Regrowth Rate Research Articles

Rhizosphere priming effects of Lolium perenne and Trifolium repens depend on phosphorus fertilization and biological nitrogen fixation

Live roots can stimulate microbial soil organic matter (SOM) decomposition and nutrient cycling, which is termed as the rhizosphere priming effect (RPE). Compared to nitrogen (N) availability, fewer studies have focused on the effect of phosphorus (P) availability on the RPE. Here we investigated the RPEs of ryegrass (Lolium perenne) and clover (Trifolium repens) with and without P fertilization (4 g P m−2) at three sampling times (Day 30, Day 44, and Day 58 after planting). A continuous 13C–CO2 labeling method was used to separate soil-derived CO2 from root-derived CO2. A nutrient budget method was applied to evaluate the rhizosphere effect on net soil N and P release for plant uptake. We found that ryegrass and clover induced positive RPEs in most plant-soil combinations, ranging from −1% to 134%. Ryegrass exhibited a larger RPE than clover by Day 30, but clover exhibited a larger RPE than ryegrass by Day 44 and Day 58, possibly due to larger shoot biomass regrowth rates, root activity, and rhizodeposition during the later stages. P fertilization significantly decreased the RPE of ryegrass by Day 44 and Day 58, but did not change the RPE of ryegrass by Day 30 and clover at all three sampling times. The reduced RPE of ryegrass with P fertilization was associated with increased microbial biomass N, more root-derived microbial C, and less shoot biomass and root-derived CO2. These findings suggest that P fertilization coupled with C supply from root exudates induced more microbial N immobilization, which reduced the RPE of ryegrass during later stages when soil N limitation negatively impacted plant growth. However, P-induced microbial N immobilization did not affect clover as much because its biological N fixation, on average 37% of total plant N, may have alleviated soil N limitation. We further observed significant positive relationships between excess net soil N and P release and the RPE by Day 58 across all planted treatments, indicating that soil N and P release by plants can be directly linked to rhizosphere C mineralization. Overall, our results demonstrate the importance of C–N–P interactions for understanding the RPE, which have significant implications for P cycling in plant-soil systems.

Success Rate of Simple Coil Embolization in Wide-Neck Aneurysm with Aneurysmal Shoulder.

Background and Objective:Wide-necked intracranial aneurysm (WIA) is one of the challenging diseases for neuro-interventionist to treat by simple coiling technique. The purpose of this study is to identify the morphology associated with successful simple coil embolization in wide neck aneurysm patients.Materials and Methods:Between January 2002 and August 2018, 102 patients with total 115 ruptured or unruptured WIA which received endovascular treatment were retrospective reviewed. Data were analyzed including demographics, aneurysm morphology, endovascular technique, angiographic outcome, complication, regrowth, and retreatment rate.Results:The mean age of patients was 61.6 years with female predominant (72.5%). Ruptured WIA was diagnosed in 71 patients (61.7%). Majority of aneurysms were located in an anterior circulation which were 74 cases (64.3%), mainly paraclinoid aneurysm (30/115). Endovascular treatment was successful in 113 cases (98.3%) which can be mainly divided into simple coil embolization 50 cases (43.5%), balloon-assisted coil embolization 26 cases (22.6%), and stent-assisted coil embolization 32 cases (27.8%). Complete, subtotal, and incomplete occlusion of WIA was achieved in 32 cases (27.8%), 62 cases (53.9%), and 18 cases (15.7%), respectively. There was 9.6% complication occurred. Regrowth and retreatment were found 20% and 15.7%, respectively.Conclusion:WIA with two-sided aneurysmal shoulder or neck width <3.6 mm. are significantly associated with successful coil embolization using simple coiling technique.

Longitudinal analysis of organ-specific tumor lesion sizes in metastatic colorectal cancer patients receiving first line standard chemotherapy in combination with anti-angiogenic treatment.

The purpose of this work is to assess the heterogeneity across organs of response to treatment in metastatic colorectal patient based on longitudinal individual target lesion diameters (ILD) in comparison to sum of tumor lesion diameters (SLD). Data were from the McCAVE trial, in which 189 previously untreated patients with metastatic colorectal carcinoma (mCRC) received either bevacizumab (control, C) or vanucizumab (experimental, E), on top of standard chemotherapy. Bayesian hierarchical longitudinal non-linear mixed effect models were fitted to the data using Hamilton Monte Carlo algorithm to characterize the time dynamics of the tumor burden, and to obtain estimates of the tumor shrinkage and regrowth rates. The ILD model brought more nuanced results than to the SLD model. Besides substantial differences in tumor size at baseline (with lesions located in liver more than twice as large as the ones in lungs), it revealed a more durable response in lesions located in lymph nodes and 'other organs' compared to liver and lungs. Specifically, in lymph nodes and 'other organs', the projected time to nadir was doubled in group E (2.12 and 2.44years respectively) compared to group C (1.07 and 1.20years respectively). This long period of tumor shrinkage associated with a slightly larger change from baseline at nadir (-51.4% in lymph nodes and -62.6% in 'other organs' in the group E, compared to -46.2% and -46.9% in group C) resulted in a clinically meaningful difference in the tumor dynamics of patients in group E compared to the group C. The proportion of variance explained by the inter-lesion variability for each model parameter was large (ranging between 10 and 56%), reflecting the heterogeneity in tumor dynamics across organs. These findings suggest that there is value in understanding both within- and between-patient variability in tumor size's time dynamics using an appropriate modeling framework, as this information may help in pairing the right treatment with individual patient profile.

A safeguard measure of endemic and endangered plant species: cryostorage of Dianthus taxa

The aim of the present study was to determine the optimum parameters for high regrowth following cryostorage (− 196 °C) of seven endemic and endangered Dianthus species. A cryopreservation approach based on a droplet-vitrification protocol was successfully applied using explants (shoot apices and axillary buds) from a collection of in vitro grown Dianthus species. The plants were micropropagated for two years prior using them as explant donors. Osmoprotection in different sucrose concentrations and various dehydration durations in the plant vitrification solution (PVS2) were tested to assess survival and regrowth following cryostorage. The regrowth rates after cryostorage ranged between 63% (D. glacialis ssp. gelidus) and 73% (D. nardiformis) and were achieved after osmoprotection in 0.5 M sucrose and 30 min dehydration in PVS2 for D. glacialis ssp. gelidus and osmoprotection in 0.25 M sucrose and 30 min dehydration in PVS2 for D. nardiformis. The morphogenetic response to liquid nitrogen storage was direct multiple shoot formation for both non-cryopreserved and cryopreserved explants for all species. This biotechnological approach can be efficiently applied for the ex situ conservation of endemic and endangered Dianthus species to ensure the long-term conservation of biodiversity.

Abstract 6010: Tumor mhicroenvironment effects on hematopoietic stem cell induced tumor growth following radiation therapy

Abstract The tumor microenvironment (TME), comprised of tumor tissue, stromal cells, extracellular matrix (ECM), bone marrow (BM)-derived immune cells, and various signaling molecules, rarely remains static. These components continuously respond to internal and external stimuli to promote tumor progression as well as regrowth after therapy. Recently, we reported that functional BM-derived hematopoietic stem and progenitor cells (HSPCs) take up residence within growing lung tumors. Interestingly, when tumors were exposed to radiation therapy (RT) there was a significant increase in HSPC numbers within tumors (p&amp;lt;0.003). These HSPCs seemed to positively affect tumor regrowth as their numbers directly correlated with regrowth rates (R2=.4875). To determine the role of HSPCs in tumor growth we proposed a mechanism wherein tumor-associated HSPCs are maintained within tumors but following exposure to RT can differentiate into tumor-supportive macrophage populations, thus aiding in tumor regrowth. To test this hypothesis, Lewis Lung Carcinoma tumors were subcutaneously generated in mice and exposed to either RT or no radiation treatment (NRT). Analysis using RT-PCR and immunohistochemistry demonstrated that RT produces TME conditions that favor the differentiation of HSPCs into tumor-supportive M2-macrophages through the increased production of colony stimulating factor 1 (CSF-1) (p&amp;lt;0.005). In addition, we show that inhibition of CSF-1R phosphorylation using a pharmacologic inhibitor (GW2580) had no effect on HSPCs numbers but resulted in significantly decreased M2 macrophage numbers resulting in decreased tumor growth and regrowth (p&amp;lt;0.005). Furthermore, we found that the interaction of HSPC-bound integrin α6 with Laminin 5-1-1 is associated with HSPC maintenance within tumors. Interestingly, Laminin 5-1-1 levels were decreased in RT treated tumors compared to NRT controls (p&amp;lt;0.005) further indicating that the RT-derived microenvironments supported HSPC differentiation into M2 macrophages. Overall, these studies define a new understanding of tumor biology in which tumor-associated HSPCs are an essential component of tumor progression and survival and identify new treatment strategies to overcome these effects and achieve more optimal clinical outcomes. Citation Format: Tyler M. Parsons, Katie Buelow, Alaa Hanna, Sandra Galoforo, George Wilson, Gerard Madlambayan. Tumor mhicroenvironment effects on hematopoietic stem cell induced tumor growth following radiation therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6010.

Abstract 2196: SRF231, a fully human CD47 antibody, potentiates the effects of opsonizing antibodies and cytotoxic chemotherapies in preclinical cancer models

Abstract CD47 is widely expressed on tumor cells and is an important checkpoint of the innate immune response. SRF231, an investigational fully human IgG4 anti-CD47 antibody, blocks CD47-SIRPα interaction and exerts anti-tumor activity via phagocytosis and cell death in a manner dependent on Fc-engagement with CD32a, leading to enhanced myeloid activity. Human IgG1 Fc-containing antibodies that target cancer antigens (opsonizing antibodies) can stimulate macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) in addition to NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Also, several chemotherapies trigger cell death response pathways that generate additional “eat-me” signals on tumor cells, rendering them more susceptible to SRF231. Given the dual mechanism of action of SRF231, combination therapies that induce ADCP or cell death were evaluated for their ability to potentiate SRF231-mediated anti-tumor responses in hematologic and solid tumor models. The effect of SRF231 alone and in combination with opsonizing antibodies was evaluated in multiple myeloma (MM) models. In vitro, SRF231 induced phagocytosis of MM cells by human monocyte-derived macrophages. Enhanced ADCP was observed with SRF231 in combination with opsonizing antibodies elotuzumab (anti-SLAMF7) and daratumumab (anti-CD38). In vivo, SRF231 monotherapy following single- and repeat-dosing regimens resulted in 50-80% tumor growth inhibition and significantly increased median survival time in the preclinical MM xenograft models OPM2 and MM1.S. Furthermore, SRF231 strongly synergized with a sub-optimal dose of elotuzumab leading to increased complete response (CR) rates in both models. The effect of SRF231 alone and in combination with chemotherapies was also assessed in non-small cell lung cancer (NSCLC) models. In vivo, SRF231 monotherapy induced anti-tumor activity and significantly increased median survival time in preclinical EGFR mutant (H1975) and EGFR wildtype (A549) NSCLC xenograft models. Cisplatin monotherapy induced modest H1975 anti-tumor activity; however, combination with SRF231 potentiated the effect of cisplatin in this model. Additionally, combination of SRF231 with docetaxel resulted in a 45% CR rate and a significant delay in H1975 tumor regrowth, as compared to a 100% regrowth rate with docetaxel monotherapy. In summary, SRF231 demonstrated significant anti-tumor activity in combination with the anti-SLAMF7 opsonizing antibody, elotuzumab, in preclinical MM xenograft models. Moreover, SRF231 potentiated the effects of taxane and platinum-based standard of care chemotherapies in preclinical NSCLC xenograft models. These results offer further guidance on the clinical development of anti-CD47 modalities in cancer treatment. Citation Format: Kshama A. Doshi, Matthew Rausch, Caroline M. Armet, Li Zhang, Alison M. Paterson, Benjamin H. Lee, Vito J. Palombella, Pamela Holland, Marisa O. Peluso. SRF231, a fully human CD47 antibody, potentiates the effects of opsonizing antibodies and cytotoxic chemotherapies in preclinical cancer models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2196.

Abstract 1675: Enhanced antitumor effect of dual EGFR and VEGFR2 inhibition in EGFR-mutated non-small cell lung cancer (NSCLC) patient-derived tumor xenograft (PDX) models

Abstract Background: NSCLC accounts for nearly 85% of all lung cancers. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for EGFR mutated NSCLCs, but these drugs often stop working after EGFR acquires additional mutations. Preclinical and clinical data suggest a stronger antitumor effect with dual blockade of the EGFR and vascular endothelial growth factor (VEGF) pathways in EGFR-mutated NSCLC. RELAY, a randomized, double-blind, phase 3 trial, demonstrated superior progression-free survival (PFS) with ramucirumab (RAM) + erlotinib compared with placebo + erlotinib in patients with untreated EGFR-mutated advanced NSCLC. Additionally, RAM was tested in a Phase 1 study with the third-generation irreversible EGFR TKI osimertinib (OSI); AstraZeneca) in NSCLC patients with advanced T790M-positive EGFR mutant tumors after progression on first-line EGFR TKI therapy. OSI can be used with L858R, exon 19 del and T790M EGFR mutant tumors. We investigated the combined use of OSI+RAM in EGFR mutated NSCLC PDX mouse models. Materials and Methods: The antimurine VEGFR2 antibody DC101 (40 mg/kg, BIW) and the EGFR TKI OSI (10 mg/kg, QD) were used in this study. Twenty-seven PDX NSCLC mouse models carrying EGFR activating and/or T790M resistance mutations, commonly detected in patients with advanced NSCLC, were evaluated at 3 independent sites. Mice were divided into 4 treatment arms: vehicle (PBS), DC101, OSI and combination (DC101+OSI). Each study arm included two transplanted mice per model. Sensitivity to DC101 and OSI monotherapies, enhancement of anti-tumor activity with the combination therapy and durability of the response were evaluated. Desirability score, a weighted composite score of six features of tumor growth curves including best median % response, number of days in best response category, time to doubling, re-growth rate (last 5 observations) relative to vehicle growth rate, last observed tumor volume and last observed day, was calculated for each treatment arm. Analysis of variance was used to compare summary scores per animal across treatments. Results: OSI alone and OSI+DC101 combination therapy had stronger antitumor effects than DC101 monotherapy in significantly more models 11 vs 1 and 12 vs 0, respectively. A small but consistent shift in favor of OSI+DC101 vs OSI was observed across most of the models. Paired t-test analyses showed a moderate but significant benefit with combination OSI+DC101 vs OSI. Overall desirability score was statistically improved with OSI+DC101 compared to either single agent. Conclusions: Dual inhibition of EGFR and VEGFR2 with OSI+DC101 had a stronger antitumor effect than those of the respective monotherapies in EGFR mutated NSCLCs in vivo. Future studies will investigate the molecular mechanisms underlying the enhanced antitumor effect of OSI+DC101 combination therapy. Citation Format: Sudhakar Chintharlapalli, Anthony Fischl, Chun Ping Yu, Philip Iversen. Enhanced antitumor effect of dual EGFR and VEGFR2 inhibition in EGFR-mutated non-small cell lung cancer (NSCLC) patient-derived tumor xenograft (PDX) models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1675.

Reactive oxygen species explicit dosimetry to predict local tumor growth for Photofrin-mediated photodynamic therapy.

Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates (ϕ). A macroscopic model was adopted to calculate reactive oxygen species concentration ([ROS]rx) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma (RIF) tumors. Singlet oxygen is the primary cytotoxic species for ROS, which is responsible for cell death in type II PDT, although other type I ROS is included in the parameters used in our model. Using a combination of fluences (50-250 J∕cm2) and ϕ (75 or 150 mW∕cm2), tumor regrowth rate, k, was determined for each condition by fitting the tumor volume versus time to V0 *exp(k*t). Treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Explicit dosimetry of light fluence rate on tissue surface, tissue oxygen concentration, tissue optical properties, and Photofrin concentration were performed. Light fluence rate at 3 mm depth (ϕ 3mm) was determined for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Initial tissue oxygenation [3 O 2]0 was measured by an Oxylite oxygen probe before PDT and used to calculate [ROS]rx,calc. This value was compared to [ROS]rx,meas as calculated with the entire tissue oxygen spectrum [3 O 2](t), measured over the duration of light delivery for PDT. Cure index, CI = 1-k/kctr , for tumor growth up to 14 days after PDT was predicted by four dose metrics: light fluence, PDT dose, and [ROS]rx,calc, and [ROS]rx,meas. PDT dose was defined as the product of the time-integral of photosensitizer concentration and ϕ at a 3 mm tumor depth. These studies show that [ROS]rx,meas best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome.

Long-term outcomes of real world 'watch and wait' data for rectal cancer after neoadjuvant chemoradiotherapy.

A 'watch and wait' (W&W) strategy after neoadjuvant long-course chemoradiotherapy (NACRT) remains controversial. Whilst encouraging short-term data exist, the strategy will be judged on long-term data. We present long-term, real-world UK data from a single National Health Service trust. An analysis was performed of a prospectively maintained W&W database over 9years between 2010 and 2018. Outcome measures include incidence and time to regrowth and overall and disease-free survival. We diagnosed 563 rectal cancers in 9years. In all, 283 patients underwent rectal resection (50.3%). NACRT was used in 155 patients for margin-threatened tumours on staging MRI. Forty-nine patients (31.6%) experienced either a 'near complete' or a complete clinical response (cCR) at their 10 weeks post-NACRT assessment (MRI and endoscopy). The median age was 69years (range 44-83), and the male to female ratio was 32:17. The median follow-up was 38months (range 12-96). The median tumour distance from the anal verge was 7cm (1-15cm). Twenty-two patients had a cCR on initial assessment and 27 patients had a 'near' cCR. Of those 27 who experienced a 'near' cCR, 17 (63%) progressed to cCR on repeat assessment and 10 (37%) did not. Of these 10 patients, seven underwent standard surgical resection and three were unfit for surgery. R0 for the seven with delayed resection was 100%. Of 39 patients (22 cCR and 17 'near' cCR who progressed to cCR) (25.2% of those receiving NACRT), six patients experienced local regrowth (15.4%). The median time to local regrowth was 29months (15-60months). One of these six patients underwent salvage abdominoperineal resection, one was advised to have contact radiotherapy and four opted against surgery and also had contact radiotherapy. The overall survival was 100% at 2 years and 90% at 5 years. Disease-free survival was 90.47% at 2years and 74.8% at 5years. A W&W treatment strategy was employed safely in this patient cohort with acceptable rates of local regrowth and survival.

Evaluation of natural growth rate and recommended age for shaving procedure by volumetric analysis of craniofacial fibrous dysplasia.

We evaluated the preoperative natural growth pattern of craniofacial fibrous dysplasia and postoperative volume changes in patients undergoing shaving procedures. Thirty-three patients who underwent serial computed tomography (CT) preoperatively and/or postoperatively were identified. The natural tumor growth rate was assessed using preoperative CT scans. The postoperative tumor regrowth rates and relevant variables were analyzed. The preoperative tumor growth rates were significantly lower in patients aged ≥ 16 years than in those aged < 16 years (P < .001). The postoperative tumor regrowth rates were significantly greater when a shaving operation was performed at age < 16 years than at age ≥ 16 years (P = .04). In patients with clinical recurrence, the postoperative remnant tumor volume was inversely correlated with the tumor regrowth rate. The tumor growth rate of craniofacial fibrous dysplasia significantly decreased after age 16. This should be considered when conducting functional and aesthetic assessments in planning for the shaving of craniofacial fibrous dysplasia.

Identifying cohort differences in children undergoing partial intracapsular tonsillectomy vs traditional tonsillectomy for sleep disordered breathing

ObjectivePartial intracapsular tonsillectomy (PIT) is a well-established technique for reducing post-operative morbidity in pediatric patients with sleep disordered breathing (SDB). Although tonsillar re-growth rates are reported as low, risks of symptom recurrence or need for completion tonsillectomy are clear disadvantages when compared to traditional tonsillectomy (TT). We aim to identify cohort differences to better guide clinical decision making and identify patient-specific factors that may influence this decision. A secondary aim was to evaluate potential risk factors for tonsillar regrowth. MethodsRetrospective chart review of pediatric patients who underwent TT or PIT for SDB between 2015 and 2019 at a tertiary care academic medical center. Records were reviewed for age, gender, race, body mass index, comorbidities, diagnosis, apnea-hypopnea index, pre-operative Brodsky tonsil size, length of stay, post-operative hemorrhage, tonsillar regrowth, symptom recurrence, and need for completion tonsillectomy. Results315 patients were included: 174 underwent TT and 141 underwent PIT. Patients undergoing TT were more likely to have a sleep study showing OSA (OR 3.01, p < 0.0001), asthma (OR 4.28, p = 0.000124), and other comorbidities (OR 4.06, p = 0.0258). The overall complication rate was 4.44% (14/315). Tonsillar regrowth was exclusive to the PIT group, occurring in 7/141 patients (4.96%). Age ≤4 years was significantly associated with increased risk of tonsillar regrowth (≤4 years: 7.69%, >4 years: 0%; p = 0.049). Race and pre-operative tonsil size were not associated with regrowth. ConclusionsOur study supports the low incidence of tonsillar regrowth in PIT and suggests an association with younger age. Moreover, we found that patients undergoing TT are more likely to be older, have OSA, asthma, and other comorbidities.

Wound occlusion and annual stem growth rates of five woodland tree species in South Africa

Sustainable management strategies for trees are informed by research on growth rates and regeneration. In a 1998 study of bark thickness and tree size, six species (all used for traditional medicine) were sampled by removing 5 cm-diameter bark disks at four height intervals on 210 stems at 15 sites in South Africa. An impromptu revisit to one site in 2003 revealed that wounds for one species exhibited very little wound occlusion. These observations prompted a 2004 study on wound occlusion and stem growth for five of the species at six sites (Albizia adianthifolia, Balanites maughamii, Elaeodendron transvaalense, Searsia chirindensis, Warburgia salutaris), where 84 stems were re-measured. There were species-specific stem growth and wound occlusion rates. In general, annual lateral stem growth at 1.3 m was inversely related to stem size (corroborated by lateral widening responses of the original wound edges). There was also a tendency for smaller and/or faster growing stems to exhibit more wound occlusion and faster rates of bark regrowth – except in W. salutaris, where smaller individuals exhibited comparatively lower rates of occlusion compared to bigger individuals. All wound occlusion was by bark edge growth (typically <3 mm y−1); only A. adianthifolia showed complete wound closure, whereas B. maughamii showed the least (17%±19%). An inverse relationship existed between density (timber and bark) and stem growth, wound occlusion and lateral widening of the old scar edges – except for S. chirindensis. Hence trees with softer wood and bark generally grew quicker and exhibited more wound occlusion than trees with harder wood and bark.

A comparison of the efficacy and tolerability of three corticosteroid treatment regimens in patients with alopecia areata

Background Topical corticosteroids (TC) and/or intralesional corticosteroids (IC) are considered first-line treatments for patch-type alopecia areata (AA). However, the efficacies of TC monotherapy, IC monotherapy, and combined topical and intralesional corticosteroids (CC) in patients with AA have never been compared. Objective To evaluate and compare the efficacy and tolerability of 3 corticosteroid treatments (TC, IC, and CC) in patients with AA. Methods A study of patients with AA who received TC, IC, or CC was conducted. Outcomes including initial hair regrowth (25% regrowth), significant hair regrowth (>80% regrowth), and adverse events were statistically compared. Cox proportional hazards regression analysis was used to identify factors that influence the treatment response. Results One hundred and forty-eight patients were eligible for analysis. The response rates of initial and significant hair regrowth were comparable among 3 treatment groups. Multivariate analysis revealed that an AA treatment duration of longer than 6 months was associated with a lower probability of significant hair regrowth. A small proportion of patients experienced adverse effects. Conclusion The 3 corticosteroid treatment regimens are effective, safe, and show no significant differences in treatment outcomes. However, an AA duration longer than 6 months portends a lack of significant hair regrowth.

Effects of ciprofloxacin concentrations on the resistance of uropathogen Escherichia coli: in vitro kinetics and dynamics simulation model

Ciprofloxacin is recommended for complicated urinary tract infection (UTIs) caused by multidrug-resistant pathogens included Escherichia coli. However, its optimum dose for UTIs remains uncertain that may cause the bacterial resistance. This study was conducted to evaluate the effects of ciprofloxacin concentrations on the resistance of E. coli. The in vitro pharmacokinetic/pharmacodynamic (PK/PD) models of ciprofloxacin 750 mg oral dose twice a day for one daywas compared to that dose of 500 mg twice a day for three days.Pharmacokinetic parameters i.e.AUC0-24 and Cmax. and pharmacodynamic parameter i.e. MIC of ciprofloxacin against E. coli which previously had MIC of 0.5 µg/mL were determined. The PK/PD parameters combination of ciprofloxacin included AUC0-24/MIC, Cmax/MIC, and T>MIC ratio were used to evaluate its antimicrobial activities which was measured based on kill and re-growth rates of bacterial colony after the ciprofloxacin administration. The result showed that MIC value against E. coli increase to 8-16 and 32-64 µg/mL after ciprofloxacin 750 and 500 mg administration, respectively, indicating the emergence of resistance. Both doses of ciprofloxacin were able to reduce the number of bacterial colony in the first two hours administration. However, after two hours administration, those both doses could make re-growth of bacterial colony. The value of AUC0-24/MIC (120.42±1.27 vs.92.62±9.36), Cmax/MIC (4.75±0.21 vs. 3.26±0.30), and (T>MIC 89.58±7.22 vs. 76.39±9.39) after ciprofloxacin administration at dose of 750 mg were higher than those at dose of 500 mg. The increase of AUC0-24/MIC and Cmax/MIC values could reduce the number of bacteria colony, however could not for T>MIC value. In conclusion, the AUC0-24/MIC and Cmax/MIC parameters of ciprofloxacincan be used to evaluate its activity. In addition, ciprofloxacin twice per day at dose 500 mg for three days and 750 mg for one day are not different in the inhibition of E. coli resistance emergence.

A mixture theory-based finite element formulation for the study of biodegradation of poroelastic scaffolds

Surgical implants, known as Tissue Engineered Nerve Guides (TENGs) are often inserted to provide alignment and mechanical support to broken or damaged nerves. These implants are designed to be poroelastic and biodegradable, and the ideal rate of degradation would be that equal to the rate of regrowth of the recovering nerve. Inspired by the design of these TENGs, we develop a mixture theory based mathematical model to simulate the degradation of a poroelastic solid immersed in a fluid bath. The temporal evolution of the solid’s mechanical and transport properties is also modeled. The model comprises of the degrading solid, the degradation reaction products, and the fluid in which the solid is immersed. The resultant governing equations are formulated in an Arbitrary Lagrangian–Eulerian (ALE) framework. The weak formulation of the partial differential equations (PDEs) so derived is numerically implemented using a finite element method (FEM). The numerical model is studied for stability and convergence rates using the Method of Manufactured Solutions.

Pediatric vestibular schwannomas: case series and a systematic review with meta-analysis.

Sporadic unilateral vestibular schwannomas are rare in the pediatric population. Little has been reported in the literature on the presentation, tumor size, response to surgical treatment, and recurrence rates in these younger patients. The authors' goal was to describe their institutional experience with pediatric sporadic vestibular schwannomas and to conduct a meta-analysis of the existing literature to provide further insight into the presentation, tumor characteristics, and surgical outcomes for these rare tumors to help direct future treatment strategies. The authors performed a retrospective review of all patients 21 years of age or younger with unilateral vestibular schwannomas and without neurofibromatosis type 2 who underwent resection by the senior authors between 1997 and 2019. A systematic review of the literature and meta-analysis was also performed by entering the search terms "pediatric" and "vestibular schwannoma" or "acoustic neuroma," as well as "sporadic" into PubMed. Presentation, treatment, clinical outcomes, and follow-up were analyzed. Fifteen patients were identified at the authors' institution, ranging in age from 12 to 21 years (mean 16.5 years). Common presenting symptoms included hearing loss (87%), headache (40%), vertigo (33%), ataxia (33%), and tinnitus (33%). At the time of surgery, the mean tumor size was 3.4 cm, with four 1-cm tumors. Four patients had residual tumor following their first surgery, 3 (75%) of whom had significant radiographic regrowth that required further treatment. The literature review identified an additional 81 patients from 26 studies with patient-specific clinical data available for analysis. This resulted in a total of 96 reported patients with an overall average age at diagnosis of 12.1 years (range 6-21 years) and an average tumor size of 4.1 cm. Pediatric vestibular schwannomas present similarly to those in adults, although symptoms of mass effect are more common, as these tumors tend to be larger at diagnosis. Some children are found to have small tumors and can be successfully treated surgically. Residual tumors in pediatric patients were found to have a higher rate of regrowth than those in their adult counterparts.

Watch-and-wait policy versus robotic resection in locally advanced rectal cancer patients after clinical complete response following chemoradiotherapy: A cost-effectiveness study (RECCOSTE).

e19374 Background: Chemoradiotheray (CR) followed by standard Surgical Resection (SR) is the standard treatment for distal locally-advanced rectal cancer (LARC) patients after a clinical compete response (cCR). Some novel approach suggested better functional results using robotic rectal resection (RRR) or avoiding surgical procedure, called Watch and Wait (WW) strategy. Methods: A Markov model-based, cost-utility analysis estimating mean costs and QALYs per patient was performed to compare SR, RRR and WW strategies for patients achieving a cCR to CRT. Rates of local regrowth, recurrence and distant metastasis were derived from series comparing WW to SR and from our previous comparative study of RRR versus SR. Lifetime incremental cost-utility ratio was calculated between strategies, and sensitivity analysis were performed to study model uncertainly. A willingness-to-pay of 30.000 per Quality Adjusted-Life Year (QALY) was used as a threshold to determine the most cost-effective treatment. Results: The base case 15-years cancer-specific survival was 93.5% (95% confidence interval [CI] 91.5-94.9] on a WW program, compared to 95.9% [95%CI 93.6-97.7] after RRR. WW was dominant relative to RRR with cost savings of $48,566.58 (95%CI $47,635.77 - $49,497.39 ) and incremental QALY of 7.47 (95%CI 1.46 – 7.48). WW was also dominant relative to LRR, with cost savings of $48,764.49 (95%CI $47,768.49 - $49,760.48 ) and incremental QALY of 7.44 (95%CI 7,43 – 7.45). WW remained dominant in sensitivity analysis unless the rate of SR fell to 73.0%). Conclusions: This study provides data of cost-effectiveness differences between SR, RRR, WW approaches in LARC after cCR, showing a benefit for WW.

Effects of several establishment modes of Miscanthus × giganteus and Miscanthus sinensis on yields and yield trends

AbstractMiscanthus is a C4 perennial grass originating from East Asia, the yields of which progressively increase in the first years of growth. Several species for bioenergy have been studied since the mid‐1980s in Europe, in particular (Miscanthus × giganteus [M. × giganteus]), due to its high yields. M. × giganteus is mainly cultivated in France and established from rhizomes. Our study aimed to assess, in field conditions, alternative establishment methods combined with an alternative species, Miscanthus sinensis (M. sinensis). We set up a multi‐environment experimental network. On each trial, we tested two treatments with M. × giganteus, established from rhizomes (G_r‐sd) and from plantlets obtained from rhizomes (G_p‐sd), and two treatments with M. sinensis seedlings transplanted in single (S_p‐sd) and double density (S_p‐dd). ANOVA was performed to compare establishment and regrowth rates across treatments, as well as yields across treatments and site‐years. A logistic model was used to describe yield trends and to compare the maximum yield reached and the rate of yield increase of both species. Results showed that miscanthus establishment from plantlets resulted in higher establishment (between 87% and 92%) and regrowth (between 91% and 94%) rates compared to establishment from rhizomes. Treatments with M. × giganteus obtained higher average yields across site‐years than those with M. sinensis, but more variable yields across site‐years. We showed a strong species effect on yields, yield components (shoot weight, shoot density and shoot number per plant) and light interception (through leaf area index). Lastly, to use M. sinensis established from transplanted plantlets as an alternative to M. × giganteus, research would be required on the breeding of M. sinensis sterile seeds to avoid risks of invasiveness.

MON-326 Non Functioning Pituitary Adenomas (NFPA): Sex Related Differences in Presentation, Clinical Features and Outcomes

INTRODUCTION: NFPA are characterized as tumors without a typical hormonal hypersecretion syndrome. They are frequently diagnosed in the sixth decade, by visual field defects, hypopituitarism or incidentally. PATIENTS AND METHODS: retrospective and observational study that included 103 patients with NFPA (60 females) who were seen between 1999 and 2019 in our hospital. We compared and analyzed patients characteristics by sex: reason for consultation, hormonal status at diagnosis, invasiveness of the tumor through MRI, treatments and outcomeRESULTS: out of 103 patients, 58,2% were women (W). Men (M) were significantly older than women (56 vs. 45 yold. p=0,002). The presence of a macroadenoma was similar in both sexes (93%W vs. 94,7% M), however tumor invasiveness was more frequent in men (50% vs. 24,6%). Most men consulted for incidental finding (47,4% vs. 29,8%); most women consulted for symptoms related to the tumor(70% vs 52%): hypogonadism 31,6% W, 13% M; galactorrhea 17% W; visual field defects 21,7% W, 23,7%M, pituitary apoplexy 11,6% M. At baseline hormonal assessment hyperprolactinemia was more frequent (50,9% vs 42%) and higher in women (mean PRL levels 75 ng/ml vs. 37 ng/ml). Hypogonadism was more frequent in men (54% vs 42%) as well as hypopituitarism (15% vs. 10,5%). Surgery was the most used therapy in both sexes (69% M vs. 73%W) but males required more frequently second surgery and radiotherapy than females (15% vs. 5% and 10% vs. 5% respectively). Gonadotropin secreting adenoma was diagnosed in 62% of men and 37,5% by tumor immunohistochemistry, in the 45% of women who presented negative immunostaining the presence of a gonadotrophic lineage is not ruled out, median Ki-67 labeling was low in both sexes (2%). After surgery 66% of men and 37% of women showed tumor remnant > 1cm (p=0,001), tumor regrowth was seen in 38,4% men and 10,4% women (p=0,03). Hypogonadism was greater in men than in women (56% vs 39%). Ninety two percent of men and 60,9% of women developed some degree of pituitary deficiency after surgery (P<0,001). Men showed a higher degree of complete hypopituitarism compared to women (pretreatment 15% vs 10,5%, post treatment 32% vs 13%). CONCLUSION: NFPA in men are usually diagnosed incidentally at an older age, are more invasive at presentation with a higher incidence of pituitary dysfunction. Moreover, they presented with greater rate of tumor regrowth and hypopituitarism after surgery. NFPA in women are diagnosed earlier due to endocrine symptoms, had lower degree of invasiveness with better outcomes after treatment. Sex related differences in NFPA may be associated with the delay in diagnosis, although a more aggressive biology cannot be discarded.

Tonsillectomy versus tonsillotomy for obstructive sleep-disordered breathing in children.

Tonsillectomy versus tonsillotomy for obstructive sleep-disordered breathing in children.