bluuebunny/crossref_metadata_2025 huggingface dataset:
OTHR-10. Diverse survival outcomes of HER2+ Breast Cancer Brain Metastases (BrCBM) presenting with isolated brain relapse compared to those with concurrent extracranial disease
Authors: Noteware Laura , Ramirez Luis , Alder Laura , Dalal Nicole , Herndon James E , Floyd Scott R , Van Swearingen Amanda E D , Anders Carey K , Sammons Sarah L
Published: August 2021

Background

In patients with isolated HER2+ BrCBM and no extracranial disease (ECD), there are no consensus guidelines on optimal treatment approaches following CNS-directed therapy. Our goal was to determine the implications of ECD at time of first HER2+ BrCBM on intracranial progression-free survival (PFS1) and overall survival (OS).

Methods

Retrospective analysis was performed on 77 patients with HER2+ BrCBM who received 1st CNS radiation from 2006–2020. Demographics, dates of metastatic and intracranial diagnosis, ECD status at 1st BrCBM, and outcomes were collected. The primary endpoint was PFS1 defined as time from first CNS radiation to the subsequent documentation of intracranial progression (RANO-BM). OS was defined as time from 1st CNS radiation and 1st metastatic disease to date of death/last known alive. ECD status was defined by RECIST1.1 from staging scans within 30 days of 1st BrCBM.

Results

In this patient cohort, 25% (19/77) had isolated brain relapse/no ECD. Median age was 50 years. Most patients (58%) developed first BrCBM during adjuvant or early-line metastatic therapy. All patients with no ECD presented with isolated brain relapse as first metastatic presentation. Patients with concurrent ECD presented with first BrCBM at a median of 16.6m (95% CI: 10.5 to 25.3) after initial metastatic presentation. Median OS from initial metastatic presentation to death was worse for patients with isolated brain relapse (25.3m, 95% CI: 16.8 to 35.3) compared to those with concurrent ECD (49.7m, 95% CI: 43.2 to 62; p=0.01). Median OS from first CNS involvement to death was not statistically different amongst groups.

Conclusions

Patients with isolated HER2+ BrCBM as their initial metastatic event have substantially worse OS compared to patients with concurrent ECD developing CNS metastases later in their disease course. This population with isolated brain relapse deserves investigation of novel treatment algorithms, including earlier introduction of brain-penetrable HER2-targeted agents.
RADI-04. Stereotactic radiosurgery in alveolar soft part sarcoma brain metastasis
Authors: Lim Jia Xu , Karlsson Bengt , Pang Angela , Balamurugan Vellayappan , Nga Vincent
Published: August 2021

Background

Alveolar soft part sarcoma (ASPS), although rare, has the highest incidence of brain metastasis amongst all sarcomas. Stereotactic radiosurgery (SRS) has been shown to be a well tolerated and effective treatment of intracranial sarcomatous metastasis. However, there is a paucity of published literature that guides radiation therapy in this condition.

Methods

This is a single centre retrospective review of all ASPS patients with intraparenchymal brain metastasis in our centre treated with stereotactic radiosurgery (SRS). SRS dosing is dichotomised into high and low dose (≥25 Gy and <25 Gy respectively) and outcomes such as local recurrence (LR) and radiation effects are noted. Successful treatment was defined as a lesion that regressed, is stable, or has less than 25% increase in tumour volume. Local recurrence (LR) was defined as increase in tumour volume by more than 25% during follow up.

Results

There were three patients with 11 ASPS metastatic brain lesions, one of which underwent retreatment. Each lesion was followed up for a mean duration of 12 months (range: 5 – 22 months). Five lesions treated with a high dose regime and six lesions were given low dose. Lesions treated with high dose SRS experienced significantly less LR (20% vs 83.3%, OR 20.0 [95%CI 0.93 – 430), p = 0.036) with no increase in undue symptomatic radiation effects. Retreatment of lesions with LR after initial SRS using a low dose regime was successful, albeit only in the single recurrent lesion.

Conclusions

We conclude that SRS can be used as a first line treatment for ASPS brain metastasis that are not surgically accessible and that using a high dose for treatment is effective and safe. Multicentre collaborative studies can be performed to validate this claim.
RADI-05. Metastatic Neoplasm Volume Kinetics Following Two-Staged Stereotactic Radiosurgery
Authors: Damron Ethan , Dono Antonio , Chafi Hatim , Martir Magda , Yu Tse-Kuan , Khwaja Shariq , Amsbaugh Mark , Tandon Nitin , Esquenazi Yoshua , Blanco Angel
Published: August 2021

Introduction

Multisession staged stereotactic radiosurgery (2-SSRS) represents an alternative approach for management of large brain metastases (LBMs), with potential theoretical advantages over fractionated SRS and represents an alternative to surgery in poor surgical candidates. We aimed to investigate the clinical efficacy and safety of 2-SSRS in patients with LBMs.

Methods

LBMs of patients treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic information was obtained. Volumetric measurements at first SSRS, second SSRS, and follow-up imaging studies were obtained.

Results

Twenty-six patients with 28 LBMs were included in the study. Fifteen patients (58%) were male. Median age at 2-SSRS was 61 years (range: 31–84). Median marginal doses for first and second SSRS were 15 Gy (range: 12–18 Gy) and 15 Gy (range: 12–16 Gy), respectively. Median duration between sessions was 32 days. Two patients (8%) failed to receive their second SSRS due to local progression. Median tumor volumes at first SSRS, second SSRS, 3-month follow-up, and 6-month follow-up were 8.7 cm3 (range: 1.5–34.7 cm3), 3.3 cm3 (range: 0.8–26.1 cm3), 1.7 cm3 (range: 0.2–10.1 cm3), and 1.4 cm3 (range: .04–20.7 cm3), respectively. The median absolute and relative decrement between S-SRS sessions was 3.7 cm3 (range: 2.8–16.5 cm3) and 49.5% (range: 17.1- 87.1%), respectively. Overall, 26 of the 28 lesions (93%) demonstrated early local control following the first SSRS with 18 lesions (69%) demonstrating a decrease in volume of >30% and 3 lesions (12%) remaining stable. Six lesions (23%) showed disease progression. There were no grade 3 adverse events.

Conclusions

Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with large, symptomatic brain metastases, especially in non-surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery series.
RADI-09. Clinical factors associated with death after radiotherapy for brain metastases
Authors: Natesan Divya , Carpenter David , Giles William , Oyekunle Taofik , Niedzwiecki Donna , Reitman Zachary , Kirkpatrick John , Floyd Scott
Published: August 2021

Introduction

It can be challenging to accurately identify patients with brain metastases who have very poor prognosis and are unlikely to benefit from radiation (RT). We characterized factors of patients who died within 30 days of receiving RT for brain metastases.

Methods

Patients who received whole brain RT (WBRT) or stereotactic radiosurgery (SRS) for brain metastases between 1/1/2017–9/30/2020 at a single institution were identified. Patient, tumor, treatment, and death variables were collected. Characteristics between those who did and did not die within 30 days were compared using the Wilcoxon Rank-Sum or Chi-Square test. Survival was estimated with Kaplan-Meier method.

Results

636 patients received WBRT (n=117) or SRS (n=519). Median age was 61. Median survival was 6 months (95% CI 5–7 months). 75 (12%) died within 30 days of RT. Patients who died within 30 days had worse median KPS (50 vs 80, p<0.001). A higher proportion who died within 30 days had innumerable intracranial metastases (45% vs 11%, p<0.001), leptomeningeal disease (16% vs 5%, p<0.001), and higher burden of neurologic symptoms at presentation (seizures (12% vs 4%, p=0.003); cranial neuropathies (32% vs 9%, p<0.001); motor/sensory deficits (51% vs 29%, p<0.001); altered mentation (60% vs 26%, p<0.001); headaches (48% vs 30%, p<0.001); steroid use (68% vs 48%, p<0.001)). Patients who died within 30 days had progressive extracranial disease (intrathoracic: 87% vs 50%; spinal: 57% vs 18%; liver/adrenal: 60% vs 24%), p<0.001. More patients who died within 30 days received inpatient RT (39% vs 4%, <0.001) and did not complete RT (24% vs 1%, p<0.001).

Discussion

Patients who died within 30 days of RT had worse KPS, intracranial/extracranial disease burden, and neurologic symptoms. Future analyses will assess whether these factors can inform a prognostic model to identify patients with poor prognosis who may be appropriate for supportive care alone.
RADI-15. Radiotheranostic Approach in Brain Tumor
Authors: Nemati Reza , Rekabpour Seyed Javad , Jokar Narges , Ahmadzadehfar Hojjat , Shooli Hossein , Jafari Esmail , Assadi Majid
Published: August 2021

Purpose

The aim of this study is feasibility and potential treatment of targeted radionuclide theranostic approach for patients with brain tumors.

Methods

For the period 2020–2021, 6 child and adult patients who had been diagnosed with brain tumors were treated using theranostic approach followed by refractory to conventional therapy. Two patients that were presented with HER-2 positive, ER and PR negative breast cancer and brain metastases as well as a history of several cycles of chemotherapy sessions and radiotherapy using gamma knife were treated with 177Lu-Trastuzumab (Herceptin). Three other patients with primary brain tumor underwent peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. The last case was a patient with refractory primary cerebral lymphoma to standard therapy with confirmed CD20-positive B-cell lymphoma who underwent 177Lu-Rituximab.

Results

A two women with HER-2 positive breast cancer and brain metastasis underwent two cycles of 177Lu-trastuzumab. Post-therapy assessment showed some improvement. Next, a man with a high-grade glioma tumor in the left frontal lobe with history of debunking surgery in combination with chemoradiation received 177Lu-DOTATATE that resulted in a short-term stable situation. Another patient presented with a right cerebellopontine angle meningioma underwent PRRT with 177Lu-DOTATATE. She had a stable disease with some improvement in the clinical status. Also, a girl with an astrocytoma in suprasellar cistern underwent 2 cycles of 177Lu-DOTATATE. The complete response was designed. Finally, a patient with refractory primary cerebral lymphoma received 177Lu-Rituximab.

Conclusion

Nuclear oncology in the field of neuro-oncology (neuroradiotheranostics) has been toward a personalized approach, effective and safe therapy. These preliminary studies might demonstrate feasibility and therapeutic potential of theranostics in patients with primary, relapsed or metastasis brain tumors. Further studies preferentially well-designed multicenter international clinical trial is warranted.
RADI-16. Efficacy of WBRT among the Sub-types of Metastatic Breast Cancer
Authors: Mathew Shija , Udaykrishna A S , Lokesh V
Published: August 2021

Objectives

To understand the effect of Whole Brain Radiation (WBRT) in terms of Age, Neurological performance, Radiological Improvement and the Overall Survival.

Methods

34 Patients [Median Age: 45 years (31- 65)] with Metastatic Breast Carcinoma who presented with Brain metastasis to the Department of Radiation Oncology at Kidwai Memorial Institute of Oncology and subjected to Whole Brain Radiotherapy/ Focal RT were taken into the study. The efficacy of WBRT was assessed among the four subtypes of MBC.

Results

39% of the patients belonged to Luminal A, 25%, 22% and 14% belonged to Luminal B, Her2 amplified and Basal respectively. Patients under Luminal A, presented with brain metastases by 25 months after the diagnosis of the primary. 60% presented with single lesion, amenable to resection and 58% underwent surgery followed by WBRT and OS fared better as compared to patients with WBRT alone with no distant recurrences on imaging and improvement in KPS. Patients with Luminal B/ HER2 amplified subgroup had predominantly oligometastatic lesions (65%), presented with brain metastases at 15 months after diagnosis of Carcinoma Breast,18% received Herceptin and Lapatinib and 33% and 22% received Herceptin and Lapatinib alone. OS was superior over WBRT alone with exaggerated radiation necrosis in those who took concurrent biological therapy and RT.In patients with Basal subtype,75%had multiple metastatic brain lesions, presented with symptoms by 10 months of diagnosis of the primary with poor KPS and OS remained poor despite WBRT.

Conclusions

Lesions being amenable for surgery, focal RT to post op cavity alone may be considered in patients with Luminal A. WBRT plus boost for those unfit for surgery. Addition of TKI +/- oral chemo for all patients with Luminal B and HER 2 amplified to Focal RT or WBRT. Triple Negative patients present with poor KPS can be considered for BSC/WBRT on case basis.
SURG-02. Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (SRS) as a treatment strategy for brain metastasis that recurred locally after initial radiosurgery (BMRS): a collaborative institutional experience
Authors: Pena-Pino Isabela , Ma Jun , Hori Yusuki , Fomchenko Elena , Dusenbery Kathryn , Reynolds Margaret , Wilke Christopher , Yuan Jianling , Barnett Gene , Chiang Veronica , Mohammadi Alireza , Chen Clark
Published: August 2021

Introduction

In independent clinical trials, ~30% of brain metastases recur locally after radiosurgery (BMRS). For these lesions, treatment with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy (LITT)) alone achieves a 12-month local control (LC12) of 54–85% while repeat SRS achieved LC12 of 54–79%. Here, we report favorable outcomes for BMRS treated with SLA followed by consolidation radiosurgery (SLA/cSRS).

Methods

Clinical outcome of 18 patients with 19 histologically confirmed BMRS treated with SLA followed by consolidation SRS and >3 months follow-up were collected retrospectively across three institutions. Local control was defined as stability or decrease in contrast-enhancing (CE) and FLAIR volume.

Results

SLA achieved ablation of 73–100% of the BMRS CE volumes. Consolidation hypo-fractionated radiosurgery (5 Gy x 5 or 6 Gy x 5) was carried out 16–40 days post-SLA (median of 26 days). With a median follow-up of 185 days (range: 93–1367 days) and median overall survival (OS) of 185 days (range: 99–1367 days), 100% LC12 was achieved. 13/18 (72%) patients that required steroid therapy prior to SLA/cSRS were successfully weaned off steroid by three months post-SLA/cSRS. Post-SLA, KPS declined for 3/19 (16%) patients and improved for 1/19 (5%) patients. No KPS changes occurred subsequent to consolidation SRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of SRS (severe headache that resolved with steroid therapy (n=1) and new-onset seizure (n=1)). Except for two patients who suffered histologically confirmed, local failure at 649 and 899 days, all other patients are either alive (n=5) or died from systemic disease progression (n=11). None of the treated patients developed symptomatic radiation necrosis.

Conclusions

This collaborative institutional experience support efficacy and safety of SLA followed by consolidation SRS as a treatment for BMRS. The treatment strategy warrants further investigations.
SURG-04. Surgical resection of symptomatic brain metastasis in patients with non-small cell lung cancer irrespective from lesion count
Authors: Jünger Stephanie T , Reinecke David , Meißner Anna-Katharina , Goldbrunner Roland , Grau Stefan
Published: August 2021

Background and Purpose

Current guidelines primarily suggest the resection in case of a limited number of brain metastases (BM). With an increasing number of local and systemic treatment options this approach needs reconsideration. Therefore, we aimed to evaluate the role of metastectomy in patients with non-small cell lung cancer (NSCLC) treated in a comprehensive setting disregarding lesion count.

Patients and Methods

In this monocentric retrospective analysis, patients receiving surgery for 1–3 BM with available demographic, clinical, and tumor-associated parameters were included. Prognostic factors for local control (LC) and overall survival (OS) were analyzed by Log rank test and Cox proportional hazards.

Results

Two-hundred-sixteen patients were included: 129 (59.7%) with single/solitary, 64 (29.6%) with 2–3, and 23 (10.6%) with more than three BM. Resection of the symptomatic BM(s) improved the patients’ Karnofsky performance index (KPI) significantly (p<0.001), enabling adjuvant radiotherapy in 199 (92.1%) and systemic treatment in 119 (55.1%) patients.

After a mean radiological follow-up of eight (1–79) months, LC was observed in 83 (38.4%) patients and was not significantly influenced by BM count (p=0.064). After a mean OS after surgery of 12.7 (0–88) months, 120 (55.6%) patients had died.

In univariate analysis, BM count showed no impact on OS (p=0.844), while age ≥/< 65 years (p=0.007), pre- and postoperative KPI ≥70 (p=0.002 and p=0.005, respectively), extra-cranial metastases (p=0.004), adjuvant radiation therapy (p<0.001), and adjuvant systemic treatment (p<0.001) did. In regression analysis the presence of extra-cranial metastases (HR 2.30 95%CI 1.53–3.48; p<0.001), adjuvant radiation therapy (HR 0.97 95%CI 0.23–0.86; p=0.016), and adjuvant systemic treatment (HR 0.37 95%CI 0.25–0.55; p<0.001) remained independent factors for survival.

Conclusions

The indication for resection of symptomatic BM in patients with NSCLC is justified even in case of multiple lesions to alleviate their neurological symptoms and to enable further treatment.
SURG-12. MALIGNANT BREAST NEOPLASM AND BRAIN METASTASES: SERIES OF CASES AND MAIN APPROACHES IN A HOSPITAL COMPLEX IN BRAZIL
Authors: de Lima Frederico Tavares , Medeiros Nataly Regina , Filho Luiz Domingues Vasconcelos , Leimig Bruno , Matias Walter , Silva Joacil Carlos , de Mello José Roberto Vieira
Published: August 2021

Introduction

With the advancement of clinical and surgical oncology, patients with breast cancer had an increase in survival. In this context, up to 30% of patients affected with metastases from this site will develop brain tumors. The latter is an important impacting factor for life quality and expectancy, therefore, it’s clinical and surgical management is essential in public health. We present some rare cases and their outcomes.

Methods

We describe a case series of 07 patients with breast cancer metastases to the brain, involving large portions of the dura, bone or skin. There were 64 surgical interventions of the disease in the period, but only those with more exuberant and atypical presentations were selected. The interventions were carried out in a hospital oncology complex in northeastern Brazil between 2016 and 2020.The diagnosis was based on the clinical description, laboratory and image exams, histopathology and surgical performance of the patients.

Results

The mean age of the patients was 49.7 years, with all patients being female. Rare presentations were observed, such as bone and skin meninges. Clinical presentations demonstrated advanced stages of the disease with a large tumor volume. Extra axial involvement was verified. All patients underwent neurosurgery for tumor removal and decompression. Biopsies were submitted to anatomopathological and immunohistochemistry examination. Corticotherapy was instituted in the immediate postoperative period and some cases had genetic analysis due to an important family history. There was a reduction in symptoms in most cases.

Conclusion

Although brain metastases are still a challenge for medical practice, their proper management can prolong and improve patients’ lives. Metastatic breast cancers seem to have a predilection for the central nervous system and their detection and intervention, even in an advanced clinical stage, sound as determinant for the control and severity of symptoms.

Keywords

Brain Neoplasms, Neoplasm Metastasis, Breast Neoplasms
Substance Use and Mental Health Outcomes from a Text Messaging-Based Intervention for Smoking Cessation Among Young People Experiencing Homelessness
Authors: Pedersen Eric R , Linnemayr Sebastian , Shadel William G , Zutshi Rushil , DeYoreo Maria , Cabreros Irineo , Tucker Joan S
Published: August 2021

Introduction

Cigarette smoking and associated high-risk behaviors are prevalent among youth experiencing homelessness (YEH), making appropriately tailored interventions targeting smoking behavior important for this group. We pilot tested a brief text-messaging intervention (TMI) as an adjunct to standard care for YEH who smoke and found promising preliminary effects of the intervention on smoking cessation. The purpose of the present study was to test the TMI’s effect on the secondary outcomes of other substance use (including use of other tobacco/nicotine devices) and mental health symptoms.

Methods

A total of 77 participants completed the pilot randomized controlled trial, with 40 receiving the TMI (174 automated text messages plus a group smoking counseling session and provision of nicotine patches). They completed an assessment at baseline and another three months later that evaluated use of other tobacco/nicotine devices, alcohol, marijuana, and anxiety and depression symptoms.

Results

We found that the TMI helped to reduce secondary substance use behaviors and mental health symptoms among the participants; mainly there were medium effects of the intervention on changes in other tobacco/nicotine use, drinking, and anxiety and depression symptoms. The intervention did not have an effect on number of marijuana use days in the past month; however, past 30-day marijuana users who received the intervention benefited by reducing the number of times they used marijuana per day.

Conclusions

In addition to helping reduce cigarette smoking, we found that a TMI for YEH was helpful in improving secondary outcomes, suggesting the promise of the TMI on benefiting YEH even beyond targeted smoking behavior.

Implications

This pilot study demonstrates that by targeting cigarette smoking using a text message-based intervention among youth experiencing homelessness, effects may be seen in other areas of functioning such as other substance use and mental health.

Trial registration

ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585.
A Novel Lateral Organ Boundary-domain Factor CmLBD2 Positively Regulates Pollen Development by Activating CmACOS5 in Chrysanthemum morifolium
Authors: Teng Renda , Wu Ze , Xu Sujuan , Hou Huizhong , Zhang Dehua , Chen Fadi , Teng Nianjun
Published: August 2021

Male sterility, as a common reproductive characteristic in plants, plays an important role in breeding, in which pollen abortion is a key factor leading to male sterility. Here, based on a low expression level gene CmACOS5 in transcriptome of pollen abortive chrysanthemum, a new transcription factor CmLBD2 of the Lateral Organ Boundaries Domain family, which could bind the promoter of CmACOS5 by yeast one-hybrid library was screened. This study revealed the origin and expression pattern of CmLBD2 in chrysanthemum and verified the functions of two genes in pollen development by transgenic means. Inhibiting the expression of CmACOS5 or CmLBD2 can lead to a large reduction in pollen and even abortion in chrysanthemum. Using yeast one-/two-hybrid, electrophoretic mobility shift assays, and luciferase reporter assays, it was verified that CmLBD2 directly binds to the promoter of CmACOS5. These results suggest that LBD2 is a novel, key transcription factor regulating pollen development. This result will provide a new research background for enriching the function of LBD family proteins and also lay a new foundation for the breeding of male sterile lines and the mechanism of pollen development.
Phytoplankton growth at low temperatures: results from low temperature incubations
Authors: Wang Xiaodong , Smith Walker O
Published: August 2021

The response of phytoplankton to different temperatures has been studied for decades, and although the general relationship of growth to temperature is known to be exponential, the responses at very low temperatures (from −2 to +2°C) are poorly constrained. To address this uncertainty, we conducted a series of growth experiments with eight species of polar phytoplankton; each was grown in batch culture at temperatures ranging from −1.5 to 4°C, and growth rates determined from changes in cell abundance and chlorophyll. We found that different species responded differently to temperature, although the general response was an increase in growth rate at higher temperatures. The mean response from all taxa was less (ca. 35% less) than predicted from the classic [Eppley, R. W. (1972) Temperature and phytoplankton growth in the sea. Fish. Bull., 7, 1063–1085.] formulation. Maximum growth rates also were most reliable when determined from changes in cell abundance. If the variability in maximum growth rates among taxa is reflective of in situ responses to polar temperature increases, it will be challenging to predict the assemblage response to elevated in situ temperatures in future years.
Mechanosensitive ion channels contribute to mechanically evoked rapid leaflet movement in Mimosa pudica
Authors: Tran Daniel , Petitjean Hugues , Chebli Youssef , Geitmann Anja , Sharif-Naeini Reza
Published: August 2021

Mechanoperception, the ability to perceive and respond to mechanical stimuli, is a common and fundamental property of all forms of life. Vascular plants such as Mimosa pudica use this function to protect themselves against herbivory. The mechanical stimulus caused by a landing insect triggers a rapid closing of the leaflets that drives the potential pest away. While this thigmonastic movement is caused by ion fluxes accompanied by a rapid change of volume in the pulvini, the mechanism responsible for the detection of the mechanical stimulus remains poorly understood. Here, we examined the role of mechanosensitive ion channels in the first step of this evolutionarily conserved defense mechanism: the mechanically evoked closing of the leaflet. Our results demonstrate that the key site of mechanosensation in the Mimosa leaflets is the pulvinule, which expresses a stretch-activated chloride-permeable mechanosensitive ion channel. Blocking these channels partially prevents the closure of the leaflets following mechanical stimulation. These results demonstrate a direct relation between the activity of mechanosensitive ion channels and a central defense mechanism of M. pudica.
NIN-like protein7 and PROTEOLYSIS6 functional interaction enhances tolerance to sucrose, ABA, and submergence
Authors: Castillo Mari-Cruz , Costa-Broseta Álvaro , Gayubas Beatriz , León José
Published: August 2021

Nitrate (NO3) assimilation and signaling regulate plant growth through the relevant function of the transcription factor NIN-like Protein7 (NLP7). NO3 is also the main source for plants to produce nitric oxide (NO), which regulates growth and stress responses. NO-mediated regulation requires efficient sensing via the PROTEOLYSIS6 (PRT6)-mediated proteasome-triggered degradation of group VII of ethylene response transcription factors through the Cys/Arg N-degron pathway. The convergence of NO3 signaling and N-degron proteolysis on NO-mediated regulation remains largely unknown. Here, we investigated the functional interaction between NLP7 and PRT6 using Arabidopsis (Arabidopsis thaliana) double prt6 nlp7 mutant plants as well as complementation lines overexpressing NLP7 in different mutant genetic backgrounds. prt6 nlp7 mutant plants displayed several potentiated prt6 characteristic phenotypes, including slower vegetative growth, increased NO content, and diminished tolerance to abiotic stresses such as high-sucrose concentration, abscisic acid, and hypoxia–reoxygenation. Although NLP7 has an N-terminus that could be targeted by the N-degron proteolytic pathway, it was not a PRT6 substrate. The potential PRT6- and NO-regulated nucleocytoplasmic translocation of NLP7, which is likely modulated by posttranslational modifications, is proposed to act as a regulatory loop to control NO homeostasis and action.
The response to TNF blockers depending on their comparator in rheumatoid arthritis clinical trials: the lessebo effect, a meta-analysis
Authors: Lopez Lea , Griffier Romain , Barnetche Thomas , Lhomme Edouard , Kostine Marie , Truchetet Marie-Elise , Schaeverbeke Thierry , Richez Christophe
Published: August 2021

Objective

To compare the effect of the biological reference agents (infliximab, etanercept, adalimumab) in RA in pivotal superiority placebo-controlled trials (reference agent vs placebo) vs their effect in equivalence active comparator-controlled trials (reference agent vs biosimilar).

Methods

The PubMed, EMBASE and Cochrane databases were searched for randomized, double-blind, controlled trials up to March 2020 comparing a biological reference agent vs placebo or biosimilar. The study assessed the ACR 20/50/70 responses of the reference agent in these groups (Reference-pbo and Reference-bs, respectively). The effect of the reference agent in both groups was estimated with 95% CI, pooled using random-effects models and then compared using a meta-regression model.

Results

We included 31 trials. The main characteristics of the population (disease duration and activity, % seropositivity and methotrexate dose) of the population in both groups were similar. The meta-analysis found a better ACR20 response to the biological originator in the Reference-bs group with a global rate of 70% (95% CI, 66, 74) compared with 59% (95% CI, 55, 62) in the reference-pbo group (P =0.001). A significant difference was also found for ACR 50 [44% (95% CI, 39, 50) vs 35% (95% CI, 31, 39), respectively, P <0.01].

Conclusion

The effect of the reference biologic agent was better when compared with an active drug to a placebo. This could be linked to an increased placebo effect in active comparator-controlled studies or a nocebo effect in placebo-controlled studies. This effect can be called the lessebo effect.
CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis
Authors: Rempenault Claire , Mielle Julie , Schreiber Kristina , Corbeau Pierre , Macia Laurence , Combe Bernard , Morel Jacques , Daien Claire Immediato , Audo Rachel
Published: August 2021

Objectives

Chemokines (CKs) are key players of immune-cell homing and differentiation. CK receptors (CKRs) can be used to define T-cell functional subsets. We aimed to characterize the CKR profile of the regulatory B-cell subset B10+ cells and investigate the CKs involved in their migration and differentiation in healthy donors and patients with RA.

Methods

RNA sequencing and cytometry were used to compare CKR expression between B10+ and B10neg cells. Migration of B10+ and B10neg cells and IL-10 secretion of B cells in response to recombinant CKs or synovial fluid (SF) were assessed.

Results

CXCR5 was expressed at a higher level on the B10+ cell surface as compared with other B cells (referred to as B10neg cells). In line with this, its ligand CXCL13 preferentially attracted B10+ cells over B10neg cells. Interestingly, synovial fluid from RA patients contained high levels of CXCL13 and induced strong and preferential migration of B10+ cells. Besides its role in attracting B10+ cells, CXCL13 also promoted IL-10 secretion by B cells. In RA patients, the level of CXCR5 on B-cell surface was reduced. The preferential migration of RA B10+ cells toward CXCL13-rich SF was lost and CXCL13 stimulation triggered less IL-10 secretion than in healthy donors.

Conclusion

Our results identify that the CXCR5/CXCL13 axis is essential for B10+ cell biology but is defective in RA. Restoring the preferential migration of B10+ within the affected joints to better control inflammation may be part of the therapeutic approach for RA.
Effect of cleaning corn on mycotoxin concentration and nursery pig growth performance
Authors: Yoder Ashton D , Stark Charles R , DeRouchey Joel M , Tokach Michael D , Paulk Chad B , Gebhardt Jordan , Woodworth Jason C , Jones Cassandra K , Zumbaugh Charles A
Published: August 2021

Mycotoxins are naturally produced hazards that result from molds grown on cereal grains and other commodities. These molds may produce carcinogenic mycotoxins, which can be harmful to humans and animals. Removing broken kernels has been demonstrated to reduce mycotoxin concentration, but with high variability. Therefore, two experiments were conducted to quantify the magnitude of natural mycotoxin concentration that may be reduced by cleaning corn. Two loads of corn that were naturally contaminated with mycotoxins were procured. Corn for Experiment 1 was contaminated with aflatoxin (1,074 parts per billion; ppb), fumonisin (8.3 parts per million; ppm), and ochratoxin A (206 ppb), while corn for Experiment 2 was contaminated with only fumonisin (5.5 ppm). Corn was cleaned by mechanical sieving. For each experiment, corn was divided into twenty 150 kg runs. Runs were randomly assigned to 1 of 4 experimental treatments: 1) no screen 2) 12.7 mm screen, 3) 4.8 mm screen, and 4) 12.7 + 4.8-mm screen. The corn cleaner was sanitized between runs. Three 5 kg corn samples were collected from each run, and analyzed for mycotoxin concentration. In Experiment 1, cleaning reduced (P < 0.05) aflatoxin and fumonisin concentration by an average of 26% and 45%, respectively, compared to the original uncleaned corn level, but did not impact (P > 0.10) ochratoxin A. The resultant screenings had nearly four times the aflatoxin (4,224 ppb) and 7.5 times the fumonisin concentration (60.4 ppm) as the uncleaned corn. In Experiment 2, cleaning reduced (P < 0.05) fumonisin concentration by 32%. The resultant screenings had 19.6 times the fumonisin concentration (65.4 ppm) as the uncleaned corn. To determine the effect that cleaning corn may have on nursery pig growth performance, 360 nursery pigs were used in Experiment 3 to evaluate the impact of cleaning or pelleting on growth performance. Treatments were arranged in a 2 × 3 factorial with corn type (uncleaned vs. cleaned) and feed form (mash vs. pelleted from either mill A or B). Neither cleaning corn nor pellet mill type affected (P > 0.19) nursery pig growth performance. Pelleting improved (P < 0.0001) gain to feed ratio (G:F) by 7.6% compared to mash diets. These data suggest that cleaning is an effective method to legally reduce aflatoxin and fumonisin concentration, but does not impact animal growth performance. Screenings should be used cautiously when feeding to animals.
Acetylation of Abelson interactor 1 at K416 regulates actin cytoskeleton and smooth muscle contraction
Authors: Wang Yinna , Liao Guoning , Wang Ruping , Tang Dale D.
Published: August 2021

Actin cytoskeletal reorganization plays an important role in regulating smooth muscle contraction, which is essential for the modulation of various physiological functions including airway tone. The adapter protein Abi1 (Abelson interactor 1) participates in the control of smooth muscle contraction. The mechanisms by which Abi1 coordinates smooth muscle function are not fully understood. Here, we found that contractile stimulation elicited Abi1 acetylation in human airway smooth muscle (HASM) cells. Mutagenesis analysis identified lysine‐416 (K416) as a major acetylation site. Replacement of K416 with Q (glutamine) enhanced the interaction of Abi1 with neuronal Wiskott‐Aldrich syndrome protein (N‐WASP), an important actin‐regulatory protein. Moreover, the expression of K416Q Abi1 promoted actin polymerization and smooth muscle contraction without affecting myosin light chain phosphorylation at Ser‐19 and vimentin phosphorylation at Ser‐56. Furthermore, p300 is a lysine acetyltransferase that catalyzes acetylation of histone and non‐histone proteins in various cell types. Here, we discovered that a portion of p300 was localized in the cytoplasm of HASM cells. Knockdown of p300 reduced the agonist‐induced Abi1 acetylation in HASM cells and in mouse airway smooth muscle tissues. Smooth muscle conditional knockout of p300 inhibited actin polymerization and the contraction of airway smooth muscle tissues without affecting myosin light chain phosphorylation and vimentin phosphorylation. Together, our results suggest that contractile stimulation induces Abi1 acetylation via p300 in smooth muscle. Acetylation at K416 promotes the coupling of Abi1 with N‐WASP, which facilitates actin polymerization and smooth muscle contraction. This is a novel acetylation‐dependent regulation of the actin cytoskeleton in smooth muscle.
Early Fusion Status After Posterior Lumbar Interbody Fusion With Cortical Bone Trajectory Screw Fixation or Traditional Trajectory Screw Fixation
Authors: Sakaura Hironobu , Ikegami Daisuke , Fujimori Takahito , Sugiura Tsuyoshi , Mukai Yoshihiro
Published: August 2021

Study Design:

A retrospective analysis of prospectively collected data.

Objective:

The aim was to examine whether posterior lumbar interbody fusion with cortical bone trajectory screw fixation (CBT-PLIF) is inferior to PLIF using traditional trajectory screw fixation (TT-PLIF) regarding early fusion status and whether the titanium-coated polyetheretherketone (PEEK) cage (TP cage) improves early fusion status compared with the same shape pure PEEK cage (P cage).

Summary of Background Data:

We recently reported that the fusion rate was relatively lower after CBT-PLIF than after TT-PLIF, although no significant difference was found and that compared with the carbon PEEK cage, the TP cage significantly reduced the incidence of vertebral endplate cysts (cyst signs) and slightly improved the early fusion rate at 1 year after CBT-PLIF.

Materials and Methods:

The subjects were 37 patients undergoing TT-PLIF using P cages (TT-P group), 24 patients undergoing CBT-PLIF using P cages (CBT-P group), 32 patients undergoing TT-PLIF using TP cages (TT-TP group), and 20 patients undergoing CBT-PLIF using TP cages (CBT-TP group). On multiplanar reconstruction computed tomography at 6 months after surgery, cyst signs were evaluated and classified into diffuse or local cysts. Early fusion status was assessed using both dynamic plain radiographs and multiplanar reconstruction computed tomography at 1-year postoperatively.

Results:

The incidence of the diffuse cyst was 27.0% in the TT-P group, 29.2% in the CBT-P group, 25.0% in the TT-TP group and 25.0% in the CBT-TP group (P>0.05). The early fusion rate was 75.7% in the TT-P group, 75.0% in the CBT-P group, 71.9% in the TT-TP group and 75.0% in the CBT-TP group (P>0.05).

Conclusions:

These results indicate that CBT-PLIF resulted in the equivalent early fusion status to TT-PLIF and that compared with the same shape P cage, the TP cage did not improve early fusion status after both TT-PLIF and CBT-PLIF.
Long Segment Anterior Cervical Discectomy and Fusion, Including C2
Authors: Spurgas Morgan P. , Entezami Pouya , Thomas James , DiRisio Darryl J.
Published: August 2021

Study Design:

A retrospective study of thirteen patients undergoing 5-level anterior spinal surgery for cervical myelopathy.

Objective:

While limited literature exists in reviewing the treatment of high cervical pathology extending caudally, we believe long segment surgery beginning at C2-3 can be accomplished with good success and is an option more patients may benefit from. We aim to describe the technique in accessing the C2-C3 disk space and efficacy of treating multilevel disease beginning at the C2 vertebral body. This includes an extensive technical report and surgical pearls.

Summary of Background Data:

Compression at the level of C2 can be daunting to access because of steep approach required. Few studies have described the technique in reaching the C2 level, with less information describing the efficacy of a 5-level anterior fusion starting at C2.

Methods:

Patients who underwent surgery between 2000 and 2016 were identified utilizing the department billing database and ICD codes. Patients age, operative indications, levels treated, length of hospital stay, fusion outcome, and operative complications were explored. Independent analysis of fusion was performed.

Results:

The average length of hospital stay was 3.9 days. Eight patients reported significant improvement of hand weakness, numbness, and/or gait at 6 months follow-up. The most frequent complication was dysphagia (23%). One patient experienced recurrent symptoms secondary to nonunion, and another patient suffered a postoperative neurological worsening because of anterior spinal artery syndrome.

Conclusion:

This retrospective review discusses the technique to visualize and fully decompress C2-C3 spinal segments. In addition, we explored the efficacy and perioperative risk in long segment anterior cervical discectomy and fusion.
Prognostic Significance of Disease Control at 12 Weeks in Patients With Advanced Pancreatic Cancer Receiving FOLFIRINOX as First-line Chemotherapy
Authors: Batra Atul , Tang Patricia A. , Cheung Winson Y.
Published: August 2021

Objectives:

The POLO (Pancreas Cancer Olaparib Ongoing) trial demonstrated improvement in progression-free survival (PFS) with olaparib maintenance in advanced pancreatic cancer (APC) patients with germline BRCA1/2 mutations who had disease control after 16 weeks of platinum-based first-line therapy. However, in the real-world, the first assessment is usually performed at 12 weeks. Therefore, this study aimed to identify the proportion of real-world patients with APC that have disease control at 12 weeks (DC12) after FOLFIRINOX, assess any associations of baseline variables with DC12, and to determine the effect of DC12 on PFS and overall survival (OS).

Methods:

APC patients treated with first-line FOLFIRINOX from 2011 to 2018 in Alberta, Canada, were identified. We conducted an analysis of baseline characteristics to identify factors associated with DC12 and to compare the PFS and OS of patients with DC12 to those with earlier disease progression.

Results:

We identified 165 APC patients treated with FOLFIRINOX with unknown BRCA1/2 status, of which 56% were men, and the median age at diagnosis was 59 years (interquartile range, 38 to 75 y). Of these, 72 (44%) had DC12. Lower serum carbohydrate antigen 19.9 and normal serum albumin were associated with a higher likelihood of DC12. The PFS and OS of patients with DC12 was significantly higher than those with earlier progression (9.3 vs. 2.5 mo; hazard ratio, 0.22; 95% confidence interval, 0.15-0.32; P<0.001; 21.6 vs. 8.9 mo; hazard ratio, 0.35; 95% confidence interval, 0.25-0.49; P<0.0001).

Conclusion:

Less than half of real-world patients treated with first-line FOLFIRINOX have DC12. Patients with APC who have higher carbohydrate antigen 19.9 and low albumin are less likely to have DC12. DC12 is significantly associated with longer PFS and OS.
Is Prone Positioning Effective in Improving Hypoxemia for Nonventilated Patients With Covid-19? A Rapid Evidence Assessment
Authors: Holmes Klair , Kazmierczak Kathryn , Irwin Kent E. , Evans Christian C.
Published: August 2021

Purpose:

A relatively high percentage of patients with COVID-19 develop hypoxemia and must be mechanically ventilated. Although prone positioning (PP) has been shown to be effective in improving peripheral oxygen saturation (SpO2) in mechanically ventilated patients with hypoxemia, whether it is effective in nonventilated patients with COVID-19 is not known. The purpose of this rapid evidence assessment was to examine the effectiveness of PP on SpO2 for nonventilated adults with COVID-19 and hypoxemia.

Methods:

The PEDro, Medline Complete, and Cochrane Central Register of Controlled Trials databases were searched. The inclusion criteria included nonventilated adults, diagnosed with COVID-19, and treated with PP. The exclusion criteria included patients on mechanical ventilation and <18 years old. The primary outcome was SpO2, and secondary outcomes included PaO2 and PaO2/FiO2 ratio. The methodologic quality was appraised using the Scottish Intercollegiate Guidelines Network Methodology Checklist 3.

Results:

Eight studies met all inclusion/exclusion criteria, and a total of 199 patients were included. All studies were cohort or retrospective design, and 4 of 8 met the acceptable threshold for risk of bias. All 5 of the studies that reported SpO2 found an increase in post-PP compared with pre-PP, and 5 studies found that PaO2, PaO2/FiO2, or both increased post-PP compared with pre-PP.

Conclusions:

Owing to heterogeneity in methods and outcomes, as well as varied results, we conclude there is low–moderate support that PP improves SpO2 and other indicators of hypoxemia in nonventilated patients with COVID-19, but not all patients may benefit. In addition, well-controlled studies are needed to confirm these results.
Short-term exposure to fine particulate air pollution and emergency department visits for kidney diseases in the Atlanta metropolitan area
Authors: Bi Jianzhao , Barry Vaughn , Weil Ethel J. , Chang Howard H. , Ebelt Stefanie
Published: August 2021

Background:

Toxicological evidence has shown that fine particulate matter (PM2.5) may affect distant organs, including kidneys, over the short term. However, epidemiological evidence is limited.

Objectives:

We investigated associations between short-term exposure to PM2.5, major PM2.5 components [elemental carbon (EC), organic carbon (OC), sulfate, and nitrate], and gaseous co-pollutants (O3, CO, SO2, NO2, and NOx) and emergency department (ED) visits for kidney diseases during 2002–2008 in Atlanta, Georgia.

Methods:

Log-linear time-series models were fitted to estimate the acute effects of air pollution, with single-day and unconstrained distributed lags, on rates of ED visits for kidney diseases [all renal diseases and acute renal failure (ARF)], controlling for meteorology (maximum air and dew-point temperatures) and time (season, day of week, holidays, and long-term time trend).

Results:

For all renal diseases, we observed positive associations for most air pollutants, particularly 8-day cumulative exposure to OC [rate ratio (RR) = 1.018, (95% confidence interval [CI]: 1.003, 1.034)] and EC [1.016 (1.000, 1.031)] per interquartile range increase exposure. For ARF, we observed positive associations particularly for 8-day exposure to OC [1.034 (1.005, 1.064)], EC [1.032 (1.002, 1.063)], nitrate [1.032 (0.996, 1.069)], and PM2.5 [1.026 (0.997, 1.057)] per interquartile range increase exposure. We also observed positive associations for most criteria gases. The RR estimates were generally higher for ARF than all renal diseases.

Conclusions:

We observed positive associations between short-term exposure to fine particulate air pollution and kidney disease outcomes. This study adds to the growing epidemiological evidence that fine particles may impact distant organs (e.g., kidneys) over the short term.