AVATAR 2.0: next level communication systems for radiotherapy through face-to-face video, biofeedback, translation, and audiovisual immersion.

Purpose: This paper discusses an advanced version of our audiovisual-assisted therapeutic ambience in radiotherapy (AVATAR) radiolucent display systems designed for pediatric radiotherapy, enabling anesthesia-free treatments, video communication, and biofeedback. The scope of the AVATAR system is expanded here in two major ways: (i) through alternative mounting systems to accommodate a broader range of radiotherapy machines (specifically to fit robotic-arm and toroidal geometry photon radiotherapy and proton radiotherapy systems) and (ii) through additional hardware to provide video-calling, optimized audio for clear communication, and combined video inputs for biofeedback, translation, and other advanced functionalities. Methods and materials: Because robustness requires strong parts and radio-transparency requires thin, light parts, three-dimensional printing was used to rapidly prototype hollow structures and to iteratively improve robustness. Two system designs were made: one that mounts superior and another that mounts inferior to the patient's head. Radiation dose measurements and calculations were conducted to assess dose perturbations at surface and depth due to the screen. Results: For 6-MV volumetric modulated arc therapy (VMAT) plans, with and without the screen, the mean and maximum dose differences inside the planning target volume were 0.2% and 2.6% of the 200 cGy prescription, respectively. For a single static beam through the screen, the maximum measured excess surface dose was 13.4 ± 0.5%, and the largest measured dose attenuation at 5-cm water-equivalent depth was 2.1 ± 0.2%. These percentages are relative to the dose without the screen at those locations. Conclusions: The radiolucent screen systems provided here are shown to give minimal dosimetric effects on megavoltage VMAT photon treatments. For static beams, however, surface dose effects should be considered when these beams pass through the thickest components of the screen. Design files are also provided.

Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, and Cost of the Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy Prospective Multi-Institutional Trial.

Purpose: The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost. Methods and Materials: The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, with rates of anesthesia use and outcomes of serial standardized anxiety and quality-of-life assessments assessed among the 81 children enrolled. A process map was created based on the trial timeline with the following components: study development time (time from conception of the trial to the accrual of the first patient, including design phase, agreement and approval phase, and site preparation phase), and accrual duration time (time from the first to last accrual). Costs and institutional success rates were calculated. Results: Time from inception of study to last accrual was 3.6 years (1313 days). The study development time was 417 days (31.7%), and accrual duration time was 896 days (68.3%), with the final 50% of accrual occurring in <6 months. Equipment cost was approximately $550 per institution and was covered by funding from the lead study institution. All 10 centers were successful with AVATAR implementation, defined as ≥50% of patients able to avoid anesthesia with the use of AVATAR, including centers with both photon and proton therapy. Conclusions: This report elaborates on the methodology and timeline of trial conception and development using data from a previously published supportive care study combining video immersion with radiation therapy among 10 cooperating pediatric oncology institutions. It highlights the potential for multicenter collaborations on prospective trials integrating supportive care therapies with radiation therapy.

Exploring the feasibility of preoperative tumor-bed boost, oncoplastic surgery, and adjuvant radiotherapy schedule in early-stage breast cancer: A phase II clinical trial.

BACKGROUND: Oncoplastic breast-conserving surgery (OBCS) improves satisfaction in patients who would fare otherwise sub-optimal cosmetic outcome, while brings challenge in tumor-bed identification during adjuvant radiotherapy. The ultra-hypofractionated breast radiotherapy further shortens treatment sessions from moderately hypofractionated regimens. To circumscribe the difficulty in tumor-bed contouring and the additional toxicity from larger boost volumes, we propose to move forward the boost session preoperatively from the adjuvant radiation part. Thus, the present study aims to evaluate the feasibility of a new treatment paradigm of preoperative primary-tumor boost before breast-conserving surgery (BCS) or OBCS followed by adjuvant ultra-hypofractionated whole-breast irradiation (u-WBRT) for patients with early-stage breast cancer. METHODS: There was a phase II study. Patients younger than 55 years old, with a biopsy confirmed mono-centric breast cancer, without lymph node involvement were enrolled. Preoperative primary-tumor boost was given by a single 10 Gy in 1 fraction, and BCS or OBCS was conducted within two weeks afterwards. Adjuvant u-WBRT (26 Gy/5.2 Gy/5 f) was given in 6 weeks postoperatively without any boost, after the full recovery from surgery. Surgical complications and patient-reported outcomes, as assessed via Breast-Q questionnaires, were documented. A propensity score matching approach was employed to identify a control group at a 1:1 ratio for BREAST-Q outcomes comparison. RESULTS: From May 2022 to September 2023, 36 patients were prospectively enrolled. Surgical complications were observed in 7 cases (19.4%), including 3 cases with Clavien-Dindo (CD) grade 1-2 and 4 cases with CD grade 3 complications. All but four patients (11.1%) started the planned u-WBRT within one week after the pre-defined due dates postoperatively (≤49 d). Four patients (11.1%) developed grade 2 radiodermatitis after chemotherapy initiation. Compared to the study group, the control patients reported higher scores in chest physical well-being ( P =0.045) and in their attitudes towards arm swelling ( P =0.01). No significant difference was detected in the other of domains (Satisfaction with Breasts, Sexual and Psychosocial Well-Being, and Adverse Effects of Radiation). With a median follow-up period of 9.8 months (2.4-18.9 mo), none had any sign of relapse. CONCLUSION: This Phase II clinical trial confirmed the technical and safety feasibility of novel radiation schedule in patients undergoing BCS or OBCS. According to the BREAST-Q questionnaire, patients who underwent novel radiation schedules reported lower satisfaction in chest physical well-being. A randomized controlled trial is necessary to further investigate these findings. Additionally, long-term follow-up is required to assess oncological outcomes.

SGMS1 facilitates osteogenic differentiation of MSCs and strengthens osteogenesis-angiogenesis coupling by modulating Cer/PP2A/Akt pathway.

Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.

Successful treatment of orbital Langerhans cell histiocytosis with stereotactic radiosurgery: A case report and literature review.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm arising from the proliferation of pathologic Langerhans cells. LCH has a spectrum of presentations predominantly affecting male pediatric patients. As LCH is a relatively uncommon diagnosis, there is no standard of care for treatment of the disease and treatment is based largely on clinical judgment, lesion characteristics, and symptoms at presentation. Here we present a case of unifocal, isolated orbital LCH in a 19-year-old young man treated initially with surgical resection. Follow-up imaging 2 months later demonstrated significant regrowth of the mass and no other sites of disease. The recurrent orbital disease was treated with stereotactic radiosurgery (SRS) to 7 Gy in one fraction. Near complete resolution of the mass was achieved with no recurrence after 1.5 years of follow-up. SRS for treatment of orbital LCH is a novel treatment not previously described in the literature which may provide benefit in select cases.

Feasibility of the Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) System for Anesthesia Avoidance in Pediatric Patients: A Multicenter Trial.

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial. METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject. RESULTS: Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P = .04) and private versus public insurance (P < .001). Both patient (P = .008) and parent (P = .006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001). CONCLUSIONS: In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction.

Time to resolution of iodine-123 metaiodobenzylguanidine (123 I-MIBG) avidity and local control outcomes for high-risk neuroblastoma following radiation therapy.

INTRODUCTION: 123 I-MIBG scan is used in neuroblastoma (NB) to monitor treatment response. Time to resolution of 123 I-MIBG avidity after radiation therapy (RT) is unknown. We sought to determine time to resolution of 123 I-MIBG avidity after RT and local failure (LF) rate. METHODS: We performed a retrospective review of children with high-risk NB who underwent 123 I-MIBG scans pre- and post-RT from 2003 to 2019. Time from RT to resolution of 123 I-MIBG activity was analysed. LF and cumulative incidence of local progression (CILP) after RT stratified by site, presence of residual disease and use of boost RT were determined. RESULTS: Forty-two patients with median age 3.9 years (1.9-4.7 years) were included, with median follow-up time 3.9 years (1.4-6.9). Eighty-six lesions were treated with RT to median dose of 21.6 Gy. Eighteen of 86 lesions were evaluable for time to resolution of MIBG avidity after RT, with median resolution time of 78 days (36-208). No LF occurred among 26 patients who received RT to primary sites after GTR, versus 4/12 (25%) patients treated with residual primary disease. 2-year CILP was 19% (12% primary disease 25% metastatic disease (P = 0.18)). 2-year CILP for non-residual primary, residual primary, non-residual metastatic and residual metastatic lesions was 0%, 42%, 11% and 30% respectively (P = 0.01) and for boosted and non-boosted residual lesions was 29% and 35% (P = 0.44). CONCLUSION: Median time to MIBG resolution after RT was 78 days. Primary lesions without residual disease had excellent local control. LF rate was higher after RT for residual disease, with no benefit for boost RT.

Effects of C-terminal amidation and heptapeptide ring on the biological activities and advanced structure of amurin-9KY, a novel antimicrobial peptide identified from the brown frog, Rana kunyuensis.

Rana kunyuensis is a species of brown frog that lives exclusively on Kunyu Mountain, Yantai, China. In the current study, a 279-bp cDNA sequence encoding a novel antimicrobial peptide (AMP), designated as amurin-9KY, was cloned from synthesized double-strand skin cDNA of R. kunyuensis. The amurin-9KY precursor was composed of 62 amino acid (aa) residues, whereas the mature peptide was composed of 14 aa and contained two cysteines forming a C-terminal heptapeptide ring (Rana box domain) and an amidated C-terminus. These structural characters represent a novel amphibian AMP family. Although amurin-9KY exhibited high similarity to the already identified amurin-9AM from R. amurensis, little is known about the structures and activities of amurin-9 family AMPs so far. Therefore, amurin-9KY and its three derivatives (amurin-9KY1-3) were designed and synthesized. The structures and activities were examined to evaluate the influence of C-terminal amidation and the heptapeptide ring on the activities and structure of amurin-9KY. Results indicated that C-terminal amidation was essential for antimicrobial activity, whereas both C-terminal amidation and the heptapeptide ring played roles in the low hemolytic activity. Circular dichroism (CD) spectra showed that the four peptides adopted an a-helical conformation in THF/H2O (v/v 1:1) solution, but a random coil in aqueous solution. Elimination of the C-terminal heptapeptide ring generated two free cysteine residues with unpaired thiol groups, which greatly increased the concentration-dependent anti-oxidant activity. Scanning electron microscopy (SEM) was also performed to determine the possible bactericidal mechanisms.

The effect of growing Rod treatment on coronal balance during serial lengthening surgeries in early onset scoliosis.

BACKGROUND: Gaining and maintaining spinal balance after surgery is of great importance for early onset scoliosis (EOS). However, tendency of balance on the coronal plane after growing rod surgery has not been studied before. This study evaluated the effect of growing rod treatment on coronal balance (CB) during serial lengthening surgeries in EOS. METHODS: All EOS patients treated with growing rod technique in our hospital from August 2002 to June 2014 were retrospectively reviewed. Radiographic data before the sixth lengthening surgery were measured on the posteroanterior X-ray images, including global CB (C7 plumbline-central sacral vertical line, C7PL-CSVL), regional CB (apical vertebrae-CSVL), Cobb angle of the main curve and pelvic inlet width (PIW). Global CB index and regional CB index were calculated as dividing global CB and regional CB by PIW, respectively. The changes of these parameters during repeated lengthening surgeries were analyzed. RESULTS: Five hundred seventy Radiographs of 67 patients, including 134 images before and after growing rod insertion surgeries and 436 images pre- and post-lengthening surgeries were measured. Global CB and global CB index did not show significant differences between every two set points during lengthening procedures (P > 0.05). The percentage of patients with C7PL-CSVL distance more than 20 mm roughly ranged from 30 to 45 % during the lengthening process. With regards to regional CB and main curve Cobb angles, there were significant differences between every two adjacent set points during the first five lengthening surgeries (P < 0.05). CONCLUSIONS: Global CB did not significantly change during serial lengthening surgeries and C7PL-CSVL distances of greater than 20 mm comprised of over one third of patients during growing rod treatment. However, worsening regional CB and Cobb angles of the main curve during lengthening intervals were corrected by lengthening manipulation and maintained at a stable level.

Identification and Characterization of Novel Antioxidant Peptides Involved in Redox Homeostasis of Frog, Limnonectes fragilis.

Previous studies have proved that a novel antioxidant system composed of various antioxidant peptides (AOPs) exists in the skin of ranid frogs, keeping the redox homeostasis. However, only a small number of AOPs have been identified so far. Here, a total of 47 cDNA sequences encoding 21 different AOPs belonging to 11 families were cloned from the skin cDNA library of Limnonectes fragilis. Among them, fragilin-A1 (VKRRGQDCIHGFCSD) and fragilin-B1 (GQFNDKRWIPFG) were also purified from skin secretions. They were selected with odorranain-Q-Lf (APIRMWYMYRKLTDMEPKPVA), the newest sequence among all 21 AOPs, to evaluate the antioxidant activities by direct free radical scavenging and lipid peroxidation inhibition assay. Results demonstrated that all peptides possessed strong DPPH and ABTS(.+) scavenging activities, and effectively inhibited lipid peroxidation in linoleic acid emulsion system during a 7- day test. No cytotoxic and hemolytic activity against human erythrocytes was observed for the three AOPs. The homology modeling analysis revealed that they all adopt tertiary structures ideally suited for the key residues to come into contact with the radicals. Current results reveal the existence of antioxidant system constituted of AOPs in the skin of the L. fragilis, and furthermore provide excellent templates for the development of novel antioxidant agents.

Dynamic Expression Profiles of Marker Genes in Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells.

OBJECTIVE: To observe the expression profiles of osteoblast-related genes in human mesenchymal stem cells (MSCs) derived from bone marrow during osteogenic differentiation. METHODS: MSCs were induced to differentiate with MSC osteogenic differentiation medium for 7, 14, 21 and 28 days respectively. Alizarin Red staining was used to detect matrix mineralization. Expression of osteoblast-related genes, including osteocalcin, osteopontin, Runt-related transcription factor 2 (Runx2), alkaline phosphatase and collagen type 1, was assessed with quantitative reverse transcription-polymerase chain reaction. RESULTS: On day 14 after induction of differentiation, cells were stained positively with Alizarin Red. The expression levels of these genes exhibited an upward trend as induction time was prolonged. Exposure to osteogenic differentiation medium less than 21 days did not significantly induce osteocalcin expression; osteocalcin expression levels in the differentiated cells induced for 21 and 28 days were 1.63 and 2.46 times as high as the undifferentiated cells respectively (all P<0.05). Stimulation with MSC osteogenic differentiation medium over 14 days significantly enhanced bone marrow-derived MSCs to express osteopontin and Runx2 genes (all P<0.05). Osteogenic differentiation medium could significantly induce the expressions of alkaline phosphatase and collagen type1 genes (all P<0.05). Their expressions reached the peak levels on day 21, which were increased more than 4- and 3-fold respectively. CONCLUSION: Human bone marrow-derived MSCs could exhibit the sequential expression pattern of osteoblast marker genes during osteogenic differentiation in vitro.

Penehyclidine hydrochloride decreases pulmonary microvascular permeability by upregulating beta arrestins in a murine cecal ligation and puncture model.

BACKGROUND: Penehyclidine hydrochloride (PHC) is a new anticholinergic drug, which has been shown to have a good curative effect for sepsis. Beta arrestins have been demonstrated to play important roles in sepsis. This study is to investigate the effects of PHC on pulmonary microvascular permeability and on expressions of beta arrestins in lung injury induced by the cecal ligation and puncture (CLP) procedure. MATERIALS AND METHODS: Thirty healthy female mice were randomly divided into three groups (n = 10 each): sham operation group (control group), CLP group (CLP group), and PHC 0.45 mg/kg group (PHC group). In the PHC group, mice were given an intraperitoneal injection of PHC 0.45 mg/kg 1 h before surgery. Mice in the other two groups received an intraperitoneal injection of the same volume of normal saline. At 12 h after surgery, serum and bronchoalveolar lavage fluid were collected to examine lung permeability index. The lung tissue samples were collected to examine expressions of myosin light chain kinase (MLCK), vascular endothelial-cadherin (VE-cadherin), vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), NF-κB, and beta arrestins. RESULTS: Compared with the control group, pulmonary microvascular permeability, MPO activity, NF-κB, VCAM-1, and MLCK expressions were significantly increased, whereas VE-cadherin and beta-arrestin protein expressions were obviously decreased in CLP group. Furthermore, compared with the CLP group, PHC group markedly decreased pulmonary microvascular permeability, MPO activity, NF-κB, VCAM-1, and MLCK expressions, and increased expressions of VE-cadherin and beta arrestins. CONCLUSIONS: This study suggests that in the CLP-induced lung injury model, PHC could reduce pulmonary microvascular permeability by upregulating expressions of beta arrestins.

Dual growing rod treatment in early onset scoliosis: the effect of repeated lengthening surgeries on thoracic growth and dimensions.

PURPOSE: To investigate changes in thoracic dimensions (TDs) following repeated lengthening surgeries after dual growing rod treatment of early onset scoliosis and thereby its effect on thoracic growth. METHODS: All EOS patients treated with dual growing rod technique in Peking Union Medical College Hospital from June 2004 to June 2014 were retrospectively reviewed. Thoracic spine height (T1-T12), total spine height (T1-S1), maximal coronal chest width and pelvic inlet width (PIW) were measured on the posteroanterior X-ray images after initial growing rod insertion surgery and after each lengthening surgery. Absolute TDs measurements were normalized by PIW. Changes of absolute and normalized TDs measurements with age and number of lengthening surgeries were analyzed. RESULTS: Radiographs of 229 surgeries of 53 EOS patients were measured, including 49 images after initial growing rod insertion surgery and 180 images of lengthening surgeries. Significant positive correlations between age and all three absolute TDs were found (P < 0.01) whereas significant negative correlations between age and all three normalized TDs (P < 0.01) were identified. Similarly, negative correlations were also identified between number of lengthening surgeries and the three normalized TDs (P < 0.01). Significant differences of normalized TDs were identified between initial surgery and the first lengthening through covariance analysis (P < 0.01). Yet, such differences were seldom seen between every two adjacent lengthening surgeries. CONCLUSIONS: Growing rod technique could maintain TDs growth through repeated lengthening procedures but the growth rate was compromised as the number of lengthening procedures increased.

What is the optimum fusion technique for adult spondylolisthesis-PLIF or PLF or PLIF plus PLF? A meta-analysis from 17 comparative studies.

STUDY DESIGN: A meta-analysis and systemic review. OBJECTIVE: To pool scientific evidence for the optimum selection in the treatment of lumbar spondylolisthesis by comparing the clinical effect of posterolateral fusion (PLF), posterior lumbar interbody fusion (PLIF), and PLIF plus PLF. SUMMARY OF BACKGROUND DATA: Clinical effect of the 3 fusion techniques has been reported in many studies. However, which is the best method is in dispute. METHODS: A systematic search was conducted in MEDLINE, EMBASE, and the Cochrane Collaboration Library from January 1950 through May 2013. Comparative studies were performed according to eligibility criteria. Weighted mean differences and risk differences were calculated for common outcomes. The final strength of evidence was expressed as different level recommended by the Grading of Recommendations Assessment, Development, and Evaluation Working Group. RESULTS: Four randomized controlled trials and 13 observational studies were eligible. PLIF was more effective than PLF in the improvement of clinical satisfaction (odds ratio [OR], 0.52; 95% confidence interval (CI), 0.31-0.89; P=0.02). No significant differences in the primary outcomes were seen between PLIF plus PLF and PLF (OR, 0.88; 95% CI, 0.47-1.64; P=0.69). For the complication rate, the differences were not significant between PLIF and PLF, and between PLIF plus PLF and PLF (OR, 2.27; 95% CI, 0.95-5.42; P=0.07; OR, 0.74; 95% CI, 0.22-2.44; P=0.62, respectively). In the secondary outcomes, PLIF was more effective than PLF in the improvement of fusion rate (P=0.0007) and reoperation rate (P=0.004). However, PLIF plus PLF failed to reveal more superiority than PLF (P>0.05). CONCLUSION: PLIF plus PLF did not show more superiority than PLF alone. PLIF alone improved clinical satisfaction and decreased complication rate compared with PLF. PLIF maybe be better than the other 2 fusion methods in the treatment of lumbar spondylolisthesis. However, conclusions need to be treated with caution because of lack of high quality of evidence. LEVEL OF EVIDENCE: 1.