Risk factors for peripherally inserted central catheter-related venous thrombosis in adult patients with cancer.

PURPOSE: The purpose of this study was to understand and analyze the risk factors of peripherally inserted central catheter (PICC)-related venous thrombosis in adult patients with cancer. METHODS: This observational cohort study included adult patients with cancer who underwent color Doppler ultrasound at the Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province, from January 1, 2017 to December 31, 2021. Univariate and multivariate logistic regression analyses were performed to determine the risk factors of PICC-related venous thrombosis. RESULTS: After risk adjustment, multivariate logistic regression analysis revealed statistically significant associations between PICC-related venous thrombosis and age > 65 years old (OR: 1.791, CI: 1.343-2.389), male sex (OR: 1.398, CI: 1.057-1.849), white blood cell count > 9.5 × 109 /L (OR: 1.422, CI: 1.041-1.942), APTT < 25 s (OR: 2.006, CI: 1.431-2.811), gastrointestinal tumor (OR: 2.191, CI: 1.406-3.414), infection (OR:7.619, CI: 5.783-10.037), the use of cisplatin (OR: 2.374, CI: 1.714-3.214), vincristine (OR: 2.329, CI: 1.447-3.749), the use of polyurethane (OR: 2.449, CI: 1.863-3.219) and open-ended catheters (OR:1.660, CI: 1.131-2.439), keeping time of the catheter (days) (OR: 1.003, CI: 1.001-1.005) were associated with PICC-related venous thrombosis. CONCLUSION: We identified that the presence of age > 65 years old, male sex, white blood cell count > 9.5 × 109 /L, APTT < 25 s, gastrointestinal tumor, infection, the use of cisplatin and vincristine, the use of polyurethane, open-ended catheters and keeping time of the catheter (days), were associated with PICC-related venous thrombosis.

Zimberelimab combined with systemic therapy extended tumor control in post-radiotherapy cervical cancer with brain metastases: A case report.

Out of the total cases of cervical cancer, brain metastases (BMs) are relatively rare, with an estimated incidence rate of 0.63% (range: 0.1%-2.2%). Additionally, BMs prognosis remains poor, and the average patient survival time following a BM diagnosis is 3 to 5 months. Few studies have addressed the effect of programmed cell death-1 inhibitors against BMs in cervical cancer, although they are an established option for recurrent/metastatic disease. Hence, we report a case involving a 54-year-old post-surgery patient with cervical cancer with a body mass index of 19.5 kg/m2 and Eastern Collaborative Oncology Group (ECOG) performance status of 3; the disease recurred with BMs 1 year later. Intensity-modulated radiation therapy concurrent with temozolomide and bevacizumab was initiated, following which zimberelimab immunotherapy combined with anlotinib was administered to extend tumor control. The patient had a progression-free survival duration of 10 months, the tumor response was assessed as a partial response based on the evaluation criteria for solid tumors (RECIST1.1), and the ECOG status improved to 1 after therapy. These findings suggest that immunotherapy-based combination therapy following radiotherapy may be a good choice for patients with cervical cancer and BMs.

Peripherally inserted central venous catheter in upper extremities leads to an increase in D-dimer and deep vein thrombosis in lower extremities.

BACKGROUND: The purpose of this study is to elucidate the association between peripherally inserted central venous catheter (PICC) in upper extremities and lower extremity deep venous thrombosis (LEDVT) by observing the changes in D-dimer. METHODS: This was a retrospective cohort study with 3452 patients (104 inserted with PICCs and 3348 without PICC) enrolled at the neurology department from April 1, 2017 to April 1, 2020. The patients underwent color Doppler ultrasound (CDU) and D-dimer examinations. LEDVT-related factors and D-dimer value were analyzed before and after PICC insertion. The predictive value of D-dimer for LEDVT was also evaluated. RESULTS: Univariate logistic regression analysis showed that PICC insertion increased the risk of LEDVT by 9 times and promoted the increase of D-dimer by 5 times. After risk adjustment, multivariate logistic regression analysis showed that PICC insertion increased the risk of LEDVT by 4 times and tripled the risk of D-dimer increase. The concentration of D-dimer was significantly increased after PICC insertion. D-dimer was unsuitable for excluding venous thrombosis in patients inserted with PICCs. CONCLUSIONS: PICC insertion increases the level of D-dimer and the risk of LEDVT. The risks of venous thrombosis need to be assessed in patients inserted with PICCs to ensure the expected clinical outcomes.

[Effect of standardized PICC training and management on the clinical effect and complication of catheterization].

OBJECTIVE: To determine the clinical effect of standardized training and management of peripherally inserted central catheter (PICC) and catheter-related complications. METHODS: A total of 610 patients were divided into a control group and an observation group, the control group (n=300) were catheterized by trainees who received "short-term intensive training", the observation group (n=310) by "system standardized training and management". The clinical efficacy of catheterization and the rate of catheter-related complications were compared. RESULTS: There was significant difference in the one-time puncture success rate, one-time cannulation success rate, the time for operation and the pain score between the 2 groups (all P<0.01), and there was also significant difference in the occurrence of catheter extrusion, plug, arrhythmia, catheter-related thrombosis, phlebitis, puncture point effusion and catheter-related infection between the 2 groups (all P<0.05). CONCLUSION: Standardized PICC training and management can improve the effect of catheterization and reduce the incidence of PICC-related complication.

[Knowledge, attitude and behavior on blood lipid among people participated in health examination in Changsha and the influential factors].

OBJECTIVE: To evaluate the knowledge, attitude and behavior on blood lipid among people in Changsha and to provide evidences for prevention and control of blood lipid abnormality. METHODS: A total of 400 cases were randomly selected on the questionnaire of the knowledge, attitude and behavior on blood lipid in ordinary adults who participate in health examination in Xiangya Hospital. Blood lipid related physical examination was conducted at the same time. The health examination participants were divided into several groups according to their sex, age, degree of education, marriage and family income. The influential factors for knowledge, attitude and behavior were analyzed. RESULTS: The knowledge score of blood lipid for health examination participants was 18.33±8.67 (total score 37), the attitude score was 6.63±2.45 (total score 9) and the behavior score was 8.32±2.65 (total score 16). The scores of female was higher than that of male in the terms of knowledge and behavior (both P< 0.05); the scores in the 40-49 age group were lower than those in the other age groups (all P< 0.05); the scores in the junior high school group were lower than those in the other education groups (all P< 0.05); the scores in the family group with less than 2 000 yuan income were lower than those in other family groups with different income (all P< 0.05). The multiple stepwise regression analysis showed that: 1) the knowledge on blood lipid score was influenced by ages and education background (both P< 0.05); 2) while the attitude of blood lipid was influenced by four factors such as education background, systemic blood pressure, blood sugar and triglyceride(all P< 0.05); 3) the behavior on blood lipid was influenced by five factors such education background, triglyceride, systemic blood pressure, blood sugar and ages (all P< 0.05). CONCLUSION: The knowledge, attitude and behavior on blood lipid among health examination participants were mostly influenced by education background, gender and ages. Thus, clinical medical staff should prevent the blood lipid abnormality through the health education and improve the knowledge in normal people. The group of 40-49 age male should be thought as the primary intervention subjects. The knowledge, attitude and behavior on blood lipid among the general population is also related to individual's blood pressure, blood sugar and triglyceride. So the clinical medical staff should also improve the knowledge of blood lipid, blood pressure and blood sugar in general population for improving their attitude and unhealthy habits. In addition, the active control of blood sugar and blood pressure can enhance the overall health status of the general population.

Whether specific genetic feature predicted immunotherapy efficacy: A case report.

RATIONALE: Blockade of programmed death protein 1 (PD-1), have been observed to have quite good efficacy in recurrent and metastatic cervical cancer. Generally, we believe that the biomarkers of PD-1 inhibitors are programmed cell death-ligand 1, tumor mutational burden, high microsatellite instability, or deficient mismatch repair. However, in the case reported below, we observed that the patient with negative existing predictive biomarkers have significant benefits after zimberelimab monotherapy, indicating that there were other biomarkers that may predict immunotherapy efficacy. However, currently, no one has explored and studied the other potential biomarkers of PD-1 inhibitors. PATIENT CONCERNS: A 51-year-old patient, diagnosed with cervical adenocarcinoma nearly 11 years ago, requested treatment. DIAGNOSES: The next-generation sequencing has shown PIK3CA E545K, SMAD4 1309-1G, and ALK E717K gene mutations, receptor tyrosine kinase 2 (ErbB-2) amplification, microsatellite stability, and low tumor mutational burden of 6.3 mutations per megabase. And immunohistochemistry revealed that the tumor was programmed cell death-ligand 1 negative. INTERVENTION: Zimberelimab monotherapy was accepted as third-line treatment. OUTCOMES: The patient had received zimberelimab for nearly 10 months, the best tumor response was PR (Response Evaluation Criteria in Solid Tumours) and no noticeable adverse reactions were observed. LESSONS: PIK3CA-E542K, ErbB2 amplification, and SMAD4 mutations could be potential biomarkers for PD-1 inhibitors, but a single instance is insufficient to validate the hypotheses. A larger number of patients or more clinical data will be necessary to determine whether these gene mutations are appropriate biomarkers for patients when treatment with PD-1 inhibitors.

Case report: Long-term intracranial effect of zimberelimab monotherapy following surgical resection of high PD-L1-expressing brain metastases from NSCLC.

Non-small cell lung cancer (NSCLC) accounted for the majority of lung cancer cases worldwide. Brain metastases (BM) frequently complicate NSCLC and portend a dismal prognosis. To control neurological symptoms, surgical resection is commonly followed by brain radiotherapy (RT). However, RT is often complicated by neurotoxicity. For patients with tumors that harbor positive driver genes, tyrosine kinase inhibitors are considered the standard of care. Nevertheless, treatment options for those without driver gene mutations are still debated. Programmed death receptor 1 (PD-1)/ligand 1 (PD-L1) inhibition has emerged as a novel therapeutic strategy for NSCLC patients with PD-L1-positive tumors, as well as for those with asymptomatic BM. However, the effect of anti-PD-1 antibodies on active BM within such specific populations is undetermined. Herein we present a case of a 65-year-old patient with NSCLC and high PD-L1-expressing BM. The patient underwent surgical resection of BM followed by first-line monotherapy with 31 cycles of zimberelimab, a novel anti-PD-1 antibody, and has already achieved 24 months of progression-free survival and intracranial recurrence-free survival. To our knowledge, this is the first report regarding the intracranial effect of zimberelimab on BM from primary lung cancer. This case report might facilitate an understanding of the intracranial effects of different anti-PD-1 antibodies for such populations.

Risk Factors for Contrast Media Extravasation in Intravenous Contrast-Enhanced Computed Tomography: An Observational Cohort Study.

RATIONALE AND OBJECTIVES: To identify the risk factors for contrast media (CM) extravasation and provide effective guidance for reducing its incidence. MATERIALS AND METHODS: We observed adult inpatients (n = 38 281) who underwent intravenous contrast-enhanced computed tomography between January 1, 2018, and December 31, 2022. Risk factors for CM extravasation were evaluated using univariate and multivariate logistic regression. RESULTS: Among the 38 281 inpatients who underwent enhanced computed tomography angiography, 3885 received peripherally inserted central venous catheters (PICCs) and 34 396 received peripheral short catheters. In 3885 cases of PICCs, no CM extravasation occurred, but in five cases, ordinary PICCs that are unable to withstand high pressure were mistakenly used; three of those patients experienced catheter rupture, and eventually, all five patients underwent unplanned extubation. Among 34 396 cases of peripheral short catheters, 224 (0.65%) had CM extravasation. Female sex (odds ratio [OR]=1.541, 95% confidence interval [CI]: 1.111-2.137), diabetes (OR=2.265, 95% CI: 1.549-3.314), venous thrombosis (OR=2.157, 95% CI: 1.039-4.478), multi-site angiography (OR=9.757, CI: 6.803-13.994), and injection rate ≥ 3 mL/s (OR=6.073, 95% CI: 4.349-8.481) were independent risk factors for CM extravasation. Due to peripheral vascular protection measures in patients with malignant tumor, there was a low incidence of CM extravasation (OR=0.394, 95% CI: 0.272-0.570). CONCLUSION: Main risk factors for CM extravasation are female, diabetes, venous thrombosis, multi-site angiography, and injection rate ≥ 3 mL/s. However, patients with malignant tumor have a low incidence of CM extravasation. CLINICAL IMPACT: Analysis of these risk factors can help reduce the incidence of CM extravasation.

Combination therapy with antibody­drug conjugate RC48 (disitamab vedotin) and zimberelimab (PD­1 inhibitor) successfully controlled recurrent HER2­positive breast cancer resistant to trastuzumab emtansine: A case report.

Options for later-line therapy are limited for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have exhibited resistance to several systemic treatments. Antibody drug conjugates (ADCs) and immune checkpoint inhibitors are novel approaches for HER2-positive breast cancer, but few reports have been published regarding the efficacy of their combinations, particularly in patients with prior ADC failure. The present report describes a case of recurrent metastatic HER2-positive breast cancer, which responded poorly to several perioperative systemic therapies, including chemotherapies, HER2-targeted antibodies, small molecule inhibitors and trastuzumab emtansine (an ADC), along with post-surgical radiotherapy. Following failure of front-line therapies for recurrent cancer located in the chest wall, combination treatment with another HER2-targeted ADC, disitamab vedotin (120 mg), and zimberelimab (240 mg), a fully humanized anti-programmed cell death protein-1 (PD-1) antibody, administered intravenously every 2 weeks, was initiated. The tumor lesions improved slightly after two cycles of treatment and shrunk markedly, and almost disappeared at the end of the sixth cycle of therapy. The patient is still in remission at present. The present findings suggest the potential efficacy of HER2-targeted ADCs combined with PD-1 inhibitors for patients with HER2-positive breast cancer, including those resistant to prior HER2-targeted ADCs.

Family Caregivers' Experiences of Caring for Patients With Head and Neck Cancer: A Systematic Review and Metasynthesis of Qualitative Studies.

BACKGROUND: Family caregivers of head and neck cancer (HNC) patients undertook heavy care tasks and role responsibilities. They were facing multiple challenges during the patients' cancer trajectory. OBJECTIVE: The aim of this study was to synthesize existing qualitative evidence regarding family caregivers' experiences of caring for HNC patients. METHODS: A meta-aggregation approach was used. Articles were collected from MEDLINE, EMBASE, CINAHL, Web of Science, PsycINFO, and Cochrane Library. Supplementary resources were collected by scrutinizing reference lists and performing citation tracking. RESULTS: A total of 20 studies were included and synthesized. Three meta-themes covering "accepting the diagnosis and treatment on patients: a distressing process," "facing changes of life and adapting to new roles," and "appreciating the external supports" were identified with 10 subthemes. There was high confidence in the evidence for "facing changes of life and adapting to new roles" and moderate confidence in the evidence for the other 2 meta-themes. CONCLUSIONS: Taking care of HNC patients is a distressing process. Caregivers took on role responsibilities and developed strategies to make adjustments to life changes, so as to provide better care for patients. External supports regarding caregiving and self-care were desired. IMPLICATIONS FOR PRACTICE: Psychological distress was common among caregivers and calls for routine clinical screening. Providing caregivers with practical strategies to deal with daily caregiving tasks was crucial. Healthcare workers can play a critical role in providing tailored support in different caregiving stages. The findings informed the interventions and future research to improve HNC caregivers' experiences.

Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma: A case report and review of literature.

BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer with a poor prognosis at advanced stage, and the standard first-line treatment for inoperable patients is chemotherapy. Although combining programmed cell death 1 (PD-1) inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors, there are few reports regarding initial immunochemotherapy in advanced MPeM. CASE SUMMARY: Here, to our knowledge, we present the first case of a patient with epithelioid subtype MPeM, who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival (PFS) and good tolerance. A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen. Computed tomography revealed a solid mass in the lower abdomen, which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy. The patient received eight cycles of pemetrexed 800 mg (day 1), cisplatin 60/50 mg (day 1-2), and zimberelimab (PD-1 inhibitor) 240 mg (day 1) every 3 wk. He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms. The best tumor response was partial remission with a final PFS of 7 mo. No immune-related adverse event occurred during the combination treatment. CONCLUSION: The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.

Different diagnostic strategies using D-dimer for peripherally inserted central catheter-related upper extremity deep vein thrombosis.

OBJECTIVE: Deep vein thrombosis (DVT) in the upper extremities caused by a peripherally inserted central venous catheter (PICC) is distinct from the typical DVT. This specific type of mural thrombus might have an effect on the D-dimer levels. In the present study, we aimed to ascertain whether the D-dimer level might be considered an independent diagnostic marker to rule out upper extremity DVT caused by PICCs. METHODS: We performed a retrospective case-cohort study of 205 patients who had undergone D-dimer measurement and color Doppler ultrasound within 14 days after placement of a PICC to December 31, 2020, from January 1, 2018. The participants were followed up for 3 months to evaluate for upper extremity DVT. In addition, different D-dimer diagnostic strategies were analyzed. RESULTS: Of the 205 included patients, 53 (25.9%) had had a negative D-dimer level. Of the 53 patients, 10 had had upper extremity DVT attributable to a PICC using color Doppler ultrasound. Of these 10 patients, 3 had developed upper extremity DVT during the 3-month follow-up. Using the various D-dimer diagnostic techniques, the negative predictive value for the D-dimer levels was 81.1%. CONCLUSIONS: The present study has shown that the different D-dimer diagnostic strategies are not effective for safely excluding the diagnosis of suspected PICC-related upper extremity DVT. Adding PICC placement as a special factor in the modified Wells score, in addition to the D-dimer level, could securely rule out PICC-related upper extremity DVT; however, the diagnostic efficacy was low.

Contrast media extravasation injury: a prospective observational cohort study.

OBJECTIVE: To identify the risk factors for moderate and severe contrast media extravasation and provide effective guidance to reduce the degree of extravasation injuries. METHODS: We observed 224 adult patients who underwent contrast media extravasation at Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province between January 1, 2018 and December 31, 2022. Risk factors for moderate extravasation injuries were evaluated using univariate and multivariate logistic regression. RESULTS: Among 224 patients, 0 (0%) had severe, 18 (8.0%) had moderate, and 206 (92.0%) had mild contrast media extravasation injury. Multivariate logistic regression analysis revealed malignant tumors (odds ratio [OR] = 6.992, 95% confidence interval [CI]: 1.674-29.208), Iohexol (OR = 9.343, 95% CI 1.280-68.214), large-volume (> 50 mL) extravasation (OR = 5.773, 95% CI 1.350‒24.695), and injection site (back of the hand) (OR = 13.491, 95% CI 3.056-59.560) as independent risk factors for moderate injury. CONCLUSION: Risk factors for moderate contrast media extravasation injury are malignant tumors, iohexol, large-volume (> 50 mL) extravasation, and back-of-the-hand injection. Analysis of these risk factors can help reduce the degree of injury after extravasation. CLINICAL RELEVANCE STATEMENT: High-risk patients with extravasation support should choose the appropriate contrast media type, avoiding back-of-the-hand injections. We recommend that patients with cancer be implanted with a high-pressure resistant central venous catheter and receive effective measures to timely detect and reduce extravasation.

D-dimer level for ruling out peripherally inserted central catheter-associated upper extremity deep vein thrombosis and superficial vein thrombosis.

AIMS: To examine the effectiveness of D-dimer values to be used as an independent diagnostic marker for excluding peripherally inserted central catheter-associated upper extremity deep vein thrombosis and superficial vein thrombosis. DESIGN: This was a retrospective case-cohort study. METHODS: Records were reviewed for 281 patients who underwent peripherally inserted central catheter insertion between 1 October 2017 and 1 October 2019. According to the modified Wells score after peripherally inserted central catheter insertion, the patients who had low vein thrombosis risk underwent a D-dimer test and colour Doppler ultrasound. RESULTS: Among 281 patients, 180 patients (64%, 95% CI: 58.2%-69.4%) had negative D-dimer results and 39 of 180 patients had vein thrombosis despite having a negative D-dimer result, resulting in a failure rate of 21.7% (95% CI: 16.3%-28.3%). The negative predictive value of peripherally inserted central catheter-associated vein thrombosis in the cancer group (80.0%, 95% CI: 73.2%-85.4%) was higher than that of the non-cancer group (60.0%, 95% CI: 35.7%-80.2%). The negative predictive value of peripherally inserted central catheter-associated deep venous thrombosis (84.9%, 95% CI: 78.7%-89.6%) was lower than that of the PICC-associated superficial venous thrombosis (91.0%, 95% CI: 85.4%-94.6%). CONCLUSION: The D-dimer levels maybe should not be used as a diagnostic index to rule out peripherally inserted central catheter-associated upper extremity vein thrombosis.

The correlation analysis between the appearance anxiety and personality traits of the medical staff on nasal and facial pressure ulcers during the novel coronavirus disease 2019 outbreak.

Aim: To investigate the psychological status of medical staff with medical device-related nasal and facial pressure ulcers (MDR PUs) during the outbreak of COVID-19, analyse the correlation between their psychological status and personality traits, so as to provide a reference for personalized psychological support. Design: A total of 207 medical staff who were treating the COVID-19 epidemic from Hunan and Hubei provinces were enrolled in this analytic questionnaire-based study. Methods: We used these measures: Eysenck Personality Questionnaire Short Scale (EPQ-RSC), Social Appearance Anxiety Scale (SAAS), Positive and Negative Affect Scale (PANAS) and demographic information forms online. Results: Medical staff wearing protective equipment are particularly susceptible to nasal and facial MDR PUs, which is increasing their social appearance anxiety; neuroticism is significantly related to social appearance anxiety and negative emotion. We should pay more attention to their psychological state, cultivate good personality characteristics and reduce negative emotions, and thereby alleviate their MDR PUs-related appearance anxiety.

Spontaneous correction of misplaced peripherally inserted central catheters.

The purpose of the present study was to examine a new protocol involving the spontaneous correction of the misplaced tip of a peripherally inserted central catheter (PICC). Patients with PICCs misplaced in the jugular or contralateral subclavian veins were recruited. All patients underwent chest X-ray (CXR) after 3 days. In addition, those whose PICC tip still was misplaced and received another CXR after 4 days. The functions of the catheters, the subjective feelings of the patients, and local symptoms of the neck and upper anterior chest wall were recorded. Among 866 patients who had PICCs, we observed 22 PICC tips misplaced in the jugular, 3 tips misplaced in the contralateral subclavian vein, and 7 tips misplaced in other locations, which was confirmed by CXR. A total of 22 PICC tips automatically returned to the superior vena cava, which included all 3 tips in the contralateral subclavian vein and 19 tips in the jugular vein. All catheters functioned normally, and the patients had no complaints. In addition, we observed no local symptoms of the neck and upper anterior chest wall. For patients experiencing a PICC misplaced in the jugular and contralateral subclavian veins, there is no need to manually replace. In addition, the function of the catheter can remain normal.

Effect of poly(ethylene glycol)-block-polylactide nanoparticles on hepatic cells of mouse: low cytotoxicity, but efflux of the nanoparticles by ATP-binding cassette transporters.

The objective of this paper is to study the effects of poly(ethylene glycol)-block-polylactide (PLA-PEG) nanoparticles on hepatic cells of mouse. Blank PLA-PEG nanoparticles have been successfully prepared and MTT assay suggested that the nanoparticles with HepG2 cell co-culture model did not cause significant changes in membrane integrity in controlled concentration range (0.001-0.1 mg/ml). Immunohistochemical analysis demonstrated that large dose of PLA-PEG nanoparticles injection (42.04 mg/kg, i.v.) did not induce hepatic cell apoptosis. From biochemical assay experiments, although the levels of SOD decreased and those of MDA, NOS increased after treatment with large dose of PLA-PEG nanoparticles injection (42.04 mg/kg, i.v.), they were all not significant (p>0.05). Then Kunming mice were treated with large dose of PLA-PEG nanoparticles (42.04 mg/kg, i.v.) and after 4 days total RNA was isolated to elucidate patterns of gene expression using a mouse cDNA-microarray (SuperArray). Treatment with nanoparticles resulted in over-expression of a lot of ATP-binding cassette (ABC) transporters, especially two ABC transporters (ABCA8 and ABCC5/MRP5), and down-regulation of GSTP1, in comparison with the control. ABCA8 could extrude low molecular weight polymers after PLA-PEG nanoparticles hydrolysis outside the cells. We also discovered that ABCC5 expressed multidrug resistance protein 5 (MRP5) to pump out conjugate (GS-X) of PLA-PEG nanoparticles with GSH. The results were confirmed by RT-PCR. Results of in vitro accumulation and efflux experiments indicated that about 51-52% (51.5% and 52.0%) intracellular PLA-PEG nanoparticles was expulsed after mouse primary hepatocytes reached a saturation uptake of nanoparticles during the concentration range of 750-1000 microg/ml. The results suggested that ABC transporters (especially ABCA8) pump out the polymers after hydrolysis from mouse hepatic cells and large dose of PLA-PEG nanoparticles make mouse hepatic cells gain drug resistance to PLA-PEG nanoparticles.

Femorally inserted central venous catheter in patients with superior vena cava obstruction: choice of the optimal exit site.

PURPOSE: This study assessed patient comfort and catheter indwelling time and decreased incidence of complications in patients with femorally inserted venous catheters (FIVCs) via different exit sites. METHODS: A group of 114 patients suffering from lung cancer complicated by superior vena cava obstruction (SVCO) underwent femoral insertion of venous catheters to facilitate chemotherapy infusion. Patients were divided into two groups: a novel (NOV) group (n = 59) with the FIVC exit site at the mid-thigh and a conventional (CON) group (n = 55) with the exit site at the groin. The clinical efficacy and safety were compared. RESULTS: There were significant differences (p<0.001) between NOV and CON groups in bleeding scores (2.44 ± 0.62 vs. 1.36 ± 0.49), catheter indwelling time (195.08 ± 39.19 days vs. 91.53 ± 32.88 days), patient comfort scores (4.20 ± 0.87 vs. 1.35 ± 0.91), and pain scores (1.64 ± 0.91 vs. 2.42 ± 1.08). Significant differences (p<0.05) were also observed in catheter-associated thrombosis (1.69% vs. 14.55%), catheter exit site infection (1.69% vs. 21.82%), and the incidence of total complications (11.86% vs. 45.45%) between the NOV and CON groups. However, the differences in success rates between the NOV and CON groups during the first attempt (98.32% vs. 98.18%) and catheter obstruction (8.48% vs. 9.09%) were not significant (p>0.05). CONCLUSIONS: Compared with the conventional exit site at the groin, the exit site at the mid-thigh for FIVCs increased patients' comfort and catheter indwelling time, and decreased the rate of complication and pain scores. However, it did not decrease the success rate in SVCO patients.