knee function and the quality of life in the two groups were recorded too. Paired sample t test was used to compare the data between the two groups. Results: There were 105 patients in each group, but 13 cases (12.4%) in experimental group and 6 patients (5.7%) in control group were lost,respectively.All the patients were followed up for (12.0±2.3) weeks. There was no significant differences in age, body mass index, gender between the two groups. At the final follow-up, the WOMAC score in the experiment group was 84.4±6.8, and it was 108.3±1.7 in the control group (t=-4.71, P<0.05);the Lysholm score of the experimental group was 65.5±4.7, and it was 41.2±1.4 in the control group (t=7.29, P<0.05); the knee range of motion in the experiment group and control group was 121°±7° and 114°±3°, respectively (t=1.83, P<0.05); the SF-36 score in the two groups was 90.0±2.8 and 75.6±1.5, respectively (t=6.15, P<0.05). Conclusion: Exercise rehabilitation plus routine therapy for patients with knee osteoarthritis can effectively improve outcome, promote functional recovery and improve quality of life.

Combined Tumors in Hematolymphoid Neoplasms: Case Series of Histiocytic and Langerhans Cell Sarcomas Arising From Low-Grade B-Cell Lymphoma.

We report an index case of histiocytic sarcoma arising in a 70-year-old patient with long-standing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The patient presented in 2017 with painful, enlarging swelling of the left neck. He had remote history of cutaneous squamous cell carcinoma with no sign of recurrence, and his CLL/SLL was thought to be in remission. Computed tomography showed mild splenomegaly and multifocal lymphadenopathy including a 3-cm left neck mass. Biopsy of the left neck mass showed CLL/SLL with associated histiocytic sarcoma. Flow cytometry demonstrated a B cell neoplasm with CLL/SLL phenotype. Despite radiation therapy, he expired 3 months after presentation. Two similar cases (CLL/SLL and histiocytic sarcoma, follicular lymphoma and Langerhans cell sarcoma) from another institution are also illustrated. The pathological features of combined tumors in lymphoid neoplasms, a general framework to the work-up to determine interrelatedness of tumor components, and the clinical relevance are discussed.

[Thrombosis after establishing internal jugular vein channel in one burn patient].

On September 7th, 2017, one female patient, aged 48 years with deep partial-thickness flame burn on face, upper limbs, trunk, and lower limbs of 40% total body surface area was admitted to the First People's Hospital of Foshan City. After admission, active fluid replacement, anti-infection, nutritional support, and other treatments were performed. After debridement and skin grafting for 3 times and blood transfusion for 2 times, the patient recovered well. On the 20th day post admission, sudden heartbeat and respiratory arrest happened, and the patient died after ineffective rescue. Autopsy showed that thrombus formed in right internal jugular vein and deep veins of lower extremities, and vascular lumina of the bilateral pulmonary artery. The direct cause of death was acute pulmonary thromboembolism, but whether the embolus originated from deep vein of lower extremity or right internal jugular vein was not clear. This case suggests that clinician should not only pay attention to the prevention of deep venous thrombosis of lower extremities of burn patients, but also the possibility of internal jugular vein thrombosis, especially for patients with internal jugular vein access.

[Clinical characteristics and antimicrobial resistance of pneumococcal infections from 9 children's hospitals in 2016].

Objective: To describe the clinical characteristics of pneumococcal infections and drug resistance of Streptococcus pneumoniae isolates from children's hospitals, which would provide reference for preventing and treating pneumococcal diseases. Methods: This was a prevalence survey. In this study, the age, specimen type, monthly distribution characteristics, and antimicrobial resistance of Streptococcus pneumoniae isolates from 9 children's hospitals in China were investigated between January 1, 2016 and December 31, 2016. The WHONET 5.6 software was used to analyze the antibiotic susceptibility of Streptococcus pneumoniae. The comparison of rates was performed by Chi-square test. Results: A total of 6 200 isolates of streptococcus pneumoniae were obtained, namely, 95.1% (5 876/6 177) from the respiratory tract specimens, 2.2% (136/6 177) from blood specimens and 0.4% (24/6 177) from cerebrospinal fluid specimens. The isolates were mainly from children older than 1 and younger than 5 years (54.7%, 3 381/6 185) . Most of strains (33.2%, 1 184/3 563) were isolated in November, December and January. Streptococcus pneumoniae isolates were completely sensitive to vancomycin (100.0%, 6 189/6 189) , linezolid (100.0%, 6 030/6 030) , moxifloxacin (100.0%, 3 064/3 064) , highly sensitive to levofloxacin (99.8%, 5 528/5 540), ertapenem (98.8%, 3 024/3 061) and lowly sensitive to erythromycin (1.7%, 102/6 016), clindamycin (3.7%, 116/3 136), and tetracycline (5%, 244/4 877), respectively. According to the parenteral susceptibility breakpoints for non-meningitis isolates, the sensitivity of Streptocococus pneumoniae to penicillin from children's hospital of Chongqing Medical University (49.3%, 892/1 809) was significantly lower than those of other hospitals (χ(2)=1 268.161, P<0.05) . Conclusions:Streptococcus pneumoniae is mainly isolated from respiratory tract, from children older than 1 and younger than 5 years and during November to January in tertiary children's hospital of China. The Streptococcus pneumoniae from children is highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin. There are also significant differences in the sensitivity of penicillin for Streptococcus pneumoniae from different hospitals.

Temperature-dependent optical constants of liquid isopropanol, n-butanol, and n-decane.

Liquid isopropanol, n-butanol, and n-decane are combustible organic compounds that are frequently used in theoretical and experimental researches on fuel combustion. In this work, the temperature-dependent optical constants of liquid isopropanol, n-butanol, and n-decane in the region 500-5500 cm-1 at ambient pressure are measured using the combined ellipsometry-transmission method. In the combined method, the optical constants are first measured by a modified ellipsometry method, and then the absorption indices for weak absorption regions are obtained by the transmission method using the refractive indices measured by the modified ellipsometry method. The refractive indices of liquid isopropanol, n-butanol, and n-decane are within the range from 1.3 to 1.45 in the studied wavelength and temperature region. The absorption indices of these liquids range from 10-5 to 10-1. In the temperature range studied, the refractive indices decrease with increasing temperature in an approximately linear manner, but the effects of the temperature on the absorption indices are much smaller. The characteristic wavenumbers of the main absorption peaks are consistent with the vibrational frequencies of major functional groups.

Exploring the Pharmacokinetic/Pharmacodynamic Relationship of Relebactam (MK-7655) in Combination with Imipenem in a Hollow-Fiber Infection Model.

Resistance to antibiotics among bacterial pathogens is rapidly spreading, and therapeutic options against multidrug-resistant bacteria are limited. There is an urgent need for new drugs, especially those that can circumvent the broad array of resistance pathways that bacteria have evolved. In this study, we assessed the pharmacokinetic/pharmacodynamic relationship of the novel ß-lactamase inhibitor relebactam (REL; MK-7655) in a hollow-fiber infection model. REL is intended for use with the carbapenem ß-lactam antibiotic imipenem for the treatment of Gram-negative bacterial infections. In this study, we used an in vitro hollow-fiber infection model to confirm the efficacy of human exposures associated with the phase 2 doses (imipenem at 500 mg plus REL at 125 or 250 mg administered intravenously every 6 h as a 30-min infusion) against imipenem-resistant strains of Pseudomonas aeruginosa and Klebsiella pneumoniae Dose fractionation experiments confirmed that the pharmacokinetic parameter that best correlated with REL activity is the area under the concentration-time curve, consistent with findings in a murine pharmacokinetic/pharmacodynamic model. Determination of the pharmacokinetic/pharmacodynamic relationship between ß-lactam antibiotics and ß-lactamase inhibitors is complex, as there is an interdependence between their respective exposure-response relationships. Here, we show that this interdependence could be captured by treating the MIC of imipenem as dynamic: it changes with time, and this change is directly related to REL levels. For the strains tested, the percentage of the dosing interval time that the concentration remains above the dynamic MIC for imipenem was maintained at the carbapenem target of 30 to 40%, required for maximum efficacy, for imipenem at 500 mg plus REL at 250 mg.