bluuebunny/crossref_metadata_2025 huggingface dataset:
Pedicle screw insertion into infected vertebrae reduces operative time and range of fixation in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis: a multicenter retrospective cohort study
Authors: Gamada Hisanori , Funayama Toru , Setojima Yusuke , Nagasawa Keigo , Nakagawa Takane , Sakashita Kotaro , Okuwaki Shun , Ogawa Kaishi , Izawa Shigeo , Shibao Yosuke , Kumagai Hiroshi , Nagashima Katsuya , Fujii Kengo , Takeuchi Yosuke , Tatsumura Masaki , Shiina Itsuo , Uesugi Masafumi , Yamazaki Masashi , Koda Masao
Published: June 2024

Background

Minimally invasive posterior fixation surgery for pyogenic spondylitis is known to reduce invasiveness and complication rates; however, the outcomes of concomitant insertion of pedicle screws (PS) into the infected vertebrae via the posterior approach are undetermined. This study aimed to assess the safety and efficacy of PS insertion into infected vertebrae in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis.

Methods

This multicenter retrospective cohort study included 70 patients undergoing minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis across nine institutions. Patients were categorized into insertion and skip groups based on PS insertion into infected vertebrae, and surgical data and postoperative outcomes, particularly unplanned reoperations due to complications, were compared.

Results

The mean age of the 70 patients was 72.8 years. The insertion group (n = 36) had shorter operative times (146 versus 195 min, p = 0.032) and a reduced range of fixation (5.4 versus 6.9 vertebrae, p = 0.0009) compared to the skip group (n = 34). Unplanned reoperations occurred in 24% (n = 17) due to surgical site infections (SSI) or implant failure; the incidence was comparable between the groups. Poor infection control necessitating additional anterior surgery was reported in four patients in the skip group.

Conclusions

PS insertion into infected vertebrae during minimally invasive posterior fixation reduces the operative time and range of fixation without increasing the occurrence of unplanned reoperations due to SSI or implant failure. Judicious PS insertion in patients with minimal bone destruction in thoracolumbar pyogenic spondylitis can minimize surgical invasiveness.
Minimally invasive versus open ileal ureter with ileocystoplasty: comparative outcomes and 5-year experience
Authors: Chen Silu , Wang Xiang , Li Zhihua , Li Xinfei , Han Guanpeng , Tao Zihao , Li Zhenyu , Zhang Peng , Zhu Hongjian , Yang Kunlin , Li Xuesong
Published: June 2024

Purpose

To present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures.

Patients and methods

From December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared.

Results

The etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC.

Conclusion

IUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.
Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England
Authors: Chen Daniel Tzu-Hsuan , Copland Emma , Hirst Jennifer A. , Mi Emma , Dixon Sharon , Coupland Carol , Hippisley-Cox Julia
Published: June 2024

Background

Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination.

Methods

We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest.

Results

Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions.

Conclusions

COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.
Drivers of autochthonous malaria cases over time: could the Central European present the African future?
Authors: Kenyeres Zoltán
Published: June 2024

Background

Results of spatial and temporal comparison of malaria hotspots and coldspots could improve the health measures of malaria control and eradication strategies. The study aimed to reveal the spatially and temporally independent correlations between the potentially most effective background variables and the number of autochthonous malaria cases.

Methods

Relationships between malaria cases and background variables were studied in 2 km × 2 km sized quadrates (10 Central European and 10 African). In addition to the current habitat structure of the African sites, annual precipitation, and annual mean temperature, data of the above parameters detected in the nineteenth and twentieth centuries and currently in the Central European sites were included in the analyses (n = 40). Mann–Whitney tests, Principal Component Analysis, and Generalized Linear Models were used for the examinations.

Results

In addition to the apparent significant positive correlation of malaria cases with annual rainfall and mean temperature, several correlations were found for habitat parameters. The cover of marshlands in the 19th-century habitat structure of Central European quadrates was considerably the same as in the recent African ones. The extent of rural residential areas was significantly smaller in the 19th-century habitat structure of Central European quadrats than in present-day African ones. According to the revealed correlations, the surface cover of rural residential areas is the main driver of the number of autochthonous malaria cases that we can directly impact.

Conclusions

The study confirmed with historical comparison that not only the annual rainfall and mean temperature, the cover of marshlands and other habitats with breeding sites, but also the elements of the rural human environment play a significant role in the high number of autochthonous malaria cases, probably through the concentration and enhancing sites for vector mosquitoes. The latter confirms that a rapid urbanization process could reduce malaria cases in the most infected areas of Africa. Until the latter happens, extensive biological control of Anopheles larvae and chemical control (both outdoor and indoor) of their imagoes, further mosquito nets, repellents, and carbon dioxide traps will need to be applied more widely in the most heavily infested areas.
Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea
Authors: Huh Da-An , Choi Yun-Hee , Kim Lita , Park Kangyeon , Lee Jiyoun , Hwang Se Hyun , Moon Kyong Whan , Kang Min-Sung , Lee Yong-Jin
Published: June 2024

Background

Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer.

Methods

We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants—sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 μm, and fine particulate matter with a diameter < 2.5 μm—were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality.

Results

The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30).

Conclusion

These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.
Circadian patterns of growth factor receptor-dependent signaling and implications for carcinogenesis
Authors: Murgo Emanuele , Falco Giorgia , Serviddio Gaetano , Mazzoccoli Gianluigi , Colangelo Tommaso
Published: June 2024

Several different signaling pathways that regulate cell proliferation and differentiation are initiated by binding of ligands to cell-surface and membrane-bound enzyme-linked receptors, such as receptor tyrosine kinases and serine-threonine kinases. They prompt phosphorylation of tyrosine and serine-threonine residues and initiate downstream signaling pathways and priming of intracellular molecules that convey the signal in the cytoplasm and nucleus, with transcriptional activation of specific genes enriching cell growth and survival-related cascades. These cell processes are rhythmically driven by molecular clockworks endowed in every cell type and when deregulated play a crucial role in cancer onset and progression. Growth factors and their matching receptor-dependent signaling are frequently overexpressed and/or dysregulated in many cancer types. In this review we focus on the interplay between biological clocks and Growth Factor Receptor-dependent signaling in the context of carcinogenesis.
A long-term prospecting study on giant viruses in terrestrial and marine Brazilian biomes
Authors: Machado Talita B. , de Aquino Isabella L. M. , Azevedo Bruna L. , Serafim Mateus S. , Barcelos Matheus G. , Andrade Ana Cláudia S. P. , Reis Erik , Ullmann Leila Sabrina , Pessoa João , Costa Adriana O. , Rosa Luiz H. , Abrahão Jônatas S.
Published: June 2024

The discovery of mimivirus in 2003 prompted the search for novel giant viruses worldwide. Despite increasing interest, the diversity and distribution of giant viruses is barely known. Here, we present data from a 2012–2022 study aimed at prospecting for amoebal viruses in water, soil, mud, and sewage samples across Brazilian biomes, using Acanthamoeba castellanii for isolation. A total of 881 aliquots from 187 samples covering terrestrial and marine Brazilian biomes were processed. Electron microscopy and PCR were used to identify the obtained isolates. Sixty-seven amoebal viruses were isolated, including mimiviruses, marseilleviruses, pandoraviruses, cedratviruses, and yaraviruses. Viruses were isolated from all tested sample types and almost all biomes. In comparison to other similar studies, our work isolated a substantial number of Marseillevirus and cedratvirus representatives. Taken together, our results used a combination of isolation techniques with microscopy, PCR, and sequencing and put highlight on richness of giant virus present in different terrestrial and marine Brazilian biomes.
A pin-based probe for electronic moisture meters to determine moisture content in a single wheat kernel
Authors: Sangha Jatinder S. , Meyer Brad , Ruan Yuefeng , Cuthbert Richard D. , Knox Ron , Xiao Gaozhi
Published: June 2024

Background

Optimum moisture in straw and grain at maturity is important for timely harvesting of wheat. Grain harvested at the right time has reduced chance of being affected by adverse weather conditions which is important to maintain grain quality and end use functionality. Wheat varieties with a short dry down period could help in timely harvest of the crop. However, measuring single kernel moisture in wheat and other small grain crops is a phenotyping bottleneck which requires characterising moisture content of the developing kernel at physiological maturity.

Results

Here we report developing a pin-based probe to detect moisture in a developing wheat kernel required for determining physiological maturity. An in-house designed pin-based probe was used with different commercially available electronic moisture meters to assess the moisture content of the individual kernels in spikes with high accuracy (R2 = 0.73 to 0.94, P < 0.001) compared with a reference method of oven drying. The average moisture values varied among different electronic moisture meters and the oven-dry method and differences in values were minimized at low kernel moisture content (< 50%). The single kernel moisture probe was evaluated in the field to predict the physiological maturity in wheat using 38% moisture content as the reference and visible notes on kernel stage.

Conclusion

The pin-based moisture probe is a reliable tool for wheat physiologists and breeders to conveniently and accurately measure moisture content in developing grain that will aid in identifying wheat germplasm with fast dry-down characteristics.
Solving integral and differential equations via fixed point results involving F-contractions
Authors: Singh Bijender , Işık Hüseyin , Singh Vizender , Singh Kuldeep
Published: June 2024

In this article, we aim to establish fixed point results within the framework of an orthogonal complete metric space by employing an F-weak contraction. Our research extends and generalizes several well-established results found in the existing literature. To substantiate the validity of our findings, we have included illustrative examples. Additionally, our discoveries empower us to ascertain both the existence and uniqueness of solutions for both differential and integral equations.
Hemolysis during open heart surgery in patients with hereditary spherocytosis — systematic review of the literature and case study
Authors: Mendrala Konrad , Czober Tomasz , Darocha Tomasz , Hudziak Damian , Podsiadło Paweł , Kosiński Sylweriusz , Jagoda Bogusz , Gocoł Radosław
Published: June 2024

Background

Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications resulting from hemolysis. Despite being the most prevalent cause of hereditary chronic hemolysis, the standards of surgical management are based solely on expert opinion.

Objective

We analyze the risk of hemolysis in HS patients after cardiac surgery based on a systematic review of the literature. We also describe a case of a patient with hereditary spherocytosis who underwent aortic valve repair.

Methods

This systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42023417666) and included records from Embase, MEDLINE, Web of Science, and Google Scholar databases. The case study investigates a 38-year-old patient who underwent surgery for an aortic valve defect in mid-2022.

Results

Of the 787 search results, 21 studies describing 23 cases of HS undergoing cardiac surgery were included in the final analysis. Hemolysis was diagnosed in five patients (one coronary artery bypass graft surgery, two aortic valve bioprosthesis, one ventricular septal defect closure, and one mitral valve plasty). None of the patients died in the perioperative period. Also, no significant clinical hemolysis was observed in our patient during the perioperative period.

Conclusions

The literature data show that hemolysis is not common in patients with HS undergoing various cardiac surgery techniques. The typical management of a patient with mild/moderate HS does not appear to increase the risk of significant clinical hemolysis. Commonly accepted beliefs about factors inducing hemolysis during cardiac surgery may not be fully justified and require further investigation.
A multiverse of α-synuclein: investigation of prion strain properties with carboxyl-terminal truncation specific antibodies in animal models
Authors: Lloyd Grace M. , Quintin Stephan , Sorrentino Zachary A. , Gorion Kimberly-Marie M. , Bell Brach M. , Long Brooke , Paterno Giavanna , Giasson Benoit I.
Published: June 2024

Synucleinopathies are a group of neurodegenerative disorders characterized by the presence of misfolded α-Synuclein (αSyn) in the brain. These conditions manifest with diverse clinical and pathophysiological characteristics. This disease diversity is hypothesized to be driven by αSyn strains with differing biophysical properties, potentially influencing prion-type propagation and consequentially the progression of illness. Previously, we investigated this hypothesis by injecting brain lysate (seeds) from deceased individuals with various synucleinopathies or human recombinant αSyn preformed fibrils (PFFs) into transgenic mice overexpressing either wild type or A53T human αSyn. In the studies herein, we expanded on these experiments, utilizing a panel of antibodies specific for the major carboxyl-terminally truncated forms of αSyn (αSynΔC). These modified forms of αSyn are found enriched in human disease brains to inform on potential strain-specific proteolytic patterns. With monoclonal antibodies specific for human αSyn cleaved at residues 103, 114, 122, 125, and 129, we demonstrate that multiple system atrophy (MSA) seeds and PFFs induce differing neuroanatomical spread of αSyn pathology associated with host specific profiles. Overall, αSyn cleaved at residue 103 was most widely present in the induced pathological inclusions. Furthermore, αSynΔC-positive inclusions were present in astrocytes, but more frequently in activated microglia, with patterns dependent on host and inoculum. These findings support the hypothesis that synucleinopathy heterogeneity might stem from αSyn strains with unique biochemical properties that include proteolytic processing, which could result in dominant strain properties.
The effect of oral nutrition supplement (ONS) on the nutritional and clinical status of patients undergoing autologous hematopoietic stem cell transplantation: study protocol for a randomized controlled clinical trial
Authors: Habibi Sajedeh , Ghoreishy Seyed Mojtaba , Imani Hossein , Barkhordar Maryam , Vaezi Mohammad , Sadeghi Erfan , Mohammadi Hamed
Published: June 2024

Introduction

Several side effects within the patients undergoing hematopoietic stem cell transplantation (HSCT), especially ones that influence nutrition intake, can cause weight loss and malnutrition. Based on studies, oral nutritional supplement (ONS) may reinforce their nutrient intake and progress clinical outcomes. The objective of this research is to investigate the effect of oral nutrition supplements on the nutritional and clinical status of patients undergoing autologous hematopoietic stem cell transplantation.

Methods

After block randomization used the website www.randomization, 38 patients will be enrolled in this study, patients will be allocated to the intervention (ONS) or control groups in a 1: 1 ratio. Patients in the ONS group will receive 250 ml of standard formula (Ensure®, Abbott Nutrition) which has 14–15% protein twice a day, in the morning and bedtime snacks for 21 days. All the procedures done in the control group will be the same as the ONS group except receiving ONS. We will examine the outcomes include; weight, appetite, hand grip strength, calf circumference, mid-arm circumference, total energy intake, protein intake, carbohydrate intake, fat intake, severity of oral mucositis, rate of infection during hospitalization, graft failure, recurrence rate after transplantation, the number of days it takes for neutrophil and platelet engraftment to occur, number of readmissions after transplantation during three months, mortality rate up to three months after transplantation and the three-day food diary record; all the evaluations will be carried out in three steps; 7 days before transplant, on the 14th day after transplantation, and on the 90th day after the transplantation.

Discussion

These patients’ weight loss and malnourishment are significant concerns. The use of ONS in patients receiving HSCT has not been the subject of any research.

Trial registration

This clinical trial was registered in Iranian Registry of Clinical Trials (http://www.irct.ir) on 2022-12-09 with the code number IRCT20220208053971N2.
Identifying and characterising digital behaviour change interventions to improve fruit and vegetable intake in low-socioeconomic status primary school children: a systematic review
Authors: Froome Hannah , Cheung Kei Long , Martin Wendy , Norris Emma
Published: June 2024

Background

Digital behaviour change interventions aiming to improve dietary intakes; specifically fruit and vegetable intake, in low-socioeconomic children are being developed and tested. However there is currently no synthesis of the characteristics or reported effectiveness of these interventions. This systematic review aims to: (1) identify existing digital interventions targeting fruit and vegetable intake in low-socioeconomic status children, (2) identify and synthesise characteristics and reported effectiveness of these interventions using the Behaviour Change Intervention Ontology.

Method

CINAHL, ERIC, PubMed, Cochrane Library, ACM Digital Library and Scopus were searched in December 2021 – February 2022 and in February–March 2024. Inclusion criteria for studies were: 1) children of low-SES families, aged between 5–11 years old; 2) Digital intervention to improve fruit and vegetable intake; 3) Comparison groups could be digital or non-digital; 4) Outcome measures were fruit and vegetable intake and antecedents to diet behaviours; 5) Randomised controlled trials (cluster and parallel designs). Characteristics of identified studies were coded using the Behaviour Change Techniques Taxonomy and Modes of Delivery, Setting and Source ontologies of the Behaviour Change Intervention Ontology.

Results

Five studies met all inclusion criteria, with majority reporting significant effects of interventions on improving fruit and vegetable intake. Most common Behaviour Change Techniques found were Goal Setting (k = 4), Problem Solving (k = 3), Instruction on how to perform a Behaviour (k = 3), and Prompts and Cues (k = 3). Characteristics relating to intervention source were unclear.

Conclusions

Digital interventions had positive outcomes in fruit and vegetable intake in children; particularly more for fruit than vegetable intake. Characteristics in digital interventions which have direct effects on child fruit and vegetable intake in low-socioeconomic families should be further investigated. Furthermore, clearer reporting on intervention characteristics is needed.
Comparative analysis of pembrolizumab and cetuximab-based therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma: Real-world data.
Authors: Hamedi Zahra , Lo Andrea Yachee , Berkman Jonathan David , Alesi Erin R.
Published: June 2024

6022

Background: The preferred treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to localized/curative treatment is pembrolizumab, either monotherapy or in combination with chemotherapy based on the results of KEYNOTE-048. Since the FDA’s approval of pembrolizumab in 2019, real-world data has been scarce. Using the TriNetX platform, we retrospectively compared survival outcomes between patients treated with pembrolizumab vs. cetuximab-based treatment. Methods: Cohorts were identified on TriNetX platform using the US Collaborative Network, which includes anonymous clinical information of patients between 2007-2023. Three cohorts were selected: patients treated with pembrolizumab monotherapy (P), patients treated with pembrolizumab and platinum+5-FU chemotherapy (P+CT), and patients treated with cetuximab and platinum+5-FU chemotherapy (C+CT). All patients had non-nasopharyngeal R/M HNSCC with no prior systemic therapy. The study objective was to compare overall survival (OS) between these three cohorts using the Kaplan-Meier method. Results: Our analysis identified 409 patients in cohort P, 161 patients in cohort P+CT, and 176 patients in cohort C+CT. Median age at initiation of treatment was 69.8, 62.2, and 57.7 years in cohort P, P+CT, and C+CT, respectively. Male percentage was 61%, 75%, and 77%, respectively. The most common primary tumor sites for cohorts P, P+CT, and C+CT were as follows: oropharynx 28%, 37%, and 48%, hypopharynx 10%, 19%, and 11%, larynx 31%, 29%, and 40%, and oral cavity 4%, 6% and 9% respectively. Information on PD-L1 and HPV (Human Papillomavirus) status was not available. Median OS was 13.7, 15, and11.4 months in cohorts P, P+CT, and C+CT, respectively. Survival probability at 5 years was 25.7% in cohort P, 32.2% in cohort P+CT, and 9.9% in cohort C+CT. Based on our analysis, patients treated with pembrolizumab (P or P+CT) demonstrated superior OS compared to those who received cetuximab-based therapy (P-Value <0.05). There was no statistically difference in median OS between P and P+CT group. (P-Value 0.6). Conclusions: Our retrospective analysis of real-world data from a large national database shows superior OS with pembrolizumab- based treatment compared to cetuximab-based treatment in the first line setting for patients with R/M HNSCC. This analysis is consistent with KEYNOTE-048 outcomes. we found no difference in OS between Pembrolizumab alone or in combination with chemotherapy. Limitations include unknown PD-L1 and HPV status. Further long-term and prospective analysis is imperative to enhance the care and outcomes of patients with metastatic HNSCC. [Table: see text]
Correlation between irAEs and treatment efficacy of anti-PD-1 single agent in patients with recurrent/metastatic head and neck squamous cell carcinoma: A monocentric real-world observational study.
Authors: Gottardi Chiara , Anile Giuseppe , Micheletto Ilaria , Krengli Marco , Carobbio Andrea Luigi Camillo , El Khouzai Badr , Taboni Stefano , Pretto Greta , Guarneri Valentina , Ghi Maria Grazia
Published: June 2024

6029

Background: Immune-related adverse events (irAEs) are associated with efficacy of ICIs-based treatment in various cancer types. The aim of this retrospective study was to assess the relationship between irAEs and outcomes in patients with recurrent/metastatic Head and Neck squamous cell carcinoma (R/M-HNSCC) treated with immune checkpoint inhibitors (ICIs) monotherapy. Methods: We retrospectively reviewed data from patients with R/M HNSCC treated with ICIs single-agent between January 2018 and June 2023 at the Istituto Oncologico Veneto of Padua. Common Terminology Criteria for Adverse Events v.5.0 was used to assess irAEs evaluation. Patients were stratified into irAEs (any grade) and non-irAEs groups. Overall survival (OS) and progression free survival (PFS) were assessed using the Kaplan-Meier method. Univariate and multivariate Cox-regression were used to compare survival outcomes. The chi-square test was used to assess the association between irAEs and objective responses (ORR). Results: A total of 89 patients were eligible for the analysis. Patients with platinum-refractory disease received nivolumab (64 patients, 72%). All the 25 patients (28%) with platinum-sensitive disease were PD-L1 positive (CPS≥1) and received pembrolizumab as first line treatment for R/M disease. Median follow-up was 8.7 months. IrAEs (any grade) were observed in 60 patients (67%), including 9 patients (10%) with grade ≥3 AEs. The most common irAEs were endocrinopathies (35%), skin events (15%), hepatic events (13%), diarrhea/colitis (10%) and lipase/amylase elevation (10%). The ORR was higher in the irAEs group than in the non-irAEs group (19.5% vs 2%, p=0.017). PFS and OS were also significantly longer in the irAEs group: median PFS was 3.9 months vs 2.1 months (HR 0.48 95% CI 0.30-0.77; p=0.003) and median OS was 12.5 months vs 4.3 months (HR 0.36 95% CI 0.21-0.60; p=0.000). The statistically significant benefit for both PFS and OS was confirmed at the multivariate analysis (Table1). Patients who experienced endocrine-related irAEs (p=0.004), diarrhea/colitis (p=0.040) and lipase/amylase increase (p=0.005) had significantly longer OS than those without the corresponding toxicity. A positive trend was observed for skin toxicity (p=0.051). Conclusions: The occurrence of irAEs was a predictor of response and survival outcomes in patients with R/M HNSCC treated with ICIs single-agent.[Table: see text]
Significance of imaging-detected extranodal extension (iENE) in locally advanced head and neck squamous cell carcinoma (LASCCHN) treated with induction chemotherapy followed by chemoradiotherapy.
Authors: Onaga Ryutaro , Enokida Tomohiro , Hiyama Takashi , Tanaka Nobukazu , Hoshi Yuta , Tanaka Hideki , Fujisawa Takao , Okano Susumu , Kuno Hirofumi , Tahara Makoto
Published: June 2024

6034

Background: Extranodal extension (ENE) of nodal metastasis is a significant prognostic factor in p16-negative SCCHN and is classified as N3b by the AJCC 8th edition. Therefore, pretreatment determination of ENE has significant clinical implications in SCCHN, and iENE has just recently been proposed. We previously discussed association with pathological ENE and iENE (Jpn J Radiol. 2020;38(6):489-506.). However, the role of iENE in non-surgical sequential therapy remains unclear. Methods: We retrospectively reviewed patients with LASCCHN originating from the oropharynx, hypopharynx, and larynx who received enhanced computed tomography (CT), then treated with induction chemotherapy (IC) with paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy (CRT) from 2013 to 2022 in our hospital. Two radiologists specializing in head and neck cancer blindly annotated the status of iENE in baseline CT images by the previously reported criteria (Oral Oncol. 2022;125:105716.). Multivariate analysis variables for event-free survival (EFS) and overall survival (OS) included the presence or absence of iENE, a response to IC, clinical T-category, performance status, smoking status, etc. Results: In the 88 patients, 67 (76.1%) had iENE and 21 (23.9%) did not at baseline. In the former and latter group, stage II/III/IV were 10.4%/26.9%/62.7% and 0%/28.6%/71.4%, HPV-positive were 37.3% and 28.6%, respectively. With the median follow-up of 37.4 months (range: 6.7-108.8), the former had significantly shorter EFS (3-y EFS: 41.9% vs. 75.6%, hazard ratio [HR]; 2.9 (1.2-7.4), p-value; 0.02) and OS (3-y OS: 72.8% vs. 100%, HR; Inf (0.01-Inf), p-value=0.003). Multivariate analysis identified the presence of iENE (HR for EFS: 2.80, 95%CI: 0.97-8.05, HR for OS: 2.93, 95%CI: 1.01-8.44) and unresponsiveness to IC (HR for EFS: 2.47, 95%CI: 1.31-4.68, HR for OS: 2.87, 95%CI: 1.13-7.26) as mutually independent unfavorable prognostic factors for both EFS and OS. Furthermore, classification based on the two factors could identify the population with a worse prognosis (Table). Conclusions: In the sequential therapy of IC followed by CRT, the current study revealed for the first time that subjects with an iENE at baseline, together with an unsatisfactory response to IC would require special attention, such as more intensified post-treatment follow-up as well as additional therapeutic interventions to improve their prognosis. [Table: see text]
Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing head and neck tumors: Outcomes from DESTINY-PanTumor02 (DP-02).
Authors: Meric-Bernstam Funda , Kim Seung Tae , Parinyanitikul Napa , Moreno Alberto , Lin Chia-Chi , Gornastolev Dmitry , Chindaprasirt Jarin , Lugowska Iwona A. , Stroyakovskiy Daniil , Jassem Jacek , Harrison Michelle L. , Ostwal Vikas S. , Michelini Flavia , Jung Lindsey , Kuptsova-Clarkson Nataliya , Puvvada Soham D. , Gan Hui Kong
Published: June 2024

6037

Background: In DP-02, T-DXd demonstrated an objective response rate (ORR) by investigator (INV) of 37.1% (95% CI 31.3, 43.2) and clinically meaningful survival outcomes in 267 pretreated pts with HER2-expressing tumors. In this post-hoc analysis, we report outcomes and characterize those with an objective response (OR) in a subset of pts with head and neck cancers (previously included in the ‘other tumor’ cohort), most of which were salivary gland tumors. Methods: This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in pts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced/metastatic disease after ≥1 systemic treatment or without treatment options. The primary endpoint was confirmed ORR by INV. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), and safety. Exploratory endpoints included efficacy outcomes by HER2 expression. Results: At data cutoff (June 2023), 24 pts with head and neck tumors (n=19 salivary gland, n=3 squamous cell carcinoma [SCC], n=1 adenoid cystic carcinoma, n=1 lacrimal gland) had received treatment (median [m] follow up: 20.8 months [range: 4.7–31.6]). Of these pts, 15 (62.5%) had received ≥2 prior treatment regimens. 10/24 pts (41.7%; 95% CI 22.1, 63.4; n=8 salivary gland, n=1 SCC, n=1 lacrimal gland) had a confirmed OR by INV; 9 responders had received prior radiation therapy, and 4 had known PD-L1 immune cell status ≥1%. The Table shows efficacy outcomes in all pts and by HER2 expression (central testing). Grade (G) ≥3 drug-related adverse events occurred in 10/24 (41.7%) pts. Adjudicated drug-related interstitial lung disease / pneumonitis occurred in 3/24 (12.5%) pts (n=1 G1; n=1 G2; n=1 G5). Conclusions: T-DXd showed clinically meaningful benefit in pretreated pts with head and neck tumors. Responses were observed across HER2 expression levels. Safety was consistent with the known profile. These data support T-DXd as a potential treatment for pretreated pts with HER2-expressing head and neck tumors. Clinical trial information: NCT04482309 . [Table: see text]
A phase II study of nivolumab in patients with recurrent or metastatic carcinosarcomas.
Authors: Kim Miso , Hong Jung Yong , Kim Min Hwan , Jung Minkyu , Kim Gun Min , Kim Kyoo Hyun , Yun Kum-Hee , Shin Su-Jin , Lee Young Han , Park Jiwoo , Lee Jeeyun , Kim Hyo Song
Published: June 2024

6041

Background: We aimed to determine the activity of anti-PD-1 inhibitor, nivolumab in metastatic and/or recurrent carcinosarcoma. Methods: In this phase 2 trial, eligible patients had histologically confirmed metastatic and/or recurrent carcinosarcoma, measurable disease, 1-3 prior chemotherapy, and adequate renal/hepatic/hematologic function. In this single arm phase 2 trial, treatment consisted of nivolumab 3 mg/kg every 2 weeks. Primary outcome was progression free rate (PFR) at 6 months and secondary outcomes included overall response rate, progression-free survival (PFS), overall survival, and safety. Results: Between July 2020 and Nov 2023, 28 patients enrolled and received trial treatment. As of the time of data cut-off (Feb 1, 2024), 4 remains on treatment. Of the 28 patients evaluable, 4 (14.3%) achieved confirmed partial response, and 9 (32.1%) had stable disease, yielding and disease control rate of 46.4%. The median PFS was 2.6 months. The pre-specified primary endpoint was met with 6-months PFR of 30.8%. The common-treatment related adverse events included urticaria (5 [17.9%]), dyspepsia (4 [14.3%]), elevated aspartate aminotransferase (3 [10.7%]), and anemia (3 [10.7%]). The genomic analysis will be available at the meeting. Conclusions: Nivolumab demonstrated promising efficacy with favourable toxicity profile in metastatic/recurrent carcinosarcoma. Clinical trial information: NCT05224999 .
Associations of ctDNA clearance and pathological response after neoadjuvant treatment in patients with locally advanced oral cancer.
Authors: Zhong Lai-ping , Zhou Zhi-hang , Huang Ying-ying , Zhang Yi-yi , Lu Yi , Li Bing , Wang Jing , Zhao Tong-chao , Ju Wu-tong , Zhu Dong-wang
Published: June 2024

6043

Background: Neoadjuvant treatment (NAT) has improved clinical outcomes in some patients with locally advanced oral squamous cell carcinoma (LAOSCC). Effective biomarkers assessing the treatment response is still lacking. Previous studies have posed the potential of circulating tumor DNA (ctDNA) in monitoring treatment response, but the underlying mechanisms behind non-shedding in tumors remain unclear. Methods: 29 LAOSCC patients received NAT followed by surgery were enrolled. Seven (24.1%), 9 (31%), and 13 (44.8%) patients received NAT of apatinib+camrelizumab, TPF chemoagents, and toripalimab+paclitaxel+cisplatin, respectively. Tumor tissues before NAT underwent whole exome sequencing and whole transcriptome resequencing. Blood samples at pre-NAT (T0), mid-NAT (T1), before surgery (T2) and after surgery (T3) were analyzed using a tumor-informed, personalized NGS assay. Multi-omics analysis, including ctDNA status, was performed with patients' clinical features and outcomes. Results: Among the 29 patients received NAT, the MPR rate was 55.2% (16/29), and the pCR rate was 27.6% (8/29). At baseline(T0), ctDNA was detectable in 25/29 (86.2%) patients, which decreased over time (T1: 77.8%; T2: 51.7%; T3: 6.9%). Persistent ctDNA at T2 indicates a higher rate of residual disease after NAT (100% non-pCR) compared to ctDNA-negative patients (42.8% non-pCR; p = 0.0047). All patients achieving pCR at T2 were ctDNA-negative (n=8, 100%) including 2 non-shedders. The PPV and NPV for predicting pCR by ctDNA clearance at T2 were 57.1% (8/14) and 100% (15/15), respectively. ARSF, CFAP47, or HAUS8 mutations at baseline were associated with significantly higher pCR rates (p<0.05). Four non-shedders with undetectable ctDNA at T0 were significantly enriched in patients with negative lymph nodes, lower clinical T stage, and high CPS score. The non-shedders had significantly lower tumor mutational burden (TMB), higher stromal score and cancer-associated fibroblast (CAF) (p<0.05). Spatial transcriptome analysis further supports that MHC-II pathway-related genes were significantly up-regulated in the non-shedders. The enhancing communication intensity between CAFs, endothelial cells and T cells might provide an anti-cancer immune microenvironment for non-shedders. Conclusions: Our results indicate that the clearance of ctDNA clearance at T2 was associated with an improved pCR rate. Furthermore, our findings shed light on the factors that prevent ctDNA release from oral squamous cell carcinoma.[Table: see text]
Tislelizumab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy versus neoadjuvant chemotherapy and concurrent chemoradiotherapy in local advanced nasopharyngeal carcinoma.
Authors: Luo Haiqing , He Jiaqi , Yi Guihua , Tang Haifeng , Yang Donghong , Li Haiwen , Yu Ying , Chen Zihong , Zhan Dechao
Published: June 2024

6045

Background: Given the recent successes of immunotherapy in local advanced nasopharyngeal carcinoma (LA-NPC), maybe it is promising to achieve better response and improve the survival of LA-NPC if immunotherapy plus neoadjuvant and concurrent chemoradiotherapy (CCRT). Therefore, we retrospectively analysed the safety and efficacy of tislelizumab plus neoadjuvant chemotherapy and CCRT and neoadjuvant chemotherapy followed CCRT in the treatment of LA-NPC. Methods: A total of 90 patients with stage III-IVa NPC were enrolled between January 2020 and March 2021 at Affiliate Hospital of Guangdong Medical University. 43 patients were treated with tislelizumab plus TP (nab-paclitaxel 260mg/m2, cisplatin 80mg/m2, Q3W, 3 cycles) regimen followed tislelizumab plus CCRT as the combination therapy group (CG) and 47 patients were treated with TP regimen followed CCRT as the observation group (OG). Results: As of January 30th, 2024, the median follow-up time is 37.5 months. The median age was 42 years (range: 16–75 years). A total of 37 patients had stage III cancer and 53 had stage IVa , with 43 and 47 patients in OG and CG, respectively. The male–female ratio in the entire cohort was approximately 2.15:1. All reported parameters were balanced between the two groups with no statistical differences. The complete response rate (CRR) in CG after neoadjuvant therapy improved significantly (37.2% in CG vs 12.8% in OG). The ORR was 88.4% in CG and 70.2% in OG, respectively. The 3-year PFS was 93.75% in CG and 80% in OG. The incidence of acute treatment related adverse events in grades 3 or 4 was 70.2% and 65.6%, respectively. The most common grade 3-4 immune-related adverse events were hypothyroidism (7.0%) and hepatotoxicity (4.7%). No patients in CG had disease progression during treatment. Conclusions: Compared with regular treatment, tislelizumab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy was feasible and well tolerated in LA-NPC patients. This trial is supportive of further prospective trials in LA-NPC.
The potential prognostic value of the head and neck advanced lung inflammation index (HN-ALI) for patients treated with immunotherapy.
Authors: Filippini Daria Maria , Carosi Francesca , Fermi Matteo , Trudu Lucia , Cabitza Eleonora , Napolitano Martina , Depenni Roberta , Nobili Elisabetta , Dominici Massimo , Molteni Gabriele , Bertolini Federica
Published: June 2024

6052

Background: The ALI is recognized as a potential prognostic and predictive biomarker for patients (pts) treated with immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer. In head and neck squamous cell carcinoma (HNSCC) its prognostic role has been acknowledged in locally advanced setting. We evaluated whether HN-ALI could provide similar value in pts with recurrent/metastatic (R/M) HNSCC undergoing treatment with ICIs. Methods: We conducted a multicentric observational retrospective study including R/M HNSCC pts treated with ICIs alone or in combination with chemotherapy from April 2016 to November 2023. The ALI was calculated as follows: BMI (kg/m2) × serum albumin (g/dL)/neutrophil-to-lymphocyte ratio (NLR). Using the bibliographic cut off value of 18, pts were divided into two groups: ALI < 18 (high inflammation) and ALI > 18 (low inflammation). The primary outcomes were overall survival (OS) and progression free survival (PFS), evaluated with the Kaplan-Meier estimator. Cox proportional hazard regression models were employed to perform multivariate analysis. Results: A total of 145 pts [105 males, median (m) age 66 years, 128 with ECOG PS < 1] were treated with ICIs (35% nivolumab, 64% pembrolizumab) across two Italian centers. Primary tumor sites were: oral cavity (35%), oropharynx (33%), larynx (14%), hypopharynx (7%), other (9%). ICIs were administered as single agents in 86 pts and in combination with chemotherapy in 59 pts. The HN-ALI was collected for 92 pts. The mPFS was 6 months (95%CI, 2.16-9.83) within the ALI group > 18 versus 1 month for the ALI group < 18 (95%CI, 0.26-1.73) (p< .001); analogously, the mOS was 17 months (95%CI, 11.63-22.36) versus 2 months (95%CI, 0.68-3.32) for the ALI group > 18 and < 18, respectively (p< .001). At the multivariate analysis, high ALI score represented an independent risk factor for better OS, also including ECOG PS and PD-L1 expression [HR 0.38; (95% CI,0.15 – 0.96), p= .042], while showing a trend towards longer disease progression [HR 0.52; (95% CI, 0.26 - 1.02), p= .058]. Conclusions: In our experience, ALI value >18 is associated with better prognosis in pts treated with ICIs alone and in combination with chemotherapy. Further analyses are warranted to validate the prognostic relevance of the ALI value in pts with HNSCC undergoing ICIs.