Cost-utility analysis of a palliative care program in Colombia.

BACKGROUND: The economic assessment of health care models in palliative care promotes their global development. The purpose of the study is to assess the cost-effectiveness of a palliative care program (named Contigo) with that of conventional care from the perspective of a health benefit plan administrator company, Sanitas, in Colombia. METHODS: The incremental cost-utility ratio (ICUR) and the incremental net monetary benefit (INMB) were estimated using micro-costing in a retrospective, analytical cross-sectional study on the care of terminally ill patients enrolled in a palliative care program. A 6-month time horizon prior to death was used. The EQ-5D-3 L questionnaire (EQ-5D-3 L) and the McGill Quality of Life Questionnaire (MQOL) were used to measure the quality of life. RESULTS: The study included 43 patients managed within the program and 16 patients who received conventional medical management. The program was less expensive than the conventional practice (difference of 1,924.35 US dollars (USD), P = 0.18). When compared to the last 15 days, there is a higher perception of quality of life, which yielded 0.25 in the EQ-5D-3 L (p < 0.01) and 1.55 in the MQOL (P < 0.01). The ICUR was negative and the INMB was positive. CONCLUSION: Because the Contigo program reduces costs while improving quality of life, it is considered to be net cost-saving and a model with value in health care. Greater availability of palliative care programs, such as Contigo, in Colombia can help reduce existing gaps in access to universal palliative care health coverage, resulting in more cost-effective care.

Establishing key research questions for the implementation of artificial intelligence in colonoscopy: a modified Delphi method.

BACKGROUND : Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. METHODS : An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers, from nine countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. RESULTS : The top 10 ranked questions were categorized into five themes. Theme 1: clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterization, determining the optimal end points for evaluation of AI, and demonstrating impact on interval cancer rates. Theme 2: technological developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false-positive rates, and minimizing latency. Theme 3: clinical adoption/integration (1 question), concerning the effective combination of detection and characterization into one workflow. Theme 4: data access/annotation (1 question), concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: regulatory approval (1 question), related to making regulatory approval processes more efficient. CONCLUSIONS : This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy.

Development of a Platform for Noncovalent Coupling of Full Antigens to Tobacco Etch Virus-Like Particles by Means of Coiled-Coil Oligomerization Motifs.

Virus-like particles are excellent inducers of the adaptive immune response of humans and are presently being used as scaffolds for the presentation of foreign peptides and antigens derived from infectious microorganisms for subunit vaccine development. The most common approaches for peptide and antigen presentation are translational fusions and chemical coupling, but some alternatives that seek to simplify the coupling process have been reported recently. In this work, an alternative platform for coupling full antigens to virus-like particles is presented. Heterodimerization motifs inserted in both Tobacco etch virus coat protein and green fluorescent protein directed the coupling process by simple mixing, and the obtained complexes were easily taken up by a macrophage cell line.

Polyp fingerprint: automatic recognition of colorectal polyps' unique features.

BACKGROUND: Content-based image retrieval (CBIR) is an application of machine learning used to retrieve images by similarity on the basis of features. Our objective was to develop a CBIR system that could identify images containing the same polyp ('polyp fingerprint'). METHODS: A machine learning technique called Bag of Words was used to describe each endoscopic image containing a polyp in a unique way. The system was tested with 243 white light images belonging to 99 different polyps (for each polyp there were at least two images representing it in two different temporal moments). Images were acquired in routine colonoscopies at Hospital Clínic using high-definition Olympus endoscopes. The method provided for each image the closest match within the dataset. RESULTS: The system matched another image of the same polyp in 221/243 cases (91%). No differences were observed in the number of correct matches according to Paris classification (protruded: 90.7% vs. non-protruded: 91.3%) and size (< 10 mm: 91.6% vs. > 10 mm: 90%). CONCLUSIONS: A CBIR system can match accurately two images containing the same polyp, which could be a helpful aid for polyp image recognition.

Review of computational methods for the detection and classification of polyps in colonoscopy imaging. / Revisión de métodos computacionales de detección y clasificación de pólipos en imagen de colonoscopia.

Computer-aided diagnosis (CAD) is a tool with great potential to help endoscopists in the tasks of detecting and histologically classifying colorectal polyps. In recent years, different technologies have been described and their potential utility has been increasingly evidenced, which has generated great expectations among scientific societies. However, most of these works are retrospective and use images of different quality and characteristics which are analysed off line. This review aims to familiarise gastroenterologists with computational methods and the particularities of endoscopic imaging, which have an impact on image processing analysis. Finally, the publicly available image databases, needed to compare and confirm the results obtained with different methods, are presented.

Computer-aided prediction of polyp histology on white light colonoscopy using surface pattern analysis.

BACKGROUND: This study aimed to evaluate a new computational histology prediction system based on colorectal polyp textural surface patterns using high definition white light images. METHODS: Textural elements (textons) were characterized according to their contrast with respect to the surface, shape, and number of bifurcations, assuming that dysplastic polyps are associated with highly contrasted, large tubular patterns with some degree of bifurcation. Computer-aided diagnosis (CAD) was compared with pathological diagnosis and the diagnosis made by endoscopists using Kudo and Narrow-Band Imaging International Colorectal Endoscopic classifications. RESULTS: Images of 225 polyps were evaluated (142 dysplastic and 83 nondysplastic). The CAD system correctly classified 205 polyps (91.1 %): 131/142 dysplastic (92.3 %) and 74/83 (89.2 %) nondysplastic. For the subgroup of 100 diminutive polyps (≤ 5 mm), CAD correctly classified 87 polyps (87.0 %): 43/50 (86.0 %) dysplastic and 44/50 (88.0 %) nondysplastic. There were no statistically significant differences in polyp histology prediction between the CAD system and endoscopist assessment. CONCLUSION: A computer vision system based on the characterization of the polyp surface in white light accurately predicted colorectal polyp histology.

Exploring the clinical potential of an automatic colonic polyp detection method based on the creation of energy maps.

BACKGROUND AND AIMS: Polyp miss-rate is a drawback of colonoscopy that increases significantly for small polyps. We explored the efficacy of an automatic computer-vision method for polyp detection. METHODS: Our method relies on a model that defines polyp boundaries as valleys of image intensity. Valley information is integrated into energy maps that represent the likelihood of the presence of a polyp. RESULTS: In 24 videos containing polyps from routine colonoscopies, all polyps were detected in at least one frame. The mean of the maximum values on the energy map was higher for frames with polyps than without (P < 0.001). Performance improved in high quality frames (AUC = 0.79 [95 %CI 0.70 - 0.87] vs. 0.75 [95 %CI 0.66 - 0.83]). With 3.75 set as the maximum threshold value, sensitivity and specificity for the detection of polyps were 70.4 % (95 %CI 60.3 % - 80.8 %) and 72.4 % (95 %CI 61.6 % - 84.6 %), respectively. CONCLUSION: Energy maps performed well for colonic polyp detection, indicating their potential applicability in clinical practice.

In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.

Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the "hallmarks of cancer" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.

Prevalence and mean number of teeth with amalgam and nonamalgam restorations, United States, 2015 through 2018.

BACKGROUND: Amalgam has been used for more than 150 years as a safe and reliable restorative material. The authors described the occurrence of amalgam and nonamalgam restorations in the United States in primary and permanent teeth across age groups and according to sociodemographic characteristics. METHODS: The authors used clinical examination data from the National Health and Nutrition Examination Survey 2015-2018 for participants 2 years and older (n = 17,040). The authors estimated the prevalence and mean number of amalgam and nonamalgam restorations in primary and permanent teeth according to age groups (2-5 years, 6-11 years, 12-15 years, 16-19 years, 20-39 years, 40-59 years, 60-79 years, and ≥ 80 years), race and ethnicity, federal poverty guideline, education, and pregnancy status. RESULTS: The prevalence of amalgam restorations ranged from 4% through 69%. Overall, amalgam restorations were more prevalent in children and adolescents from racial and ethnic minority groups and families at lower poverty levels and with lower education. The mean number of teeth with nonamalgam restorations was higher than those with amalgam restorations in primary teeth of children aged 6 through 11 years, permanent teeth of those 12 through 15 years and 20 through 39 years, and women aged 20 through 49 years, regardless of pregnancy status. The mean number of amalgam restorations was higher than that for nonamalgam restorations in older age groups. CONCLUSIONS: Nonamalgam restorations were the most common in the primary teeth of children older than 5 years and in the permanent teeth of adults younger than 40 years. Amalgam restorations were more common in older adults. Amalgam and nonamalgam restorations were equally common in children younger than 5 years. PRACTICAL IMPLICATIONS: The study findings suggest a shift from amalgam to alternative restorative materials in the United States.

In vivo computer-aided diagnosis of colorectal polyps using white light endoscopy.

Background and study aims Artificial intelligence is currently able to accurately predict the histology of colorectal polyps. However, systems developed to date use complex optical technologies and have not been tested in vivo. The objective of this study was to evaluate the efficacy of a new deep learning-based optical diagnosis system, ATENEA, in a real clinical setting using only high-definition white light endoscopy (WLE) and to compare its performance with endoscopists. Methods ATENEA was prospectively tested in real life on consecutive polyps detected in colorectal cancer screening colonoscopies at Hospital Clínic. No images were discarded, and only WLE was used. The in vivo ATENEA's prediction (adenoma vs non-adenoma) was compared with the prediction of four staff endoscopists without specific training in optical diagnosis for the study purposes. Endoscopists were blind to the ATENEA output. Histology was the gold standard. Results Ninety polyps (median size: 5 mm, range: 2-25) from 31 patients were included of which 69 (76.7 %) were adenomas. ATENEA correctly predicted the histology in 63 of 69 (91.3 %, 95 % CI: 82 %-97 %) adenomas and 12 of 21 (57.1 %, 95 % CI: 34 %-78 %) non-adenomas while endoscopists made correct predictions in 52 of 69 (75.4 %, 95 % CI: 60 %-85 %) and 20 of 21 (95.2 %, 95 % CI: 76 %-100 %), respectively. The global accuracy was 83.3 % (95 % CI: 74%-90 %) and 80 % (95 % CI: 70 %-88 %) for ATENEA and endoscopists, respectively. Conclusion ATENEA can accurately be used for in vivo characterization of colorectal polyps, enabling the endoscopist to make direct decisions. ATENEA showed a global accuracy similar to that of endoscopists despite an unsatisfactory performance for non-adenomatous lesions.

Complications and Comorbidities in Hispanic Patients Who Develop Traumatic and Non-traumatic Acute Compartment Syndrome.

Acute compartment syndrome (ACS) is a medical emergency that remains under-recognized and understudied. This study aimed to identify risk factors for the traumatic and non-traumatic presentation of ACS within a majority Hispanic population. A four-year retrospective analysis of medical records in a single institution revealed 26 with traumatic and 21 non-traumatic patients presenting with ACS. Traumatic ACS occurred in younger males following fractures, as previously described in the field. After controlling for age differences, non-traumatic ACS occurred in older patients with multiple comorbidities, increased use of statins, and anticoagulants as compared to the traumatic ACS group. A large proportion (80%) of the non-traumatic ACS group also presented with hypertension. Patients taking anticoagulants and statins should be carefully monitored for ACS development after non-traumatic qualifying events and advanced age. Further studies should identify how statins interact with the patients' racial/ethnic profile and the incidence of comorbidities to promote earlier identification and reduce morbidities.

A Classic Presentation of Desmoplastic Small Round Cell Tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare malignancy, of uncertain differentiation, which more commonly affects adolescents and young adult males; it usually has an intra-abdominal location. We describe the case of a 35-year-old male who presented initially with occasional abdominal pain, and subsequently with abdominal mass sensation, without any other associated symptoms. Imaging studies reported an intra-abdominal mass located in mesogastrium, right hypochondrium, and right lumbar region, without clear evidence of infiltration to secondary structures, but with clear peritoneal spread to greater omentum and pelvis. Definitive diagnosis of DSRCT is based on histologic and immunohistochemical findings. Standard treatment includes intensive neoadjuvant chemotherapy, surgical cytoreduction, and radiotherapy. Despite this multidisciplinary approach, DSRCT has a poor prognosis and a high mortality rate at five years.

Steady-state persistence of respiratory syncytial virus in a macrophage-like cell line and sequence analysis of the persistent viral genome.

Long-term infection by human respiratory syncytial virus (hRSV) has been reported in immunocompromised patients. Cell lines are valuable in vitro model systems to study mechanisms associated with viral persistence. Persistent infections in cell cultures have been categorized at least as in "carrier-state", where there exist a low proportion of cells infected by a lytic virus, and as in "steady-state", where most of cells are infected, but in absence of cytophatic effect. Here, we showed that hRSV maintained a steady-state persistence in a macrophage-like cell line after 120 passages, since the viral genome was detected in all of the cells analyzed by fluorescence in situ hybridization, whereas only defective viruses were identified by sucrose gradients and titration assay. Interestingly, eight percent of cells harboring the hRSV genome revealed undetectable expression of the viral nucleoprotein N; however, when this cell population was sorted by flow cytometry and independently cultured, viral protein expression was induced at detectable levels since the first post-sorting passage, supporting that sorted cells harbored the viral genome. Sequencing of the persistent hRSV genome obtained from virus collected from cell-culture supernatants, allowed assembling of a complete genome that displayed 24 synonymous and 38 nonsynonymous substitutions in coding regions, whereas extragenic and intergenic regions displayed 12 substitutions, two insertions and one deletion. Previous reports characterizing mutations in extragenic regulatory sequences of hRSV, suggested that some mutations localized at the 3' leader region of our persistent virus might alter viral transcription and replication, as well as assembly of viral nucleocapsids. Besides, substitutions in P, F and G proteins might contribute to altered viral assembly, budding and membrane fusion, reducing the cytopathic effect and in consequence, contributing to host-cell survival. Full-length mutant genomes might be part of the repertoire of defective viral genomes formed during hRSV infections, contributing to the establishment and maintenance of virus persistence.

Generation of J(0) Bessel beams with controlled spatial coherence features.

An alternative method to generate J(0) Bessel beams with controlled spatial partial coherence properties is introduced. Far field diffraction from a discrete number of source points on an annular region is calculated. The average for different diffracted fields produced at several rotation angles is numerically calculated and experimentally detected. Theoretical and experimental results show that for this particular case, the J(0) Bessel beam is a limit when the number of points tends towards infinity and the associated complex degree of coherence is also a function of the number of points.

Highly efficient macrolactonization of ω-hydroxy acids using benzotriazole esters: synthesis of Sansalvamide A.

A facile and mild macrolactonization reaction of ω-hydroxy acids was developed based on the transesterification of benzotriazole esters. Treatment of ω-hydroxy acids with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and 1-hydroxy benzotriazole (HOBT) in chloroform provided macrolactones in excellent yields. The reactions were performed under basic, neutral and acidic conditions using N,N-dimethylaminopyridine (DMAP), tetrabutylammonium tetrafluoroborate (TBABF(4)) and BF(3)·Et(2)O, respectively. A calcined hydrotalcite was also used instead of DMAP. Finally, to test the scope of the protocol in the synthesis of biologically relevant macrolactones, the total synthesis of Sansalvamide A was carried out.

Polyp Segmentation with Fully Convolutional Deep Neural Networks-Extended Evaluation Study.

Analysis of colonoscopy images plays a significant role in early detection of colorectal cancer. Automated tissue segmentation can be useful for two of the most relevant clinical target applications-lesion detection and classification, thereby providing important means to make both processes more accurate and robust. To automate video colonoscopy analysis, computer vision and machine learning methods have been utilized and shown to enhance polyp detectability and segmentation objectivity. This paper describes a polyp segmentation algorithm, developed based on fully convolutional network models, that was originally developed for the Endoscopic Vision Gastrointestinal Image Analysis (GIANA) polyp segmentation challenges. The key contribution of the paper is an extended evaluation of the proposed architecture, by comparing it against established image segmentation benchmarks utilizing several metrics with cross-validation on the GIANA training dataset. Different experiments are described, including examination of various network configurations, values of design parameters, data augmentation approaches, and polyp characteristics. The reported results demonstrate the significance of the data augmentation, and careful selection of the method's design parameters. The proposed method delivers state-of-the-art results with near real-time performance. The described solution was instrumental in securing the top spot for the polyp segmentation sub-challenge at the 2017 GIANA challenge and second place for the standard image resolution segmentation task at the 2018 GIANA challenge.

Effect of methyl jasmonate and salicylic acid on the production of metabolites in cell suspensions cultures of Piper cumanense (Piperaceae).

Elicitation of cell suspensions culture is a strategy that could increase the production of secondary metabolites under controlled conditions. This research evaluated the effect of methyl jasmonate-MeJA and salicylic acid-SA as elicitors on the production of metabolites in cell suspensions of P. cumanense. The type of elicitor (MeJA or SA), the concentration of elicitor (10 µM and 100 µM), and time of exposition (3, 12, 24 h) on cell suspension were evaluated. Metabolic profiles of intracellular and extracellular extracts were analyzed by UHPLC-DAD and GC-MS. Differential production of metabolites was dependent on the type of elicitor, its concentration, and the time of exposition. Treatments with 100 µM SA were conducted to high production of 5-hydroxymethylfurfural (6.3 %), phenol (6.5 %), and (Z)-9-octadecenamide (8.8 %). This is the first report of elicitation on cell suspensions in the Piper genus and contributes to understanding the effect of MeJA and SA on metabolite production in plant cell culture.