[Artificial intelligence for medical information departments : construction and evaluation of a decision-making tool to identify and prioritize stays of which the PMSI coding could be optimized, and to ensure the revenues generated by activity-based pricing]. / L'intelligence artificielle au service des départements d'information médicale : construction et évaluation d'un outil d'aide à la décision pour cibler et prioriser les séjours à contrôler et fiabiliser les recettes hospitalières générées par la tarification à l'activité.

BACKGROUND: Medical Information Departments help to optimize the hospital revenues generated by activity-based pricing. A review of medical files, selected after the targeting of coding summaries, is organized. The aim is to make any corrections to the diagnoses or coded procedures with a potential impact on the pricing of the stay. Targeting is of major importance as a means of concentrating resources on the files for which coding can be effectively improved. The tools available for targeting can be optimized. We have developed a decision-making support tool to make targeting more efficient. The objective of our study was to evaluate the performance of this tool. METHODS: The tool combines an artificial intelligence module with a rule-based expert module. A predictive score is assigned to each coding summary that reflects the probability of a revalued stay. Evaluation of the performance of this tool was based on a sample of 400 stays of at least 3 nights of patients hospitalized at the Paris Saint-Joseph Hospital from 1st November to 31st December 2019. Each stay was reviewed by a coding expert, without knowledge of the score assigned and without help from expert queries. Two main assessment criteria were used: area under the ROC curve and positive predictive value (PPV). RESULTS: The area under the ROC curve was 0.70 (CI 95% [0.64-0.76]). With a revalued coding rate of 32%, PPV was 41% for scores above 5, 65% for scores above 8, 88% for scores above 9. CONCLUSION: The study made it possible to validate the performance of the tool. The implementation of new variables could further increase its performance. This is an area of development to be considered, particularly with in view of generalizing individual invoicing in hospitals.

[Knowledge assessment of the coding using CSARR nomenclature, two years after its establishment]. / Bilan de l'appropriation du CSARR, deux ans après sa mise en place.

BACKGROUND: French post-acute care and rehabilitation facilities describe and code their activity through the Program for Medicalization of Information Systems (PMSI). A new specific catalogue of rehabilitation procedures (CSARR) has been implemented to code rehabilitation acts since 2013. This study aimed to assess the coherence of the coding of the rehabilitation acts using the CSARR two years after its establishment through the analyze of 3 main items regarding patients and therapists. METHODS: We analyzed the use of CSARR for coding rehabilitation acts from the PMSI national database for post-acute care and rehabilitation, in 2015. Analyses were made on specific items characterizing rehabilitation acts: "number of patients", "type of therapists" and "number of therapists". RESULTS: There were 72,014,731 rehabilitation acts coded in 2015 using CSARR nomenclature; 86% were individual rehabilitation acts. All acts of CSARR, except one, were used to describe rehabilitation activities. Physiotherapists coded the majority of rehabilitation acts (47%), then nurses (14%). Coding errors were identified as the "number of patients", coded with more than one patient for individual acts (13% of the acts) or with less than 2 patients for groups (6% of the acts), or the "number of therapists" coded with only one therapist for rehabilitation acts requiring several professionals. CONCLUSION: This first assessment indicated a good level of appropriation of the CSARR coding rules in the national PMSI database by post-acute care and rehabilitation facilities. However, a simplification of this catalogue and therapist training could increase the quality of the rehabilitation data.

Functional relationships between three novel homozygous mutations in the ACTH receptor gene and familial glucocorticoid deficiency.

Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by a glucocorticoid adrenal insufficiency without mineralocorticoid deficiency. Mutations of the ACTH receptor (MC2-R) gene have been reported in some FGD cases, but only a few of them have been functionally studied. We reported clinical features and MC2-R gene analysis in three families. For each proband, an homozygous mutation was identified after amplification and sequencing of the whole intronless MC2-R gene. One mutation converted Val-142 located in the second intracellular loop to Leu. Another mutation in the sixth transmembrane domain converted Ala-233 to Pro. The last mutation converted the negatively charged Asp-103 in the first extracellular loop to an uncharged Asn. Functional studies of these mutations as well as the S120R mutation were performed after stable transfection of M3 cells and measurement of ACTH-induced cAMP production. For the S120R, V142L, and A233P mutated MC2-R, cAMP production curves were similar to that obtained with M3 parental cells, confirming that these mutations are responsible for the FGD in the affected patients. The D103N-mutated MC2-R had an impaired cAMP response to physiological doses of ACTH, but the maximal response at very high concentrations of ACTH was similar to that obtained for the wild-type MC2-R. All these results demonstrated clear relationships based on functional studies between MC2-R homozygous mutations and FGD phenotype.

Radio-prevention of micrometastases.

In developed countries, the cancer incidence is about 150,000 cases per year and half of people with cancer may die from the extension of the primary tumour in secondary deposits. This disaster costs more than 2 billion euro per year. People with cancer are often treated with surgery and/or radiotherapy of localized primary tumour and chemo-prevention of occult disseminated micrometastases. Since chemotherapy essentially targets cycling tumour cells, quiescent micrometastases which may contain only one cell may escape. We previously reported that human melanoma clones with high metastatic potential and low gangliosides content appeared very radiosensitive to low-dose ionizing radiation both in culture and in immunosuppressed animals. This exquisite radiosensitivity was observed with the highly metastatic single cells which were resting at the time of irradiation. These data are consistent with the dose-response relationship for the radiotherapy of secondary deposits which appears linear with no threshold. Highly metastatic cells at an early stage of growth also appear very sensitive to chemicals and activated immune cells. We propose the medical hypothesis according to which the spread of resting micrometastases should be prevented by a single fraction of total-body irradiation delivered at a dose sufficiently low (below 0.2 Gy) to avoid normal tissue radiotoxicity. Radio-prevention may complement standard treatments for patients with metastases and may be delivered even for patients in whom no distant metastases were detected on tumour diagnosis (M0 stage).

Predictive factors for complications in children with laryngeal damage at extubation.

OBJECTIVES: To determine which factors contribute to early complications when intubated children show macroscopic lesions at extubation. STUDY DESIGN: Retrospective review of 96 consecutive medical records of children aged 1 day to 15 years. Patients were divided into three groups depending on the extent of the subsequent treatment required: medical, reintubation, and surgical. METHODS: Age, sex, clinical history, and macroscopic features of the lesions were collected and data were compared in each group. RESULTS: Underlying noninfectious respiratory diseases and young age were found to be risk factors for higher incidence of complications, but not prolonged or multiple intubations. Edema, especially in the glottic area, was a risk factor for surgical treatment. Multiple lesions were risk factors for reintubation. CONCLUSIONS: History of intubation, its cause, and lesions discovered at extubation can provide the basis for definition of an "at risk" profile for intubated children.

Functional expression of the human ACTH receptor gene.

The ACTH receptor is the type 2 (MC2R) among the melanocortin receptor family and is expressed almost exclusively in the adrenal cortex. The human MC2R (hMC2R) was very difficult to express in heterologous cell lines. We have succeeded in transient and stable expression of hMC2R using the M3 melanoma cells. Moreover, we have found that the expressed hMC2R in M3 cells showed similar ACTH binding affinity and coupling to adenylate cyclase as the MC2R of normal human adrenal cells, contrarily to most of the other expression cell models. In these conditions, we have been able to test several mutant hMC2R described in patients with the familial glucocorticoid deficiency syndrome (FGD) using this cell line.

The gangliosides as a possible molecular coupling factor between the proportion of radiosensitive cells in vitro and the metastatic potential in vivo within a human melanoma cell line.

With an experimental model of spontaneous lung metastases in immunosuppressed newborn rats, seven clones and variants with different metastatic potential and gangliosides expression were derived from a single parental human melanoma cell line M4Be. The cellular radiosensitivity of M4Be and its seven sublines was estimated using an in vitro colony assay. The total amount of gangliosides in M4Be and its seven sublines was determined by cell extraction and thin-layer chromatography, while the expression of GD3 gangliosides was estimated by flow cytometry with a monoclonal antibody. The radiation-cell survival curves of most clones and variants derived from M4Be showed a zero dose extrapolation clearly lower than 100%, suggesting that two populations of cells of very different radiosensitivity coexist within each of these clones and variants. Although the proportion of radiosensitive cells could be estimated from the shape of the survival curve, its radiosensitivity is too high to be properly evaluated by the colony assay. The eight survival curves differ essentially in the proportion of radiosensitive cells--which varied from 0% to 40% among M4Be and its seven sublines--whereas the cellular radiosensitivity of the radioresistant population was similar among them. The metastatic potential in vivo of M4Be and its seven sublines was not significantly related to the cellular radiosensitivity of their corresponding radioresistant population, but significantly increased with the fraction of radiosensitive cells. This relationship is valid only when the highly metastatic cells are cultured for no more than five passages in vitro as the fraction of radiosensitive cells is rapidly lost during subcultures. The relationship remains valid in vivo as metastatic melanoma-bearing newborn rats whole body irradiated with 20 cGy show no lung metastasis compared with controls. The radiosensitive cell fraction is inversely correlated with both the total ganglioside content (r = 0.84, P < 0.02) and the number of cells positively labelled with the monoclonal antibody directed to GD3 (r = 0.92, P < 0.001). The incubation of a radiosensitive clone with the exogenous bovine brain ganglioside GM1 significantly increases the proportion of radioresistant cells and suppresses its metastatic potential, while the inhibition of the endogenous gangliosides synthesis in the radioresistant cell line M4Be increases the proportion of radiosensitive cells. This study provides a possible explanation for the correlation between the metastatic potential and the proportion of radiosensitive cells within the seven sublines derived from a single parental human melanoma cell line.

Gangliosides protect human melanoma cells from ionizing radiation-induced clonogenic cell death.

With an experimental model of spontaneous lung metastases of melanoma developed in this laboratory, a range of sublines (variants and clones) with different metastatic potential and ganglioside expression was established from a single human melanoma cell line M4Be. Using an in vitro clonogenic assay and provided that cells were cultured for no more than five passages, variations in cellular radioresistance of M4Be and seven sublines derived from M4Be were detected. This study shows a positive correlation between the cell intrinsic radioresistance of M4Be and its seven sublines and their total ganglioside content. More precisely, the proportion of radioresistant cells in M4Be and the seven sublines correlated with the number of cells determined by flow cytometry that were positively labelled with a monoclonal antibody directed to GD3 disialoganglioside. Blocking the cellular biosynthesis of gangliosides with the inhibitor Fumonisin B1 or cleaving with Vibrio cholerae neuraminidase the cell surface ganglioside-bound sialic acid in a radioresistant poorly metastatic subline increased its radiosensitivity in vitro. In contrast, enrichment of a radiosensitive metastatic subline with exogenous bovine brain GM1 increased its radioresistance in vitro. These results suggest that, in the radiation dose range important for radioprotection (0-1 Gy), membrane gangliosides radioprotect human melanoma cells in vitro.

Surface expression of GD3 disialogangliosides in human melanoma cells is correlated to both metastatic potential in vivo and radiosensitivity in vitro.

With an experimental model of spontaneous lung metastases of melanoma developed in this laboratory, 7 sublines (variants and clones) with different metastatic potential and ganglioside expression were established from a single human melanoma cell line M4Be. Clones and variants derived from M4Be have been characterized at their surface by their gangliosides expression that were determined by flow cytometry with monoclonal antibodies. Gangliosides are membrane glycolipids containing sialic acid. Using an in vitro clonogenic assay and provided that cells were cultured for no more than 5 passages, variations in the cellular radiosensitivity of M4Be and of the 7 sublines were detected. This study shows that the lower the expression of GD3 disialoganglioside at the cell surface, both the higher their radiosensitivity in vitro and their metastatic potential in vivo. These results suggest that highly metastatic human melanoma cells are radiosensitive and deficient in surface gangliosides. Strengthening of this hypothesis arise from experiments showing that the incubation of radiosensitive cells with exogenous ganglioside significantly increases their radioresistance in vitro and reduces their metastatic potential in vivo.

Correlation between the radiosensitivity in vitro of clones and variants derived from a human melanoma cell line and their spontaneous metastatic potential in vivo.

With an experimental model of spontaneous lung metastases of human melanoma in immunosuppressed newborn rats, a large panel of clones and variants with different metastatic potential were derived from a single human melanoma parental cell line (M4Be). Seven clones and variants from M4Be were selected, respectively, for their low (parental, clone 1), intermediate (clones 2 and 3, subvariant 1-) and high (variant 1, subvariant 1+, clone 4) metastatic potential. This paper investigates the relationship between the in vivo metastatic potential of the eight cell lines and their sensitivity to ionizing radiation in vitro (range 0.05-7 Gy). The radiosensitivity was estimated from the mean inactivation dose, a parameter equal to the area under the survival curve plotted in linear coordinates. Examination of the eight survival curves, obtained with cells cultured for no more than five passages after defrost, shows that clone 1, subvariant 1- and the M4be parental line are the most radioresistant cells, clone 4 and subvariant 1+ are the most radiosensitive cells, while clones 2 and 3 and variant 1 showed an intermediate response to radiation. The metastatic potential in vivo of the parental line and the seven sublines is significantly correlated to their radiosensitivity in vitro: the higher the metastatic potential, the higher the radiosensitivity.

Radiosensitivity in vitro of clonogenic and non-clonogenic glioblastoma cells obtained from a human brain tumour.

Cells obtained from a human glioblastoma (G5) were characterized and used to develop an assay measuring their radiosensitivity in vitro. Surviving fractions were estimated 12 days after irradiation by image analysis of the total surface occupied by the cells. This report evaluates 4 experimental factors which may influence the radiosensitivity in vitro of G5 cells: passage number, delay between plating and irradiation, cell density and clonal heterogeneity. The radiosensitivity of the G5 cell line was found to be passage-independent at least between passages 12 and 75. Experimental conditions influence the radiosensitivity as surviving fraction at 2 Gy (SF2) range from 90% (5,000 cells/well, irradiation 72 h after seeding) to 49% (2,500 cells per well, irradiation 24 h after seeding). The heterogeneity of the radiosensitivity is large at the clonal level as SF2 of six clones isolated from the G5 line were 45%, 50%, 72%, 74%, 79% and 84%. Finally, when G5 cells were irradiated at low cell density and at the beginning of the growth phase, the radiosensitivity measured with this assay is comparable to that obtained with a standard colony assay. We propose that this assay may be useful to determine the intrinsic radiosensitivity of cells obtained from human tumours.

[Basal lamina and metastatic potential of two tumorigenic clones from a human colonic adenocarcinoma cell line]. / Lame basale et potentialités métastatiques de deux clones tumorigènes issus d'une lignée d'adénocarcinome du colon humain.

We isolated from a human colonic adenocarcinoma cell line two clones with highly different metastatic abilities. One of them, which spreads rapidly in culture, produces, when injected in immunosuppressed newborn rats, well differentiated epithelial like tumors limited by a continuous basal lamina and never produces lung metastasis. The other clone, which spreads slowly in culture, produces undifferentiated tumors of irregular shape and with usually no basal lamina; tumor cells are often dispersed in the stroma and metastases are observed in the lungs. These two clones may hence constitute a model for the study of the link between the presence or absence of a basal lamina in human tumors and their ability to metastasize.