Cellulose synthesis complexes are homo-oligomeric and hetero-oligomeric in Physcomitrium patens.

The common ancestor of seed plants and mosses contained homo-oligomeric cellulose synthesis complexes (CSCs) composed of identical subunits encoded by a single CELLULOSE SYNTHASE (CESA) gene. Seed plants use different CESA isoforms for primary and secondary cell wall deposition. Both primary and secondary CESAs form hetero-oligomeric CSCs that assemble and function in planta only when all the required isoforms are present. The moss Physcomitrium (Physcomitrella) patens has seven CESA genes that can be grouped into two functionally and phylogenetically distinct classes. Previously, we showed that PpCESA3 and/or PpCESA8 (class A) together with PpCESA6 and/or PpCESA7 (class B) form obligate hetero-oligomeric complexes required for normal secondary cell wall deposition. Here, we show that gametophore morphogenesis requires a member of class A, PpCESA5, and is sustained in the absence of other PpCESA isoforms. PpCESA5 also differs from the other class A PpCESAs as it is able to self-interact and does not co-immunoprecipitate with other PpCESA isoforms. These results are consistent with the hypothesis that homo-oligomeric CSCs containing only PpCESA5 subunits synthesize cellulose required for gametophore morphogenesis. Analysis of mutant phenotypes also revealed that, like secondary cell wall deposition, normal protonemal tip growth requires class B isoforms (PpCESA4 or PpCESA10), along with a class A partner (PpCESA3, PpCESA5, or PpCESA8). Thus, P. patens contains both homo-oligomeric and hetero-oligomeric CSCs.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

Influence of cement-augmented pedicle screws with different volumes of polymethylmethacrylate in osteoporotic lumbar vertebrae over the adjacent segments: a 3D finite element analysis.

BACKGROUND: Polymethylmethacrylate (PMMA) is commonly used for cement-augmented pedicle screw instrumentation (CAPSI) to improve the fixation stability and reduce the risk of screw loosening in the osteoporotic thoracolumbar spine. Biomechanical researches have shown that various dose of cement (1-3 ml) can be injected to enhance screw stability. To date, there have been no studies on the relationship between adjacent segment degeneration and the volume of PMMA. This study aimed to explore the influence of CAPSI with different volumes of PMMA in osteoporotic lumbar vertebrae over adjacent segments by using finite element analysis. METHODS: Seven different finite element models were reconstructed and simulated under different loading conditions, including (1) an intact model, (2) three single-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml), and (3) three double-level CAPSI models with different volumes of PMMA (1, 1.73, and 2.5 ml). To improve the accuracy of the finite element analysis, the models of the injectable pedicle screw and bone cement were created by using a three-dimensional scanning machine and the CAPSI patient's CT data, respectively. The range of motion (ROM), the stress of intervertebral discs, and the stress of facet in the adjacent segment were comparatively analyzed among the different models. RESULTS: The ROMs of the different segments were compared with experimental data, with good agreement under the different load conditions (21.3°, 13.55°, 13.99°, and 6.11° in flexion, extension, bending, and rotation at L3-S1 level, respectively). Compared with the intact model, the ROM, disc stresses, and facet stress in adjacent segments were found to be higher in the six operative models. Otherwise, with a larger volume of PMMA injected, the ROM, disc stresses, and facet stress slightly increased at the adjacent segment. However, the differences were insignificant with the biggest difference less than 3.8%. CONCLUSIONS: CAPSI could increase the incidence of disk degeneration in the adjacent segment, while within a certain range, different volumes of PMMA provided an approximate impact over the adjacent segment degeneration.

Comparison of Clinical Outcomes of Prostatic Artery Embolization with 50-µm Plus 100-µm Polyvinyl Alcohol (PVA) Particles versus 100-µm PVA Particles Alone: A Prospective Randomized Trial.

PURPOSE: To evaluate the safety and efficacy of prostatic artery embolization (PAE) using the combination of 50-µm and 100-µm polyvinyl alcohol (PVA) particles versus 100-µm PVA particles alone in the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Over a 5-year period, 120 patients treated with PAE for lower urinary tract symptoms (LUTS) secondary to BPH were randomized to undergo embolization with 50-µm plus 100-µm PVA particles (group A) or 100-µm PVA particles alone (group B). Mean follow-up time was 34 months (range, 12-57 mo). There were no differences between groups regarding baseline data. Primary outcome measurements included change in International Prostate Symptom Score (IPSS) and incidence of adverse events. Secondary outcome measurements included procedure-associated pain, prostate ischemia measured on magnetic resonance (MR) imaging 1 week after PAE, and changes over time in quality of life (QOL) questionnaire, peak urinary flow rate (Qmax), postvoid residual (PVR) volume, prostate volume (PV), prostate-specific antigen (PSA) level, and International Index of Erectile Function (IIEF) were evaluated. Recurrence of LUTS following PAE was defined as relief of LUTS temporally but increased IPSS ≥ 8 or QOL score ≥ 3 or decrease in Qmax to < 7 mL/s. RESULTS: Mean follow-up periods were 35 months ± 22 in group A and 33 months ± 25 in group B (P = .629). No differences between groups regarding procedural details, pain scores, or adverse events were noted (P > .05). At 24 month of follow-up, patients in group A had a greater decrease in mean IPSS (18.7 ± 12.5 vs 14.8 ± 13.5), QOL score (3.7 ± 1.5 vs 2.4 ± 1.8), Qmax (10.5 mL ± 9.5 vs 6.8 mL ± 5.0), PVR (92.0 mL ± 75.0 vs 60.0 mL ± 55.0), and PV (37.0 mL ± 19.5 vs 25.5 mL ± 15.0) compared with patients in group B (P < .05 for all). Mean ratios of prostate ischemic volume at 1 week after PAE were 70% ± 20 in group A and 41% ± 25 in group B (P = .021); mean PSA levels at 24 hour after PAE were 92.5 ng/mL ± 55.0 in group A and 77.5 ng/mL ± 45.0 in group B (P = .031); LUTS recurrence rates were 3.6% in group A and 14.6% in group B (P = .024). The mean IIEF-5 was not significantly different from baseline in either group. CONCLUSIONS: PAE with 50-µm plus 100-µm PVA particles resulted in greater improvement in clinical and imaging outcomes and no significant differences in adverse events compared with 100-µm PVA particles alone.

Risk factor analysis for re-collapse of cemented vertebrae after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP).

PURPOSE: Re-collapse of cemented vertebrae occasionally occurs after percutaneous augmentation. However, the potential risks still remain unclear. Several articles have reported some possible risk factors which were not consistent or comprehensive. This study aimed to make a retrospective review on patients with osteoporotic vertebral compression fracture (OVCF) after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) and to further analyse the risk factors for treated vertebral refracture. METHODS: All patients receiving the PKP/PVP with bilateral approach were retrospectively reviewed from January 2014 to January 2016, among whom 230 patients with single level augmentation (30 in refracture group and 200 in the non-refracture group) were enrolled according to inclusion criteria. The following covariates were reviewed: gender, age, height, weight, body mass index (BMI), bone mineral density (BMD), serum bone turnover markers, surgical parameters including approach, cement volume, anterior height, and Cobb angle restoration. Binary logistic regression analysis was used to determine the relative risk of re-collapse of cemented vertebrae. RESULTS: Regarding the patient data, weight, BMI, and BMD were of statistical significance in refracture group (P < 0.01), among which only low BMD was a risk factor to cemented vertebral re-collapse (P = 0.022, OR = 4.197). In respect of surgical variables, the better restoration of anterior height and Cobb angle was found in refracture group (P < 0.05), both of which might increase the refracture risk but not be risk factors (P = 0.065, OR = 0.891, and P = 0.937, OR = 0.996, respectively). Besides, less injected cement (3.30 ± 0.84 ml vs 4.46 ± 1.10 ml, P = 0.000, OR = 19.433) and PKP (P = 0.007, OR = 13.332) significantly boosted the potential risk of refracture (P < 0.001). CONCLUSION: Patients with low BMD, or undergoing PKP, or receiving a low volume of injected cement might have a high risk of re-collapse in surgical vertebrae.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

Expiratory Velopharyngeal Obstruction: Sleep Endoscopy-Guided Treatment Strategies to Prevent Oral Breathing During Sleep.

OBJECTIVE: Obstructive sleep apnea (OSA) is a prevalent disorder, with oral breathing influencing its severity. Expiratory velopharyngeal obstruction (EVO), observed during drug-induced sleep endoscopy (DISE), may contribute to oral breathing in OSA patients. EVO results in obstruction between the pharynx and nasal cavity during expiration. This study aims to identify factors associated with positive EVO during DISE. STUDY DESIGN: Case series. SETTING: Tertiary Medical Center. METHODS: Seventy-two OSA patients underwent clinical evaluation, polysomnography, and DISE, utilizing interventions like intraoral negative airway pressure (iNAP), mouth closure, and oral appliances (OAs) in supine positions with head rotation. The findings, classified under velopharynx, oropharynx, tongue base, epiglottis, included the presence of EVO. RESULTS: The results demonstrated that interventions including mouth closure and iNAP were associated with increased observation of EVO (43.1% and 34.7%) compared to OA (20.1%). However, head rotation was associated with decreased presence of EVO during DISE compare to supine (26% vs 35.8%). Noticeably, per 1 year increase of age was associated with an increased odds of EVO (odds ratio: 1.03, 95% confidence interval: 1.01-1.06). However, no other baseline characteristics were significantly associated the odds of EVO. CONCLUSION: Our study reveals the effectiveness of head rotation and OA in reducing EVO and improving mouth breathing in OSA patients, offering valuable insights for future treatment strategies.

Precisely targeted drug delivery by mesenchymal stem cells-based biomimetic liposomes to cerebral ischemia-reperfusion injured hemisphere.

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.

Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

Outcomes of transarterial embolization for large symptomatic focal nodular hyperplasia in 17 pediatric patients.

BACKGROUND: To evaluate the safety and the long-term outcomes of transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus N-Butyl cyanoacrylate (NBCA) in the treatment of children with large symptomatic focal nodular hyperplasia (FNH). METHODS: This is a retrospective case serial study. Children (aged <18 years) with FNH were treated. Indications for TAE were patients who were presenting with FNH related abdominal pain and the maximum diameter of FNH is more than 7 cm, and who were not candidates for surgical treatment. Technical success, adverse events, symptoms relief rate, and changes in the lesion size after TAE were evaluated. RESULTS: Between January 2003 and February 2018, 17 pediatric patients were included. Technical success was achieved in all patients. Mean follow-up was 67.5 months. All patients had complete resolution of abdominal symptom. The mean largest diameter of the lesions decreased from 10.5 cm to 1.9 cm (P < 0.01). The mean volume reduction rate was 96.9%. The complete resolution of the FNH was observed in 16 patients. No further therapy was needed for all patients. CONCLUSIONS: TAE with LBE plus NBCA appears to be a safe and effective treatment in pediatric patients with large symptomatic FNH. It could be considered as the first-line treatment for symptomatic large FNH.

Outcomes of patients with mucoepidermoid carcinoma of minor salivary gland in palate undergoing radical resection followed by submental flap reconstruction.

OBJECTIVE: To investigate the outcomes of patients with mucoepidermoid carcinoma of the palate undergoing pedicled facial-submental artery island flap (FSIF) reconstruction following resection. PATIENTS AND METHODS: 41 patients with early stage disease and 9 patients with advanced-stage disease underwent radical excision and neck dissection. 37 IIb, 4 class IIa and 9 IIIb maxillary defects were reconstructed with FSIF, folded FSIF or folded FSIF with titanium mesh respectively. The skin paddles were 3 × 8 to 5 × 15 cm and 3 × 8 to 5 × 14 cm, respectively. 5 patients with high grade disease were treated with cobalt 60 adjuvant radiotherapy after operation. RESULTS: One flap failure occurred, yielding a success rate of 98.0% in the reconstruction of palate II and III defects with FSIF or titanium mesh. The patients were seen for follow-up for 16-60 months postoperative. 76.0% patients alive with no disease (AND); 14.0% patients alive with disease (AD) and 10.0% died of disease (DD). Rates of AND, AD and DD differed significantly according to histopathologic grade and TNM stage (P < 0.001); rates of AND, AD and DD differed obviously according to necrosis of the tumors lymph node metastasis, and tumour cell anaplasia and treatment (P < 0.05). CONCLUSIONS: Radical resection with wide safety margins of normal tissues including neck dissection is the mainstay of treatment modality. The patients with high grade disease should be treated with postoperative radiotherapy. The FSIF is a reliable and safe method for repairing Brown class II maxillary defects.

Comparison of 3 techniques of surgical treatment of carotid body tumors.

OBJECTIVE: Carotid body tumors (CBTs) are benign but challenging. This study compared outcomes of 3 techniques of the surgical treatment of CBTs. STUDY DESIGN: This retrospective observational study was conducted from April 2013 to March 2019. The 38 patients enrolled in the study had primary tumors, including 1 with bilateral tumors and another with adrenal gland pheochromocytoma. We collected data on age, sex, size of tumor, Shamblin classification, treatment, blood loss, operative time, hospital stay, complications, and recurrence. Statistical analyses were performed using IBM SPSS Statistics version 20 software. RESULTS: Twenty-four patients were male, and 12 were female, and they ranged in age from 11 to 71 years. Cases were assigned to Shamblin groups I (n = 6), II (n = 19), and III (n = 14). Tumor size ranged from 2.0 × 2.0 cm to 5.0 × 6.0 cm. Eleven CBTs underwent blunt dissection (BD), 20 underwent BD plus resection of external carotid artery division plus vessels of encapsulation with allograft dermal matrix (BD + RECA + VE), and 8 tumors underwent surgical resection of tumors plus common carotid artery-internal carotid artery artificial vascular reconstruction (SR +C-IAVR). No perioperative death or stroke occurred. There was a significant difference between Shamblin groups I, II, and III in terms of the size of the tumor, type of treatment used, blood loss, operative time, hospital stay, and complications. Six patients had mandibular branch facial nerve transient paresis; 7 patients had hypoglossal nerve dysfunction; 3 patients had Horner syndrome; and dysphasia occurred in 2 patients. The patients were seen in follow-up for 16 to 45 months, and 1 recurrence was observed. CONCLUSIONS: Three surgical techniques-BD, BD + RECA + VE, and SR + C-IAVR-are safe and feasible for the treatment of CBTs according to Shamblin classifications.

Long-term efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease.

This study aimed to evaluate the efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease. Twenty-five patients with stage III Kümmell disease who received bone cement-augmented pedicle screw fixation at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2009 and December 2015 were enrolled. All patients were females with a history of osteoporosis. The vertebral Cobb angle (V-Cobb angle), the fixed segment Cobb Angle (S-Cobb angle), pelvic parameters, visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI) were assessed preoperatively, postoperatively and at the final follow-up. Complications, loosening rate, operation time, and intraoperative bleeding were recorded. The average lumbar vertebral density T-value was - 3.68 ± 0.71 SD, and the average age was 71.84 ± 5.39. The V-Cobb angle, S-Cobb angle, and Sagittal Vertical Axis (SVA) were significantly smaller postoperatively compared to the preoperative values. The VAS and ODI at 1 month after surgery were 3.60 ± 1.00 and 36.04 ± 6.12%, respectively, which were both significantly lower than before surgery (VAS: 8.56 ± 1.04, ODI: 77.80 ± 6.57%). Bone cement-augmented pedicle screw fixation is a safe and effective treatment for stage III Kümmell disease. It can effectively correct kyphosis, restore and maintain sagittal balance, and maintain spinal stability.

[Engineering progress in microbial production of polyhydroxyalkanoates].

Polyhydroxyalkanoates (PHAs) are polymers obtained by esterification of hydroxy fatty acid monomers. Due to similar mechanical characteristics of traditional petroleum-based plastics, 100% biodegradability and biocompatibility, PHAs are considered to be one of the most potential green materials. However, the application and promotion of PHAs as a green and environmentally friendly material are difficult because of the high production costs. This article focuses on the current methods to reduce production cost of PHAs effectively, such as cell morphology regulation, metabolic pathway construction, economic carbon source utilization and open fermentation technology development. Despite most research results are still limited in laboratory, the research methods and directions provide theoretical guidance for the industrial production of economic PHAs.

Comprehensive treatment of massive macroglossia due to venous and lymphatic malformations.

This study evaluated the outcomes of comprehensive treatment for massive macroglossia. Eleven patients with massive macroglossia due to venous malformations (VMs) and lymphatic malformations (LMs) underwent incision excision of two-thirds of the central wedge of the tongue; two of these patients underwent resection of lesions in the lower lip or floor of the mouth during initial treatment. In subsequent treatment, three patients underwent orthognathic surgery or resection of lesions in the lower lip and submental region, and four patients underwent one or two sclerotherapies. No patient had complications resulting from anaesthesia or surgery. Patients were followed up at 6 months postoperative, and all signs associated with the lesions had disappeared. The mean follow-up duration was 30.8 months. The aesthetic outcome was excellent for nine patients and satisfactory for two. Nine patients could take a soft diet and two a solid diet. Eight patients presented normal speech and three presented intelligible speech. Comprehensive treatment including incision excision of two-thirds of the central wedge of the tongue, as well as orthognathic surgery, the resection of lesions in the oral and maxillofacial region, and sclerotherapy, is effective for patients with massive macroglossia due to VMs and LMs.

Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial.

IMPORTANCE: Plinabulin is a novel, non-granulocyte colony-stimulating factor (GCSF) small molecule with both anticancer and neutropenia-prevention effects. OBJECTIVE: To assess the efficacy and safety of plinabulin compared with pegfilgrastim for the prevention of chemotherapy-induced neutropenia following docetaxel chemotherapy in patients with non-small lung cancer. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized, open-label, phase 2 clinical trial of 4 treatment arms that was conducted in 19 cancer treatment centers in the United States, China, Russia, and Ukraine. Participants were adult patients with non-small cell lung cancer whose cancer had progressed after platinum-based chemotherapy. Data were collected from April 2017 through March 2018 and analyzed from August 2019 through February 2020. INTERVENTIONS: All patients received docetaxel 75 mg/m2 on day 1 and were randomly assigned to 1 of 3 doses of plinabulin (5, 10, or 20 mg/m2) on day 1 or to pegfilgrastim 6 mg on day 2. Patients were treated every 21 days for 4 chemotherapy cycles. MAIN OUTCOMES AND MEASURES: The primary end point was the determination of the recommended phase 3 dose of plinabulin based on the days of severe neutropenia during chemotherapy cycle 1. Daily complete blood cell counts and absolute neutrophil counts were drawn during times of anticipated neutropenia during cycle 1. RESULTS: Of the 55 patients randomized and evaluated, the mean (SD) age was 61.3 (10.2) years, and 38 (69.1%) were men. With each escalation of the plinabulin dose, the incidence of any grade of neutropenia decreased. There were no significant differences in mean (SD) days of severe neutropenia among those treated with pegfilgrastim (0.15 [0.38] days) when dosed at day 2 vs plinabulin 20 mg/m2 (0.36 [0.93] days; P = .76) when dosed at day 1, and no safety signals were detected. CONCLUSIONS AND RELEVANCE: Single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim. Plinabulin 40 mg fixed dose, which is pharmacologically equivalent to 20 mg/m2, will be compared with pegfilgrastim 6 mg in the phase 3 portion of this trial. Noninferior days of severe neutropenia will be the primary end point, and bone pain reduction, thrombocytopenia reduction, and quality of life maintenance will be secondary end points. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03102606.

The Effect and Safety of Polymethylmethacrylate-Augmented Sacral Pedicle Screws Applied in Osteoporotic Spine with Lumbosacral Degenerative Disease: A 2-Year Follow-up of 25 Patients.

BACKGROUND: A high rate of instrumentation failure is frequently seen in osteoporotic spines, especially at the sacral segment because of the great shear stress. Several techniques of sacral pedicle screw placement, such as bicortical and tricortical fixation, have been developed; however, the problems of loosening and pulling out of the screws are still a concern. Recently, the polymethylmethacrylate (PMMA)-augmented pedicle screws have been shown to strengthen the purchase in osteoporotic spine, but there are few reports on the effect of S1 pedicle screw with PMMA augmentation. METHODS: Seventy-five patients receiving cement-augmented pedicle screws at lumbosacral vertebra were enrolled and divided into 3 groups by different patterns of S1 pedicle screw placement: S1 pedicle screw with PMMA augmentation (group A, 25 patients), S1 bicortical pedicle screw fixation (group B, 25 patients), and S1 tricortical pedicle screw fixation (group C, 25 patients). The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were assessed preoperatively and at the last follow-up. Besides, the complications, loosening rate, and fusion rate were recorded. RESULTS: The VAS and ODI scores at the last follow-up were significantly improved in the 3 groups compared with preoperative results. Better pain relief and functional improvement at the last follow-up was seen in group A compared with the other 2 groups; however, no significant difference was detected between groups B and C. Although the lowest screws loosening rates and the highest fusion rate were found in group A, no significant difference among these 3 groups. Furthermore, longer fusion segments and larger postoperative pelvic incidence-lumbar lordosis (PL-LL) were found as risks related to S1 screw loosening without cement augmentation. CONCLUSIONS: The S1 pedicle screws with PMMA augmentation achieved better stability with less screw loosening in the osteoporotic spine with lumbosacral degenerative diseases compared with bicortical/tricortical fixation at S1. This procedure is especially recommended for patients with long segment fixation and large postoperative PI-LL, but there is also a risk of bone cement leakage and a learning curve.

Augmented pedicle trajectory applied on the osteoporotic spine with lumbar degenerative disease: mid-term outcome.

PURPOSE: To compare the safety and efficiency of cement-augmented pedicle screw with traditional pedicle screw technique applied on the patients in the osteoporotic spine with lumbar degenerative diseases. METHODS: Fifty-six patients followed up at least 2 years were enrolled in our institute with retrospectively reviewed from January 2009 to June 2014, diagnosed as lumbar spondylolisthesis, or lumbar stenosis, with T score ≤- 2.5 SD of BMD, and received less than three-segment PLIF or TLIF. All patients were divided into 2 groups: 28 (2 males, 26 females) in polymethylmethacrylate-augmented pedicle screw group (PSA) group, the other 28 (3 males, 25 females) in traditional pedicle screw group (TPS). Surgical data including the operation time, intra-operative blood loss, hospitalization day and surgical complications were recorded, as well as the radiological parameters measured from the postoperative X-rays and CT scans containing the rates of fusion, screw loosening, and cage subsidence incidence. In addition, the visual analog scores (VAS) and Oswestry Disability Index (ODI) were evaluated preoperatively and postoperatively. RESULTS: The average follow-up period was 34.32 months (ranging from 24 months to 51 months). Compared with PSA group, operation time and average hospital stay in the TPS group decreased significantly (P < 0.05). While no statistical difference for blood loss between 2 groups (P > 0.05). At 2 years postoperation, from CT-scans, 2/172 screws loosening and 1/56 segment non-union occurred in PSA group, with significantly lower incidence than those in TPS group (8/152 screws loosening and 6/50 segments non-union occurred, P < 0.05). Regarding the cage subsidence, 24 segments found height loss (5.30 ± 1.92 mm) in PSA group without difference compared with that of 19 segments (4.78 ± 1.37 mm) in TPS group (P > 0.05). Besides, the number and the location of cages and the leakage of the cement were found out little related with the subsidence in the PSA group (P > 0.05). After surgeries, VAS and ODI at 1 month, 6 months, 12 months, and last follow-up improved significantly in two groups (P < 0.05). There were no significant differences in VAS and ODI preoperatively and postoperatively between 2 groups (P > 0.05). In addition, eight patients with asymptomatic trajectory PMMA leakages were detected. CONCLUSION: Cement-augmented pedicle screw technique is effective and safe in the osteoporotic spine with lumbar degenerative diseases, with better fusion rates and less screw loosening incidence. There is no difference in the fusion rate and loosening rate between the two groups in the single segment patients; however, there are better fusion rate and lower pedicle screw loosening rate of the PSA group in the double or multiple group patients.

Randomized Controlled Trial on Effects of a Brief Clinical-Based Intervention Involving Planning Strategy on Self-Care Behaviors in Periodontal Patients in Dental Practice.

BACKGROUND: Strengthening adherence to self-care behaviors in patients with periodontal disease (PD) and reducing the plaque index is crucial for improving PD treatment. We evaluated the effectiveness of a theory of planned behavior (TPB)-based health education intervention involving a planning strategy on self-care behaviors in patients with PD. METHODS: A randomized controlled trial was conducted; 158 and 139 patients comprised the experimental group (EG) and control group (CG), respectively. Both groups received a leaflet, and the EG also received a planning intervention, which was a brief one-on-one counseling session with a planning sheet. Data were collected using a self-administered questionnaire. RESULTS: Between-group comparisons of TPB measures revealed significant differences in all domains when controlling for baseline covariates. The EG exhibited significantly higher levels of action and coping planning than the CG at two-week follow-up (effect size (ES) = 5.54 and 5.57, respectively) and six-week follow-up (ES = 5.66 and 5.66, respectively). Between-group differences in changes of brushing behaviors increased significantly. More frequent use of dental floss was observed in the EG than in the CG at two-week and six-week follow-ups (24.7% and 22.8%, respectively). CONCLUSIONS: The intervention involving planning strategy effectively promoted adherence to self-care behaviors in patients with PD.

Liposomal Antitumor Vaccines Targeting Mucin 1 Elicit a Lipid-Dependent Immunodominant Response.

The tumor-associated antigen mucin 1 (MUC1) has been pursued as an attractive target for cancer immunotherapy, but the poor immunogenicity of the endogenous antigen hinders the development of vaccines capable of inducing effective anti-MUC1 immunodominant responses. Herein, we prepared synthetic anti-MUC1 vaccines in which the hydrophilic MUC1 antigen was N-terminally conjugated to one or two palmitoyl lipid chains (to form amphiphilic Pam-MUC1 or Pam2 -MUC1). These amphiphilic lipid-tailed MUC1 antigens were self-assembled into liposomes containing the NKT cell agonist αGalCer as an adjuvant. The lipid-conjugated antigens reshaped the physical and morphological properties of liposomal vaccines. Promising results showed that the anti-MUC1 IgG antibody titers induced by the Pam2 -MUC1 vaccine were more than 30- and 190-fold higher than those induced by the Pam-MUC1 vaccine and the MUC1 vaccine without lipid tails, respectively. Similarly, vaccines with the TLR1/2 agonist Pam3 CSK4 as an adjuvant also induced conjugated lipid-dependent immunological responses. Moreover, vaccines with the αGalCer adjuvant induced significantly higher titers of IgG antibodies than vaccines with the Pam3 CSK4 adjuvant. Therefore, the non-covalent assembly of the amphiphilic lipo-MUC1 antigen and the NKT cell agonist αGalCer as a glycolipid adjuvant represent a synthetically simple but immunologically effective approach for the development of anti-MUC1 cancer vaccines.