A nitrous oxide/oxygen fixed mixture to reduce pain induced by the hypodermic injection: study protocol for a randomized, controlled trial.

BACKGROUND: Patients with hematological malignancies received multiple hypodermic injections of recombinant human granulocyte colony-stimulating factor. Procedural pain is one of the most common iatrogenic causes of pain in patients with hematological malignancies. It is also identified as the most commonly occurring problem in clinical care in the Department of Hematology and Oncology at Shenzhen University General Hospital. However, providing immediate relief from pain induced by hypodermic injection of recombinant human granulocyte colony-stimulating factor remains a major challenge. This trial aims to evaluate the safety and analgesic efficacy of a fixed nitrous oxide/oxygen mixture for patients with hematological malignancies and experiencing procedural pain caused by hypodermic injection of recombinant human granulocyte colony-stimulating factor in the department. METHODS: The nitrous oxide/oxygen study is a single-center, randomized, double-blind, placebo-controlled trial involving patients with hematological malignancies who require hypodermic injections of recombinant human granulocyte colony-stimulating factor for treatment. This trial was conducted in the Hematology and Oncology Department of Shenzhen University General Hospital. A total of 54 eligible patients were randomly allocated to either the fixed nitrous oxide/oxygen mixture group (n = 36) or the oxygen group (n = 18). Neither the investigators nor the patients known about the randomization list and the nature of the gas mixture in each cylinder. Outcomes were monitored at the baseline (T0), immediately after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T1), and 5 min after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T2) for each group. The primary outcome measure was the score in the numerical rating scale corresponding to the highest level of pain experienced during hypodermic injection of recombinant human granulocyte colony-stimulating factor. Secondary outcomes included the fear of pain, anxiety score, four physiological parameters, adverse effects, total time of gas administration, satisfaction from both patients and nurses, and the acceptance of the patients. DISCUSSION: This study focused on the safety and analgesic efficacy during hypodermic injection of recombinant human granulocyte colony-stimulating factor procedure. Data on the feasibility and safety of nitrous oxide/oxygen therapy was provided if proven beneficial to patients with hematological malignancies during hypodermic injection of recombinant human granulocyte colony-stimulating factor and widely administered to patients with procedural pain in the department. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2200061507. Registered on June 27, 2022. http://www.chictr.org.cn/edit.aspx?pid=170573&htm=4.

Advanced LD pumped 3.3 J/1 Hz nanosecond Nd:glass preamplifier for SG-II upgrade laser facility.

We demonstrate a laser-diode-pumped multipass Nd:glass laser amplifier with a range of advanced characteristics. The amplifier exhibits high extraction efficiency, enables arbitrary shaping of spatial beam intensity, and effectively suppresses frequency modulation to amplitude modulation conversion. Our approach achieves excellent beam quality via thermal lensing and thermal depolarization compensation. When a 1.82 mJ/5 ns laser pulse was injected into the amplifier, the output energy reached up to 3.3 J with a repetition rate of 1 Hz at a central wavelength of 1053.3 nm. The near-field modulation of the amplified output beam was below 1.2, and the far-field focusing ability of the beam was 90% at 2.9 times the diffraction limit. This laser amplifier system holds potential for integration as a preamplifier within the SG-II upgrade high power laser facility.

Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis.

PURPOSE: To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients. METHODS: A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens. RESULTS: Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70-0.86), Lap-Cap (0.64, 0.59-0.69), Tra-Cap (0.63, 0.56-0.70), Cap (0.50, 0.45-0.56), Ner (0.59, 0.51-0.69), Per-Tra-Cap (0.68, 0.59-0.79), and Ner-Cap (0.72, 0.64-0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52-0.99), Cap (0.68, 0.49-0.96), and Ner (0.65, 0.45-0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22-56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%). CONCLUSIONS: These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.

Clinicopathological features and prognosis of patients with pregnancy-associated breast cancer: A matched case control study.

AIM: We aimed to clarify tumor features and prognosis of pregnancy-associated breast cancer (PABC) among Chinese women. METHODS: PABC was defined as breast cancer diagnosed during pregnancy or within a year after delivery. Patients with PABC were selected from breast cancer cases of women ≤45 years treated at our institution between December 2012 and December 2017, and one non-PABC control was matched for stage, age, and year of diagnosis for each case. RESULTS: Forty-one women with PABC were identified (22 diagnosed during pregnancy and 19 within 1 year of delivery). There were significantly more progesterone receptor (PR)- and triple-negative tumors in the PABC (56.1% and 24.4%, respectively) than in the non-PABC group (31.7% and 4.9%, respectively) (P = .045 and .026, respectively). Human epidermal growth factor receptor 2 positivity was the same in both groups (31.7%). Median disease-free survival (DFS) was 29.0 months (95% confidence interval [CI], 6.5-51.5 months) in the PABC and 40.9 months (95% CI, 22.8-58.8 months) in the non-PABC group (P = .167). Median overall survival (OS) was 82.8 months in the PABC (95% CI, 39.3-126.5 months) versus 80.1 months (95% CI, 56.7-103.6 months) in the non-PABC group (P = .131). CONCLUSION: Histological features were similar in both groups, except that PR- and triple-negative tumors were more frequent in the PABC group. Survival analyses show similar OS for patients with PABC and non-PABC. DFS tended to be shorter in the PABC group; however, this difference was not statistically significant.

Prognostic Value of Plasma HER2 Gene Copy Number in HER2-Positive Metastatic Breast Cancer Treated with First-Line Trastuzumab.

OBJECTIVE: Patients with HER2-positive metastatic breast cancer (MBC) benefit from trastuzumab-based therapy but eventually develop intrinsic or acquired resistance. Whether plasma HER2 gene copy number (GCN) could predict survival after trastuzumab treatment remained controversial. We evaluated the prognostic value of plasma HER2 GCN using low-coverage whole-genome sequencing (LC-WGS). METHODS: The plasma was collected from HER2-positive MBC patients whose pre-therapeutic samples were available before first-line trastuzumab-based treatment. Plasma DNA was extracted and assessed by LC-WGS for HER2 GCN. The optimal cut-off point for HER2 GCN to shorter survival was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 49 patients were retrieved from 2013 to 2017, among whom 21 had multiple organ involvement (≥3 sites). Variations of HER2 GCN in pre-therapeutic plasma ranged from 1.89 to 23.86 (median = 2.59). ROC analysis identified the optimal cut-off point for HER2 GCN as 2.82 (P = 0.005), with 23 patients had high-level HER2 GCN and 26 in the low-level group. Both progression-free survival (PFS, P = 0.032) and overall survival (OS, P = 0.006) were adversely associated with high-level HER2 GCN. In multivariate analyses, high HER2 GCN was independently associated with shorter PFS [hazard ratio (HR) = 2.042, P = 0.037], while both high HER2 GCN (HR = 4.909, P = 0.004) and more metastatic organs (HR = 4.019, P = 0.011) were negative prognostic factors for OS. CONCLUSION: In this population of patients with HER2-positive MBC, individuals with high HER2 GCNs in plasma had worse prognosis after trastuzumab-based therapy. Plasma HER2 GCN may be a prognostic marker in these patients.

Efficacy of platinum in advanced triple-negative breast cancer with germline BRCA mutation determined by next generation sequencing.

OBJECTIVE: To compare the efficacy of platinum- and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer (TNBC) and analyze the relationship between their efficacy and BRCA gene status. METHODS: Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology, Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy. A total of 114 patients had BRCA1/2 gene tested by next generation sequencing (NGS) using peripheral blood, and we analyzed the correlation between their efficacy and BRCA1/2 gene status. RESULTS: Non-platinum-based chemotherapy (NPCT) was administered to 129 and platinum-based chemotherapy (PBCT) to 91 study patients. The clinical benefit rate (CBR) and median progression-free survival (PFS) were not statistically different between NPCT and PBCT groups. The median overall survival (OS) was 30.0 and 22.5 months for PBCT and NPCT group, respectively [P=0.090, hazard ratios (HR)=0.703]. BRCA status was assessed in 114 patients, 14 of whom had deleterious germline BRCA1/2 (gBRCA) mutations (seven in each group). In PBCT group, the CBR was 85.7% and 35.1% for patients with and without deleterious gBRCA mutations, respectively (P=0.039). The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious gBRCA mutations, respectively (P=0.001, P=0.161, respectively). Patients in PBCT group had significantly greater rates of grade 3-4 anemia (5.5%vs. 0%) and thrombocytopenia (8.8% vs. 0%), whereas palmar-plantar erythrodysesthesia (12.4% vs. 0%) and peripheral neuropathy (8.6% vs. 1.1%) occurred more frequently in NPCT group. CONCLUSIONS: Platinum-based regimens are more effective in patients with deleterious gBRCA mutations, but no difference in patients without BRCA gene mutations, so non-platinum is an option in patients without BRCA gene mutations considering the toxicity and side effect. And we recommend that patients with advanced TNBC should have BRCA gene test.

Detection of ESR1 Mutations Based on Liquid Biopsy in Estrogen Receptor-Positive Metastatic Breast Cancer: Clinical Impacts and Prospects.

Endocrine therapy is the main treatment option for estrogen receptor-positive (ER+) breast cancer (BC). Compared with other clinical subtypes, ER+ BC patients usually have a more favorable prognosis. However, almost all ER+ BCpatients develop endocrine resistance and disease progression eventually. A large number of studies based on liquid biopsy suggest that ESR1 mutations may play a key role in this process. For patients with ER+ metastatic BC (MBC), ESR1 is an important prognostic factor and may associate with the resistance to endocrine therapy, like aromatase inhibitors. The advances of sequencing technologies allow us to conduct longitudinal monitoring of disease and unveil the clinical implications of each ESR1 sub-clone in ER+ MBC. Moreover, since the ESR1-related endocrine resistance has not been fully addressed by existing agents, more potent cornerstone drugs should be developed as soon as possible. Herein, we reviewed the recent progress of detecting ESR1 mutations based on liquid biopsy and different sequencing technologies in ER+ MBC and discussed its clinical impacts and prospects.

Prognostic and clinicopathological value of PD-L1 expression in primary breast cancer: a meta-analysis.

PURPOSE: To evaluate the association between PD-L1 expression (PD-L1+) and clinicopathological characteristics and effect on prognosis in primary breast cancer (PBC). METHODS: A systematic search of the PubMed, Web of Science, and Embase databases was conducted in November 2018. Studies detecting PD-L1 using immunohistochemistry, and concerning its prognostic or clinicopathological significance in PBC were included. The HR with 95% CI for survival, and the events for clinicopathological features were pooled. RESULTS: Forty-seven studies were included, with a total of 14,367 PBC patients. PD-L1+ tumor cells (TCs) were associated with ductal carcinomas, large tumor size, histological Grade 3 tumors, high Ki-67, ER and PR negative, and triple-negative breast cancer; and also, related to high tumor-infiltrating lymphocytes (TILs) and PD-1 expression. PD-L1+ TCs were significantly associated with shorter disease-free survival (DFS, HR = 1.43, 95% CI 1.21-1.70, P < 0.0001) and overall survival (OS, HR = 1.58, 95% CI 1.14-2.20, P = 0.006). And the HRs of PD-L1+ TCs on DFS and OS were higher (1.48 and 1.70, respectively) and homogeneous when using whole tissue section, compared with tumor microarrays. However, PD-L1+ TILs related to better DFS (HR = 0.45, 95% CI 0.28-0.73, P = 0.001) and OS (HR = 0.41, 95% CI 0.27-0.63, P < 0.0001). CONCLUSION: PD-L1 expression on TCs associates with high-risk clinicopathological parameters and poor prognosis in PBC patients, while PD-L1+ TILs may relate to a better survival. Comprehensive assessment of TCs and TILs is required when evaluating the clinical relevance of PD-L1 expression in future studies.

Single-Port Laparoscopic Surgery Is Feasible and Safe for Hepatic Left Lateral Sectionectomy for Benign Liver Lesions.

BACKGROUND AND OBJECTIVES: The feasibility and safety of single-port laparoscopic surgery for left lateral liver lobectomy are largely unknown. This study is aimed at comparing the effectiveness and safety between single-port laparoscopic (SPL) and conventional multiport laparoscopic (CL) surgeries for hepatic left lateral sectionectomy. METHODS: A total of 65 patients receiving laparoscopic hepatic left lateral sectionectomy between January 2008 and July 2015 were included and divided into the SPL group (n = 40) and the CL group (n = 25). RESULTS: There was no significant difference in the operative time, estimated intraoperative blood loss, length of hospital stay, and incidences of postoperative complications (biliary leakage, hemorrhage, and contusion at incision) between groups (all P > 0.05). However, the SPL group had a significantly lower VAS pain score (at 24 h but not 7 days postoperation) and higher cosmetic satisfaction scores (at both 2 months and 6 months postoperation) than the CL group (all P < 0.01). Moreover, multivariate linear regression analysis further confirmed the superior pain score and cosmetic outcome in the SPL group. CONCLUSIONS: Single-port laparoscopic hepatic left lateral sectionectomy is a safe and feasible treatment for patients with lesions in the left hepatic lobe. Patients with benign lesions in the left hepatic lobe are more suitable to receive single-port laparoscopic hepatic left lateral sectionectomy than those with malignancies.

Role of Toll-Like Receptor Signaling in the Pathogenesis of Graft-versus-Host Diseases.

Graft-versus-host disease (GVHD) and infection are major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the leading causes of morbidity and mortality in HSCT patients. Recent work has demonstrated that the two complications are interdependent. GVHD occurs when allo-reactive donor T lymphocytes are activated by major histocompatibility antigens or minor histocompatibility antigens on host antigen-presenting cells (APCs), with the eventual attack of recipient tissues or organs. Activation of APCs is important for the priming of GVHD and is mediated by innate immune signaling pathways. Current evidence indicates that intestinal microbes and innate pattern-recognition receptors (PRRs) on host APCs, including both Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), are involved in the pathogenesis of GVHD. Patients undergoing chemotherapy and/or total body irradiation before allo-HSCT are susceptible to aggravated gastrointestinal epithelial cell damage and the subsequent translocation of bacterial components, followed by the release of endogenous dangerous molecules, termed pathogen-associated molecular patterns (PAMPs), which then activate the PRRs on host APCs to trigger local or systemic inflammatory responses that modulate T cell allo-reactivity against host tissues, which is equivalent to GVHD. In other words, infection can, to some extent, accelerate the progression of GVHD. Therefore, the intestinal flora's PAMPs can interact with TLRs to activate and mature APCs, subsequently activate donor T cells with the release of pro-inflammatory cytokines, and eventually, induce GVHD. In the present article, we summarize the current perspectives on the understanding of different TLR signaling pathways and their involvement in the occurrence of GVHD.

[Research Progres on Relationship between the Graft-Versus-Host Disease and Cytomegalovirus Infection--Review].

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of leukemia patients can improve overall survival and disease-free survival, and reduce relapse. Although the allo-HSCT is more widely used in the treatment of leukemia, but the graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infections are the common complications, and are the major cause of mortality for patients following allo-HSCT. Previous studies showed that there might be a mutual promotive relationship between GVHD and CMV infection, but the clear relationship remained to be elucidated. The relationship of GVHD and CMV has been the focus of clinical research. Recently, a great progress has been made on researches of the relationship and its mechanism between GVHD and CMV infection. In this article, the relationship and its mechanism between GVHD and CMV infection after allo-HSCT are reviewed.

Patellar non-eversion in primary TKA reduces the complication rate.

PURPOSE: This study was designed to evaluate the isolated benefits of patellar non-eversion in total knee arthroplasty (TKA). METHODS: This systematic review and meta-analysis was conducted following the PRISMA statement. A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was performed in August 2014. Randomized controlled trials (RCTs) that considered the handling of the patella as the only variable were included in our review. Quality assessment of RCTs was performed according to the CONSORT statement. The meta-analysis was performed to pool the available data for some parameters. RESULTS: The searches of the MEDLINE/PubMed, Cochrane Library, and Embase databases yielded 10 RCTs, and five RCTs were selected for inclusion in the review. This results suggested that tourniquet time [mean difference (MD) = -5.69; 95% confidence interval (CI) -9.77 to -1.60], length of hospitalization (MD = 1.24; 95% CI 0.54-1.94) and the incidence of complications [odds ratio (OR) = 2.23; 95% CI 1.12-4.44] differed significantly between the eversion group and non-eversion group. No differences in postoperative pain, alignment, and the Insall-Salvati ratio were observed between the groups. CONCLUSION: The patellar non-eversion approach offers a shorter length of hospitalization and lower incidence of postoperative complications, but requires more operative time. The merits of patellar non-eversion for recovery of knee function remain controversial, and more high-quality RCTs are needed to draw clear conclusions. In general, avoidance of patellar eversion is recommended when exposing the knee joint for TKA.

[Recent research progress on the relation of B-ALL associated cytogenetic and molecular genetic abnormalities with B-ALL prognosis].

In recent years, standardized treatment based on the risk stratification has been applied to clinical diagnosis and treatment of leukemia, which significantly improves the remission rate of ALL. However, relapse after remission remains an important challenge for long term efficacy. Chromosomal karyotype analysis is often used clinically to study the genetic features of ALL. As leukemia-specific markers, the cytogenetic and molecular genetic abnormalities can be used to evaluate prognosis and make an effective and optimal therapy. Furthermore, they are also used to track minimal residual disease. Therefore, the cytogenetic and molecular genetic abnormalities may become a monitor and a new target for the treatment of leukemia. This review briefly introduces the structure and physiological function of B-ALL associated cytogenetic and molecular genetic abnormalities, focusing on their prognostic effect on B-ALL.