Need For Treatment Research Articles

Comparison of knowledge, self-perception about malocclusion and orthodontic treatment need amongst undergraduate dental students

ABSTRACT Introduction Perception regarding malocclusion and esthetics is affected by knowledge, age, race, gender, social background, and exposure. This study compares knowledge and awareness of undergraduate dental students regarding malocclusion, its impact on oral and mental health, and students’ self- perceived need for orthodontic treatment. Material and Methods A multi-centre cross-sectional study evaluated 424 questionnaires. They were assessed and compared on knowledge, awareness, and self-perception regarding malocclusion. Results were reported in percentages and compared using chi-square test. Results Most of the respondents were females, (82.1%). 4th year students were most aware about malocclusion’s effects on caries (86.8%), plaque (98.1%) and gingivitis (85.8%), p-value was significant, 0.000. Mostly, 3rd year students favoured well-aligned teeth, 91.5%, (p = 0.431); 2nd year students mostly, regarded aligned teeth important for esthetics (96.2%) p = 0.042; 4th year students mostly reported self-perceived need for orthodontic treatment, 43.4% (p = 0.048) and thought malocclusion affected one’s self-esteem 86.8% (p = 0.031), acceptance amongst peers 51.9% (p = 0.000) and mental health 52.8% (p = 0.000). Conclusion Knowledge and self-perception regarding malocclusion did not have a direct relation with the level of education of the dental students studied.

Syphilis in pregnancy and adverse birth outcomes: Anationwide longitudinal study in Brazil.

The present study aimed to evaluate the association between syphilis in pregnancy and low birth weight, small for gestational age, and preterm birth. This longitudinal study used Brazilian National Information System for livebirths (SINASC) linked to the gestational syphilis cases from Notifiable Diseases Information System (SINAN) from 2011 to 2017. Descriptive statistics and logistic regression were used to compare the birth outcomes of pregnant women with and without syphilis. The study protocol was approved by the Research Ethics Committee of the Institute of Collective Health of the Federal University of Bahia (CAAE: registration no. 18022319.4.0000.5030). A total of 17 930 817 live births were included in the study. Of these, 155 214 (8.7/1000) were exposed to syphilis during pregnancy. Maternal syphilis increased the odds of low birth weight (aOR 1.88, 95% CI: 1.85-1.91), small for gestational age (aOR 1.53, 95% CI: 1.51-1.56), and preterm birth (aOR 1.35, 95% CI: 1.33-1.37). Higher odds were observed for pregnant women with VDRL titer ≥64 and untreated maternal syphilis when compared to mothers without syphilis. Analysis stratified by prenatal care showed higher odds for all adverse birth outcomes for mothers attending ≤6 prenatal appointments. Our findings showed a strong association between gestational syphilis and adverse birth outcomes with increased odds observed among women with higher VDRL titers, lack of treatment, and fewer prenatal appointments. These results highlight the need for adequate screening and treatment for gestational syphilis during pregnancy to mitigate the risk of adverse birth outcomes.

Mapping quality of life after balloon dilatation in subglottic stenosis using Dyspnea index and Short Form Health Survey-36.

An accurate diagnosis and proper treatment plan are required to restore an adequate patent airway in fibrotic subglottic stenosis (SGS). Currently, the definitive treatment entails single-stage balloon dilatation with steroid injections. The primary aim was to evaluate successful airway restoration and general quality of life in cases with SGS in northern Sweden using robust patient reported outcomes. All participants with need of surgical treatment due to SGS that had been referred to the department of otorhinolaryngology, University Hospital of Umeå from September 2020 to August 2023 was included. Exclusion criteria included malignant, extrathoracic or cartilaginous cause, age < 18years, or incompetent to sign consent documents. We assessed the patient-reported outcome measures pre- as well as 3months postoperatively. Of the 40 cases fulfilling the eligibility criteria's, 33 cases completed the Dyspnea index (DI) and the short form health survey (SF-36) pre- as well as 3months post-operatively. Receiver operating characteristics showed significant improvement in DI as well as in SF 36 scores post-operatively. Evaluation of balloon dilatation in SGS in this cohort follow-up analysis shows clear improvement in patient quality of life using robust PROM 3months postoperatively, ensuring the use of a safe and well-tolerated procedure.

Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database.

This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan. The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines. In this study, 2236 patients with mTNBC (median age 66.0years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively. This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Patient satisfaction and sexual issues in vulvar lichen sclerosus treatment: a monocentric certified dysplasia unit survey analysis.

Vulvar lichen sclerosus (VLS) is an underestimated chronic disease. It can cause significant symptom burden and sexual dysfunction. This study aimed to evaluate patient satisfaction and current challenges in the management of VLS in a certified dysplasia unit, particularly during the COVID-19 pandemic. This survey analyzed patients who had been diagnosed with VLS and treated at our DKG-certified dysplasia unit. The study was conducted during the COVID-19 pandemic in the Department of Gynecology and Obstetrics at the University of Aachen. The questionnaire contained 43 questions on general treatment, diagnostic delays, disease education, psychologic and sexual issues, and specific questions regarding the COVID-19 pandemic. The questionnaires were distributed between January 2021 and September 2023. This study included 103 patients diagnosed with VLS, who were treated at our certified dysplasia unit. Overall, 48% of the patients were satisfied with the success of the therapy. Most participants reported psychologic problems (36.8%), fear of cancer (53.3%), or sexual restrictions (53.3%). Among the patients, 38% were bothered by the regular application of topical cortisone. However, 72% were willing to undergo treatment for more than 24months. The COVID-19 outbreak in March 2020 had a significant negative impact on general VLS care from the patient's perspective (3.83/5 before vs. 3.67/5 after; p = 0.046). There was a general request for booklets to inform and educate the patients about their disease. Furthermore, the respondents demanded a telephone hotline to answer the questions and wished for follow-up visits via e-mail to cope better with their current situation. This study highlights the need for more effective treatments for VLS and an increased awareness of psychologic and sexual distress. To ensure patient well-being and satisfaction, it is imperative to offer individualized care with adequate disease education in a team of specialists from various disciplines.

Investigating Patient Satisfaction Through Web-Based Reviews of Norwegian Dentists: Quantitative Study Using the Meaning Extraction Method.

Challenging encounters in health care professions, including in dentistry, are relatively common. Challenging encounters can be defined as stressful or emotional situations involving patients that could impact both treatment outcomes and patients' experiences. Through written web-based reviews, patients can share their experiences with health care providers, and these posts can be a useful source for investigating patient satisfaction and their experiences of challenging encounters. This study aims to identify dominant themes from patient-written, web-based reviews of dentists and investigate how these themes are related to patient satisfaction with dental treatment. The study data consisted of 11,764 reviews written by dental patients, which included 1- to 5-star ratings on overall satisfaction and free-text comments. The free-text comments were analyzed using Linguistic Inquiry and Word Count software, and the meaning extraction method was used to group words into thematic categories. These themes were used as variables in a multilevel logistic regression analysis to predict patient satisfaction. Eight themes emerged from the analyses, of which 6 (75%)-explanation (odds ratio [OR] 2.56, 95% CI 2.16-3.04; P<.001), assurance (OR 3.61, 95% CI 2.57-5.06; P<.001), performance assessment (OR 2.17, 95% CI 1.84-2.55; P<.001), professional advice (OR 1.81, 95% CI 1.55-2.13; P<.001), facilities (OR 1.78, 95% CI 1.08-2.91; P=.02), and recommendation (OR 1.31, 95% CI 1.12-1.53; P<.001)-increased the odds of high patient satisfaction. The remaining themes (2/8, 25%)-consequences of treatment need (OR 0.24, 95% CI 0.20-0.29; P<.001) and patient-centered care (OR 0.62, 95% CI 0.52-0.74; P<.001)-reduced the odds of high patient satisfaction. The meaning extraction method is an interesting approach to explore patients' written accounts of encounters with dental health professionals. The experiences described by patients provide insight into key elements related to patient satisfaction that can be used in the education of dental health professionals and to improve the provision of dental health services.

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience

Objectives: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. Methodology: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children´s Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). Results: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive–inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). Conclusion: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

Abstract PO1-16-07: Patient Characteristics and Treatment Sequencing Among HER2-low Metastatic Breast Cancer Patients with Rapid vs. Delayed Progression on First-line Endocrine Therapy

Abstract Background Patients with HER2-low (IHC 1+ or 2+ and negative ISH) and hormone-receptor positive (HR+) metastatic breast cancer (mBC) who rapidly progress on first-line (1L) endocrine therapy may experience different treatment pathways than those with delayed progression. The goal of this multisite study is to describe the characteristics, treatment patterns and outcomes of these patients with rapid vs. delayed progression. Methods This was a retrospective cohort study of HER2-low, HR+, mBC patients who received 1L endocrine-based treatment regimen at the Huntsman Cancer Institute, Moffitt Cancer Center, and the Winthrop P. Rockefeller Cancer Institute between 2017 and 2021. With no conventional definition, our study defined rapid progression as disease progression within 12 months of 1L treatment initiation vs &amp;gt;12 months/no progression during study follow-up as delayed progression. Demographic and clinical characteristics, and 1L and second-line (2L) treatment patterns were assessed using descriptive statistics. Using Kaplan-Meier analysis, overall survival (OS) was estimated from treatment initiation to death while progression-free survival (PFS) was estimated from treatment initiation to death or disease progression according to physician notes in patients’ charts. Censoring was performed at the date of last follow-up or 31 Dec 2021, whichever occurred earlier. Results The study included 118 patients who received 1L endocrine therapy (see table), mostly in combination with a CDK4/6 inhibitor (n = 87, 73.7%). Rapid progression was observed for 25 (21.2%) patients with a median 1L PFS and OS of 6.4 months (95% CI: 5.4-8.2) and 20.5 months (95% CI: 14.4-30.5), respectively, compared to delayed progressors (median 1L PFS = 30.5 months, 95% CI: 21.5-54.2 and median OS = 62.1 months, 95% CI: 46.4 -upper bound not reached). Rapid progressors were more likely than delayed progressors to be current smokers (n = 6, 24.0% vs n = 7, 7.5%, p = 0.015) or had liver metastasis at diagnosis of advanced disease (n = 11, 44.4% vs n = 17, 18.3%, p = 0.007) but less likely to have bone as the only metastasis site (n = 6, 24.0% vs n = 46, 49.5%, p = 0.023). A smaller proportion of rapid progressors were on CDK4/6 inhibitors in 1L (n = 17, 68.0%) compared to delayed progressors (n = 70, 75.3%) but the difference was not statistically significant. A substantial proportion of rapid progressors (68%, n = 17) continued to receive endocrine therapy in 2L, including endocrine therapy alone (n = 6, 24.0%), endocrine therapy with targeted therapy (n = 6, 24.0%) and endocrine therapy with CDK4/6 inhibitors (n = 5, 20.0%). Among patients on 1L endocrine therapy who continued to a 2L treatment, 2L PFS and OS of rapid progressors (n = 24) were 5.7 months (95% CI: 3.2-10.6) and 14.1 months (95% CI: 6.8-24.2), respectively, compared to 9.2 months (95% CI: 3.1-13.7) and 29.2 months (95% CI:14.4- upper bound not reached) among delayed progressors (n = 39). Conclusion In this study of patients with HER2-low and HR+ mBC, many patients with rapid disease progression on 1L endocrine-based regimens continued to receive endocrine therapy in their next line of therapy and experienced poor clinical outcomes. This preliminary chart review study highlights the unmet need for more effective treatments for patients with rapid progression on 1L endocrine-based regimens. Further research with a larger sample size is warranted to confirm these findings. Patient characteristics and treatment patterns Demographic characteristics and treatment patterns of stage IV breast cancer patients with HER2-low disease and received 1L endocrine therapy Citation Format: Chia Jie Tan, Connor Willis, Trang Au, Matthew Schabath, Chenghui Li, Kristen Kelley, Xiaoqing Xu, Leah Park, Clara Lam, Sandhya Mehta, Jackie Kwong, Diana Brixner, David Stenehjem. Patient Characteristics and Treatment Sequencing Among HER2-low Metastatic Breast Cancer Patients with Rapid vs. Delayed Progression on First-line Endocrine Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-07.

Abstract PO2-24-03: Soluble E-cadherin promotes inflammatory breast cancer tumorigenesis via PDIA4-mediated suppression of ferroptosis

Abstract Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer known for its rapid progression and high metastatic potential without known distinctive drivers. Currently, there are no FDA-approved targeted therapies specifically for IBC patients, highlighting the urgent need for novel and effective treatments. Through our investigation of metastatic xenograft IBC sublines, we have identified soluble E-cadherin (sEcad), an extracellular proteolytic fragment of full-length E-cadherin, as a protein associated with IBC tumor progression. We hypothesize that sEcad promotes IBC tumorigenesis by suppressing ferroptosis. Methods: MDA-IBC3 (ER–/HER2+) and SUM149 (ER–/HER2–) IBC cell lines were used in this study. Stable overexpression of sEcad in IBC cell lines was achieved using lentiviral vectors. Cell death for ferroptosis was measured by propidium iodide staining using flow cytometry. Mass spectrometry and Bio-ID-based proteomics assays were used to identify sEcad-interacting proteins and potential mechanisms. For in vivo studies, control and sEcad -overexpressing SUM149 and MDA-IBC3 cells were injected into the cleared mammary fat pads of SCID/Beige mice and tumor growth was monitored via caliper measurements. Serum sEcad levels from IBC patients (n=301) were analyzed by ELISA. Results: High serum sEcad levels in IBC patients correlated with poorer OS (p=0.02) and earlier development of metastasis (p=0.006). Overexpression of sEcad in IBC cell lines enhanced cell proliferation and colony formation in vitro. Mice injected with sEcad-overexpressing SUM149 and MDA-IBC3 cells had significantly higher tumor growth rates compared to controls (SUM149: p=0.007; MDA-IBC3: p=0.006). Mechanistically, mass spectrometry and Bio-ID assays identified Protein Disulfide Isomerase Family A Member 4 (PDIA4) as a novel binding partner of sEcad, which was validated through co-immunoprecipitation. Additionally, sEcad increased the expression of PDIA4, an enzyme that plays a role in cellular redox regulation and protein folding. PDIA4 has been shown to regulate key players of ferroptosis such as ATF4, SLC7A11. Our results showed that, compared to controls, sEcad-overexpressing IBC cells displayed significant resistance to ferroptosis inducers, including RSL3, FIN56, and sulfasalazine. Knockdown of PDIA4 in sEcad high-expressing cells significantly increased their sensitivity to ferroptosis-promoting drugs. Moreover, we found that PDIA4 regulates ATF4 to impact ferroptosis-mediated cell death in IBC cells. Conclusions: Our study shows that sEcad affects ferroptosis through PDIA4, impacting tumorigenesis in IBC. These findings uncover a novel and pivotal role for sEcad in IBC tumor growth and progression, providing new insights and potential therapeutic targets for IBC patients. Citation Format: Xiaoding Hu, Yun Xiong, Emilly Villodre, Juhee Song, Debu Tripathy, Wendy Woodward, Savitri Krishnamurthy, Junjie Chen, Bisrat Debeb. Soluble E-cadherin promotes inflammatory breast cancer tumorigenesis via PDIA4-mediated suppression of ferroptosis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-24-03.

At the Forefront: Social Workers' Role in Psilocybin Treatment for Depression and Substance Misuse.

This article underscores the critical role of social workers in harnessing the potential therapeutic benefits of psilocybin for treating major depressive disorder (MDD) and substance use disorder (SUD). Contemporary treatments for MDD often have side effects, and the success rate for SUD treatments remains low. The pervasiveness of MDD, combined with the challenges in treating SUD, highlights a need for innovative treatments. This article provides an overview of the resurgence of literature over the past two decades that illuminates the therapeutic promise of psilocybin for mental health treatment; clinical trials elucidate the efficacy of psilocybin-assisted therapy in mitigating MDD and demonstrate great promise in reducing SUD symptoms. The long-lasting posttreatment effect emphasizes its potential as a novel treatment modality. Furthermore, psilocybin's recognition as a "breakthrough therapy" by the U.S. Food and Drug Administration (FDA) and the accelerating pace of psychedelic reform bills indicate growing acceptance and interest in its therapeutic capacities. Psilocybin-assisted therapy emerges as a potent treatment option, showcasing remarkable effectiveness even after a single dose. Recommendations and pathways for social workers to be involved in psilocybin-assisted therapy investigation, advocacy, and implementation are provided.

Abstract PO1-19-10: Durvalumab + datopotamab deruxtecan in patients with PD-L1 positive advanced/metastatic triple-negative breast cancer: Arm 8 of the phase 1b/2, open label, platform BEGONIA study

Abstract Background: Patients (pts) with advanced/metastatic triple-negative breast cancer (a/mTNBC) have limited treatment options and poor prognosis. Immune checkpoint inhibitors combined with chemotherapy is the standard of care for pts with PD-L1 positive tumors; still, most pts progress within a year, highlighting a need for new treatments. BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of durvalumab (D), an anti–PD-L1 monoclonal antibody, with or without paclitaxel, in combination with novel oncology therapies as first-line treatment for a/mTNBC (NCT03742102). Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (TROP2) IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via a plasma stable, tumor selective, tetrapeptide-based cleavable linker. TROP2 is broadly expressed on breast and other epithelial tumors and Dato-DXd monotherapy showed antitumor activity in heavily pretreated mTNBC pts (Bardia SABCS 2022 P6-10-03). Pts treated with Dato-DXd+D in Arm 7 of BEGONIA showed a 74% objective response rate (ORR) with median 7.2 months follow-up (Schmid SABCS 2022 PD11-09). Although responses were observed in both PD-L1–high and –low-expressing tumors, most pts (87%) had PD-L1–low-expressing tumors. In Arm 8 of BEGONIA, pts determined to have PD-L1 positive tumors by pre-existing/local testing will be recruited and treated with Dato-DXd+D to evaluate efficacy and safety in a PD-L1–high population. Methods: Eligible female pts are aged ≥18 years with untreated unresectable, locally advanced or mTNBC; ≥6 months between completion of treatment for earlier-stage breast cancer and recurrence of distant disease; ≥12 months since prior taxane therapy; ECOG PS 0/1; adequate organ function; and ≥1 nonirradiated measurable lesion. For inclusion in Arm 8, a PD-L1 positive tumor as determined by local immunohistochemistry (IHC) testing is required (either pre-existing or obtained during prescreening). Exclusion criteria for Arm 8 are clinically significant corneal disease; history or suspicion of interstitial lung disease/pneumonitis; underlying pulmonary disorder; prior exposure to immune-mediated therapy; or prior treatment with an ADC containing a topoisomerase I inhibitor. Arm 8 will evaluate Dato-DXd (6 mg/kg) + D (1120 mg) given intravenously every 3 weeks until disease progression or unacceptable toxicity. Tumors will be assessed per RECIST v1.1 every 6 weeks for 48 weeks, then every 12 weeks thereafter. A safety run-in will not occur for Arm 8, as Dato-DXd+D was evaluated in Arm 7 and was tolerable with no DLTs reported. Part 1 of Arm 8 will enroll 30 pts. The primary endpoint of Part 1 is safety and tolerability. A futility analysis will be performed with an option to expand Arm 8 to Part 2, where an additional 27 pts will be enrolled if expansion criteria are met. The primary endpoint for Part 2 is ORR. Secondary endpoints include ORR (Part 1 only), testing for antidrug antibodies and treatment pharmacokinetics (Part 1 only), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). ORR will be summarized with descriptive statistics and 95% Clopper-Pearson confidence intervals. Kaplan-Meier analysis will be used for DoR, PFS, and OS. All tumor response and survival endpoints will be based on investigator assessments. Additional PD-L1 testing with the VENTANA PD-L1 (SP263) Assay will be performed on pretreatment tumor samples; high expression is defined as ≥10% of the tumor area populated by PD-L1–expressing tumor or immune cells. TROP2 expression will be assessed by IHC. Enrollment is ongoing. Funding: AstraZeneca/Daiichi Sankyo Citation Format: Peter Schmid, Cynthia Ma, Robert Huisden, Ross Stewart, Katrin Heider, Petra Vuković, Neelima Denduluri. Durvalumab + datopotamab deruxtecan in patients with PD-L1 positive advanced/metastatic triple-negative breast cancer: Arm 8 of the phase 1b/2, open label, platform BEGONIA study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-10.

Abstract PO1-21-01: A Case of High Grade Metastatic Encapsulated Papillary Carcinoma and a Look at Current Treatment Guidelines

Abstract Background: Encapsulated papillary carcinoma is a well-documented malignancy in the world of breast surgery. It is often described as a less invasive form of breast cancer, with a more indolent clinical course. Most EPC pathology demonstrates low grade tumors, with rare findings of metastases at time of diagnosis. EPC currently accounts for 1-2% of all breast cancers. It is distinguished by its fibrovascular core, which is covered with epithelium with or without a myoepithelial layer. Despite EPC being well-recognized, current management remains controversial. Most commonly, however, it is treated and managed as an in-situ disease. Case Presentation: We present a case of a 64-year-old female who initially presented with a painless lump in her left breast, which on biopsy demonstrated DCIS involved with a papillary lesion. On excision, the patient was upstaged to IDC in a background of EPC. She then underwent re-excision with confirmed negative margins. Despite this, over the following months, the patient continued to have increased pain, swelling, and an episode of superficial thrombophlebitis. She was taken back to the OR at this time and was found to have a new mass with a large feeding vein. Pathology was significant for high grade multifocal EPC with small and large vessel lympho-vascular invasion. Lesion noted to be metachronous. Additionally, metastases to the axilla were identified, requiring an axillary dissection. Conclusion: High grade encapsulated papillary carcinoma is a rare member of the indolent papillary breast cancer family. This unusually invasive type of cancer should be treated and managed in a more aggressive fashion, like its clinically similar cousin invasive ductal carcinoma. The current management standard of treating EPC as in situ disease is not robust enough and can lead to disease recurrence and need for repeat resection and treatment. Citation Format: Nicholas Gore MD, Madeline Silva MD, Carissia Calvo-Strube MD. A Case of High Grade Metastatic Encapsulated Papillary Carcinoma and a Look at Current Treatment Guidelines [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-21-01.

Abstract PO5-24-12: IRX5010, a Highly Selective RARγ Nuclear Receptor Agonist Compound Inhibits In Vivo Growth of Murine EMT-6 Triple Negative Breast Cancer and Human JIMT-1Her2+ Breast Cancer By Induction of Tumor-Infiltrating Effector Memory T-cells

Abstract Research Objectives and Rationale: Previously, RARγ agonism has been shown to play an essential role in CD8 T-cell-mediated immunity to infectious pathogens. However, we found no previous reports on effects of RARγ agonists on in vivo tumor growth of triple negative or Her2+ breast cancers. Here we explored whether RARγ could play a critical role in T-cell-mediated immunity in these breast cancers, using potent highly selective novel RARγ agonist compounds. Experimental methods and results: We synthesized and screened compounds for selective transactivation of RAR γ in reporter assays. Three highly potent compounds, demonstrating highly selective RARγ transactivation at less than one nanomolar concentrations, were selected for further evaluation of potential anti-cancer activities in vitro. None of the three evaluated compounds demonstrated significant inhibitory effects on in vitro growth of EMT-6 triple negative breast cancer cells at concentrations of 20-100 millimolar, indicating that the three compounds have insignificant direct inhibitory effects on EMT-6 cancer cell growth in vitro. We then examined the effects of one of the compounds in vivo in a syngeneic mouse model of EMT-6 triple negative breast cancer. Treatment with the most potent of the three compounds, IRX5010, demonstrated dose response inhibition of in vivo growth of EMT-6 tumors. Inhibition of tumor growth at day 17 relative to vehicle was 59% and 69% respectively in mice treated with IRX5010 at 10 or 25 mg/kg/day. A cohort treated with 50 mg/kg/day was sacrificed early on day 12 due to excessive weight loss and deaths of some of the animals. This cohort experienced a 73% inhibition of tumor growth relative to vehicle. Gross necropsies of animals in the 25 and 50 mg/kg/day dose groups did not show observable pathologic findings in any major organ. Flow cytometry was performed on freshly excised tumors on the day of termination of the in-life portion of the study in the 10 and 25 mg/kg/day dose groups. Tumors from mice treated with IRX5010 had increased intratumoral numbers of Total CD45+ cells; Total CD3+, Total CD4+, and Total CD8+ T-cells per mg of tumor tissue, relative to vehicle controls. IRX5010 treated mice also had increased intratumoral CD4+IL-17+ T-helper cells; and increased CD4+CD62L- and CD8+CD62L- T-effector memory T-cells per mg of tumor tissue relative to vehicle-treated control mice. We also conducted an experiment of treatment with IRX5010 in mice transplanted with human immune cells (to provide a human immune system) to examine its effects on xenografted human Her2+ JIMT-1 cancer cells. In this model, treatment with IRX5010 at 10 mg/kg/day resulted in a 17% inhibition of tumor growth relative to vehicle control over 26 days of treatment. Flow cytometric analysis showed that tumors from the IRX5010 treated mice contained increased numbers per mg of tumor tissue of intratumoral human CD8+ T-cells, most of which were CD8+ CD7- CD45RA+ terminally differentiated effector memory phenotype T-cells. Conclusions: Treatment with IRX5010, a potent and highly selective RARγ nuclear receptor agonist compound demonstrated substantial treatment effects relative to vehicle control on inhibition of growth of murine triple negative breast cancer in vivo, despite having essentially no growth inhibitory effect on these cells in vitro. Treatment of xenografted human Her2+ tumors in mice with humanized immune systems resulted in a moderate inhibition of Her2+ breast cancer growth relative to vehicle controls. In both models, treatment with IRX5010 induced tumor infiltrating T-lymphocytes of largely effector memory phenotypes, demonstrating an effect on the tumor immune microenvironment. These data identify RARγ and RARγ agonists as a new treatment target and novel treatment modality for breast cancers, especially for the highly unmet need for new and better treatments for triple negative breast cancer. Citation Format: Martin Sanders, Mary Topalovski, Vidyasagar Vuligonda. IRX5010, a Highly Selective RARγ Nuclear Receptor Agonist Compound Inhibits In Vivo Growth of Murine EMT-6 Triple Negative Breast Cancer and Human JIMT-1Her2+ Breast Cancer By Induction of Tumor-Infiltrating Effector Memory T-cells [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-12.

Effect of weight loss and exercise on joint pain in patients with osteoarthritis and obesity

Osteoarthritis (OA), the most common joint disease, coexists with obesity in most of the world’s population. According to the forecast of the World Health Organization, the number of patients with these diseases is expected to increase, which represents a serious medical and social problem due to increased disability, the need for surgical treatment, an increase in comorbid diseases, treatment complications and mortality in this group of patients. OA and obesity have common pathogenetic mechanisms, and the development of one disease increases the risk of developing the other, which can become the beginning of a vicious circle. In recent years, obesity is considered not only as a biomechanical factor (excessive load on the joint, destruction of articular cartilage), but also as a cause of metabolic syndrome and systemic inflammatory effects. Inflammatory cytokines, especially IL-1β and TNF-α, drive catabolic pathways and promote the progression of OA. There is compelling evidence that weight loss reduces pain and joint inflammation and improves prognosis in patients with OA. The review presents data on the prevalence of OA and obesity, the role of immune disorders in these diseases, and indicates methods of pharmacological and non-pharmacological treatment of OA. General principles and specific updated recommendations of the European League Against Rheumatism for non-drug treatment of OA of the hip and knee joints are outlined, and recommendations for weight loss through dietary interventions and exercise are formulated.

Natural history of renal angiomyolipoma in a high-volume center: our experience during more than 15years of follow up.

To describe the natural history of AML, the clinical results and the need for treatment during long-term follow-up of renal AML. Retrospective study of patients diagnosed with AML by computed tomography or nuclear magnetic resonance between 2001 and 2019, with at least two follow-up images. Clinical and imaging variables, need for intervention, complications and follow-up time were recorded. Statistical analysis was performed using SPSS 22.0. 111 patients and 145 AML were included. The median follow-up was 6.17years (range 0.7-18.1, IQR 11.8-12.2). The median tumor size at diagnosis was 13mm (IQR 7.5-30), with 24 (16.4%) being ≥ 4cm. Most presented as an incidental finding (85.5%); in 3 (2.1%) cases, the presentation was as a spontaneous retroperitoneal hematoma. The main indication for intervention was size ≥ 4cm in 50%. Eighteen (12%) patients received a first intervention, being urgent in 3. Embolization was performed in 15 cases and partial nephrectomy in 3. The need for reintervention was recorded in five: two underwent partial nephrectomy and two total nephrectomy; one patient required a new urgent embolization. Of the non-operated patients, 43% decreased in size or did not change, while 57% increased, with the median annual growth being 0.13mm (IQR -0.11 to 0.73). There were no differences in the median growth in tumors measuring ≥ 4cm (0.16mm) at diagnosis vs. < 4cm (0.13mm) (p = 0.9). The findings of this study suggest that AML typically demonstrate a slow-progressing clinical course during long-term follow-up. Moreover, our observations, which cast doubt on tumor size as a reliable predictor of adverse clinical outcomes, advocate for a less intensive monitoring strategy in both monitoring frequency and choice of imaging modality.

Nanoemulsion based in-situ Gel for Ocular Delivery of Brimonidine Tartrate

Background: Brimonidine tartrate is currently used to treat glaucoma; however, conventional ocular formulations have some disadvantages in terms of treating disorders like glaucoma, as less than 5% of the drug reaches a posterior segment of the eye; hence, there is a need for sustained treatment. Objective: The objective of this study was to develop a self-nanoemulsion (SNEDDS) in-situ gel of brimonidine tartrate to investigate the sustained-release effect to improve ocular bioavailability. Method: Oil, surfactant, and co-surfactant were screened using the pseudo-ternary phase diagram (TPD) by aqueous-titration method based on the drug solubility. Nanoemulsions were evaluated for the pH, viscosity, % drug content, % transmittance, dispersibility, particle size, zeta-potential, TEM, and conductivity test. Nanoemulsion was incorporated into in-situ gel and evaluated for gelling capacity, pourability, gel strength, in vitro drug release study, and drug release kinetics. Result: Castor oil (10%) as oil phase, Acrysol K-140 (10%) as surfactant, and PEG 400 (20%) as cosurfactant were selected in preparation of SNEDDS from TPD. Evaluation parameters of SNEDDS were found in an acceptable range. % Drug release showed the controlled release up to 8 hrs. Optimum % drug content and % CDR were 100.25% and 92.46% after 12hrs, respectively. Optimized SNEDDS in-situ gel followed the Higuchi model via diffusion mechanism having 0.99 R² value and exhibiting sustained release up to 12 hr. Stability study proved no significant changes during storage. In vitro, the ocular irritancy test proved suitable for ocular delivery. Conclusion: A sustained-release formulation was obtained by developing brimonidine tartrate SNEDDS in-situ gel as a stable formulation without irritancy during ocular administration.

The value of a remote orthodontic assessment for children having permanent teeth extracted under general anaesthesia.

Introduction The number of children undergoing dental extractions under general anaesthetic (GA) remains high. The newly published Royal College of Surgeons guidelines in 2023 take a less prescriptive approach on balancing and compensating extractions for first permanent molars. In an effort to maintain an effective and efficient patient care pathway, an orthodontic remote assessment triage model was developed in West Dorset for the special care dentistry and community dental service.Aims The orthodontic triage form is now used across Dorset. This service evaluation assesses whether the form is still effective despite the upscaling. Furthermore, qualitative feedback was obtained from the clinicians involved in referring and triaging.Design The sample of 352 forms consisted of children aged 16 years or younger undergoing GA for dental extractions for whom orthodontic triage had been requested between March 2019 and March 2023. The clinician feedback was collected using a questionnaire.Results This service evaluation found that 53.1% of patients had their treatment plan modified following an orthodontic assessment. Positive feedback from all clinicians involved suggests there is potential to expand this model to other services.Discussion Involving the orthodontist can address orthodontic concerns which has the potential to simplify or obviate the need for future orthodontic treatment. Remote assessment reduces the need for face-to-face appointments. The clinician perspective influences willingness to further develop and expand the current pathway.Conclusion Remote triage has proved successful in Dorset. There is potential to build an initiative between primary and secondary care in the hopes of creating a universal national proforma to increase access to orthodontic opinions for children requiring dental extractions.

Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

Salvimulticanol from Salvia multicaulis suppresses LPS-induced inflammation in RAW264.7 macrophages: in vitro and in silico studies.

Sustained inflammatory responses can badly affect several vital organs and lead to chronic inflammation-related disorders, such as atherosclerosis, pneumonia, rheumatoid arthritis, obesity, diabetes, Alzheimer's disease, and cancers. Salvia multicaulis is one of the widely distributed plants that contains several biologically active phytochemicals and diterpenoids with anti-inflammatory effects. Therefore, finding alternative and safer natural plant-extracted compounds with good curative anti-inflammatory efficiencies is an urgent need for the clinical treatment of inflammation-related diseases. In the current study, S. multicaulis Vahl was used to extract and isolate two compounds identified as salvimulticanol and candesalvone B methyl ester to examine their effects against inflammation in murine macrophage RAW264.7 cells that were induced by lipopolysaccharide (LPS). Accordingly, after culturing RAW264.7 cells and induction of inflammation by LPS (100ng/ml), cells were exposed to different concentrations (9, 18, 37.5, 75, and 150µM) of each compound. Then, Griess assay for detection of nitric oxide (NO) levels and western blotting for the determination of inducible nitric oxide synthase (iNOS) expression were performed. Molecular docking and molecular dynamics (MD) simulation studies were employed to investigate the anti-inflammatory mechanism. Our obtained results validated that the level of NO was significantly decreased in the macrophage cell suspensions as a response to salvimulticanol treatment in a dose-dependent manner (IC50: 25.1 ± 1.2µM) as compared to the methyl ester of candesalvone B which exerted a weaker inhibition (IC50: 69.2 ± 3.0µM). This decline in NO percentage was comparable with a down-regulation of iNOS expression by western blotting. Salvimulticanol strongly interacted with both the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex and the inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ) to disrupt their inflammatory activation due to the significant hydrogen bonds and effective interactions with amino acid residues present in the target proteins' active sites. S.multicaulis is a rich natural source of the aromatic abietane diterpenoid, salvimulticanol, which exerted a strong anti-inflammatory effect through targeting iNOS and diminishing NO production in LPS-induced RAW264.7 cells in a mechanism that is dependent on the inhibition of TLR4-MD-2 and IKKβ as activators of the classical NF-κB-mediated inflammatory pathway.

Practice and relevance of sports psychiatry in promoting athletes’ mental health in Japan

Abstract: Introduction: This article outlines the important and varied role of sports psychiatrists in Japan and highlights the unique challenges and contributions of sports psychiatry to improving the mental health and performance of athletes. The report emphasizes the need for accurate assessment, diagnosis and treatment of mental health problems in athletes and recognizes the cultural stigmas and pressures specific to competitive sport in Japan. Methods: The paper first reviews the development of sports psychiatry with reference to the founding principles of the International Society for Sports Psychiatry and the Japan Association of Sports Psychiatry. It examines the integration of sport into psychiatric care and vice versa and indicates the value of research in the relationship between exercise and mental well-being. Results: This paper also explores the development of comprehensive diagnostic guidelines, the creation of tailored therapeutic approaches in clinical practice, the promotion of collaborative research to advance the field, and the educational development of psychological specialists. The role of sport psychiatrists in education and public awareness is examined, as well as the importance of destigmatizing mental illness in sport and improving mental health literacy among athletes and their support networks. Conclusion: Overall, this article describes the evolving and multifaceted role of sports psychiatrists in Japan, highlighting their crucial contributions to athlete care, research, education and public awareness. It advocates a flexible and adaptable approach to meeting the ever-changing demands of sports and upholding the mental health needs of athletes.