Two Hematological Markers Predicting the Efficacy and Prognosis of Neoadjuvant Chemotherapy Using Lobaplatin Against Triple-Negative Breast Cancer.

BACKGROUND: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. METHODS: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. RESULTS: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002). CONCLUSION: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.

Pyrotinib-based therapeutic approaches for HER2-positive breast cancer: the time is now.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a highly aggressive subtype associated with poor prognosis. The advent of HER2-targeted drugs, including monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) and antibody-drug conjugates, has yielded improved prognosis for patients. Compared with widely used monoclonal antibodies, small-molecule TKIs have unique advantages including oral administration and favorable penetration of blood-brain barrier for brain metastatic BC, and reduced cardiotoxicity. Pyrotinib is an irreversible TKI of the pan-ErbB receptor, and has recently been shown to be clinically effective for the treatment of HER2-positive BC in metastatic and neoadjuvant settings. This review highlights the development on the application of pyrotinib-based therapeutic approaches in the clinical settings of HER2-positive BC.

PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827-0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.

Dramatic Response to Pyrotinib and T-DM1 in HER2-Negative Metastatic Breast Cancer With 2 Activating HER2 Mutations.

HER2 signaling is activated in response to somatic HER2 mutations, which are often found in invasive lobular breast cancer (ILC) and are associated with poor prognosis. Tyrosine kinase inhibitors (TKIs) have demonstrated considerable antitumor activity in patients with HER2-mutated advanced breast cancer (BC). Further, several clinical trials have indicated that HER2-targeted antibody-drug conjugates (ADCs) exhibit promising efficacy in lung cancer with HER2 mutations, and the efficacy of ADCs against HER2-mutated BC is currently being evaluated. Several preclinical studies have demonstrated that the therapeutic efficacy of ADCs in HER2-mutated cancer can be enhanced by the addition of irreversible TKIs, but the potential of such a combined treatment regimen for the treatment of HER2-mutated BC has not been reported. Herein, we describe a case in which a patient with estrogen receptor-positive/HER2-negative metastatic ILC with 2 activating HER2 mutations (D769H and V777L) exhibited a significant and durable response to anti-HER2 treatment with pyrotinib (an irreversible TKI) in combination with ado-trastuzumab emtansine, which was administered after multiple lines of therapy that had resulted in disease progression. Further, based on the evidence from the present case, TKI plus ADC seems to be a promising combination anti-HER2 regimen for patients with HER2-negative/HER2-mutated advanced BC, although further rigorous studies are warranted to confirm these findings.

Confirmatory Factor and Rasch Analyses Support a Revised 14-Item Version of the Organizational, Policies, and Practices (OPP) Scale.

Background The long version of the organizational, policies and practices (OPP) had a high burden and short versions were developed to solve this drawback. The 11-item version showed promise, but the ergonomic subscale was deficient. The OPP-14 was developed by adding three additional items to the ergonomics subscale. The aim of this study is to evaluate the factor structure using confirmatory factor and Rasch analyses in healthy firefighters. Methods A sample of 261 firefighters (Mean age 42 years, 95 % male) were sampled. A confirmatory factor and Rasch analyses were used to assess the internal consistency, factor structure and other psychometric characteristics of revised OPP-14. Results The OPP-14 demonstrates sound factor structure and internal consistency in firefighters. Confirmatory factor analysis confirmed the consistency of the original 4-domain structure (CFI = 0.97, TLI = 0.96, and RMSEA = 0.053). The 5 items showing misfit initially with disordered thresholds were rescored. The four subscales satisfied Rasch expectations with well target and acceptable reliability. Conclusions The OPP-14 scale shows a promising factor structure in this sample and remediated deficits found in OPP-11. This version may be preferable for musculoskeletal concerns or work applications where ergonomic indicators are relevant.

Prevalence and incidence of dementia among indigenous populations: a systematic review.

BACKGROUND: Indigenous populations may be at increased risk, compared with majority populations, for the development of dementia due to lower education levels and socio-economic status, higher rates of diabetes, hypertension, cardiovascular disease and alcohol abuse, an aging population structure, and poorer overall health. This is the first systematic review investigating the prevalence and incidence of dementia in indigenous populations worldwide. METHODS: This systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE, Embase, and PsycInfo for relevant papers published up to April 2015. Studies were included if they reported prevalence or incidence, the disease typically occurred after the age of 45, the study population included indigenous people, and the study was conducted in the general population. RESULTS: Fifteen studies representing five countries (Canada, Australia, the USA, Guam, Brazil) met the inclusion criteria. Dementia prevalence ranged from 0.5% to 20%. Retrospective studies relying on medical records for diagnoses had much lower prevalence rates and a higher risk of bias than population-based prospective studies performing their own diagnoses with culturally appropriate cognitive assessment methods. CONCLUSIONS: The prevalence of dementia among indigenous populations appears to be higher than it is for non-indigenous populations. Despite a building body of evidence supporting the need for dementia research among indigenous populations, there is a paucity of epidemiological research, none of which is of high quality.

A modified evidence-based practice- knowledge, attitudes, behaviour and decisions/outcomes questionnaire is valid across multiple professions involved in pain management.

BACKGROUND: A validated and reliable instrument was developed to knowledge, attitudes and behaviours with respect to evidence-based practice (EBB-KABQ) in medical trainees but requires further adaptation and validation to be applied across different health professionals. METHODS: A modified 33-item evidence-based practice scale (EBP-KABQ) was developed to evaluate EBP perceptions and behaviors in clinicians. An international sample of 673 clinicians interested in treatment of pain (mean age = 45 years, 48% occupational therapists/physical therapists, 25% had more than 5 years of clinical training) completed an online English version of the questionnaire and demographics. Scaling properties (internal consistency, floor/ceiling effects) and construct validity (association with EBP activities, comparator constructs) were examined. A confirmatory factor analysis was used to assess the 4-domain structure EBP knowledge, attitudes, behavior, outcomes/decisions). RESULTS: The EBP-KABQ scale demonstrated high internal consistency (Cronbach's alpha = 0.85), no evident floor/ceiling effects, and support for a priori construct validation hypotheses. A 4-factor structure provided the best fit statistics (CFI =0.89, TLI =0.86, and RMSEA = 0.06). CONCLUSIONS: The EBP-KABQ scale demonstrates promising psychometric properties in this sample. Areas for improvement are described.

Prevalence of Fabry disease in stroke patients--a systematic review and meta-analysis.

BACKGROUND: Fabry disease is an uncommon but treatable cause of stroke. Enzyme replacement therapy helps improve neurologic symptoms. We conducted a systematic review and meta-analysis to evaluate the prevalence of Fabry disease in stroke patients. METHODS: We searched MEDLINE and EMBASE databases for relevant articles published in English up to February 2013. Studies that reported incidence or prevalence of Fabry disease in stroke patients were included. Two reviewers independently assessed studies to determine eligibility, validity, and quality. Meta-analysis was performed to calculate the prevalence of Fabry disease by etiology and gender. RESULTS: Nine studies (n = 8302 patients) met the inclusion criteria. Eight studies (n = 8148) examined the prevalence of Fabry disease in young stroke patients. Overall qualities of included studies were moderate to high. The prevalence of Fabry disease ranged from .4% to 2.6% on strokes of any etiologies. In cryptogenic stroke, the prevalence ranged from .6% to 11.1%, 4.5% in men (95% confidence interval [CI] = 3.2%-6.3%) and 3.4% in women (95% CI = 1.0%-10.7%). The prevalence of Fabry disease in patients with all etiologies was similar in men (.9% [95% CI = .3%-2.3%]) and (1.4% [95% CI = .7%-2.7%]) in women. CONCLUSIONS: Fabry disease may explain approximately 1% of all strokes in the young, including 3%-5% of cryptogenic strokes. The confirmation of Fabry disease may be challenging as there are different criteria for men and women. Early recognition of Fabry disease may help initiate the appropriate treatment to decrease the risk of subsequent complications.

A systematic review of prognostic factors for return to work following work-related traumatic hand injury.

STUDY DESIGN: Systematic review. INTRODUCTION: Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. PURPOSE: To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. RESULTS: We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. CONCLUSION: Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. LEVEL OF EVIDENCE: 2a.

The Role of Innate Immunity in Osteoarthritis and the Connotation of "Immune-joint" Axis: A Narrative Review.

Osteoarthritis (OA) is a degenerative disease that results in constriction of the joint space due to the gradual deterioration of cartilage, alterations in subchondral bone, and synovial membrane. Recently, scientists have found that OA involves lesions in the whole joint, in addition to joint wear and tear and cartilage damage. Osteoarthritis is often accompanied by a subclinical form of synovitis, which is a chronic, relatively low-grade inflammatory response mainly mediated by the innate immune system. The "immune-joint" axis refers to an interaction of an innate immune response with joint inflammation and the whole joint range. Previous studies have underestimated the role of the immune-joint axis in OA, and there is no related research. For this reason, this review aimed to evaluate the existing evidence on the influence of innate immune mechanisms on the pathogenesis of OA. The innate immune system is the body's first line of defense. When the innate immune system is triggered, it instantly activates the downstream inflammatory signal pathway, causing an inflammatory response, while also promoting immune cells to invade joint synovial tissue and accelerate the progression of OA. We have proposed the concept of the "immune-joint" axis and explored it from two aspects of Traditional Chinese Medicine (TCM) theory and modern medical research, such as the innate immunity and OA, macrophages and OA, complement and OA, and other cells and OA, to enrich the scientific connotation of the "immune-joint" axis.

Safety and efficacy of anlotinib combined with taxane and lobaplatin in neoadjuvant treatment of clinical stage II/III triple-negative breast cancer in China (the neoALTAL trial): a single-arm, phase 2 trial.

Background: Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/ß, and fibroblast growth factor receptors 1-4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients with TNBC. Methods: Patients with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12 mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 ,d1, q3w or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0) and the secondary endpoints include breast pCR (bpCR), axillary pCR (apCR), residual cancer burden (RCB), objective response rate (ORR), survival, and safety. Exploratory endpoints were efficacy biomarkers based on Fudan University Shanghai Cancer Center Immunohistochemical (FUSCC IHC) classification for TNBC and next-generation sequencing (NGS) of DNA from tumor tissue and blood samples of patients with 425-gene panel. This trial is registered with www.chictr.org.cn (ChiCTR2100043027). Findings: From Jan 2021 to Aug 2022, 48 patients were assessed and 45 were enrolled. All patients received at least one dose of study treatment and underwent surgery. The median age was 48.5 years (SD: 8.7), 71% were nodal involved, and 20% had stage III. In the intention-to-treat population, 26 out of 45 patients achieved pCR (57.8%; 90% CI, 44.5%-70.3%), and 39 achieved residual cancer burden class 0-I (86.7%; 95% CI, 73.2%-94.9%). The bpCR and apCR rate were 64.4% (29/45) and 71.9% (23/32), respectively. No recurrence or metastasis occurred during the short-term follow-up. Based on the FUSCC IHC-based subtypes, the pCR rates were 68.8% (11/16) for immunomodulatory subtype, 58.3% (7/12) for basal-like immune-suppressed subtype and 33.3% (4/12) for luminal androgen receptor subtype, respectively. NGS revealed that the pCR were 77% (10/13) and 50% (14/28) in MYC-amplified and wild-type patients, respectively, and 78% (7/9) and 53% (17/32) in gBRCA1/2-mutated and wild-type patients, respectively. The median follow-up time of the study was 14.9 months (95% CI: 13.5-16.3 months). There was no disease progression or death during neoadjuvant therapy. No deaths occurred during postoperative follow-up. In the safety population (N = 45), Grade 3 or 4 treatment emergent adverse events occurred in 29 patients (64%), and the most common events were neutropenia (38%), leukopenia (27%), thrombocytopenia (25%), anemia (13%), and hypertension (13%), respectively. Interpretation: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and encouraging antitumor activity for patients with clinical stage II/III TNBC. Funding: Chongqing Talents Project, Chongqing Key Project of Technology Innovation and Application Development and Chongqing Outstanding Youth Natural Science Foundation.

DNA microarray gene expression profile of Mycobacterium tuberculosis when exposed to osthole.

Tuberculosis (TB), affecting one-third of the global population, kills an estimated two to three million people every year. The development of drug resistance is becoming a serious threat to any attempt to control this disease, which underscores the need for new agents targeting Mycobacterium tuberculosis (M. tuberculosis). Osthole (7-methoxy-8-isopentenoxycoumarin) is a coumarin derivative present in many medicinal plants. Previous studies have shown that osthole possesses antimycobacterial effects, however, the action mechanism of osthole is unclear. In the study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to osthole. Analysis of the microarray data revealed that a total of 478 genes were differentially regulated by osthole. Of these, 241 genes were upregulated, and 237 genes were downregulated. Some of the important genes that were significantly regulated are related to different pathways such as fumarate reductase, class I peroxidase, cell wall, nitrate respiration, and protein synthesis. Real-time quantitative RT-PCR was performed for chosen genes to validate the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis when exposed to osthole.

Predictive and prognostic value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors: A systematic review and meta-analysis.

This systematic review and meta-analysis study investigates the predictive and prognostic value of PIK3CA mutations for HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs). A search of the Medline, Embase, and Cochrane Library databases yielded 17 eligible studies (1706 patients). In 10 neoadjuvant studies, the pathological complete response rate was significantly higher in wild-type PIK3CA (WT) patients than in mutated PIK3CA (MT) patients (OR = 0.45; 95% CI = 0.31-0.65; P < 0.001). In five metastasis studies, the pooled objective response rate was significantly higher in WT patients than in MT patients (OR = 0.40; 95% CI = 0.23-0.70; P = 0.001). Four metastasis studies indicated that PIK3CA mutations had a marginally significant relationship with poor progression-free survival and overall survival. Thus, PIK3CA mutations have predictive value for the treatment response of early/advanced-stage HER2-positive breast cancer treated with TKI-containing regimens.

Causal associations between type 1 diabetes and COVID-19 infection and prognosis: a two-sample Mendelian randomization study.

INTRODUCTION: It has been suggested that type 1 diabetes was associated with increased COVID-19 morbidity and mortality. However, their causal relationship is still unclear. Herein, we performed a two-sample Mendelian randomization (MR) to investigate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. RESEARCH DESIGN AND METHODS: The summary statistics of type 1 diabetes were obtained from two published genome-wide association studies of European population, one as a discovery sample including 15 573 cases and 158 408 controls, and the other data as a replication sample consisting of 5913 cases and 8828 controls. We first performed a two-sample MR analysis to evaluate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. Then, reverse MR analysis was conducted to determine whether reverse causality exists. RESULTS: MR analysis results showed that the genetically predicted type 1 diabetes was associated with higher risk of severe COVID-19 (OR=1.073, 95% CI: 1.034 to 1.114, pFDR=1.15×10-3) and COVID-19 death (OR=1.075, 95% CI: 1.033 to 1.119, pFDR=1.15×10-3). Analysis of replication dataset showed similar results, namely a positive association between type 1 diabetes and severe COVID-19 (OR=1.055, 95% CI: 1.029 to 1.081, pFDR=1.59×10-4), and a positively correlated association with COVID-19 death (OR=1.053, 95% CI: 1.026 to 1.081, pFDR=3.50×10-4). No causal association was observed between type 1 diabetes and COVID-19 positive, hospitalized COVID-19, the time to the end of COVID-19 symptoms in the colchicine treatment group and placebo treatment group. Reverse MR analysis showed no reverse causality. CONCLUSIONS: Type 1 diabetes had a causal effect on severe COVID-19 and death after COVID-19 infection. Further mechanistic studies are needed to explore the relationship between type 1 diabetes and COVID-19 infection and prognosis.

Case Report: Four cases of SARS-CoV-2-associated Guillain-Barré Syndrome with SARS-CoV-2-positive cerebrospinal fluid detected by metagenomic next-generation sequencing: a retrospective case series from China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often absent or at low levels in the cerebrospinal fluid (CSF) of patients with previous SARS-CoV-2-associated Guillain-Barré syndrome (GBS). This has led to speculation that SARS-CoV-2-associated GBS is more likely mediated by post-infectious immunity or a parainfection. This understanding has influenced the development of treatment regimens for SARS-CoV-2-associated GBS. This paper reports our experience with four Chinese patients with SARS-CoV-2-associated GBS who tested positive for SARS-CoV-2 RNA in the CSF. They developed symptoms of peripheral nerve damage 4-15 days after fever and confirmed SARS-CoV-2 infection, all of whom presented with progressive weakness of both lower limbs; three with autonomic nerve function impairment such as constipation and urination disorder; and one with polycranial neuritis and Miller-Fisher syndrome. Three patients were tested for anti-ganglioside antibodies, and one tested positive for GD1a-IgG. Four patients recovered well after treatment with anti-viral drugs combined with intravenous immunoglobulin. The present results showed that SARS-CoV-2 RNA can be detected via mNGS in the CSF of some patients with SARS-CoV-2-associated GBS, suggesting that SARS-CoV-2-associated GBS may have multiple pathogeneses.

Efficacy of adjuvant chemotherapy/maintenance chemotherapy after induction chemotherapy and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Experiences of two centers.

BACKGROUND AND OBJECTIVE: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MATERIAL AND METHODS: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. RESULTS: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects. CONCLUSIONS: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC.

A multicenter single-arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

The objective of this multicenter, single-arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy-THPy) in the treatment of patients with stage II-III HER2-positive breast cancer. The present study enrolled patients with stage II-III HER2-positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21-day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention-to-treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7-75.8%), while the objective response rate was 89.1%. In the post-hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy-THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II-III HER2-positive breast cancer.

Delirium in acute stroke: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Delirium is common in the early stage after hospitalization for an acute stroke. We conducted a systematic review and meta-analysis to evaluate the outcomes of acute stroke patients with delirium. METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library databases, and PsychInfo for relevant articles published in English up to September 2011. We included observational studies for review. Two reviewers independently assessed studies to determine eligibility, validity, and quality. The primary outcome was inpatient mortality and secondary outcomes were mortality at 12 months, institutionalization, and length of hospital stay. RESULTS: Among 78 eligible studies, 10 studies (n=2004 patients) met the inclusion criteria. Stroke patients with delirium had higher inpatient mortality (OR, 4.71; 95% CI, 1.85-11.96) and mortality at 12 months (OR, 4.91; 95% CI, 3.18-7.6) compared to nondelirious patients. Patients with delirium also tended to stay longer in hospital compared to those who did not have delirium (mean difference, 9.39 days; 95% CI, 6.67-12.11) and were more likely to be discharged to a nursing homes or other institutions (OR, 3.39; 95% CI, 2.21-5.21). CONCLUSIONS: Stroke patients with development of delirium have unfavorable outcomes, particularly higher mortality, longer hospitalizations, and a greater degree of dependence after discharge. Early recognition and prevention of delirium may improve outcomes in stroke patients.

Predictors of functional outcome change 18 months after anterior ulnar nerve transposition.

OBJECTIVE: To determine which variables derived from the electrodiagnostic examination were predictive of patient self-reported symptoms and disability at 18 months after anterior ulnar nerve transposition. DESIGN: Retrospective cohort study. SETTING: Electrodiagnostic laboratories affiliated with a tertiary care center. PARTICIPANTS: Patients (N=73) with cubital tunnel syndrome (CuTS). INTERVENTIONS: Patients were randomly assigned to one of the anterior transpositions of the ulnar nerve (subcutaneous or submuscular). MAIN OUTCOME MEASURES: Outcome was a patient-rated ulnar elbow evaluation (PRUNE). Predictors were all variables derived from the electrodiagnostic examination and characteristics of participants, as well as the preoperative clinical status. A stepwise multivariable linear regression analysis was used to determine the relative importance of the selected variables on the change in PRUNE scores. RESULTS: Above-elbow compound muscle action potentials amplitude and proportional compound muscle action potentials amplitude decreasing from above elbow to below elbow were predictors of change score of the PRUNE at 18 months after operation (R(2)=16%). Sex and preoperative PRUNE also showed predictive information (R(2)=14% and 15%, respectively). CONCLUSIONS: CuTS is predominantly a clinical diagnosis. Electrophysiologic studies are important supplemental examinations for the diagnosis of CuTS because they not only contribute to diagnosis, but are also important prognostic features. Females may have more improvement with regard to functional outcomes than males when undergoing surgical intervention.

The effects of Jiawei Duhuo Jisheng mixture on Wnt/ß-catenin signaling pathway in the synovium inflamed by knee osteoarthritis: An in vitro and in vivo experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Knee osteoarthritis (KOA) is one of the common age-degenerative diseases. Recent studies have demonstrated that the pathogenesis of KOA is closely related to synovial lesions. Jiawei Duhuo Jisheng mixture (JDJM) has shown great potential in the treatment of KOA. However, the effect and mechanism of JDJM on synovial lesions of KOA remain unclear. AIM OF THE STUDY: The regulatory effect of JDJM on the Wnt/ß-catenin signaling pathway in KOA inflamed synovium was studied via in vitro and in vivo experiments, respectively. MATERIALS AND METHODS: For the in vitro experiment, fibroblasts were isolated from the rabbit synovium with KOA. The fibroblasts were grouped as follows: the vehicle group was given 0.5% FBS; the inhibitor group was treated with 0.5% volume fraction of XAV939; the normal serum groups and JDJM serum groups were treated with 5%, 10%, and 20% volume fractions of normal serum and JDJM-containing serum. The expression levels of Wnt3a, ß-catenin, Cyclin D1, metalloproteinase-7(MMP-7) and cyclooxygenase-2(COX-2) were detected by different assays 48 and 72 h after the intervention. For the in vivo experiment, the rabbit KOA model was prepared using the improved Hulth modeling method, whereby all rabbits were randomly divided into normal control, model control, positive control, and traditional Chinese medicine (TCM) groups. The expression levels of Wnt3a, ß-catenin, Cyclin D1, MMP-7 and COX-2 were detected by different assays in the 2, 4, and 8 weeks of treatment. RESULTS: In the two test results of in vitro experiments, the normal serum group was compared with the JDJM-containing serum group with the same volume fraction, demonstrating that mRNA transcription and protein expression levels of Wnt3a, ß-catenin, Cyclin D1, MMP-7, and COX-2 in the latter decreased (P < 0.05), with more pronounced effects observed in the group treated with 20% volume fraction of JDJM serum. Compared with the inhibitor group, there was no significant difference (P > 0.05) in the mRNA transcription and protein expression levels, i.e., Wnt3a, ß-catenin, Cyclin D1, and MMP-7 were observed in the JDJM serum groups, except for a significant decrease (P < 0.05) in the level of mRNA transcription and protein expression of COX-2. Based on the in vivo experiment, compared to the model control group, articular cartilage, synovial hyperplasia, and the inflammatory reaction of the TCM group at different treatment times were significantly improved. The mRNA transcription level of Wnt3a, ß-catenin, Cyclin D1, MMP-7 and COX-2 detected by RT-qPCR and the protein expression level of Wnt3a, ß-catenin, Cyclin D1, MMP-7 and COX-2 detected by Western blot were significantly reduced (P < 0.05), and the effect was more evident at the eighth week. CONCLUSION: JDJM can regulate the synovial Wnt/ß-catenin signaling pathway in KOA models, reduce the mRNA transcription and protein expression levels of Wnt3a, ß-catenin, Cyclin D1, MMP-7, and COX-2 in the synovium, thus inhibiting synovial inflammation and protecting articular cartilage, which could be the key mechanism of action in treating this disease.