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Gynecologic Oncology Jun 2024To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).
OBJECTIVE
To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).
METHODS
A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors.
RESULTS
A total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84-91), 98% [95% CI (96-99), and 92% [95% CI (87-95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS.
CONCLUSION
PBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.
PubMed: 38941964
DOI: 10.1016/j.ygyno.2024.06.010 -
Boletin Medico Del Hospital Infantil de... 2024This essay challenges the idea of progress as technological development in relation to medicine by focusing on people rather than things. It analyzes how the prevalence...
This essay challenges the idea of progress as technological development in relation to medicine by focusing on people rather than things. It analyzes how the prevalence of such an idea of progress leads contemporary societies to a technofetishism that degrades community life and medical practice, contributing to the medicalization of social life. It is argued that the realization of technological potentialities depends on their forms of use, that the main motive of technological development is unlimited profit, and the priority developments are those that enhance social control which maintains the status quo. Intelligence as an intelligence quotient is criticized by proposing it as an attribute of the human being as a whole, manifested in the ways of thinking and acting of human beings in their circumstances, where affectivity and critical thinking are essential for their development; it is emphasized that its antecedent is the harmonic concert of planetary life, which contrasts with the prevailing human disharmony. It is proposed that artificial intelligence is the latest creation of technofetishism, which deposits vital attributes in technology, and that its use will accentuate the degradation of human and planetary life. Another idea of medical progress is proposed, based on forms of organization that is conducive to the development of inquisitive, critical, and collaborative skills that promote permanent improvement, whose distant horizon is dignified progress: the spiritual, intellectual, moral, and convivial sublimation of collectivities in harmony with the planetary ecosystem.
Topics: Artificial Intelligence; Humans; Medicalization
PubMed: 38941644
DOI: 10.24875/BMHIME.M24000071 -
Boletin Medico Del Hospital Infantil de... 2024This essay questions, with regard to medicine, the idea of progress as technological development by focusing on people rather than things. It analyzes how the...
This essay questions, with regard to medicine, the idea of progress as technological development by focusing on people rather than things. It analyzes how the predominance of such an idea of progress converts today's societies to techno-fetishism that degrades community life and medical practice, contributing to the medicalization of social life. It is argued that the realization of technological potentialities depends on their forms of use; that the main motive of technological development is unlimited profit and that priority developments are those that enhance the social control that maintains the status quo. The intelligence as an intelligence quotient is criticized by proposing it as an attribute of the human being as a whole, manifested in the ways of thinking and proceeding of people in their circumstances, where affectivity and critical thinking are essential for their development; it is emphasized that its antecedent is the harmonic concert of planetary life that contrasts with the prevailing human disharmony. It is proposed that artificial intelligence is the most recent creation of techno-fetishism that deposits vital attributes in technology and that its forms of use will accentuate the degradation of human and planetary life. Another idea of medical progress is proposed, based on forms of organization conducive to the development of inquisitive, critical and collaborative skills that promote permanent improvement, whose distant horizon is dignifying progress: spiritual, intellectual, moral and convivial sublimation of collectivities in harmony with the planetary ecosystem.
Topics: Artificial Intelligence; Humans; Medicalization; Intelligence; Medicine
PubMed: 38941639
DOI: 10.24875/BMHIM.24000007 -
Science Advances Jun 2024Seismic observations of impacts on Mars indicate a higher impact flux than previously measured. Using six confirmed seismic impact detections near the NASA InSight...
Seismic observations of impacts on Mars indicate a higher impact flux than previously measured. Using six confirmed seismic impact detections near the NASA InSight lander and two distant large impacts, we calculate appropriate scalings to compare these rates with lunar-based chronology models. We also update the impact rate from orbital observations using the most recent catalog of new craters on Mars. The snapshot of the current impact rate at Mars recorded seismically is higher than that found using orbital detections alone. The measured rates differ between a factor of 2 and 10, depending on the diameter, although the sample size of seismically detected impacts is small. The close timing of the two largest new impacts found on Mars in the past few decades indicates either a heightened impact rate or a low-probability temporal coincidence, perhaps representing recent fragmentation of a parent body. We conclude that seismic methods of detecting current impacts offer a more complete dataset than orbital imaging.
PubMed: 38941463
DOI: 10.1126/sciadv.adk7615 -
Journal of Experimental Botany Jun 2024Plants use a combination of sophisticated local and systemic pathways to optimize growth depending on heterogeneous nutrient availability in the soil. Legume plants can...
Plants use a combination of sophisticated local and systemic pathways to optimize growth depending on heterogeneous nutrient availability in the soil. Legume plants can acquire mineral nitrogen (N) either through their roots or via a symbiotic interaction with N-fixing rhizobia bacteria housed in so-called root nodules. To identify shoot-to-root systemic signals acting in Medicago truncatula plants at N-deficit or N-satiety, plants were grown in a split-root experimental design, in which either high or low N was provided to a half of the root system, allowing the analysis of systemic pathways independently of any local N response. Among the plant hormone families analyzed, the cytokinin trans-Zeatin accumulated in plants at N-satiety. Cytokinin application by petiole feeding led to an inhibition of both root growth and nodulation. In addition, an exhaustive analysis of miRNAs revealed that miR2111 accumulates systemically under N-deficit in both shoots and non-treated distant roots, whereas a miRNA related to inorganic Phosphate (Pi)-acquisition, the miR399, does so in plants grown at N-satiety. These two accumulation patterns are dependent on CRA2 (Compact Root Architecture 2), a receptor required for CEP (C-terminally Encoded Peptide) signaling. Constitutive ectopic expression of the miR399 reduced nodule numbers and root biomass depending on Pi availability, suggesting that the miR399-dependent Pi-acquisition regulatory module controlled by N-availability affects the development of the whole legume plant root system.
PubMed: 38941269
DOI: 10.1093/jxb/erae281 -
ELife Jun 2024Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we...
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
Topics: SARS-CoV-2; Coronavirus Nucleocapsid Proteins; Mutation; COVID-19; Humans; Intrinsically Disordered Proteins; Phosphoproteins; Nucleocapsid Proteins; Thermodynamics; Protein Stability
PubMed: 38941236
DOI: 10.7554/eLife.94836 -
Acta Microbiologica Et Immunologica... Jun 2024The aim of this prospective pilot study was to compare culture and microbiome results of the removed tonsils of patients with assumed distant focal disease (11 patients)...
The aim of this prospective pilot study was to compare culture and microbiome results of the removed tonsils of patients with assumed distant focal disease (11 patients) and those who underwent a tonsillectomy, due to other reasons, such as recurrent tonsillitis, tonsil stones or snoring (nine patients). Aerobic culture was carried out for samples taken from the surface of the tonsils by swabs before tonsillectomy for all 20 patients. The squeezed detritus and the tissue samples of removed tonsils, taken separately for the right and left tonsils, were incubated aerobically and anaerobically. The microbiome composition of tissue samples of removed tonsils was also evaluated. Based on the culture results of the deep samples Staphylococcus aureus was the dominating pathogen, besides a great variety of anaerobic and facultative anaerobic bacteria present in the oral microbiota in those patients who underwent tonsillectomy due to distant focal diseases. Microbiome study of the core tissue samples showed a great diversity on genus and species level among patients of the two groups however, S. aureus and Prevotella nigrescens were present in higher proportion in those, whose tonsils were removed due to distant focal diseases. Our results may support previous findings about the possible triggering role of S. aureus and P. nigrescens leading to distant focal diseases. Samples taken by squeezing the tonsils could give more information about the possible pathogenic/triggering bacteria than the surface samples cultured only aerobically.
PubMed: 38941152
DOI: 10.1556/030.2024.02279 -
Breast Cancer Research and Treatment Jun 2024Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with...
PURPOSE
Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results.
METHODS
Postmenopausal women with HR+ BC who were 45-57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method.
RESULTS
This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85-2.81), DRFS (HR = 1.51; 95% CI 0.73-3.11), OS (HR = 1.64; 95% CI 0.75-3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84-4.63) when compared with patients without OFR.
CONCLUSION
In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.
PubMed: 38940981
DOI: 10.1007/s10549-024-07411-w -
Clinical & Experimental Metastasis Jun 2024Whether cancer cells metastasize from the primary site to the distant sites via the lymphatic vessels or the blood vessels directly into the circulation is still under... (Review)
Review
Whether cancer cells metastasize from the primary site to the distant sites via the lymphatic vessels or the blood vessels directly into the circulation is still under intense study. In this review article, we follow the journey of cancer cells metastasizing to the sentinel lymph nodes and beyond to the distant sites. We emphasize cancer heterogeneity and microenvironment as major determinants of cancer metastasis. Multiple molecules have been found to be associated with the complicated process of metastasis. Based on the large sentinel lymph node data, it is reasonable to conclude that cancer cells may metastasize through the blood vessels in some cases but in most cases, they use the sentinel lymph nodes as the major gateway to enter the circulation to distant sites.
PubMed: 38940900
DOI: 10.1007/s10585-024-10288-0 -
Alternative Therapies in Health and... Jun 2024Colorectal cancer is a malignant tumor with high mortality, but is hard to detect at its early stage. Recent studies highlighted the crucial roles of Ezrin protein and...
OBJECTIVE
Colorectal cancer is a malignant tumor with high mortality, but is hard to detect at its early stage. Recent studies highlighted the crucial roles of Ezrin protein and MMP-9 in the development and malignancy of colorectal cancer, but Ezrin protein and MMP-9 in early diagnosis of colorectal cancer require further investigation. Therefore, we aimed to investigate their roles in the occurrence and metastasis of colorectal cancer, and to analyze their clinical significance in diagnosing and treating colorectal cancer.
METHOD
The diagnosis of collected colorectal cancer tissue and adjacent tissue samples from colorectal cancer patients confirmed by clinical symptoms was performed using Hematoxylin Eosin staining. The expression levels of Ezrin and MMP-9 in 50 colorectal cancer tissue and 50 cases adjacent colorectal cancer tissue were detected by the immuno-histochemical MaxVision method. The relationship between the positive expression rate of Ezrin and MMP-9 in colorectal cancer tissue and clinical pathological factors was analyzed, and the correlation between Ezrin and MMP-9 was examined.
RESULTS
The positive expression rate of Ezrin in colorectal cancer tissue (78%) was significantly higher compared to adjacent non-cancerous tissues (6.0%) (P < .05). There was no significant correlation of gender/age and Ezrin/MMP-9 expressions (P > .05). The expression level of Ezrin exhibited statistically significant differences in the pathological factors including tumor diameter, depth of invasion, degree of differentiation, presence or absence of lymph node metastasis, and distant metastasis (P < .05). Additionally, the positive expression rate of MMP-9 in colorectal cancer tissue (76%) was markedly elevated compared to adjacent tissues (8.0%) (P < .05). The expression level of MMP-9 showed statistically significant differences in the pathological factors including tumor diameter, depth of invasion, degree of differentiation, presence or absence of lymph node metastasis, and distant metastasis (P < .05). In addition, the expression of Ezrin and MMP-9 in colorectal cancer tissue showed a significant positive correlation (r=0.637, P < .01).
CONCLUSION
Ezrin and MMP-9 may synergistically participate in the occurrence, invasion, and metastasis of colorectal cancer. The combined assessment of Ezrin and MMP-9 expression levels in colorectal cancer patients holds significant potential for clinical diagnosis and personalized therapeutic applications.
PubMed: 38940787
DOI: No ID Found