Abstract Objectives To evaluate the extent of agreement between two blood collection methods for electrolytes, central venous blood sampling by the push-pull technique versus venipuncture, and to mitigate errors in blood sampling by a potassium-based quality control procedure. Methods A comparative within-subject study was carried out for adult patients in the intensive care unit. Intraclass correlation coefficients (ICCs) were used to estimate concordance, and Bland–Altman analysis and clinically acceptable limits were used to compare the equivalence of the two methods. An in-house checklist was designed to identify errors made by nurses throughout central venous blood sampling by the push-pull technique, the corrective training and quality control procedure were conducted, and the rate of errors, incidence of hemolysis and distribution of potassium concentrations were comparatively analyzed for the quality of central venous blood sampling before and after the quality control procedure. Results All the ICCs of 220 paired blood samples displayed excellent reliability, except for potassium. Most of the electrolyte variables were within the clinically acceptable limits, and the results showed that the potassium concentrations did not seem to sufficiently affect clinical decision-making. A total of 30 nurses accepted 90 observations before and after the quality control procedure, and the results showed that blood exposure and repeated disconnections of the line in the push-pull technique were always the main problems throughout the process of central venous blood sampling. In addition, after improvement, the number of patients with hypokalemia or hyperkalemia tended to decrease, but the difference was not statistically significant. For all of the blood samples, only three push-pull paired samples received hemolysis notice. Conclusions Central venous blood sampling by the push-pull technique could be an acceptable substitute for most electrolytes via venipuncture, but caution should be exercised for potassium-based quality control procedures.
The aim of this study was to explore whether a robot-assisted (RA) technique has advantages over the conventional fluoroscopy-assisted (FA) technique in clinical and radiological outcomes and whether it could decrease the incidence of mis-implantations of pedicle screws in adolescent idiopathic scoliosis (AIS) correction surgery. A total of 101 patients with AIS were recruited (RA group: 45 patients underwent RA screw insertion; FA group: 56 patients underwent FA screw insertion). When comparing the radiological data between the two groups, the major and secondary curves were both corrected proficiently with no difference in Cobb angle comparison at the last follow-up, suggesting that both the RA technique and the FA technique could lead to efficient radiographic correction and similar clinical outcomes (all, p > 0.05). In the RA group, operation time, blood loss, and transfusion volume were significantly greater than those in the FA group, while the accuracy of screw implantations in patients with AIS with a thoracic scoliotic curve in the RA group was higher than that in the FA group. In conclusion, both the RA and FA techniques could approach proficient radiographic correction and similar clinical outcomes in AIS surgery. Compared with the conventional fluoroscopy technique, the RA technique might improve the accuracy of screw implantations in patients with AIS with a thoracic scoliotic curve, while the increased operation time, blood loss, and transfusion volume might be the disadvantages due to the preliminary stage of the learning curve.
Over the past decade, immunotherapy, especially cell-based immunotherapy, has provided new strategies for cancer therapy. Recent clinical studies demonstrated that adopting cell transfer of tumor-infiltrating lymphocytes (TILs) for advanced solid tumors showed good efficacy. TIL therapy is a type of cell-based immunotherapy using the patient’s own immune cells from the microenvironment of the solid tumor to kill tumor cells. In this review, we provide a comprehensive summary of the current strategies and challenges in TIL isolation and generation. Moreover, the current clinical experience of TIL therapy is summarized and discussed, with an emphasis on lymphodepletion regimen, the use of interleukin-2, and related toxicity. Furthermore, we highlight the clinical trials where TIL therapy is used independently and in combination with other types of therapy for solid cancers. Finally, the limitations, future potential, and directions of TIL therapy for solid tumor treatment are also discussed.
Abstract The soluble fullerenated poly(p-methylstyrene) with different C60 contents was prepared through the reaction of carbanion intermediates of poly(p-methylstyrene)[PPMS], which were obtained by proton abstraction with NaH, with C60 in the heterogeneous medium. Covalent grafting of electrophilic C60 moieties onto the PPMS backbone resulted in the enhancement of absorption at longer wavelengths and thermal stability of the polymer. The paramagnetic species in the fullerenated PPMS results from the π-π stereo-electron interplay between C60 and the adjacent p-methylphenyl groups of PPMS.
Abstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30 th , 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2 nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).
Abstract Small interfering RNA (siRNA)-based RNA interference has emerged as a promising therapeutic strategy for the treatment of a wide range of incurable diseases. However, the safe and effective delivery of siRNA therapeutics into the interior of target cells remains challenging. Here, we disclosed novel amphiphilic peptide dendrimers (AmPDs) that composed of hydrophobic two lipid-like alkyl chains and hydrophilic poly(lysine) dendrons with different generations (2C 18 -KK 2 and 2C 18 -KK 2 K 4 ) as nanovehicles for siRNA delivery. These AmPDs are able to self-assemble into supramolecular nanoassemblies that are capable of entrapping siRNA molecules into nanoparticles to protect siRNA from enzymatic degradation and promote efficient intracellular uptake without evident toxicity. Interestingly, by virtue of the optimal balance of hydrophobic lipid-like entity and hydrophilic poly(lysine) dendron generations, AmPD 2C 18 -KK 2 K 4 bearing bigger hydrophilic dendron can package siRNA to form stable, but more ready to disassemble complexes, thereby resulting in more efficient siRNA releasing and better gene silencing effect in comparison with AmPD 2C 18 -KK 2 bearing smaller dendron. Additional studies confirmed that 2C 18 -KK 2 K 4 can capitalize on the advantages of lipid and peptide dendrimer vectors for effective siRNA delivery. Collectively, our AmPD-based nanocarriers indeed represent a safe and effective siRNA delivery system. Our findings also provide a new perspective on the modulation of self-assembly amphiphilic peptide dendrimers for the functional and adaptive delivery of siRNA therapeutics.
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