bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of osimertinib plus consolidative stereotactic ablative radiation (SABR) in advanced EGFR mutant non-small cell lung cancer (NSCLC): Results from a multi-center phase II trial.
Authors: Rashdan Sawsan , Sampath Sagus , Iyengar Puneeth , Dowell Jonathan , Ahn Chul , Westover Kenneth D. , Zhang Yuanyuan , Cole Suzanne , Massarelli Erminia , Amini Arya , Koczywas Marianna , Gerber David E
Published: June 2024

8518

Background: Despite high response rates to EGFR inhibitors, patients with advanced EGFR mutant NSCLC generally experience disease progression within two years (osimertinib median PFS 18.9 months, median OS 38.6 months). We sought to determine whether administration of SABR to residual sites of disease at the time of expected best response to EGFR inhibition could prolong disease control. Methods: This was a multi-center single-arm phase 2 study. Eligible patients had advanced EGFR mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; no prior treatment with EGFR inhibitors or immune checkpoint inhibitors; and no history of interstitial lung disease. Patients with stable or responding disease after 8 weeks of osimertinib received SABR to persisting lesions, followed by continued osimertinib until progression or intolerance. At subsequent progression, patients could receive further SABR and continue osimertinib if deemed clinically feasible and appropriate. The primary endpoint was progression-free survival (PFS); secondary endpoints included duration on osimertinib, toxicity, and overall survival (OS). Results: A total of 43 patients (32 women, 11 men) were enrolled and initiated osimertinib, of whom 29 (67%) received SABR. Reasons SABR was not administered included inadequate response (9%), insufficient residual disease (19%), and other (5%). At a median follow-up of 35.7 months (95% CI, 28.8, 37.6), 42 evaluable patients had a median PFS of 32.6 months and a median OS of 45.7 months. The median duration of osimertinib was 31.5 months. Grade ≥3 toxicities included one incidence each (2%) of the following: pain at the site of radiation, paronychia, liver enzyme elevation, fatigue, hyponatremia, diarrhea, and pneumonitis. Conclusions: Osimertinib plus consolidative SABR appears to provide a PFS and OS benefit when considered against historical data with osimertinib alone. This treatment strategy may offer a well-tolerated and practical approach to improving outcomes for patients with advanced EGFR mutant NSCLC. Clinical trial information: NCT03667820 .
Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05.
Authors: Lisberg Aaron , Ahn Myung-Ju , Kitazono Satoru , Cho Byoung Chul , Blumenschein George R. , Shum Elaine , Pons-Tostivint Elvire , Goto Yasushi , Yoh Kiyotaka , Paz-Ares Luis G. , Heist Rebecca Suk , Baas Paul , Planchard David , Perol Maurice , Felip Enriqueta , Su Wu-Chou , Zebger-Gong Hong , Lan Lan , Liu Chelsea , Sands Jacob
Published: June 2024

8593

Background: Brain metastases (mets) occur frequently in pts with NSCLC, particularly pts with certain AGAs, and indicate poor prognosis. For pts with AGAs, treatment options are limited once targeted therapy and platinum-based chemotherapy (Pt-CT) become ineffective. The phase 2 TROPION-Lung05 trial (NCT04484142) of Dato-DXd has demonstrated systemic efficacy and a manageable safety profile in heavily pretreated pts with a/m NSCLC with AGAs who progressed following targeted therapy and Pt-CT; here we report an exploratory analysis of intracranial (IC) efficacy. Methods: Pts were treated with Dato-DXd 6 mg/kg IV Q3W. Pts with clinically stable brain mets were eligible. IC responses were assessed by blinded independent central review (BICR) of cranial CT/MRI (CNS BICR; per CNS RECIST) at baseline (BL) and Q6W. Systemic objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR, defined as CR+PR+SD or non-CR/non-PD lasting ≥6 mo), progression-free survival (PFS) by BICR per RECIST 1.1 and treatment-related adverse events (TRAEs) were determined in pts with and without BL brain mets. Results: In total 53/137 (39%) treated pts had BL brain mets; 29/53 (55%) had an EGFRmutation. Pts with BL brain mets had a median (range) of 3 (2–6) prior systemic therapies in the a/m setting, including targeted therapy and Pt-CT with/without immune checkpoint inhibitors; 15/53 (28%) had untreated brain mets. At data cutoff (Dec 14, 2022), median (range) study and treatment durations among pts with BL brain mets were 14.8 (9.7–20.5) and 3.2 (0.7–17.2) mo, respectively. Of these pts, 18/53 (34%) had measurable IC target lesions (3 untreated) and 35/53 (66%) had only non-target IC lesions. In 18 pts with target lesions, IC ORR was 22% (95% CI, 6–48), including 1 of 3 pts with untreated target lesions; IC DCR was 72% (95% CI, 47–90); IC CBR was 44% (95% CI, 22–69). Reduction in the sum of diameters of brain lesions was seen in 10/18 (56%). Median time to IC response was 1.5 (range, 1.3–5.4) mo; median duration of IC response was 5.5 (95% CI, 3.4–NE) mo Systemic efficacy and safety were similar in pts with and without BL brain mets (Table). Conclusions: Dato-DXd showed encouraging IC activity consistent with systemic responses in pts with a/m NSCLC with AGAs, supporting further investigation of Dato-DXd in pts with brain mets. Clinical trial information: NCT04484142 . [Table: see text]
Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in non-small-cell lung cancer (NSCLC) with KRAS G12C mutation: Results from a phase Ib/II study.
Authors: Song Zhengbo , Li XingYa , Lin Rongbo , Yuan Yuan , Shi Huaqiu , Liu Ying , Luo Yongzhong , Lv Tangfeng , Zhang Yiping , Zhu Yinxin , Wang Zaiqi
Published: June 2024

8605

Background: KRAS G12C mutation is present in about 12-14% of NSCLC population. Ifebemtinib (IN10018) is a highly potent and selective oral inhibitor of focal adhesion kinase (FAK). D-1553 (garsorasib) is a novel oral and potent KRAS G12C inhibitor. Preclinical data showed that ifebemtinib in combination with KRAS G12C inhibitors had synergistic anti-cancer effect in multiple KRAS G12C mutant cancer models. This study is to evaluate the safety and antitumor activity of ifebemtinib combined with D-1553 in solid tumors with KRAS G12C mutation. Here we report the preliminary data from phase II part of front-line NSCLCs with KRAS G12C mutation. Methods: Locally advanced or metastatic NSCLC subjects without prior systemic anti-cancer therapy were enrolled. Subjects were required to have KRAS G12C mutation in tumor tissues. All subjects were assigned to the recommended phase II dose (RP2D) of ifebemtinib (100mg qd) + D-1553 (600mg bid). Results: As of 31 January 2024, 33 front-line NSCLC subjects with KRAS G12C mutation were enrolled and received the combination therapy. Median age was 65yrs (range 58, 83), 93.9% were male, and 81.8% had stage IV metastatic disease. Median study follow-up (FU) was 2.2 months (range 1.1, 9.2). The safety profile of the combination therapy is comparable to each single agent without additive toxicities. No ifebemtinib- or D-1553-related death was reported. Four subjects (12.1%) had ifebemtinib-related SAEs (diarrhea, enteritis, oedema peripheral and proteinuria) as assessed by investigators, and all SAEs were also considered D-1553 related. Six subjects (18.1%) had ≥ Grade 3 ifebemtinib-related AEs as assessed by investigators, and all were also D-1553 related AEs. The majority of ifebemtinib-related AEs were CTCAE Grade 1 or 2. There was no event leading to study treatment discontinuation. We have observed continuing tumor shrinkage in almost all subjects who had at least 2 tumor assessments. Among 16 subjects with ≥ 3 months FU, preliminary efficacy found that 14 had best overall response of partial response (PR) including 12 confirmed PRs and 2 unconfirmed but still in treatment, 1 had stable disease (SD), and 1 had progressive disease (PD). The overall response rate (ORR) was 87.5% (95%CI: 56.6, 96.2), and disease control rate (DCR) was 93.8% (95%CI: 63.6, 98.5). The median duration of response (DOR), median progression-free survival (PFS) and overall survival (OS) have not been reached. Conclusions: The combination of ifebemtinib and D-1553, as a dual-oral regimen, showed promising antitumor activity and manageable safety profile in KRAS G12C mutant front-line NSCLC population. Long term follow-up is needed to assess the potential of such novel combo. Clinical trial information: NCT06166836 ; NCT05379946 .
Bevacizumab in combination with chemotherapy for treating patients with advanced RET+ non-small cell lung cancer.
Authors: Aldea Mihaela , Marinello Arianna , Monnet Isabelle , de Saint Basile Hortense , Cousin Sophie , Duruisseaux Michaël , Calles Antonio , Metro Giulio , Zugazagoitia Jon , Massa Giacomo , Gomez Patricia , Tabbò Fabrizio , Russo Alessandro , Fallet Vincent , Lindsay Colin R , Bria Emilio , Eisert Anna , Guisier Florian , Planchard David , Besse Benjamin
Published: June 2024

8647

Background: RET inhibitors (RETi) are currently the preferred first-line treatment in advanced RET fusion-positive (RET+) non-small cell lung cancer (NSCLC). Despite impressive efficacy of RETi, resistance is inevitable, and the optimal therapy beyond RETi remains unclear. Immunotherapy has shown limited efficacy in these patients. This study aims to investigate the impact of adding bevacizumab to chemotherapy regimens on treatment outcomes. Methods: This multicenter, retrospective study included patients with RET+ advanced NSCLC who received either a platinum-doublet chemotherapy (D) (+/-anti-PD-L(1) agents (ICB)) or a non-platinum monotherapy (M), with or without bevacizumab (Bev). Non-platinum agents were limited to pemetrexed, paclitaxel, or docetaxel. Only the first administration of the regimen was considered. Objective responses (OR), progression-free survival (PFS), and overall survival (OS) from the start of treatment were compared between patients receiving and not receiving Bev. Results: Of 185 patients, 20 received Bev in doublet chemotherapy (D+Bev, none with ICB) and 165 did not (D, 68 with ICB). Additionally, 40 underwent single-agent chemotherapy, with 8 on Bev (M+Bev) and 32 without (M). D+Bev patients were younger (median age: 54 vs. 61 years, p=0.026), less often treated with RETi (55% vs. 79%, p=0.023), with no other demographic or disease-related group differences. Both D+Bev and D had a median of 1 treatment line [IQR 1-1]. M+Bev and M had a median of 3 and 2 treatment lines, respectively (p=0.3), and numerically more M+Bev patients had brain metastases (25% vs. 13%, p=0.6). In the D+Bev vs D (+/-ICB) comparison, the OR was 55% vs 47% (p=0.7), and the median PFS was significantly longer in the D+Bev group (17 months vs. 8.8 months, p=0.018). When comparing D+Bev with D+ICB, D+Bev still showed a significant advantage in median PFS (17 months vs 9.7 months, p=0.05). The median OS was 51.4 months for D+Bev compared to 38.7 months for D (p=0.89). Multivariate analysis revealed that Bev use was independently associated with longer PFS (hazard ratio [HR] 0.4, p=0.01), while ECOG>1 (HR 4.3, p<0.0001) and male sex (HR 1.7, p=0.01) were associated with shorter PFS. In the M+Bev versus M group, the OR was 13% versus 25% (p=0.6), median PFS was 2.4 months versus 4.1 months (p=0.06), and median OS was 12.1 months versus 39 months (p=0.06). Conclusions: Bevacizumab with platinum-doublet chemotherapy seems to outperform platinum-doublet with or without ICB in progression-free survival. Prospective research is needed to evaluate the extent of bevacizumab's benefit for RET+ NSCLC.
Decision making in oncology: Unleashing the power of artificial intelligence—Beyond the question of feasibility.
Authors: Gil Deza Ernesto , Garcia Gerardi Carlos , Gil Deza Lourdes , Abal Mariana , Smolje Leonel , Jaunarena María del Huerto , Tognelli Flavio A , Norese Gabriela , Martin Reinas Gaston , Gercovich Daniela
Published: June 2024

9021

Background: This study examines how consulting artificial intelligence (Chat GPT, Bard) or electronic tools (Apps, Journal or Guidelines) affects the decision-making process in Oncology Fellows. Methods: In the OSCE IOHM-USAL 2023, Oncology Fellows (2022 and 2023 cohorts) individually answered stations I and II, both spontaneously and after AI consultation. Group responses for stations III and IV were also gathered. Sign tests compared pre- and post-consultation responses in stations I and II while the impact of AI in stations III and IV was individually assessed on a five-point scale (0= Null and 5= Extremely useful). Results: 15 Oncology Fellows participated in OSCE 2023- 14 Females. Median age: 30 (r=28-36). A) Stations I - II Cases: Case1: 70 y. Non smoker. PS 0. Stage IV NSCLC. PS 0. EGFR mutated E746 _A750. PDL1 90%. Case 2: 52 y. Postmenopausal Stage II Luminal B Her2 negative Breast cancer (pT2, pN1, M0). Case 3: 35 yo. Advanced colon cancer. Stage IV. BRAF p(V600E) c.1799 A>C. No Micorsatellite Instability. B) Station III (Ethics Committee), the following cases were addressed: 4. “BRCA1: Insured, not excluded”. 5. “Smoke vs. oath? Tough choice” 6. “Follow Lynch path, or HMO exit”. In all three cases, 3/15 students reported finding AI useful in the discussion. C) Station IV (Tumor board), the following cases were addressed: 7. “Postmenopausal NOS IBC (pT1c pNmic Luminal B Her2 negative)”. 8. “Oncology emergency in a 22 y male patient testicular tumor pending pathology”. In Case 7, 3/15 students reported finding AI useful in the discussion. In Case 8, 4/15 students reported finding AI useful. Conclusions: 1. A study of 15 oncology fellows found no appreciable influence of AI on clinical decision-making. 2. Analysis of eight cases (individual/collective) identified anchor value, optimistic denial, and confirmation bias in reasoning and processing. 3. Fellow training in critical AI analysis and outcome evaluation is imperative. [Table: see text]
Roll out and influence of an educational program: Talking about risk, uncertainties of testing in genetics (TRUSTING).
Authors: Jenkins Valerie A. , Habibi Ruth , Hall Virginia , Leonard Pauline , Lawn Annaliese , Naik Jay , Papps-Williams Rachel , Fallowfield Lesley
Published: June 2024

9025

Background: Family history clinics face significant capacity issues making calls for genetic testing of all breast cancer (BC) patients problematic. Mainstreaming of services by health care professionals (HCPs) is needed but many lack confidence and familiarity with genetic counseling. Following successful development and evaluation of the TRUSTING educational program (Fallowfield et al. BJC 2022), facilitators were trained to roll out workshops for BC HCPs. Here we report the workshops’ effect on participants’ knowledge, skills, and self-confidence and influence on mainstreaming. Methods: 1 surgeon, 3 oncologists, 1 nurse specialist facilitated the 8-hr program in pairs. Workshop content included didactic components to enhance knowledge and various exercises to promote self-awareness about individual participants’ tolerance to uncertainty and risk. Groups discussed 6 filmed scenarios showing interactions between surgeons and geneticists with the proband (triple negative BC and BRCA2 pathogenic gene alteration), her sister (BRCA2 +) and their anxious cousin (BRCA2 -). Pre-workshop, participants completed: - 1) an 18-item multiple choice knowledge questionnaire about gene testing in breast cancer 2) a 9-item questionnaire exploring self-confidence when discussing/advising patients about different aspects of BRCA testing, results, and treatments and 3) an Intolerance to Uncertainty Scale. Knowledge and self-confidence together with general feedback questions about overall satisfaction with facilitators and the event were assessed post workshop. Follow-up questionnaires sent 3-12 mths later examined the impact TRUSTING workshops had made on participants’ own practice and implementation of mainstreaming in their clinic. Results: 120 participants (61 surgeons; 41 nurses; 9 oncologists; 9 other) attended 12 UK workshops. There were improvements post workshop in knowledge (mean change = 6.57; 95% CI 5.97 to 7.16; p<0.001) and self-confidence (mean change = 2.64; 95% CI 2.33 to 2.95; p<0.001). Feedback about the facilitators’ approach was uniformly high (mean range 9.65 to 9.90 /10). Most found workshops useful, enjoyable, and informative; 98% would definitively recommend them to colleagues. Follow up data revealed that attendance significantly impacted individuals’ own practice with 59% reporting it had improved their discussions about genetic testing with patients. When asked about mainstreaming more generally 81% reported it as “OK” or “working very well”, others (16%) that it had not yet started or (3%) that it was problematic. Conclusions: Discussing the implications of pathogenic gene alterations on patients’ treatment and risk-reducing interventions is complex when patients are already coming to terms with a BC diagnosis. The TRUSTING educational program is an effective means of helping HCPs now involved in the mainstreaming of genetic testing.
Training of clinical oncologists in Africa: Results of a regional survey.
Authors: Okwunze Franklin Kenechukwu , Yesufe Abdu Adem , Abdou Aalaa Mahmoud Hassan , Omoleye Olasubomi Jimmy , Senyuy Wah Praise , Grover Surbhi , Anakwenze Chidinma Pamela
Published: June 2024

9026

Background: Africa grapples with a significant human resource shortage in cancer care. The vast majority of practicing oncologists are clinical oncologists, performing the roles of both medical and radiation oncologists. Building a sustainable oncology workforce depends on robust training pipelines. However, the distribution and characteristics of oncology training programs across the continent have not been described. Methods: A cross-sectional study was conducted to outline the landscape of postgraduate clinical oncology training in Africa. A semi-structured electronic questionnaire designed to collect data on locations and capacity of training centers, components of training curriculum, and administration of training programs was distributed via e-mail between February and May 2023 to board-certified clinical oncology consultants practicing in Africa. Participants were identified through the personal contacts of the co-authors. Results: Responses were received from 31 oncologists practicing in 24 countries. We identified 74 centers in 16 countries (67%) with ongoing clinical oncology training, and Egypt, South Africa, and Tunisia accounted for two-thirds of all training centers identified. Duration of training ranged from 4 to 8 years. Each year, about 230 residents commence training, and 198 graduate from training and join the workforce. More than half of the countries with available data require an internship and passing an entrance examination before commencing training. Almost all countries require trainees to pass an exit examination and submit a thesis before completing training. We obtained data on training components in 19 (26%) centers, and all centers provide training in chemotherapy administration and radiotherapy techniques. However, marked variations were observed in the exposure to modern radiotherapy techniques, with 10 (53%) centers including IGRT and 5 (26%) including IMRT. More than three-quarters of respondents reported that most trainees find jobs in the government service after completing training. Conclusions: Clinical oncology training programs in Africa are relatively limited in number. Moreover, there is a wide variation in the existing programs in terms of training duration and components of curriculum. There is tremendous potential for expansion to countries without training, which can be facilitated by partnerships with existing training programs on the continent. Furthermore, regional coordination and accreditation is vital to ensure uniformity.
Integration of a focused podcast curriculum (PC) to improve hematology oncology fellow (HOF) knowledge: A multi-center cluster randomized controlled trial.
Authors: Patel Vivek , Tawagi Karine , Armstrong Samantha Ann , Hausrath Daniel , Abuali Inas , Taasan Sean , Mian Agrima , Wilson Nathaniel R. , Egert Daniel , Stoen Ericson , Itani Aleena , Berardi Giuliana , Lee Yurhee , Pachika Pranali Santhoshini , Mistry Ronak
Published: June 2024

9041

Background: Several studies demonstrate widespread use of medical podcasts as learning resources. Utility of integration of educational podcasts in fellowship curricula remains unknown. Here we describe a multicenter cluster randomized trial comparing a supplemental PC with standard curriculum (SC) to SC alone for HOF. Methods: HO fellowship programs in the United States were eligible. One HOF from each program was invited via email to participate as a local PI. The trial protocol was reviewed by program directors for approval. Programs were cluster randomized to novel PC with SC (intervention) or SC alone (control). Permuted block randomization stratified by program size was performed using STATA. The PC arm was given access to a website developed by the study team with links to podcasts episodes (PE) covering 4 topics: breast oncology, myeloma, bleeding disorders, and HIT. Written show notes (SN) were provided as separate links. PE and SNs were previously developed employing an inductive approach and released by The Fellow on Call and Two Onc Docs podcasts and are freely available. Pre and post qualitative surveys (QS) and knowledge assessments (KA) were administered via REDCAP. QS utilized a 7-point Likert score. KAs were peer reviewed by expert disease-specific faculty. QS and KA links were included on the PC website. To maintain blinding, the SC arm was given a separate website with these links. HOF participation was voluntary. To improve enrollment, at minimum, QS completion was required; KA was optional. Baseline data was obtained from October to November 2023. Post data cut off will be June 2024. Power calculation was based on mean difference in comfort level and knowledge. Assuming a mean improvement by 0.5 points for QS, a total sample size of 210 HOF, 11 clusters in each arm would provide at least 80% power assuming a standard deviation (SD) of 1, intracluster correlation coefficient (ICC) of 0.05, and coefficient of variation of cluster sizes of 0.7. For improvement in KA by 10%, a total sample size of 60 HOF would provide the same power assuming SD of 15%. We therefore planned to recruit 30 HO programs to account for non-response rates. IRB review deemed the study exempt. Results: Baseline characteristics from 28 randomized programs are presented below. Conclusions: This is the first randomized education trial in graduate medical education of its kind with a priori power calculations. Our innovative use of HOF as local PIs may have led to increased participation in KAs. Recruited sites will serve as a consortium for future multicenter education research. Interim analysis will be presented at ASCO 2024. [Table: see text]
CYP17A1 Pathogenic Variants in 26 Chinese Patients With 17α-Hydroxylase Deficiency by Targeted Long-Read Sequencing
Authors: Cao Yaqing , Zhao Zhiyuan , Lu Lin , Zhang Xiaoxia , Zhang Wei , Sun Bang , Tong Anli , Chen Shi , Wang Xi , Mao Jiangfeng , Wu Xueyan , Nie Min
Published: June 2024

Background

17α-hydroxylase/17,20-lyase deficiency (17-OHD) is a rare subtype of congenital adrenal hyperplasia caused by homozygous or compound heterozygous pathogenic variants in the CYP17A1 gene.

Purpose

This study aimed to identify and characterize pathogenic variants in individuals with 17-OHD and to classify and validate the pathogenicity of novel variants.

Methods

Variants were identified via targeted long-read sequencing (TLRS) of the entire CYP17A1 gene in enrolled 17-OHD patients. The American College of Medical Genetics and Genomics (ACMG) guidelines were employed to assess the pathogenicity of novel variants. Minigene splicing assays were utilized to determine the impact of variants on RNA splicing.

Results

This study encompassed 26 patients with 17-OHD, detecting 2 trans pathogenic variants per patient using the TLRS method. A total of 20 pathogenic variants in the CYP17A1 were identified, with variant c.985_987delinsAA being the most frequent (28/52 alleles), followed by variant c.1459_1467del (4/52 alleles). Five novel variants including c.280T > C, c.470T > A, c.636_637del, c.866A > G, and c.1095del, were classified as pathogenic/likely pathogenic ones according to ACMG criteria. The minigene splicing assays revealed c.866A > G in exon 5 causes a frameshift due to a 104 base pair deletion, while c.470T > A generates 2 transcripts, with the vast majority spliced like the wild-type and a small fraction lacking 35 base pairs in the 5′ flank of exon 3.

Conclusion

The TLRS can determine the cis/trans orientation of 2 distant variants. Five novel pathogenic variants were reported, broadening the spectrum of the CYP17A1 pathogenic variants. The variant c.866A > G, located deep in the exon, affects gene function through mechanisms of aberrant splicing.
Successful Pregnancy in Isolated 17,20-lyase Deficiency Without Glucocorticoid Use or Assisted Reproduction Techniques
Authors: de Oliveira Julia Martins , Genari Celso Monteiro , Sobral Paulo Marcelo , Kater Claudio Elias , Costa-Barbosa Flavia Amanda
Published: June 2024

Isolated 17,20-lyase deficiency (ILD) is a partial form of 17α-hydroxylase/17,20-lyase deficiency that typically presents with infertility and lack of pubertal development. Successful live births have been achieved using assisted reproductive techniques. We present a case of spontaneous pregnancy in an 18-year-old female with ILD without reproduction treatments or glucocorticoid use. She presented to our clinic with absence of pubarche and oligomenorrhea and had typical external genitalia and complete breast development. Follicular phase progesterone and estradiol were within reference values, and androgen levels were undetectable. Corticosterone was increased, and cortisol responded partially to the ACTH-stimulation test. This profile raised a suspicion for ILD, which was confirmed by the finding of the homozygous p.R347H variant in the CYP17A1 gene. Sex steroid replacement and glucocorticoid use during stress were prescribed. She returned 2 years later 20 weeks pregnant. Her gestation was uneventful, and a full-term healthy male was born. This phenomenon could be partially explained by sufficient estrogen synthesis via residual 17,20-lyase enzymatic activity. Intermittent estradiol use may have favored uterine development and fine-tuned the pituitary-gonadal axis rhythm. Normal progesterone levels may have permitted an adequate endometrial “implantation window” without glucocorticoid use. Finally, elevated corticosterone may have compensated for the partial cortisol deficiency.
Street Scenes: Langston Hughes, Lyric Pop, and Walter Benjamin’s Baudelaire
Authors: Kilbane Matthew
Published: June 2024

This article frames Langston Hughes’s 1947 collaboration with composer Kurt Weill on the “Broadway opera” Street Scene as a privileged opportunity to explore modern history’s extraordinary claims on poetic language and the limitations of allegoresis as a critical mode. Foregrounding Hughes’s understudied career as a pop songwriter, the article argues that the fragmented, unruly archive of the poet’s songwriting demands to be read allegorically, after the fashion of Walter Benjamin’s writings on Charles Baudelaire, whose own fusion of lyric and commodity forms anticipates Hughes’s pop lyrics. Ultimately, when we position Hughes as a successor of sorts to Benjamin’s Baudelaire, that “poet in the age of high capitalism,” we are invited at least temporarily to relieve the allegorical gaze of its restless search for hidden springs of critical agency and to relieve it, too, of its quest for the consolations of utopia. Hughes’s collaborative work on Street Scene instead teaches us how to locate and extol in seemingly compromised cultural artifacts an allegorical resourcefulness that precedes reception and is in fact synonymous, in Hughes’s case, with poetic making.
Las costuras de Buenos Aires a mediados del siglo xix: Una historia social con perspectiva de género del trabajo de la aguja y el hilo
Authors: Mitidieri Gabriela
Published: June 2024

Hacia 1850, en Buenos Aires, la costura era una actividad que realizaban diferentes personas en sitios diversos. Podía ser parte de un oficio artesanal, una labor femenina, un castigo productivo o una de las tareas que se esperaban del servicio doméstico. Observar esas distinciones y distancias vuelve a la aguja y al hilo un prisma para interrogarnos por las jerarquías sociales –de género, raza y edad– que estructuraron este mercado de trabajo e incidieron en la construcción de nociones de derechos y justicia, así como para identificar el lugar que ocupó este puerto sudamericano en una trama global de procesos de industrialización, nuevas pautas de consumo y movimientos migratorios. A través del análisis de un nutrido corpus documental, este estudio realiza un aporte desde la historia social con perspectiva de género al ofrecer una mirada del período al ras de experiencias sociales de trabajo.
“The Age of Malice”: Estupro, Consent, and the Foundations of Victim Blaming in the Criminal Courts of Buenos Aires, 1853–1878
Authors: Ogden Julia
Published: June 2024

This article examines the judicial treatment of pubescent, female victims of sexual assault in Buenos Aires, Argentina, between 1853 and 1878, dates that span the decades between the national constitution and the adoption by Buenos Aires Province of new penal legislation. Centering the case of 13-year-old Irene Mestosini, it analyzes the prosecution of estupro cases through the paradigm of rape culture and victim blaming. It exposes how, by casting pubescent girls as malicious because of their physical and mental development, authorities blamed them for their assault while dismissing men's aggressive sexuality. By illustrating the ways in which physiological development worked alongside legal cultures, class expectations, and heteronormative gender norms to create a culture of impunity around sexual assault, this article suggests that modern notions of acceptable and unacceptable sexuality emerged in Buenos Aires earlier than in other parts of Latin America, where honor remained a central concern well into the twentieth century.
Colonial Exiles: The Tambora Volcanic Explosion, Environmental History, and Swiss Immigration to Nova Friburgo, Brazil, 1815–1821
Authors: Clavel Damian , Hecht Susanna B.
Published: June 2024

The 1815 eruption of the Indonesian volcano Mount Tambora triggered a subsistence crisis in Europe, especially in Switzerland. This article retraces the founding of Nova Friburgo, a colony in the mountains near Rio de Janeiro composed of several hundred Swiss families, mostly from the rural canton of Fribourg. This study shows how the unusual central European settler migration to the Brazilian tropics was facilitated by a new class of entrepreneurial go-betweens, acting as dynamic mediators between the effects that the climatic catastrophe caused by Tambora had on Swiss agriculture and politics and the development requirements for building new settlements in a metamorphosing South American continent. By positioning Brazil in the broader environmental history of Tambora, as well as the fallout from the Napoleonic Wars, this article sheds light on how the study of climatic teleconnections requires multiple scales of analysis to understand better how the different politics and scopes of action, and sets of unlikely processes, move into play. These teleconnections were, in fact, socially mediated with eventually wide-reaching social and racial transformations that became foundational prototypes for Brazilian land colonization throughout the nineteenth and into the twentieth century.
The Crying Statue in Early Qing Drama
Authors: Kelly Thomas
Published: June 2024

Should the theatrical fantasy of a statue coming to life involve an actor performing the role of a thing, or a prop taking the place of a human? Proceeding from contests between Hong Sheng 洪昇 (1645–1704) and acting troupes over the staging of the “Crying Statue” 哭像 (Kuxiang) scene in his dramatic masterpiece Palace of Lasting Life (Changsheng dian 長生殿), this article examines how the figure of the living icon became a focal point in broader struggles to conceptualize the relationship between theater and rituals of mourning. Actors staged this complicated scene as an “auspicious sacrifice” (jiji 吉祭), one that foregrounds the transcendence of love over lifeless matter. Hong, conversely, insists on the function of the scene as an “unpropitious rite” (xiongdian 凶奠), a solemn meditation on mortality and the collective expression of grief. By redirecting focus from the object to the space and social dynamics of mourning, Hong questions the drive to bestow on things a life that is not their own.
Excited Delirium
Authors: Beliso-De Jesús Aisha M.
Published: June 2024

In 1980, Charles Wetli---a Miami-based medical examiner and self-proclaimed “cult expert” of Afro-Caribbean religions---identified what he called “excited delirium syndrome.” Soon, medical examiners began using the syndrome regularly to describe the deaths of Black men and women during interactions with police. Police and medical examiners claimed that Black people with so-called excited delirium exhibited superhuman strength induced from narcotics abuse. It was fatal heart failure that killed them, examiners said, not forceful police restraints. In Excited Delirium, Aisha M. Beliso-De Jesús examines this fabricated medical diagnosis and its use to justify and erase police violence against Black and Brown communities. Exposing excited delirium syndrome's flawed diagnostic criteria, she outlines its inextricable ties to the criminalization of Afro-Latiné religions. Beliso-De Jesús demonstrates that it is yet a further example of the systemic racism that pervades law enforcement in which the culpability for state violence is shifted from the state onto its victims. In so doing, she furthers understanding of the complex layers of medicalized state-sanctioned violence against people of color in the United States.
Validation and Comparison of Common Thoracolumbar Injury Classification Treatment Algorithms and a Novel Modification
Authors: Withrow Joseph , Trimble Duncan , Narro Analisa , Monterey Michael , Sheinberg Dallas , Dono Antonio , Haley Lauren , Cruz Marco Martinez , Zaragoza Jennifer , Li Wen , Quinn John
Published: June 2024

BACKGROUND AND OBJECTIVES:

The most common thoracolumbar trauma classification systems are the Thoracolumbar Injury Classification and Severity Score (TLICS) and the Thoracolumbar AO Spine Injury Score (TL AOSIS). Predictive accuracy of treatment recommendations is a historical limitation. Our objective was to validate and compare TLICS, TL AOSIS, and a modified TLICS (mTLICS) that awards 2 points for the presence of fractured vertebral body height loss >50% and/or spinal canal stenosis >50% at the fracture site.

METHODS:

The medical records of adult patients with acute, traumatic thoracolumbar injuries at an urban, Level 1 trauma center were retrospectively reviewed. TLICS, mTLICS, and TL AOSIS scores were calculated for 476 patients using computed tomography, MRI, and the documented neurological examination. Treatment recommendations were compared with treatment received. Standard validity measures were calculated.

RESULTS:

Treatment recommendations matched actual treatments in 95.6% (455/476) of patients for mTLICS, 91.3% (435/476) for TLICS, and 92.6% (441/476) for TL AOSIS. The differences between the accuracy of mTLICS and TLICS (95.6% vs 91.3%, P < .001) and between mTLICS and TL AOSIS (95.6% vs 91.3%, P = .003) were significant. The sensitivity of mTLICS was higher than that of TLICS (96.3% vs 81.3%, P < .001), and the sensitivity of TL AOSIS was higher than that of TLICS (92.5% vs 81.3%, P < .001). The specificity of mTLICS was equal to that of TLICS (95.3%) and higher than that of TL AOSIS (95.3% vs 92.7%, P = .02). The modifier led to substantial outperformance of mTLICS over TLICS due to 38 patients (20 of whom received surgery) moving from a TLICS score of <4 to a mTLICS score equal to 4.

CONCLUSION:

All systems performed well. The mTLICS had improved sensitivity and accuracy compared with TLICS and higher accuracy and specificity than TL AOSIS. The sensitivity of TL AOSIS was higher than that of TLICS. Prospective, multi-institutional reliability and validity studies of this mTLICS are needed for adoption.
The T1/T2 Ratio is Associated With Resectability in Patients With Isocitrate Dehydrogenase–Mutant Astrocytomas Central Nervous System World Health Organization Grades 2 and 3
Authors: Weller Jonathan , de Dios Eddie , Katzendobler Sophie , Corell Alba , Dénes Anna , Schmutzer-Sondergeld Michael , Javanmardi Niloufar , Thon Niklas , Tonn Joerg-Christian , Jakola Asgeir S.
Published: June 2024

BACKGROUND AND OBJECTIVES:

Isocitrate dehydrogenase (IDH)–mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas.

METHODS:

Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS.

RESULTS:

The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 vs 4.6 cm3, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01).

CONCLUSION:

The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.
Preoperative Prediction of Long-Term Survival After Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma
Authors: Konishi Takanori , Takano Shigetsugu , Takayashiki Tsukasa , Suzuki Daisuke , Sakai Nozomu , Hosokawa Isamu , Mishima Takashi , Nishino Hitoe , Suzuki Kensuke , Nakada Shinichiro , Ohtsuka Masayuki
Published: June 2024

Background

Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy.

Patients and Methods

A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated.

Results

The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery.

Conclusions

We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.
Многоязычие добровольное, естественное или принудительное
Authors: Krasowska Helena
Published: June 2024

The article describes different types of multilingualism of Poles in Chisinau. The author comes to the conclusion that the voluntary multilingualism among the Poles in Chisinau was caused by several factors, first of all, it was inspired by the language policy implemented in school education, in administration. Polyakov Chisinau also characterizes the natural multilingualism that arose as a result of mixed marriages. Among the Poles of Chisinau, we also encounter a kind of imposed multilingualism, when the authorities introduced the Moldovan language into schools, state-administrative institutions, but the Russian language was also imposed, as mentioned by the respondents. As a result, a language conflict arose not only in Chisinau, but also in the Republic of Moldova as a whole. The language conflict is thus a consequence of political conflicts in the state.
Régimen jurídico del teletrabajo. Comentario de la sentencia del Tribunal Supremo, Sala de lo Social, de 19 de septiembre de 2023 (rec. 260/2021).
Authors: Carmona Pozas Francisco
Published: June 2024

Motivado por una legislación coyuntural de urgencia, en especial el Real Decretoley 8/2020, de medidas urgentes extraordinarias para hacer frente al impacto económico y social del “Covid-19” y el Real Decreto-ley 28/2020 de trabajo a distancia, la sentencia de referencia despliega un interesante estudio a partir de su conflicto central, cifrado en un diferente tratamiento empresarial de sus trabajadores en orden al cómputo del tiempo carente de actividad productiva debido a desconexiones que impidan la prestación, incidencia imputable a la empresa suministradora. Del mismo tenor litigioso se plantea el cómputo del tiempo para atender las necesidades fisiológicas de los trabajadores, excluibles del resto de descansos y computables de forma autónoma. El sindicato accionante dedujo demanda de conflicto colectivo frente a la empresa, reclamando como “tiempo de trabajo” aquella incidencia debidamente acreditada (interrupción de suministro) e igualmente pausa autónoma y tiempo de trabajo efectivo computable en los supuestos de necesidades fisiológicas
Effects of brisk walking with or without music on body composition, standing balance, cardiovascular parameters, and salivary biomarkers in older women
Authors: Jinakote Metee , Jeeratantorn Punika , Surapolchai Lapol , Dornbunlon Punkorn , Yoysungnoen Bhornprom , Kasiyaphat Atchareeya
Published: June 2024

This study aimed to assess and compare changes in body composition, standing balance, cardiovascular parameters, and salivary biomarkers, particularly salivary antioxidant status, after brisk walking training with or without music in older women. Twenty-four subjects were randomly assigned to brisk walking groups: with music (BWM) (n = 12) or without music (BW) (n = 12). Eighteen subjects completed the exercise training (9 in each group), and their data were used for analysis. The research protocols were classified into three phases: pretraining phase, training phase, and posttraining phase, while the data collection was divided into four sessions: resting condition, during treadmill exercise testing, immediately posttreadmill exercise testing, and 5-min posttreadmill exercise testing defined as after the cool-down session. The results showed that 8 weeks of home-based brisk walking with or without music did not improve standing balance, blood pressure, salivary biomarkers including total protein concentration, and antioxidant status but maintained or prevented the decline of these parameters. Only the BWM group reduced fat mass relative to increasing fat-free mass (P < 0.05) and improved recovery heart rate (P < 0.05) by modifying cardiac autonomic control in posttreadmill exercise testing. Therefore, brisk walking with preferred music can be a tool to delay the progression of cardiovascular dysfunction in older women. A longer duration of the exercise program and larger groups of participants are needed for further investigation of brisk walking with or without music on physiological and biochemical changes.
Effects of robot rehabilitation on the motor function and gait in children with cerebral palsy: a systematic review and meta-analysis
Authors: Lim Jae-Hyun , Kang Eun-Young , Park Se-Ju , Kim Byeong-Geun
Published: June 2024

This study was to determine the effects of robot rehabilitation on motor function and gait in children with cerebral palsy (CP) and the effect of robot type. Inclusion criteria were children with any type of CP, robot rehabilitation studies, non-robot rehabilitation comparison groups, outcomes related to motor function and gait, and randomized controlled trials. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science databases were searched. Risk of bias was assessed using physiotherapy evidence database. Seven studies with a total of 228 participants were selected. Motor function was significantly improved in three studies comparing robot rehabilitation and control groups (standard mean difference [SMD], 0.79; 95% confidence intervals [CIs], 0.34–1.24; I2 = 73%). Gait was not significantly improved in five studies comparing robot rehabilitation and control groups (SMD, 0.27; 95% CI, -0.09 to 0.63; I2 = 45%). When comparing effects by robot type, robotic-assisted gate training (RAGT) showed significant improvements in both motor function (SMD, 0.89; 95% CI, 0.36–1.43; I2 = 77%) and gait (SMD, 0.62; 95% CI, 0.12–1.11; I2 = 44%). Robot rehabilitation effectively improved motor function, and among the robot types, RAGT was found to be effective in improving motor function and gait.
The Role of Performance in Constructing Muslim Citizenship in the 2019–20 Anti-CAA Protests: New Trends in Indian Muslim Belonging Today
Authors: Michael Jaclyn A.
Published: June 2024

Scholars of Indian religious traditions have described how Muslims belong to Indian society as a charismatic other, a sectarian minority, and a liminal community (Ahmad and Reifeld 2004; Gold 2013; Sila-Khan 2004; Robinson 1979). While these are important analyses, they do not adequately address recent developments in Muslim self-statement and identification that are determinedly Indian and Muslim, grounded in a rejection of the limited terms of their acceptance and inclusion. This article identifies a new trend in understanding Indian Muslim affiliation, one that is continually shaped by the long-standing question of Muslim belonging. I turn to data from contexts of public and private performances of Muslim identities that emerged throughout India, and around the world, in response to the official exclusion of Muslims from the premises of citizenship in the 2019 CAA (Citizenship Amendment Bill) legislation. From late 2019 to early 2020, Muslims and their allies in the anti-CAA movement publicly recited poetry, staged theatrical performances in the street, and organized a weeks-long women-led sit-in in Delhi to collectively reject the exclusionary premises of the new citizenship legislation and argue that being Muslim and Indian is no contradiction. How the question of Muslim affiliation is articulated and contested in genres of performance not only newly theorizes Muslim belonging in India today, but also reveals the important role of performance in constructing notions of religion, community, and nation.