bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).
Authors: Hoeppner Jens , Brunner Thomas , Lordick Florian , Schmoor Claudia , Kulemann Birte , Neumann Ulf Peter , Folprecht Gunnar , Keck Tobias , Benedix Frank , Schmeding Maximilan , Reitsamer Ernst , Bruns Christiane J. , Lock Johan F. , Reichert Benedikt , Ghadimi Michael , Wille Kai , Gockel Ines , Izbicki Jakob R. , Utzolino Stefan , Grimminger Peter Philipp
Published: June 2024

LBA1

Background: The most effective multimodal approach for treatment of resectable locally advanced esophageal adenocarcinoma (EAC) is under debate. A prior ranking question is if neoadjuvant chemoradiation therapy or perioperative chemotherapy is superior. ESOPEC (NCT02509286) is a multicenter prospective randomized trial comparing neoadjuvant CROSS (41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative FLOT (5-FU/ leucovorin/oxaliplatin/docetaxel) and surgery for the curative treatment of EAC. Methods: Patients with cT1 cN+ cM0 or cT2-4a cNany cM0 resectable EAC were eligible. The primary endpoint is overall survival (OS; 90% power; hazard ratio [HR] 0.645, 218 events needed; one sided significance level of 2.5%). Analysis is by intention-to-treat in all randomized patients. The effect of treatment on OS is estimated using Cox regression stratified by study site, and including N stage (N0, N+), and age as covariates. Results: Between Feb 2016 and Apr 2020, 438 patients from 25 sites in Germany were randomly assigned to two treatment groups (221 FLOT; 217 CROSS). Baseline characteristics (male sex 89.3%, median age 63 [range 30-86], cT3/4 80.5%; cN+ 79.7%) were well balanced between both arms. Neoadjuvant treatment was started in 403 patients (207 FLOT; 196 CROSS). Surgery was done in 371 patients (191 FLOT; 180 CROSS). R0 resection was achieved in 351 patients (180 FLOT; 171 CROSS). 90 days postsurgical mortality was 4.3% (3.2% FLOT; 5.6% CROSS). After a median follow up of 55 months, 218 patients had died (97 FLOT; 121 CROSS). Median OS was 66 (95% CI 36 – not estimable) months in the FLOT arm, and 37 (95% CI 28 – 43) months in the CROSS arm. The 3-year OS rates were 57.4% (95% CI 50.1 – 64.0%) for FLOT and 50.7% (95% CI 43.5 – 57.5%) for CROSS (HR 0.70, 95% CI 0.53-0.92, p=0.012). In 359 patients with available tumor regression status, pathological complete response was achieved in 35 (19.3%, 95%-CI 13.9 – 25.9%) in FLOT and in 24 (13.5%, 95%-CI 8.8 – 19.4%) in CROSS. Conclusions: Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS. Funding: The trial was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 264590883. Clinical trial information: NCT02509286 .
A-BRAVE trial: A phase III randomized trial with avelumab in early triple-negative breast cancer with residual disease after neoadjuvant chemotherapy or at high risk after primary surgery and adjuvant chemotherapy.
Authors: Conte Pier Franco , Dieci Maria Vittoria , Bisagni Giancarlo , Schmid Peter , Fotia Vittoria , Piacentini Federico , De Laurentiis Michelino , Favaretto Adolfo G. , Tamberi Stefano , Bianchi Giulia Valeria , Zamagni Claudio , Cinieri Saverio , Corsi Domenico C. , Del Mastro Lucia , Ferro Antonella , Gennari Alessandra , Mion Marta , Musolino Antonino , De Salvo Gian Luca , Guarneri Valentina
Published: June 2024

LBA500

Background: Prognosis of pts with early triple negative breast cancer (TNBC) is still poor and new effective treatments are needed. TNBC is the most immunogenic BC subtype, and this may account for sensitivity to immune checkpoint inhibitors. The A-BRAVE trial was designed to evaluate the efficacy of avelumab, an anti PD-L1 antibody, as adjuvant treatment for pts with early TNBC at high risk. Methods: This is a phase III, multicentric, randomized adjuvant study comparing 1 year of treatment with the anti PD-L1 avelumab vs observation for TNBC pts considered at high risk of relapse. Pts were enrolled after they completed standard treatment with curative intent including surgery and neoadjuvant/adjuvant chemotherapy. High risk was defined as: 1) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (Stratum A), 2) >pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (Stratum B). Pts were randomly assigned (1:1, balanced for strata A and B) to Avelumab 10 mg/kg I.V. q2w for 1 year or observation. Co-primary endpoints were disease free survival (DFS) in the total population and in Stratum A. 474 pts were needed to detect, in the total population, an improvement from 60% to 73.6% 3-year DFS rate (HR 0.6; 90% power, 1-sided test, alfa 2%). 172 DFS events were required to perform the event-driven analysis. Assuming a proportion of 70-80% pts enrolled in Stratum A, the expected power to detect an HR 0.6 at alpha allocated in this subgroup is 70-79%. Overall survival was a secondary endpoint. Results: From June 2016 to October 2020, 477 pts were randomly assigned from 64 Italian and 6 UK centers. 11 pts (3 avelumab, 8 control) withdrew consent immediately after randomisation and are excluded from further analyses. 378 pts entered Stratum A (83%), of whom 99 (57 avelumab, 42 control) received further chemotherapy after surgery prior to enrollment in the trial. Efficacy results for the two co-primary DFS endpoints and the secondary OS endpoints are reported in the table. Conclusions: One year adjuvant avelumab versus control does not significantly improve DFS in high-risk TNBC patients. Nevertheless, the secondary enpoind OS was significanlty improved with avelumab vs control. RFS and DMFS will also be reported. A centralised collection of tumor tissue, plasma and feces has been performed and will allow a number of correlative studies. Clinical trial information: NCT02926196 . [Table: see text]
Adjuvant PD-1 blockade with camrelizumab in high-risk locoregionally advanced nasopharyngeal carcinoma (DIPPER): A multicenter, open-label, phase 3, randomized controlled trial.
Authors: Ma Jun , Sun Ying , Liang Ye-Lin , Liu Xu , Shen Liangfang , Hu Weihan , Hu Guangyuan , Xie Fangyun , Huang Ying , Zou Guorong , Zhang Ning , Chen Chuanben , Chen Xiaozhong , Zhu Xiaodong , Yuan Yawei , Yang Kunyu , Jin Feng , Hong Shu-Bin , Zhao Hongyun , Li Ji-Bin
Published: June 2024

LBA6000

Background: Patients with high-risk locoregionally advanced nasopharyngeal carcinoma (NPC) often experience disease relapse even after receiving standard-of-care treatment, e.g. induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). The benefit of PD-1 inhibitor as adjuvant treatment following IC+CCRT in locoregionally advanced NPC remains unclear. Methods: Patients with high-risk locoregionally advanced NPC (T4N1M0 or T1-4N2-3M0) who have received gemcitabine and cisplatin (GP) IC and CCRT were recruited at 11 centers in China. They were randomly assigned (1:1) within 2 weeks after the last radiation dose to receive intravenous camrelizumab (200 mg once every 3 weeks for 12 cycles; Camrelizumab Arm) or observation (Standard-therapy Arm). The primary endpoint was event-free survival (EFS). It is estimated that approximately 442 patients would provide 80% power to detect a hazard ratio (HR) of 0.52 with a log-rank test at a two-sided α level of 0.05. Quality of life (QoL) was assessed by EORTC-C30. Results: A total of 450 patients were randomly assigned to the Camrelizumab Arm (n=226) and the Standard-therapy Arm (n=224). After a median follow-up of 37 months (corresponding to 41 months when calculated from the start of standard therapy), the estimated 3-year EFS was 86.9% in the Camrelizumab Arm and 77.4% in the Standard-therapy Arm (intention-to-treat population; HR 0.61, 95% CI 0.38–0.96; P = 0.03). The incidence of grade 3-4 adverse events (AEs) was 11.2% in the Camrelizumab Arm and 3.2% in the Standard-therapy Arm, including grade 3-4 immune-related AEs in 8 (3.9%) patients in the Camrelizumab Arm. Reactive capillary endothelial proliferation was the most common adverse event related to camrelizumab (RECP, 87.8%, 4 (1.8%) patients had grade 3 RECP). Treatment-related deaths occurred in 1 (<1%) patients in the Camrelizumab group (subarachnoid hemorrhage) and 1 (<1%) patients in the Standard-therapy group (nasopharyngeal necrosis). During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of adjuvant camrelizumab. Conclusions: Adjuvant PD-1 blockade with camrelizumab significantly improved EFS in high-risk locoregionally advanced NPC, with mild toxicity and comparable quality of life. Clinical trial information: NCT03427827 . [Table: see text]
Covalent FAPI PET enables accurate management of medullary thyroid carcinoma: A prospective single-arm comparative clinical trial.
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Jian Wang , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Lin Xinfeng , Men Tianyu , An Changming , Li Nan , Liu Chen , Zhu Yi-Ming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: June 2024

LBA6018

Background: Localizing medullary thyroid carcinoma (MTC) lesions is crucial for treatment decision, but the detection using the current imaging modalities is unsatisfied. Previously, we reported a 68Ga-labeled targeted covalent radiopharmaceutical fibroblast activation protein inhibitor (68Ga-TCR-FAPI), which demonstrated improved and sustained tumor targeting. This study aimed to head-to-head compare the 68Ga-TCR-FAPI PET-CT and the currently approved 18F-FDG PET-CT in detecting MTC. Methods: This was a prospective, single-center, open-labeled, single-arm comparative imaging trial. MTC patients with serum calcitonin>10 pg/ml and without targeted therapy were eligible. Serum calcitonin level, 68Ga-TCR-FAPI PET-CT and 18F-FDG PET-CT were acquired within a maximum interval of 30 days. Images were independently interpreted by 3 readers to calculate the patient-based and region-based detection rate. Quantitative PET parameters were calculated from the lesion ROI and compared between 68Ga-TCR-FAPI and 18F-FDG PET-CT. The accuracy of imaging findings was validated on lesions with histopathology or calcitonin-based follow-up. The primary outcome was patient-based detection rate, and the secondary outcome included region-based detection rates, metabolic parameters comparison and diagnostic accuracy. Results: 50 patients were enrolled between May 11th, 2023 and Feb. 1st, 2024. 68Ga-TCR-FAPI exhibited significantly higher patient-based detection rate than 18F-FDG PET-CT (98% vs. 66%, p=0.0002). Detection rates were also superior for 68Ga-TCR-FAPI in head and neck (72% vs. 50%, p=0.0098), thorax (50% vs. 34%, p=0.0269), abdomen (28% vs. 10%, p=0.0077) and skeleton (54% vs. 16%, p<0.0001). On quantitative analysis, SUVmax was significantly higher in 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (11.71±9.16 vs. 2.55±1.73, p<0.0001). Diagnostic accuracy was substantially greater with 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (96.7% vs. 43.3%, p<0.0001) based on 60 histopathological validated lesions from 15 patients who underwent surgery. Notably, 60% (30/50) patients directly benefited from 68Ga-TCR-FAPI PET-CT, with 66.7% (10/15) experiencing changes in surgical plans, and 100% (6/6) of the newly diagnosed MTC with R0 resection achieved biochemical cure at 1-month post-surgery. Conclusions: 68Ga-TCR-FAPI PET-CT displayed higher detection rate, metabolic value and diagnostic accuracy than 18F-FDG PET-CT in MTC patients, and should be integrated into MTC evaluation at initial diagnosis and persistent disease. Clinical trial information: NCT06084767 . [Table: see text]
Long term results of phase 3 randomized study evaluating the addition of low dose nivolumab to palliative chemotherapy in head and neck cancer.
Authors: Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Shah Minit Jalan , Peelay Zoya Ravish , Nawale Kavita Prakash , Bhagyavant Priyanka , Sawant Riddhi , Kolkur Manali , Prabhash Kumar
Published: June 2024

LBA6054

Background: The addition of low-dose nivolumab to metronomic chemotherapy (MC) improved 1-year overall survival in relapsed and refractory head and neck squamous cell carcinoma (HNSCC). However, sustained benefit over the long term is an important aspect of immunotherapy and it has never been studied in a prospective randomized study for low-dose nivolumab. Methods: This was an open-label randomized phase 3 superiority study. Adult patients (age= or >18 years), ECOG PS (0-1), relapsed -recurrent or newly diagnosed advanced HNSCC, and normal organ functions were eligible. Patients were randomly assigned 1:1 to oral metronomic chemotherapy consisting of methotrexate 9 mg/m2 weekly, celecoxib 200 mg twice daily, and erlotinib 150 mg daily, with (TMC-I) or without (TMC) with intravenous nivolumab 20 mg flat dose once-every-3-weeks. Systemic therapy was continued till the development of intolerable side effects or progression of disease. The primary endpoint was overall survival (OS). Landmark analysis was performed to compare OS between 2 arms. Results: The median follow-up was 32.5 months (95% CI 29.6-32.7). The 1 year, 2 year and 2.5 year OS were 20% (95%CI 11.9-29.7) versus 35.5% (95%CI 25-46.2) {Hazard ratio (HR)= 0.6534, 95%CI 0.4473 -0.956: P=0.028}, 5.3% (95%CI 1.7-12.3) versus 18.4 %(95%CI 10.7-27.8) {HR= 0.6318, 95%CI 0.4476 -0.8919: P=0.009} and 5.3% (95%CI 1.7-12.3) versus 17.1 % (95%CI 9.66.-26.3) {HR= 0.6379, 95%CI 0.4524 -0.8993: P=0.01} in the TMC and the TMC-I arms respectively. The benefit of the addition of nivolumab was independent of other factors like age, gender, ECOG PS, Site of malignancy, time to failure, PDL1 score, and previous exposure to platinum (Table). Conclusions: The addition of low-dose nivolumab to triple metronomic chemotherapy leads to a tripling of OS thus suggesting that even low-dose nivolumab has sustainable benefits. The benefit observed is irrespective of known prognostic factors in HNSCC. Clinical trial information: CTRI/2020/11/028953 . [Table: see text]
Radiation therapy (RT)-free pembrolizumab plus chemotherapy (P+C) for PD-L1 TPS ≥50% locally advanced non-small cell lung cancer (LA-NSCLC): Primary analysis from multicenter single arm phase II study (Evolution trial; WJOG11819L).
Authors: Hata Akito , Ninomaru Taira , Okada Hideaki , Kogure Yoshihito , Oki Masahide , Katakami Nobuyuki , Kijima Takashi , Yokoyama Toshihide , Matsumoto Hirotaka , Sato Yuki , Kato Terufumi , Sugawara Shunichi , Sawada Takeshi , Yoshimura Kenichi , Seto Takashi , Nakagawa Kazuhiko , Okamoto Isamu , Yamamoto Nobuyuki
Published: June 2024

LBA8050

Background: Standard of care for unresectable LA-NSCLC is chemoradiation therapy (CRT) followed by durvalumab (D). Survival curves of P monotherapy/P+C for PD-L1 TPS ≥50% stage IV NSCLC suggested possible comparable survival to CRT for stage III patients (pts). Moreover, some studies of neoadjuvant C+immunotherapy (I) for stage III pts have demonstrated high pathological complete response and major pathological response rates, implying potentially outstanding efficacy of C+I for earlier stage. We thus hypothesized P+C without RT in PD-L1 ≥50% LA-NSCLC pts provides a comparable efficacy to CRT followed by D while avoiding CRT-induced severe toxicities. Methods: This is a phase II study conducted by West Japan Oncology Group. P with platinum plus pemetrexed (PEM) (non-squamous) or P with carboplatin plus nab-paclitaxel (squamous) was administered every 3 weeks without RT. After four cycles of induction P+C, P with PEM (non-squamous) or P alone (squamous) was continued until progression or 2 years. The primary endpoint was 2 year-PFS rate (threshold/expected: 20%/45%). Results: Between May 2020 and February 2022, 21 pts were enrolled. Median age was 73 (range, 53-89). Stage IIIA/B/C included 11 (52%)/7 (33%)/3 (14%), respectively. Histologic subtypes were 14 (67%) adenocarcinoma, 5 (24%) squamous cell carcinoma, and 2 (10%) others. Median follow-up period was 29.9 (range, 0.3-44.2) months. Median number of P administrations was 30 (range, 1-35). The primary endpoint was met with 2-year PFS rate of 67% (90% CI: 46-83%). At the time of data cut-off, 13 (62%) of 21 pts were still progression-free. Median PFS and OS were not reached. Two-year OS rate was 85%. Centrally reviewed tumor response: 8 (38%) CR; 9 (43%) PR; 3 (14%) SD; and 1 (5%) NE were confirmed, resulting in overall response rate (ORR) of 81% and disease control rate of 95%. ORRs/2-year PFS rates of PD-L1 TPS 50-79% and 80-100% were 67%/56% and 92%/75%, respectively. Non-hematological AEs ≥grade 3 were observed in 11 (52%) pts, including: 2 (10%) pneumonitis; 2 (10%) pneumonia; 1 (5%) diarrhea; 1 (5%) ALT elevation; and 1 (5%) acute heart failure. There was one (5%) grade 5 AE (pneumonia). Conclusions: RT-free P+C provided long-lasting responses in approximately two-thirds of pts. Higher PD-L1 TPS cases achieved higher RR, including some CRs and higher 2-year PFS rate. To confirm our hypothesis that RT-free P+C can be a less toxic curative option in selected LA-NSCLC pts with PD-L1 TPS ≥50%, further data is warranted. Clinical trial information: NCT04153734 .
Random Occurrence or Real Association? Primary Hyperparathyroidism in a Young Man With Sickle Cell Disease
Authors: Lopez Fanas Raul , Fouad Rateb , Swedish Kristin A
Published: June 2024

A 32-year-old man with sickle cell disease (SCD) was admitted to the hospital for sickle cell crisis, during which laboratory workup revealed primary hyperparathyroidism. His treatment regimen included hydration, calcitonin, and calcimimetics. A parathyroid nuclear scan revealed anomalous parathyroid tissue. The precise relationship between primary hyperparathyroidism (PHPT) and SCD remains incompletely understood but may involve factors such as vitamin D deficiency, elevated erythropoietin levels, and the influence of growth factors on the development of parathyroid adenomas. Furthermore, the concurrent occurrence of both PHPT and SCD at an earlier age may potentiate adverse long-term outcomes. Effective management of PHPT in SCD entails addressing hypercalcemia and treating the underlying cause of hyperparathyroidism. While a potential association between PHPT and SCD exists, further research is essential to better elucidate their interaction, prevalence, clinical presentations, and outcomes.
The Loss of Estradiol by Androgen Deprivation in Prostate Cancer Patients Shows the Importance of Estrogens in Males
Authors: Coelingh Bennink Herjan J T , Prowse Amanda , Egberts Jan F M , Debruyne Frans M J , Huhtaniemi Ilpo T , Tombal Bertrand
Published: June 2024

The role of estradiol (E2; an estrogen) in men needs to be more appreciated. In this review, we address the clinical situations that allow the study of the clinical consequences of E2 deficiency in men and discuss the effects of restoration of levels of this reproductive steroid hormone. In men with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT), E2 is suppressed along with testosterone, leading to side effects affecting the quality of life. These include hot flashes, arthralgia, fatigue, mood changes, cognition problems, weight gain, bone loss, and increased risk of cardiovascular disease. Transdermal E2 alone for ADT has shown equivalent testosterone suppression compared to gonadotropin-releasing hormone (GnRH) agonists while also preventing estrogen-deficiency side effects, including hot flashes and bone loss. Co-treatment of ADT with fetal estrogen estetrol (E4) has shown significant improvements of estrogen-deficiency symptoms. These observations emphasize the need to raise awareness of the importance of estrogens in men among clinicians and the lay public.
Prevalence and Characteristics of Low-renin Hypertension in a Primary Care Population
Authors: Shah Sonali S , Libianto Renata , Gwini Stella May , Rusell Grant , Young Morag J , Fuller Peter J , Yang Jun
Published: June 2024

Introduction

Low-renin hypertension is an underrecognized subtype of hypertension with specific treatment options. This study aims to identify the prevalence in primary care and to compare patient characteristics to those with normal-renin hypertension and primary aldosteronism (PA).

Methods

In a cohort study, patients with treatment-naïve hypertension were screened for PA with plasma aldosterone and direct renin concentrations. Patients with an elevated aldosterone-to-renin ratio [≥70 pmol/mU (≥2.5 ng/dL:mU/L)] underwent confirmatory testing. All screened patients were then classified as having (1) normal-renin hypertension, (2) low-renin hypertension (direct renin concentration <10mU/L (plasma renin activity ∼<1 ng/mL/hour) and not meeting the criteria for PA), or (3) confirmed PA.

Results

Of the 261 patients, 69 (26.4%) had low-renin hypertension, 136 (51.9%) had normal renin hypertension, and 47 (18.0%) had PA. Patients with low-renin hypertension were older and more likely to be female compared to normal-renin hypertension (57.1 ± 12.8 years vs 51.8 ± 14.0 years, P < .05 and 68.1% vs 49.3%, P < .05, respectively) but similar to PA (53.5 ± 11.5 years and 55.3%). However, in an adjusted binomial logistic regression, there was no association between increasing age or sex and low-renin hypertension. The median aldosterone concentration was lower compared to patients with normal-renin hypertension and PA: 279 pmol/L (216-355) vs 320 pmol/L (231-472), P < .05 and 419 pmol/L (360-530), P < .001.

Conclusion

At least a quarter of treatment-naïve hypertensive patients in primary care had a low direct renin concentration but did not meet the criteria for PA. Patient characteristics were similar, aside from a lower aldosterone concentration compared to patients with normal-renin hypertension and PA. Further research is needed to understand the underlying pathophysiology of low-renin hypertension and the optimal first-line treatment.
The Medipol Combination: Novel Rectointercostal Fascial Plane Block and Pectointercostal Fascial Plane Block for Postoperative Analgesia Management After Cardiac Surgery: A Report of 15 Cases
Authors: Ciftci Bahadir , Omur Burak , Alver Selcuk , Akin Ayse Nurmen , Yildiz Yahya , Tulgar Serkan
Published: June 2024

The parasternal blocks cannot cover the T7 and lower anterior and lateral branches of the thoracoabdominal nerves. In the open heart surgeries, chest drainage tubes are generally outside the target of the parasternal blocks. Recently, Tulgar et al described a novel interfascial plane block technique named “recto-intercostal fascial plane block” (RIFPB). RIFPB is performed between the rectus abdominis muscle and the sixth to seventh costal cartilages. RIFPB targets the anterior and lateral cutaneous branches of the T6–T9 thoracoabdominal nerves. In this clinical report, we want to share our experiences about pectointercostal plane block and RIFPB combination (Medipol Combination) after cardiac surgery.
Emergency Medical Planning for an Ultramarathon Open Water Swim: A Case Review of “Swim Tuff”
Authors: Martin David G. , Eason Christianne M. , Huggins Robert A. , Tuff Ben , Casa Douglas J.
Published: June 2024

Ultramarathon open water swimming (OWS) events are one of the toughest endurance challenges in the world. The sport has gained notoriety with athletes swimming across the English Channel, Diana Nyad swimming from Cuba to Florida, and the 5- and 10-km OWS in the Olympic schedule. The athletes who participate are exposed to dangerous conditions that expose risks inherent to the sport. The optimal time to prepare for an emergency is before it happens. The aim of this paper is to present an emergency action plan (EAP) designed for the “Swim Tuff” event, a record-breaking ultramarathon swim that took place in Rhode Island, United States. This article identifies an overview of Swim Tuff, the challenges experienced, and how the team designed and implemented risk mitigation strategies. The professionals looking over athletes completing an OWS should be educated and aware of the unique circumstances inherent to the sport.
Platelet-Poor versus Platelet-Rich Plasma for the Treatment of Muscle Injuries
Authors: Raum George , Kenyon Charles , Bowers Robert
Published: June 2024

Muscle injury in sport results in significant lost time and potential for reinjury for athletes. Autologous blood product, namely, platelet-rich plasma (PRP), has been investigated for possible augmentation of the treatment timeline with prevention of reinjury; however, conflicting results have been identified. A growing body of basic science and clinical literature is forming that supports the use of platelet-poor plasma (PPP) for muscle injury. The purpose of this study was to provide a background of the basic science of PRP versus PPP for muscle injury and to identify and review the clinical evidence for both autologous blood products, including the author’s clinical experience utilizing the blood products. At the tissue level, PRP causes myoblast proliferation while PPP has led to myoblast induction, potentially identifying improved native muscle healing. Conflicting studies have been identified for the use of PRP for muscle injury. A growing body of positive results for PPP was identified, but high-quality comparative studies are needed.
O Ensino de filosofia na formação jurídica contemporânea: A importância das questões fundamentais
Authors: Câmara Ferreira da Costa André , Sousa de Carvalho Harley
Published: June 2024

No artigo, apresentamos, de modo dedutivo e bibliográfico, a filosofia como uma prática preocupada com questões de ser e de validade, mas uma prática cujo acesso a essas questões é amplo, reflexivo, crítico e, aparentemente, contrário à criação apressada de produtos imediatamente transformadores. A partir dessa concepção, posicionamos a filosofia na formação jurídica contemporânea, terreno em que se sente, atualmente, uma grande e agitada tendência para a transformação tecnológica, sobretudo para a disruptiva. Diante desse modelo emergente na formação do jurista, a filosofia tem um papel interrogante: o de perguntar o porquê do direito, para depois criticar e, se for o caso, acomodar o para quê das novas tecnologias. Assim, a filosofia ajudaria a dizer se o modelo emergente é mesmo urgente ou apenas insurgente. Ao promover a conscientização dos juristas quanto aos fundamentos da sua prática, repelindo como critérios essenciais a eficiência e a competividade, a filosofia também colaboraria com a construção de uma práxis mais solidária.
Da sala à cozinha extensão universitária como práxis transformadora no ensino jurídico
Authors: OLIVEIRA ADEILDO , Oliveira Silva Filho Francisco Cláudio
Published: June 2024

A extensão universitária permite o desenvolvimento de pesquisas empíricas e de impacto social no direito, além de incrementar o ensino jurídico crítico com base na compreensão de problemas práticos. O trabalho aborda a extensão universitária a partir do projeto “Fome de Direitos: Direito à Alimentação Adequada e Acesso à Justiça”, desenvolvido por professores e estudantes do Curso de Direito do Centro Universitário Christus (Campus Parquelândia) em parceria com a Cozinha Popular Dona Lucimar, na cidade de Fortaleza (Ceará, Brasil). O objetivo do trabalho é discutir a prática da extensão universitária para o desenvolvimento do ensino e da pesquisa no direito e para contribuir no acesso à justiça e às políticas públicas pela comunidade parceira do projeto. São objetivos específicos: discutir os fundamentos teóricos e normativos da extensão universitária no direito; descrever as ações do projeto “Fome de Direitos” e discutir os impactos da extensão para o ensino e a pesquisa jurídicos. O método de pesquisa é dedutivo e descritivo, e, como procedimentos metodológicos, tem-se a revisão bibliográfica, o estudo de caso e a análise de dados primários e secundários. Como resultados, verifica-se que o projeto de extensão despertou o senso crítico e o interesse dos educandos para o problema da insegurança alimentar no Brasil e para conhecer a organização da Cozinha Comunitária localizada nas proximidades da Instituição de Ensino. Na prática de ensino, a temática foi discutida a partir dos fundamentos teóricos das disciplinas de Hermenêutica, Teoria do Direito e Direito Constitucional.
Atacama Large Aperture Submillimeter Telescope (AtLAST) science: Our Galaxy
Authors: Klaassen Pamela , Traficante Alessio , Beltrán Maria , Pattle Kate , Booth Mark , Lovell Joshua , Marshall Jonathan , Hacar Alvaro , Gaches Brandt , Bot Caroline , Peretto Nicolas , Stanke Thomas , Arzoumanian Doris , Duarte Cabral Ana , Duchêne Gaspard , Eden David , Hales Antonio , Kauffmann Jens , Luppe Patricia , Marino Sebastian , Redaelli Elena , Rigby Andrew , Sánchez-Monge Álvaro , Schisano Eugenio , Semenov Dmitry , Spezzano Silvia , Thompson Mark , Wyrowski Friedrich , Cicone Claudia , Mroczkowski Tony , Cordiner Martin , Di Mascolo Luca , Johnstone Doug , van Kampen Eelco , Lee Minju , Liu Daizhong , Maccarone Thomas , Saintonge Amélie , Smith Matthew , Thelen Alexander , Wedemeyer Sven
Published: June 2024

As we learn more about the multi-scale interstellar medium (ISM) of our Galaxy, we develop a greater understanding for the complex relationships between the large-scale diffuse gas and dust in Giant Molecular Clouds (GMCs), how it moves, how it is affected by the nearby massive stars, and which portions of those GMCs eventually collapse into star forming regions. The complex interactions of those gas, dust and stellar populations form what has come to be known as the ecology of our Galaxy. Because we are deeply embedded in the plane of our Galaxy, it takes up a significant fraction of the sky, with complex dust lanes scattered throughout the optically recognizable bands of the Milky Way. These bands become bright at (sub-)millimetre wavelengths, where we can study dust thermal emission and the chemical and kinematic signatures of the gas. To properly study such large-scale environments, requires deep, large area surveys that are not possible with current facilities. Moreover, where stars form, so too do planetary systems, growing from the dust and gas in circumstellar discs, to planets and planetesimal belts. Understanding the evolution of these belts requires deep imaging capable of studying belts around young stellar objects to Kuiper belt analogues around the nearest stars. Here we present a plan for observing the Galactic Plane and circumstellar environments to quantify the physical structure, the magnetic fields, the dynamics, chemistry, star formation, and planetary system evolution of the galaxy in which we live with AtLAST; a concept for a new, 50m single-dish sub-mm telescope with a large field of view which is the only type of facility that will allow us to observe our Galaxy deeply and widely enough to make a leap forward in our understanding of our local ecology.
Large Language Models and OpenLogos: An Educational Case Scenario
Authors: Pavlova Andrijana , Gerazov Branislav , Barreiro Anabela
Published: June 2024

Large Language Models (LLMs) offer advanced text generation capabilities, sometimes surpassing human abilities. However, their use without proper expertise poses significant challenges, particularly in educational contexts. This article explores different facets of natural language generation (NLG) within the educational realm, assessing its advantages and disadvantages, particularly concerning LLMs. It addresses concerns regarding the opacity of LLMs and the potential bias in their generated content, advocating for transparent solutions. Therefore, it examines the feasibility of integrating OpenLogos expert-crafted resources into language generation tools used for paraphrasing and translation. In the context of the Multi3Generation COST Action (CA18231), we have been emphasizing the significance of incorporating OpenLogos into language generation processes, and the need for clear guidelines and ethical standards in generative models involving multilingual, multimodal, and multitasking capabilities. The Multi3Generation initiative strives to progress NLG research for societal welfare, including its educational applications. It promotes inclusive models inspired by the Logos Model, prioritizing transparency, human control, preservation of language principles and meaning, and acknowledgment of the expertise of resource creators. We envision a scenario where OpenLogos can contribute significantly to inclusive AI-supported education. Ethical considerations and limitations related to AI implementation in education are explored, highlighting the importance of maintaining a balanced approach consistent with traditional educational principles. Ultimately, the article advocates for educators to adopt innovative tools and methodologies to foster dynamic learning environments that facilitate linguistic development and growth.
Developing Inclusive Community Platforms: A Catalyst for DEI Community
Authors: Costantini Hiroko , Nihei Misato , Ono Takazumi , Tanabe Kai , Motomura Yoichi
Published: June 2024

Developing inclusive communities is important to enhance individuals’ well-being yet this brings the challenge of actively engaging and leveraging the diversity of residents in communities. Such significant social challenges are prominent in Japan, a focus of this article, as the most advanced aging society in the world and thus relevant to European and other countries. This paper explains a major government initiative that takes an innovative approach through leveraging a social technology, a Digital Twin of a community, to understand and address inclusiveness of a community leveraging population approach. The purpose of this letter is to provide researchers and policy makers insights into the approach taken to stimulate reflection on the potential for adaptation and replication.
Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial
Authors: Ellis Jayne , Nsangi Laura , Bangdiwala Ananta , Hale Gila , Gakuru Jane , Kagimu Enock , Mugabi Timothy , Kigozi Enos , Tukundane Asmus , Okirwoth Michael , Kandole Tadeo Kiiza , Cresswel Fiona , Harrison Thomas S. , Moore David , Fielding Katherine , Meya David , Boulware David , Jarvis Joseph N.
Published: June 2024

Background Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24–45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. Protocol The IMPROVE trial (Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease) is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, 1HP pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured with intensive sampling in a pharmacokinetic sub-study of 15 eligible participants. Discussion The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN registration ISRCTN18437550 (05/11/2021)
Eligibility for obesity management in Peru: Analysis of National Health Surveys from 2014 to 2022
Authors: Bernabe-Ortiz Antonio , Carrillo-Larco Rodrigo M.
Published: June 2024

Background The prevalence of overweight and obesity has increased fastest in low- and middle-income countries in the last decades. Together with this rising prevalence, pharmacological and surgical interventions for obesity have emerged. How many people need these treatments is unknown. We quantified the prevalence of people in need of pharmacological and surgical treatment for obesity in Peru between 2014 and 2022. Methods Repeated cross-sectional analysis of national health surveys in Peru was conducted. Eligibility for pharmacological treatment for obesity was: body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 alongside type 2 diabetes or hypertension (self-reported). Eligibility for bariatric surgery were BMI ≥40 kg/m2 or BMI between 35 to 39.9 kg/m2 linked to weight-related health problems. We used Poisson regressions to identify associated factors with eligibility for obesity management. Results Across years, 260,131 people (mean age 44.0 and 54.5% were women) were studied, 66,629 (27.7%; 95% CI: 27.4% - 28.1%) were eligible for obesity medication, and 5,263 (2.5%; 95% CI: 2.4% - 2.6%) were eligible for bariatric surgery. Female sex, older age, higher socioeconomic level and study year were associated with higher probability of eligibility for both obesity medication and bariatric surgery. Conclusions Eligibility for obesity management has increased over time in Peru. There is a need to strengthen policies to tackle overweight and obesity in Peru, acknowledging that some individuals may benefit from pharmacological and surgical interventions.
A feasibility study of controlled human infection with intradermal Bacillus Calmette–Guérin (BCG) injection: Pilot BCG controlled human infection model
Authors: Carter Emma , Morton Ben , ElSafadi Dima , Jambo Kondwani , Kenny-Nyazika Tinashe , Hyder-Wright Angela , Chiwala Gift , Chikaonda Tarsizio , Chirwa Anthony E. , Gonzalez Sanchez Jonathan , Yip Vincent , Biagini Giancarlo , Pennington Shaun H. , Saunderson Paula , Farrar Madlen , Myerscough Christopher , Collins Andrea M. , Gordon Stephen B. , Ferreira Daniela M.
Published: June 2024

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden. Efforts to find novel vaccines are hampered due to the need for large-scale, prolonged, and costly clinical trials. Controlled human infection models (CHIMs) for TB may be used to accelerate vaccine development by ensuring only the most promising vaccine candidates are selected for phase 3 trials, but it is not currently possible to give participants Mycobacterium tuberculosis as a challenge agent. This study aims to replicate and refine an established BCG CHIM at the Liverpool School of Tropical Medicine. Participants will receive an intradermal injection with licensed BCG vaccine (Statens Serum Institut strain). In phase A, participants will undergo punch biopsy two weeks after administration, paired with minimally invasive methods of skin sampling (skin swab, microbiopsy, skin scrape). BCG detection by classical culture and molecular methods will be compared between these techniques and gold standard punch biopsy. Techniques meeting our pre-defined sensitivity and specificity criteria will be applied in Phase B to longitudinally assess intradermal BCG growth two, seven and fourteen days after administration. We will also measure compartmental immune responses in skin, blood and respiratory mucosa in Phase B. This feasibility study will transfer and refine an existing and safe model of BCG controlled human infection. Longitudinal BCG quantification has the potential to increase model sensitivity to detect vaccine and therapeutic responses. If successful, we aim to transfer the model to Malawi in future studies, a setting with endemic TB disease, to accelerate development of vaccines and therapeutics relevant for underserved populations who stand to benefit the most. Registration: ISRCTN: ISRCTN94098600 and ClinicalTrials.gov: NCT05820594
La narración polifónica del estallido social chileno en el paisaje lingüístico de Santiago.
Authors: Calvi Maria Vittoria
Published: June 2024

A partir de un corpus de 1500 fotografías de grafitis, carteles y otros textos escritos, recogidas en noviembre de 2019 en diferentes barrios centrales de Santiago, el presente trabajo analiza la imbricación entre el espacio, las prácticas lingüísticas y el proceso de politización de la protesta. En primer lugar, se explorará la semiótica transgresiva de los grafitis (Pennycook, 2009) y su papel en el proceso de des- y re-territoralización; en segundo lugar, el análisis se centrará en el fenómeno de la polifonía discursiva (Bajtín, 1981; Ducrot, 1986). Desde esta perspectiva, el PL del estallido social chileno puede verse como conjunto heteroglósico de voces, en conexión con el contexto inmediato, con el pasado de Chile desde la dictadura de Pinochet y con los movimientos de protesta globales, pasados y contemporáneos.
Anotación y explotación de variantes gráficas de base fonética en el corpus Oralia Diacrónica del Español.
Authors: Calderón Miguel , Vaamonde Gael
Published: June 2024

Los corpus históricos de referencia disponibles para el español son de gran utilidad para investigar aspectos de carácter léxico y morfosintáctico, pero resultan inadecuados para extraer información de tipo fonético. Conscientes de esta necesidad, se están creando en los últimos años corpus especializados que prestan especial cuidado en el rigor gráfico de las transcripciones. El objetivo de este trabajo es doble. Por un lado, proponemos algunas líneas de mejora en la recolección de datos históricos que sean fiables para realizar estudios fonéticos. Por otro lado, presentamos el corpus especializado Oralia Diacrónica del Español, prestando especial atención a los aspectos que convierten a ODE en una herramienta idónea para abordar estudios cuantitativos sobre fonética histórica. Usando los datos de ODE, analizamos un estudio de caso, el de las grafías indicadoras de seseo y ceceo, con el objeto de demostrar la utilidad de este corpus para la investigación en fonética histórica del español clásico y moderno.
Rutas y caminos hacia otras formas de habitar Bogotá-Región
Authors: Cepeda Valencia Juliana
Published: June 2024

La presente propuesta se construyó como piloto buscando entender y ubicar las aquí llamadas formas dignas de co-existencia en Bogotá-Región, las cuales hemos definido como estrategias implementadas desde las comunidades de base para la búsqueda de vida digna, y que proporcionan un ambiente sano en el territorio. En esta categoría social la dignidad se identifica como derecho inalienable y mínimo óptimo, y la co-existencia define el desafío de vivir en medio de la realidad múltiple, desafiante, cambiante y compleja de Colombia. Estas formas pueden así tomar múltiples expresiones, por lo que nos hemos enfocado en propuestas que priorizan, dentro de su búsqueda de la dignidad, tanto la autonomía alimentaria como la protección de la vida en todas sus manifestaciones. En este acercamiento hemos encontrado que uno de los aspectos más llamativos de estos espacios es la forma como las iniciativas asumen los desafíos como oportunidades de crecimiento encaminadas a habitar dignamente su territorio; también, que estas iniciativas se posicionan desde una fuerte identidad colectiva que lleva implícito el rescate de valores colectivos relacionados con la confianza y el afecto: no es gratuito que los integrantes incluyan el término familia para hablar de aquellos que componen su colectivo. Proponemos que son la construcción de confianza, afecto y autonomía los motores que permiten a las formas dignas de co-existencia su búsqueda de dignidad y co-existencia a través de la continua reexistencia o reinvención. Lo anterior, aunado a la importancia de las relaciones dentro de las formas dignas de co-existencia, pues muchas de estas iniciativas, que buscan mejorar y posibilitar relaciones entre productores o entre productores y consumidores, nos permiten establecer un vínculo claro entre las experiencias documentadas y la ética del cuidado identificando que los valores de interdependencia, relacionalidad y solidaridad son desde los que las formas dignas de co-existencia operan y posibilitan la dignidad en los territorios y la armonización que permite espacios productivos, al mismo tiempo que sustentables.
Vibratory insertion of press-fit acetabular components requires less force than a single blow technique
Authors: Niki Yasaman , Huber Gerd , Behzadi Kambiz , Morlock Michael M.
Published: June 2024

Aims

Periprosthetic fracture and implant loosening are two of the major reasons for revision surgery of cementless implants. Optimal implant fixation with minimal bone damage is challenging in this procedure. This pilot study investigates whether vibratory implant insertion is gentler compared to consecutive single blows for acetabular component implantation in a surrogate polyurethane (PU) model.

Methods

Acetabular components (cups) were implanted into 1 mm nominal under-sized cavities in PU foams (15 and 30 per cubic foot (PCF)) using a vibratory implant insertion device and an automated impaction device for single blows. The impaction force, remaining polar gap, and lever-out moment were measured and compared between the impaction methods.

Results

Impaction force was reduced by 89% and 53% for vibratory insertion in 15 and 30 PCF foams, respectively. Both methods positioned the component with polar gaps under 2 mm in 15 PCF foam. However, in 30 PCF foam, the vibratory insertion resulted in a clinically undesirable polar gap of over 2 mm. A higher lever-out moment was achieved with the consecutive single blow insertion by 42% in 15 PCF and 2.7 times higher in 30 PCF foam.

Conclusion

Vibratory implant insertion may lower periprosthetic fracture risk by reducing impaction forces, particularly in low-quality bone. Achieving implant seating using vibratory insertion requires adjustment of the nominal press-fit, especially in denser bone. Further preclinical testing on real bone tissue is necessary to assess whether its viscoelasticity in combination with an adjusted press-fit can compensate for the reduced primary stability after vibratory insertion observed in this study.

Cite this article: Bone Joint Res 2024;13(6):272–278.