Nevin Manimala

Support Care Cancer. 2024 Mar 2;32(3):203. doi: 10.1007/s00520-024-08412-7.

ABSTRACT

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT).

METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL.

RESULTS: Patients’ symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL.

CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.

PMID:38430411 | DOI:10.1007/s00520-024-08412-7

Cancer Immunol Immunother. 2024 Mar 2;73(4):72. doi: 10.1007/s00262-024-03640-6.

ABSTRACT

BACKGROUND: Inhibition of the adenosine 2A receptor (A_2AR) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the A_2AR antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.

METHODS: Patients with histologically/cytologically confirmed disease progressing within 6 months on ≥ 2 therapy lines were randomly assigned to either Module 1 (AZD4635 + durvalumab) or Module 2 (AZD4635 + oleclumab). Primary endpoints were objective response rate per RECIST v1.1 and prostate-specific antigen (PSA) response rate. Secondary endpoints included radiological progression-free survival (rPFS), overall survival, safety, and pharmacokinetics.

RESULTS: Fifty-nine patients were treated (Module 1, n = 29; Module 2, n = 30). Median number of prior therapies was 4. One confirmed complete response by RECIST (Module 1) and 2 confirmed PSA responses (1 per module) were observed. The most frequent adverse events (AEs) possibly related to AZD4635 were nausea (37.9%), fatigue (20.7%), and decreased appetite (17.2%) in Module 1; nausea (50%), fatigue (30%), and vomiting (23.3%) in Module 2. No dose-limiting toxicities or treatment-related serious AEs were observed. In Module 1, AZD4635 geometric mean trough concentration was 124.9 ng/mL (geometric CV% 69.84; n = 22); exposures were similar in Module 2. In Modules 1 and 2, median (95% CI) rPFS was 2.3 (1.6 -3.8) and 1.5 (1.3- 4.0) months, respectively. Median PFS was 1.7 versus 2.3 months for patients with high versus low blood-based adenosine signature.

CONCLUSION: In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile.

CLINICAL TRIAL: gov identifier: NCT04089553.

PMID:38430405 | DOI:10.1007/s00262-024-03640-6

Theor Appl Genet. 2024 Mar 2;137(3):64. doi: 10.1007/s00122-024-04568-2.

ABSTRACT

An improved estimator of genomic relatedness using low-depth high-throughput sequencing data for autopolyploids is developed. Its outputs strongly correlate with SNP array-based estimates and are available in the package GUSrelate. High-throughput sequencing (HTS) methods have reduced sequencing costs and resources compared to array-based tools, facilitating the investigation of many non-model polyploid species. One important quantity that can be computed from HTS data is the genetic relatedness between all individuals in a population. However, HTS data are often messy, with multiple sources of errors (i.e. sequencing errors or missing parental alleles) which, if not accounted for, can lead to bias in genomic relatedness estimates. We derive a new estimator for constructing a genomic relationship matrix (GRM) from HTS data for autopolyploid species that accounts for errors associated with low sequencing depths, implemented in the R package GUSrelate. Simulations revealed that GUSrelate performed similarly to existing GRM methods at high depth but reduced bias in self-relatedness estimates when the sequencing depth was low. Using a panel consisting of 351 tetraploid potato genotypes, we found that GUSrelate produced GRMs from genotyping-by-sequencing (GBS) data that were highly correlated with a GRM computed from SNP array data, and less biased than existing methods when benchmarking against the array-based GRM estimates. GUSrelate provides researchers with a tool to reliably construct GRMs from low-depth HTS data.

PMID:38430392 | DOI:10.1007/s00122-024-04568-2

J Relig Health. 2024 Mar 2. doi: 10.1007/s10943-024-02003-w. Online ahead of print.

ABSTRACT

Patients who have previously undergone coronary artery bypass surgery (CABG) were prone to death anxiety during the COVID-19 pandemic. It appears that spiritual well-being and appropriate coping strategies may mitigate the harmful effects of death anxiety. Therefore, this study aimed to determine the level of death anxiety in patients with CABG during the COVID-19 pandemic and investigate the relationship between spiritual well-being, coping strategies and death anxiety.This cross-sectional study was conducted on 100 patients with CABG history in Tehran from June 2021 to February 2022. The face-to-face questionnaire, containing questions on demographics, Templer’s death anxiety scale, the spiritual well-being questionnaire, and the ways of coping questionnaire was administered to collect data. Statistical analysis was performed using descriptive-analytical statistics, correlation tests, and logistic regression models.Participants’ mean age was 55.59 ± 12.78 years. The mean death anxiety score was 10.00 ± 2.16, with 87% of participants reporting high levels and 13% reporting low levels of death anxiety. Based on the results, there was a significant negative correlation between death anxiety and coping strategies, as well as subscales of distancing, seeking social support, accepting responsibility, and planful problem-solving. Logistic regression showed that with the increase in the score of spiritual well-being, the odds of having high levels of death anxiety decreased (p < 0.05). Furthermore, increasing the total score of coping strategies, and the score of self-controlling, seeking social support, accepting responsibility, and planful problem-solving, significantly reduced the odds of high levels of death anxiety (p < 0.05).The study showed that patients with a CABG history experienced high death anxiety during the COVID-19 pandemic. According to the findings, spiritual well-being and coping strategies, especially self-controlling, seeking social support, accepting responsibility, and planful problem-solving, may reduce the odds of severe death anxiety. These should be considered as effective targets for psychological intervention in these patients.

PMID:38430384 | DOI:10.1007/s10943-024-02003-w

Int J Comput Assist Radiol Surg. 2024 Mar 2. doi: 10.1007/s11548-024-03068-4. Online ahead of print.

ABSTRACT

PURPOSE: New deep learning and statistical shape modelling approaches aim to automate the design process for patient-specific cranial implants, as highlighted by the MICCAI AutoImplant Challenges. To ensure applicability, it is important to determine if the training data used in developing these algorithms represent the geometry of implants designed for clinical use.

METHODS: Calavera Surgical Design provided a dataset of 206 post-craniectomy skull geometries and their clinically used implants. The MUG500+ dataset includes 29 post-craniectomy skull geometries and implants designed for automating design. For both implant and skull shapes, the inner and outer cortical surfaces were segmented, and the thickness between them was measured. For the implants, a ‘rim’ was defined that transitions from the repaired defect to the surrounding skull. For unilateral defect cases, skull implants were mirrored to the contra-lateral side and thickness differences were quantified.

RESULTS: The average thickness of the clinically used implants was 6.0 ± 0.5 mm, which approximates the thickness on the contra-lateral side of the skull (relative difference of -0.3 ± 1.4 mm). The average thickness of the MUG500+ implants was 2.9 ± 1.0 mm, significantly thinner than the intact skull thickness (relative difference of 2.9 ± 1.2 mm). Rim transitions in the clinical implants (average width of 8.3 ± 3.4 mm) were used to cap and create a smooth boundary with the skull.

CONCLUSIONS: For implant modelers or manufacturers, this shape analysis quantified differences of cranial implants (thickness, rim width, surface area, and volume) to help guide future automated design algorithms. After skull completion, a thicker implant can be more versatile for cases involving muscle hollowing or thin skulls, and wider rims can smooth over the defect margins to provide more stability. For clinicians, the differing measurements and implant designs can help inform the options available for their patient specific treatment.

PMID:38430381 | DOI:10.1007/s11548-024-03068-4

Int J Comput Assist Radiol Surg. 2024 Mar 2. doi: 10.1007/s11548-024-03073-7. Online ahead of print.

ABSTRACT

PURPOSE: Osteonecrosis of the femoral head (ONFH) is a severe bone disease that can progressively lead to hip dysfunction. Accurately segmenting the necrotic lesion helps in diagnosing and treating ONFH. This paper aims at enhancing deep learning models for necrosis segmentation.

METHODS: Necrotic lesions of ONFH are confined to the femoral head. Considering this domain knowledge, we introduce a preprocessing procedure, termed the “subtracting-adding” strategy, which explicitly incorporates this domain knowledge into the downstream deep neural network input. This strategy first removes the voxels outside the predefined volume of interest to “subtract” irrelevant information, and then it concatenates the bone mask with raw data to “add” anatomical structure information.

RESULTS: Each of the tested off-the-shelf networks performed better with the help of the “subtracting-adding” strategy. The dice similarity coefficients increased by 10.93%, 9.23%, 9.38% and 1.60% for FCN, HRNet, SegNet and UNet, respectively. The improvements in FCN and HRNet were statistically significant.

CONCLUSIONS: The “subtracting-adding” strategy enhances the performance of general-purpose networks in necrotic lesion segmentation. This strategy is compatible with various semantic segmentation networks, alleviating the need to design task-specific models.

PMID:38430380 | DOI:10.1007/s11548-024-03073-7

Cancer Immunol Immunother. 2024 Mar 2;73(4):70. doi: 10.1007/s00262-024-03643-3.

ABSTRACT

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).

METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed.

RESULTS: Prespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48-1.72) and 0.69 (0.39-1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs.

CONCLUSIONS: bTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME. Trial registration ClinicalTrials.gov identifier NCT02551159.

PMID:38430375 | DOI:10.1007/s00262-024-03643-3

Clin Oral Investig. 2024 Mar 2;28(3):187. doi: 10.1007/s00784-024-05574-w.

ABSTRACT

AIM: The present retrospective cohort study aimed to evaluate luxated permanent teeth for pulp prognosis and risk factors.

METHODOLOGY: Case records and radiographs of 224 patients, involving 427 luxated permanent teeth, referred for treatment at the Dental Trauma Center-School of Dentistry, Universidade Federal de Minas Gerais, (DTC-SD-UFMG) from 2014 to 2022, were assessed for pulp prognosis classified as vitality, necrosis and pulp canal obliteration (PCO). A competing risk survival analysis estimated the hazards of the three outcomes, and the effect of demographic, clinical and treatment variables was tested using a cause specific Cox regression model.

RESULTS: Pulp vitality was found in163 teeth (38.2%), pulp necrosis in 120 teeth (28.1%) and 55 teeth (12.9%) developed PCO. Pulp vitality decreased in the presence of concomitant crown fractures (HR 0.38 95% CI [0.2-0.8] p = 0.006). The risk of pulp necrosis (HR 0.62 95% CI [0.4-0.96] p = 0.03) was lower in cases with open apices but increased with concomitant crown fractures (HR 4.0 95% CI [2.6-6.1] p = 0.001) and intrusions (HR 2.3 95% CI [1.2-4.1] p = 0.007). Lateral or extrusive luxations (HR 3.0 95% CI [1.3-6.9] p = 0.001) and open apices (HR 2.4 95% CI [1.2-4.7] p = 0.01) showed higher rates of PCO.

CONCLUSION: Type of luxation, the diameter of the apical foramen, and the presence of concomitant crown fractures were main determinants of pulp prognosis after luxation injuries in permanent teeth.

CLINICAL RELEVANCE: Pulp prognosis after tooth luxation is dependent on the presence and direction of tooth displacement together with infection control.

CLINICAL TRIAL REGISTRATION: Not applicable.

PMID:38430349 | DOI:10.1007/s00784-024-05574-w

Biol Trace Elem Res. 2024 Mar 2. doi: 10.1007/s12011-024-04128-1. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the potential bioaccumulation of arsenic (As), copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb) and mercury (Hg) in the haemolymph and corpus of Mytilus galloprovincialis and Tapes decussatus from Lake Faro. The lake is particularly prone to the accumulation of substances that are potentially toxic to aquatic organisms, due to the input of pollutants from urban and agricultural sources and the low rate of water exchange. The combination of saltwater from the Tyrrhenian Sea, the Strait of Messina and freshwater from hilly aquifers has created brackish conditions in the lake, resulting in an area of high commercial shellfish productivity. As, Cd, Cu, Pb and Zn were determined using a single quadrupole inductively coupled plasma mass spectrometer; Hg was determined using a direct mercury analyser (DMA-80). Physicochemical parameters of the water from Lake Faro were also performed. Statistical analysis was carried out using GraphPad Prism 9.0 (GraphPad Software, Inc., Boston, MA, USA) and Shapiro-Wilk normality was applied. Concentrations of Cd, Hg and Pb below the permitted MRLs in Mytilus galloprovincialis and Tapes decussatus used as ”biological indicators” show that Lake Faro is not at risk of contamination by these pollutants and, moreover, is free of health problems for the consumer based on regulatory limits.

PMID:38430347 | DOI:10.1007/s12011-024-04128-1

Curr Nutr Rep. 2024 Mar 2. doi: 10.1007/s13668-024-00522-2. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Acute Myeloid Leukaemia (AML) constitutes a mere 1% of global cancer cases. This scoping review aims to investigate the association between nutrition and the development of AML, providing a foundation for future research in this field.

RECENT FINDINGS: A systematic search was conducted across PubMed, EBSCO, Taylor and Francis, Science Direct and Cochrane Library using specific keywords. Inclusion criteria comprised observational studies and clinical trials examining the association between nutrition and the development of AML. Articles selected for analysis were restricted to those published in English between 1990-2023, and available as full text articles. Among the twenty-five articles that were screened, only six met the criteria for data extraction. Four studies did not reveal statistically significant correlations between nutrition and the development of AML, while two studies provided evidence for significant associations. The findings indicated increased AML risk associated with (a) heightened caloric intake, consumption of white potatoes, and red meat (pork and beef) and (b) diminished consumption of vegetables, seafood, nuts, and seeds. The scarcity of comprehensive studies exploring the connection between nutrition and AML, highlights the urgent need for additional research, encompassing pre-clinical studies. This imperative is critical for enhancing our understanding of the molecular mechanisms that underlie the connection between diet and the aetiology of AML. Such knowledge is paramount in advancing effective strategies for both prevention and management of this significant disease.

PMID:38430336 | DOI:10.1007/s13668-024-00522-2