Graft Monitoring Device and Method

Abstract

TITLE OF THE INVENTION: GRAFT MONITORING DEVICE AND METHOD The graft monitoring device comprises: - a means (51, 52) for communicating with a central unit of a mobile perfusion machine (50) comprising a transport container (54) for the graft under perfusion, this communication means being configured to receive from this central unit physiological parameter values ​​of a graft during transport, including at least the graft temperature, and - a means (53) for predicting the evolution of physiological parameter values ​​during graft transport. Figure for the abstract: Figure 7

Description

Title of the invention: Graft monitoring device and method Technical field of the invention

[0001] The present invention relates to a device and method for monitoring grafts. It applies, in particular, to tracking grafts during their transport from a hospital where a donor is located to a hospital where a recipient is located. State of the art

[0002] It is recalled that the term "graft" covers organ or tissue transplantation and blood transfusions, these transplanted or transfused elements being called "grafts".

[0003] During the transport of a graft, which can last many hours, numerous environmental constraints must be continuously observed to prevent damage to the graft and to minimize the risk of rejection by the recipient's body. Containers such as the one described in utility certificate CN202255520U, which monitor temperature changes, are known. However, implementing these containers requires replacing all transport equipment and their functionality is too limited to guarantee the quality of graft transport.

[0004] US application 2011 / 173023 discloses an organ transport device incorporating a temperature sensor. WO application 2020 / 192513 discloses a mechanical perfusion preservation device for an organ. AU application 2019213360 discloses a transportable device for the preservation and monitoring of an ex vivo lung. These devices are particularly expensive and unsuitable for transporting grafts in countries with lower medical budgets. Description of the invention

[0005] The present invention aims to remedy all or part of these drawbacks.

[0006] To this end, the present invention relates to a graft monitoring device, which includes:

[0007] - a means of communication with a central unit of an perfusion machine mobile unit comprising a transport crate for the perfusion of the graft, this means of communication being configured to receive from this central unit physiological parameter values ​​of a graft during transport, including at least the temperature of the graft and - a means of predicting the evolution of physiological parameter values ​​during graft transport.

[0008] Thanks to these provisions, any mobile infusion machine can be transformed into A communicating machine capable of making predictions about the evolution of the graft and therefore its suitability for transplantation. These predictions are preferably sent regularly to the organ procurement and transplantation coordinators, surgeons, members of the transport team responsible for transporting the graft, and / or members of the medical team awaiting the graft for transplantation. The quality of transport can thus be assessed, and the evolution of the graft's suitability for transplantation can be estimated.

[0009] In embodiments, the prediction implementation means is based on machine learning carried out on the basis of physiological parameter values ​​obtained during previous transports.

[0010] In embodiments, the prediction embodiment means is configured to perform at least one prediction of physiological parameter values ​​for the time of arrival of the graft at its implantation site in the body of a recipient patient.

[0011] In some embodiments, the device includes a geolocation means and evaluation of the time of arrival of the graft at its implantation site in the recipient patient's body.

[0012] In embodiments, in which the prediction implementation means is configured to propose at least one path of the graft.

[0013] In embodiments, the means for making predictions is configured to make predictions of the evolution of physiological parameters of the graft according to several scenarios of evolution of operating instructions of the transport box and display of these predictions.

[0014] In embodiments, the device includes a means of communication with a central unit of a perfusion machine configured to receive physiological parameter values ​​of the graft during transport.

[0015] In some embodiments, the housing further comprises a control means configured to control one of two operating modes of the housing depending on the measured temperature, between: - a first operating mode in which the unit has a nominal energy consumption, when the graft temperature is below a first predetermined temperature limit value and - a second operating mode in which the unit has reduced energy consumption, when the graft temperature is above the first limit value.

[0016] Thanks to these provisions, the risk of the housing itself contributing to a temperature increase of the graft is limited.

[0017] In some embodiments, the control means is configured to, if the temperature If the graft temperature crosses a second predetermined temperature limit value, higher than the first predetermined temperature limit value, put the device into standby mode for a first predetermined period.

[0018] Thanks to these provisions, the housing no longer provides heat to the graft.

[0019] In embodiments, the housing further comprises a means for detecting the absence of movement and a control means configured to control a third operating mode of the housing in which the housing has a reduced nominal consumption, when the housing is stationary for a period greater than a second predetermined period and / or to transmit a remote alert when the housing is stationary for a period greater than a third predetermined period.

[0020] Thanks to these provisions, when the device is immobile, its autonomy is increased by reducing its electrical consumption and / or those responsible for the transplantation are warned of the immobility of the graft, which may imply a risk to the success of this transplantation.

[0021] In some embodiments, the housing further comprises a means for measuring the distance between the geographical position of the housing and at least one first predetermined geographical position, and a control means configured to control one of two operating modes of the device according to each measured distance, between

[0022] - a third operating mode in which the housing transmits its position geographically regularly, when each distance exceeds a predetermined distance limit value and

[0023] - a fourth mode of operation in which the means of communication is inhibited, when at least one measured distance is less than said predetermined distance limit value.

[0024] Thanks to these provisions, the housing eliminates the risks of electromagnetic interference with the electronic systems of airports and aircraft.

[0025] In embodiments, the box includes a distance measurement means configured to measure a distance to arrival between the geographic position of the box and a second predetermined geographic position, the destination of the graft, and a control means configured to command the sending of a message to at least one predetermined recipient terminal when the distance to arrival is less than a fourth predetermined limit value.

[0026] Thanks to these provisions, the medical team in charge of the transplantation into the recipient's body is notified in advance of the imminent arrival of the graft. This increases the chances of success of the operation.

[0027] In some embodiments, the housing further comprises a means for measuring distance configured to measure a distance to arrival between the geographic position of the case and a second predetermined geographic position, the destination of the graft, a padlock configured to prohibit the opening of the transport case, and a control means configured to allow the opening of the padlock when the distance to arrival is less than a third predetermined distance limit value.

[0028] Thanks to these provisions, the transport container is locked for practically the entire duration of the transport.

[0029] In embodiments, the housing further comprises a distance measurement means configured to measure a distance between the geographical position of the housing and a predetermined route and a control means configured to trigger a remote alert if the distance to the route is greater than a fourth predetermined distance limit value.

[0030] Thanks to these provisions, those responsible for the transplant are warned of the change in the path of the graft, which may involve a risk to the success of this transplant.

[0031] In embodiments, the housing further comprises an oximeter configured to measure the oxygen available in the graft and / or the oxygen consumption of the graft and a control means configured to trigger a remote alert when the available oxygen falls below a predetermined seventh value and / or when the oxygen consumption of the graft falls below a predetermined oximetry limit value.

[0032] Thanks to these provisions, the risks of graft deterioration due to lack of oxygen are anticipated and can be taken into account by those responsible for graft transfer.

[0033] In embodiments, the housing further comprises a hygrometer configured to measure the humidity in the atmosphere of the transport bag and a control means configured to trigger a remote alert when the humidity becomes greater than a predetermined humidity limit value.

[0034] Thanks to these provisions, the opening of the transport bag can be detected and this event can be taken into account.

[0035] In embodiments, the housing further includes a light sensor configured to measure the light in the carrying bag and a control means configured to trigger a remote alert when the light becomes greater than a predetermined light limit value.

[0036] Thanks to these provisions, the opening of the transport bag or transport case can be detected and this event can be taken into account.

[0037] In some embodiments, the housing further comprises an accelerometer and a control means configured to trigger a remote alert when acceleration becomes greater than a predetermined acceleration limit value.

[0038] Thanks to these provisions, a shock to the graft can be detected and taken into account. Brief description of the figures

[0039] Other advantages, purposes and particular features of the invention will become apparent from the following non-limiting description of at least one particular embodiment of the device and method of the invention, with reference to the accompanying drawings, in which:

[0040] [Fig. 1] schematically represents a first particular embodiment of the device that is the subject of the invention and of the systems with which the device communicates,

[0041] [Fig.2] schematically represents an electronic circuit of a second particular embodiment of the device that is the subject of the invention,

[0042] [Fig.3] schematically represents, in top perspective, a closed housing of the device, an electronic circuit of which is illustrated in [Fig.2],

[0043] [Fig.4] schematically represents the constituent elements of the information chain up to the hospital services, of the second embodiment of the device that is the subject of the invention,

[0044] [Fig.5] represents, in the form of a flowchart, a first sequence of steps of a first particular embodiment of the process which is the subject of the invention,

[0045] [Fig.6] represents, in the form of a flowchart, the continuation of the first sequence of steps illustrated in [Fig.5],

[0046] [Fig.7] schematically represents the constituent elements of the information chain up to the hospital services, of a third embodiment of the device that is the subject of the invention,

[0047] [Fig.8] represents, in the form of a flowchart, a second sequence of steps of a second particular embodiment of the process which is the subject of the invention,

[0048] [Fig.9] represents, in the form of a flowchart, the continuation of the second sequence of steps illustrated in [Fig.8] and

[0049] [Fig. 10] represents, in the form of a logic diagram, a third succession of steps of embodiments of the invention. Description of the implementation methods

[0050] The present description is given by way of non-limiting grammar, each feature of an embodiment being able to be advantageously combined with any other feature of any other embodiment.

[0051] It should be noted from the outset that the figures are not to scale.

[0052] Figure 1 represents schematically a graft transport system 10 12, system 10 comprising a self-contained unit 11 configured to accompany the graft 12 in a transport case 14 or in a transport bag 13, itself transported in the transport case 14. The self-contained transport case 14, of a known type, includes a unit 15 for maintaining environmental conditions around the graft bag 13 and a lid 16. The term "self-contained" here means that the case 14 includes, or is connected to, a mobile power source enabling the transport of the graft. The transport case 14 is thus preferably temperature-controlled to maintain a temperature profile during the transport of the graft, for example, a fixed temperature (e.g., 10°C or 37°C). The case 11 includes a temperature sensor 22 that measures the temperature on the surface of the graft 12 or in the transport case 14.

[0053] In the embodiment illustrated in [Fig. 1], the housing 11 communicates, for example via a mobile telephone network 18, cellular or satellite, with a server 19 for storing and processing measured data, particularly temperature, and with at least one terminal 20 at the destination of the graft, referred to as the "recipient". The housing 11 preferably also includes a geographic position sensor (see [Fig. 2]), for example based on the processing of positioning signals from Earth satellites. The housing 11, to be placed in the transport housing 14 of a graft 12, is thus preferably equipped with a geolocation means in addition to a telecommunications means for transmitting the measured temperature and position values ​​and assisting in the monitoring of the transport of the graft 12.Preferably, the housing 11 communicates with a padlock 17 which locks the opening of the transport case 14 in order to control the opening of the padlock 17 and prevent accidental opening of the case 14.

[0054] In the second embodiment, illustrated in figures 2 to 4, a first autonomous unit 23 is located in the transport case and a second autonomous unit 24 is located outside the transport case 14. This reduces the amount of heat generated inside the transport case while increasing the remote communication range of the device, this communication being carried out by the unit 24. The units 23 and 24 communicate with each other via wireless communication.

[0055] The electronic circuit 30 of the housing 24 comprises: - A control means comprising a processor 31, - A temperature sensor 32, - A humidity sensor 33, preferably positioned in the same location and integrated into the same component as the temperature sensor 32, - A 34 UART interface (for "Universal Asynchronous Receiver Transmitter") for flashing. This interface is a communication port (means of communication). It allows access to all the card's information by connecting it to a computer. - A 35 SIM card reader (from the English "Subscriber Identity / identification Module"), the SIM card being a chip containing a microcontroller and memory, used in mobile telephony to store subscriber-specific information for a mobile network, - A modem module 36, preferably 3G / 4G / 5G / LTE, for example GSM or satellite communication, and including a geolocation means 46 ("GPS" for Global Positioning System). Preferably, the modem module 36 communicates with the microcontroller 31 via UART, - Indicator lights 38 for the status of the housing 24, for example light-emitting diodes, - A battery 40 is recharged by a battery charger 41 connected to a connector 42 accessible from outside the housing 24, for example, a USB port (Universal Serial Bus, a standard for serial computer buses). The electronic board is equipped with an electronic component for regulating the charging of the lithium battery 40. The 220V / 5V charger 41 is external and is connected via the USB-C port 42. - A 43-bit flash memory, a rewritable semiconductor mass storage device, that is to say, a memory possessing the characteristics of RAM but whose data does not disappear when the power is turned off, - A motion sensor 45, for example a MEMS type accelerometer (English acronym for "Microelectromechanical Systems" for microelectromechanical system).

[0056] The circuit of the housing 23 comprises, connected to the microcontroller 31 via short-range communication components 21 and 44, for example a communication module implementing the Bluetooth protocol (registered trademark): - A temperature and humidity probe 37 inside the transport case, i.e., the temperature and humidity of the graft 12, and - A light sensor 39 inside the transport case.

[0057] Optionally, an atmospheric pressure sensor (not shown) inside the housing 14 is incorporated into the housing 23.

[0058] The processor 31, which implements a computer program stored in the flash memory 43, can thus: - Communicating over a mobile phone network, using the SIM card reader 35 and the modem module 36, - To know the geographical position of box 24, using the geolocation method 46 for modem module 36, - Detect shocks, using the accelerometer 45, - Detect movements, using the modem module's geolocation method 46 36 and / or the accelerometer 45, - Measure the temperature of the graft, using the external temperature and humidity sensor 37, - Measure the humidity around the graft, with the humidity sensor 33, - Measure the light level inside the graft transport bag 13, with the light level sensor 39 and - Indicate its operating status, with indicator lights 38.

[0059] The processor 31 can therefore remotely detect and report the following events or incidents: - Increase in graft temperature, for example because the transport case 14 is in the sun or in a hot environment or has an air conditioning failure, which triggers an immediate alert, - Impact on the graft, which could damage it - Increased humidity and / or light showing an opening in the graft sac, - Altitude (determined by pressure) and speed (determined by geographical position) indicating periods of transport by aircraft, i.e. airplane or helicopter, - Immobility of the transport container 14 and - Abnormal trajectory of the transport case 14 in relation to the intended destination.

[0060] Although the transport time of a graft is very generally less than 24 hours, the battery 40 is sized for a longer operating time of the case 24, for example several days, or even a week, with a communication period of the captured data of ten minutes and a reading of the sensors every second.

[0061] A closed case 24 can be seen in [Fig.3]. Its dimensions are, for example, 9.5 centimeters x 7 centimeters x 3 centimeters.

[0062] The casing 23 and, optionally, the casing 24, are preferably generally rectangular in shape. The materials constituting the external surfaces of the casing 23 are food-grade and medical-grade (USP, acronym for "US Pharmacopoeia," Class VI, which assesses the suitability of plastics intended for use as containers or accessories for parenteral preparations). These materials are chosen to prevent the diffusion of particles into the graft. These materials include, for example, ABS (acrylonitrile butadiene styrene, a thermoplastic polymer), PP (polypropylene), PC (polycarbonate), PU (polyurethane), and SEBS (polystyrene-β-poly(ethylene-propylene)-β-polystyrene). Preferably, the casing 23 has an overmolding of the entire periphery of the casing and, in particular, of its corners. The overmolding material is flexible, for example, Soft silicone, with rounded shapes and no protruding features, and a smooth surface. Housings 23 and 24 are waterproof (IP68 rating, protection against prolonged immersion).

[0063] On the upper surface of the housing 24 are the light-emitting diodes (“LEDs”) 38. The two upper green LEDs provide information on the battery level (higher LED = 100-75% and lower LED = 75-25%). The lower blue LED indicates the activity of the Modem Module 36 (for example, a slow flash means Modem Module 36 is on and a faster flash means Modem Module 36 is connected to the network and / or sending data).

[0064] Figure 4 shows the constituent elements of the information chain extending from the unit 24 to the hospital services. Figure 4 also shows the units 23 and 24 associated with the transport container 14. The unit 24 communicates with the server 19 either via a mobile telephone network 18 or via a satellite communication network 25. The server stores the data it receives from the unit 24 and transmits information to computers 27 and communicating mobile terminals 28 of a computer network 26 of a hospital receiving the graft 12.

[0065] Figures 5 and 6 show steps of a particular embodiment 60 of the method of the invention. This method 60 is intended to be implemented by the housing 24, possibly in conjunction with the server 19, and the housing 24 is intended to implement this method 60.

[0066] During a step 61, an operator loads, into the memory of the device, the geographical position of the destination of the graft as a second predetermined geographical position and, optionally, the position of the starting point and the planned route.

[0067] During step 62, an operator or the server loads contact details, such as mobile phone numbers and / or email addresses, into the device's memory. These details include, for example, the contact information of transplant coordinators, organ procurement coordinators, surgeons, members of the transport team responsible for transporting the graft, and / or members of the medical team awaiting the graft for transplantation.

[0068] During step 63, an operator triggers the regular operation of the device. During step 64, an operator physically attaches the device to a graft by placing the device in contact with the graft in a transport bag, and this transport bag in a transport case, which is itself activated to ensure a suitable environment for the graft.

[0069] During step 65, an operator closes the padlock securing the transport case. During step 66, the device collects the captured values ​​of graft temperature, external temperature, humidity, light intensity, and geo- graphic and movement and stores them in his memory.

[0070] During step 67, the unit determines its geographical position. During step 68, the unit or the server determines whether this geographical position is near an airport, i.e., within a predetermined distance limit from a first predetermined geographical position, for example, one kilometer, or whether the pressure and / or speed values ​​represent a phase of transport of the transport container by airplane or helicopter. If the result of both tests is negative, during step 69, the unit transfers the captured data to the server 19 and proceeds to step 70. If the result of at least one of the tests in step 68 is positive, step 69 is not performed. The unit thus avoids generating electromagnetic interference for the electronic systems of the airport or the aircraft.

[0071] Thus, the processor 31 or the server 19 constitutes a means of measuring distance between the geographical position of the box and at least one first predetermined geographical position and a control means configured to control one of two operating modes of the device according to each measured distance, between a first operating mode in which the device transmits its geographical position regularly, when each distance is greater than a first predetermined distance limit value and a second operating mode in which the communication means is inhibited, when at least one measured distance is less than said first limit value.

[0072] During step 70, the device determines whether it is stationary. If so, during step 71, the processor 31 slows down the data communication rate to the server 19, for example, from a period of ten minutes to a period of twenty minutes. This increases its battery life, and it proceeds to step 72. If the result of test 70 is negative, the processor 31 returns to the nominal communication rate, and during step 72, the device determines whether the graft temperature exceeds a first temperature limit value. For example, for a liver graft, which must remain between 2°C and 6°C, the first limit value could be 5.5°C or 6°C.

[0073] If the result of test 72 is positive, during step 73, the unit immediately sends an alert to all contacts whose coordinates it has and changes its operating mode to reduce its power consumption and heat generation. For example, the unit switches from a nominal operating mode to a degraded operating mode that consumes less power. For example, the degraded operating mode reduces the measurement rate and reduces or stops local communication with the lock or external sensors, the determination of the geographic position, and the display of information.

[0074] Thus, the processor uses one of the two operating modes of the device in Depending on the measured temperature, the device operates between two modes: a first mode in which the device has nominal energy consumption when the graft temperature is below a predetermined temperature limit, and a second mode in which the device has reduced energy consumption when the graft temperature is above said limit. Conversely, the unit transmits the measured graft temperature to the contacts and server 19 at a faster rate, for example, every minute. The switch to the reverse operating mode occurs as soon as the graft temperature falls below the first predetermined limit.

[0075] In embodiments, if the temperature of the graft crosses another temperature limit value, for example one degree Celsius higher than the first, the box sends a new alert and goes into standby mode for a predetermined period, for example ten minutes, to momentarily stop any electricity consumption likely to contribute to the warming of the graft.

[0076] During step 74, the device determines its distance to the graft's destination. During step 75, the device estimates the remaining travel time to the destination. During step 76, the device determines whether the distance to the destination and / or the travel time are less than certain distance (e.g., 20 kilometers) or time (e.g., 30 minutes) limits. If not, the device proceeds to step 79. If so, during step 77, the device sends a message notifying the graft recipients of its arrival. Then, during step 78, if the distance to the destination is less than a certain distance limit, for example, two kilometers (to account for the size of the largest hospital sites, whose location could have been simplified to a single point), the device unlocks the lock 17.

[0077] During step 79, the device determines whether its position indicates an abnormal trajectory, for example, by being outside an ellipse containing the starting and ending points and their surroundings over a distance of ten or twenty kilometers, and whose smaller radius is half the distance between the starting and ending points. If so, during step 80, the device sends an alert message and its geographical position to all contacts whose coordinates it has. If not, the device returns to step 66.

[0078] It is noted that the operation of the device is stopped by the receiving team of the plugin or by server 19.

[0079] In all the steps described above in which the processor 31 performs a determination, alternatively, it is the server 19 that performs this determination, alone or jointly with the box.

[0080] In addition, server 19 performs machine learning, based on feedback medical teams (recipient profile, necrosis observed on the graft upon arrival, graft rejection, disease of the transplanted organ, ...), best conditions for transporting the graft (duration, evolution of captured values, donor profile ...), risks incurred, by recipient profile, with a graft arriving at its destination.

[0081] The implementation of the invention improves logistics for all types of organ transplantation. A transplant begins with the transplant surgeon's decision to initiate the procedure. This involves harvesting the graft from the deceased donor, transporting it from the donor facility to the recipient facility, and finally, performing the transplant. From the perspective of a procurement coordinator implementing the device that is the subject of the invention, the successive steps are: - The collection coordinator connects to a dedicated site hosted by server 19, identifies himself, and declares a new transport. - The coordinator fills in the donor's crystal number (anonymous identification number), as well as the Ic / lcs transplant types. They also select the recipient institution and choose the transplant coordinator(s) for the selected institution (they can set "all" coordinators by default). - Once the transport has been validated, to officially launch and create the trip, the transplant coordinators of the chosen establishment receive an alert via notification, short message ("SMS"), or phone call. - the coordinator can then follow the race and associated events live.

[0082] Upon arrival of the chosen transporter, the organ procurement or transplantation coordinator physically attaches the device to the graft in the transport bag and places this bag in the transport crate. Optionally, a code visible on the device, for example a QR code ("Quick Response"), is scanned to identify the device.

[0083] Each contact can follow the key stages of the transplant and access essential information via the sensor, including temperature, and verify that it is within the expected temperature range. If it is not, they receive an alert notification.

[0084] It is also possible to determine and validate the number of preservation bags used during transplantation. These fluid-filled bags are used to improve graft viability during transport and for the patient awaiting transplantation. They are used only after the organ has been harvested. The organ is immersed in this preservation fluid, for example, IGL-1 or Custodiol (trademarks).

[0085] At the end of the race, the coordinators can export the data to have better paperless management of their transplants.

[0086] As can be understood from the preceding description, the graft monitoring device of the invention comprises, in a housing configured to accompany the graft in a transport bag, itself transported in a transport case, a graft temperature sensor and a means of communicating the graft temperature. Thus, the housing is physically attached to the graft. It can monitor all variations in transport conditions and, in particular, the evolution of the graft temperature. These transport conditions are regularly communicated to the procurement and transplantation coordinators, the surgeons, the members of the transport team responsible for transporting the graft, and / or the members of the medical team awaiting the graft for transplantation.

[0087] In some embodiments, the housing further comprises a control means configured to control one of two operating modes of the housing depending on the measured temperature, between: - a first operating mode in which the unit has a nominal energy consumption, when the graft temperature is below a first predetermined temperature limit value and - a second operating mode in which the unit has reduced energy consumption, when the graft temperature is above the first limit value.

[0088] This limits the risk that the housing itself contributes to a temperature increase in the graft.

[0089] In some embodiments, the control means is configured so that, if the graft temperature exceeds a second predetermined temperature limit value that is higher than the first predetermined temperature limit value, the housing is put into standby mode for a first predetermined period. Thus, the housing no longer supplies heat to the graft if the latter is close to an irreversible degradation temperature.

[0090] In some embodiments, the unit further comprises a means for detecting the absence of movement and a control means configured to activate a third operating mode for the unit, in which the unit has a reduced nominal power consumption when the unit remains stationary for a period exceeding a second predetermined duration, and / or to transmit a remote alert when the unit remains stationary for a period exceeding a third predetermined duration. Thus, when the unit is stationary, its autonomy is increased by reducing its power consumption, and / or those responsible for the transplantation are notified of the graft's immobility, which could pose a risk to the success of the transplantation.

[0091] In some embodiments, the housing further comprises a means for measuring distance between the geographical position of the casing and at least one first predetermined geographical position and a control means configured to control one of two operating modes of the device depending on each measured distance, between: - a third operating mode in which the device transmits its geographical position regularly, when each distance exceeds a predetermined distance limit and - a fourth mode of operation in which the means of communication is inhibited, when at least one measured distance is less than said predetermined distance limit value.

[0092] The housing thus eliminates the risks of electromagnetic interference with the electronic systems of airports and aircraft.

[0093] In some embodiments, the device includes a distance measurement means configured to measure the distance to arrival between the device's geographic location and a second predetermined geographic location, the destination of the graft, and a control means configured to send a message to at least one predetermined recipient terminal when the distance to arrival is less than a fourth predetermined limit value. Thus, the medical team in charge of the transplantation into the recipient's body is notified in advance of the graft's imminent arrival, thereby increasing the chances of a successful operation.

[0094] In some embodiments, the container further comprises a distance measurement means configured to measure the distance to arrival between the container's geographic position and a second predetermined geographic position, the destination of the graft; a padlock configured to prevent the transport container from being opened; and a control means configured to allow the padlock to be opened when the distance to arrival is less than a third predetermined distance limit. Thus, the transport container is locked for virtually the entire duration of the transport.

[0095] In some embodiments, the device further includes a distance measurement means configured to measure the distance between the device's geographic location and a predetermined path, and a control means configured to trigger a remote alert if the distance to the path exceeds a fourth predetermined distance limit. This alerts those responsible for the transplant to the change in the graft's path, which could pose a risk to the success of the transplant.

[0096] In some embodiments, the housing further comprises an oximeter configured to measure the oxygen available in the graft and / or the oxygen consumption of the graft and a control means configured to trigger a remote alert When available oxygen falls below a predetermined seventh value and / or when graft oxygen consumption falls below a predetermined oximetry limit, the risks of graft deterioration due to oxygen deprivation are anticipated and can be taken into account by those responsible for the graft transfer.

[0097] In some embodiments, the housing further comprises a hygrometer configured to measure the humidity in the atmosphere of the transport bag and a control means configured to trigger a remote alert when the humidity exceeds a predetermined limit value. Thus, the opening of the transport bag can be detected and this event can be taken into account.

[0098] In some embodiments, the housing further comprises a light sensor configured to measure the light level inside the carrying bag and a control means configured to trigger a remote alert when the light level exceeds a predetermined limit. Thus, the opening of the carrying bag or case can be detected and this event can be taken into account.

[0099] In some embodiments, the housing further includes an accelerometer and a control means configured to trigger a remote alert when the acceleration exceeds a predetermined acceleration limit value. Thus, an impact on the graft can be detected and taken into account.

[0100] A list of operating parameters for all or part of the embodiments of the invention and for determining the limit values ​​whose crossing is monitored is given below.

[0101] a / first predetermined temperature limit value: set according to the graft and its sensitivity to ambient temperature for the envisaged transport time. Value determined by applying a safety margin in relation to the results of published scientific studies and / or by machine learning according to the graft rejection rate and / or other disturbances following transplantation (length of hospitalization, return to hospital, post-operative drug treatments, sensations felt by the recipient, ...).

[0102] b / second predetermined temperature limit value: set in the same way as the first predetermined temperature limit value, it has a lower safety margin than the first predetermined temperature limit value.

[0103] c / first predetermined time: estimated cooling time of the graft to return below the first predetermined temperature limit value. It is preferably set according to the type of graft and the type of transport container.

[0104] d / Second predetermined duration: fixed according to the normal stops (determined arbitrarily or by learning) for a graft transport (stop for exiting a parking lot, for crossing traffic lights, stop signs, tollbooths, for a break at a motorway service area, etc.). The third predetermined duration is longer than the second predetermined duration.

[0105] e / first predetermined geographical position: this is the position of the airports.

[0106] f / first predetermined distance limit value: this is a perimeter representing the airport area, for example with a radius of two kilometers.

[0107] g / second predetermined geographical position: this is the position of the destination of the transport vehicle.

[0108] h / second predetermined distance limit value: this is a distance corresponding to the advance notice required for the medical team responsible for the graft recipient to be ready. This distance corresponds, for example, to a travel time estimated by vehicle guidance software, for the vehicle to its destination, equal to the required advance notice period, for example 30 minutes.

[0109] i / predetermined recipient terminal: this is at least one telecommunications terminal of the medical team in charge of the graft recipient.

[0110] j / third predetermined distance limit value: this is a perimeter around the destination location, corresponding, for example, to the perimeter of a hospital where the medical team in charge of the graft recipient is located.

[0111] k / predetermined route: this is the planned route for transporting the graft, for example determined by vehicle guidance software to an airport and then from another airport to the graft's destination. This route may be reassessed during transport, in particular to take into account traffic conditions.

[0112] 1 / fourth predetermined distance limit value: this is a tolerance around of the predetermined route, for example ten or twenty kilometers.

[0113] m / predetermined oximetry limit value: set according to the graft and its sensitivity to its oxygen consumption for the planned transport duration. Value determined by applying a safety margin in relation to the results of published scientific studies and / or by machine learning according to the graft rejection rate and / or other disturbances following transplantation (length of hospitalization, return to hospital, post-operative drug treatments, sensations felt by the recipient, ...).

[0114] n / predetermined humidity limit value: this is the humidity limit allowing detection of the opening of the transport container.

[0115] o / predetermined brightness limit value: set to detect an opening of the transport case or carrying bag and not detect the light intensity emitted by the light-emitting diodes in the case.

[0116] p / predetermined acceleration limit value: set according to the graft and its sensitivity to shocks. Value determined by applying a safety margin in relation to the results of published scientific studies and / or by machine learning according to the graft rejection rate and / or other disturbances following transplantation (length of hospitalization, return to hospital, post-operative drug treatments, sensations felt by the recipient, ...).

[0117] In the third embodiment, illustrated in [Fig. 7] with the information transmission chain already shown in [Fig. 4], the device comprises two housings: a housing 51, similar to housing 24, except that it is connected to a mobile infusion machine 50 comprising the transport housing 54. The connection between the infusion machine 50 and the housing 51 is wired or wireless and allows the housing 51 to collect operating data and values ​​captured by the sensors of the infusion machine 50. In the embodiment illustrated in [Fig. 7], the connection between the housing 51 and the infusion machine 50 includes USB connectors 52.

[0118] The central unit of the perfusion machine 50 can thus provide the following physiological data, depending on the graft considered: - The temperatures of the infused blood, the graft preservation solution, the ice bath and / or the debubbler, - The estimated glucose level in the blood or in the graft, - The bile produced, - The potential of hydrogen, pH, - The lactate level, - The enzyme level, - Flow rates (vena cava, portal vein and / or artery), - Blood pressures (arterial, venous, systolic and diastolic pressures, and / or their average over a predetermined period), - The vascular resistance indices of the graft, - The level of gases in the blood (oxygen and / or air) - Arterial blood gas analysis, - Heart rate, - Hematocrit, - Mixed oxygen saturation, - Respiratory rate, - Tidal volume, and / or - Positive expiratory pressure.

[0119] The central unit of the perfusion machine 50 can also provide operating data for the following machine: - Pump speed and / or flow rates, - Error codes, - Graft identification number, - Elapsed infusion time, - Current date and time. - The open or closed status of the transport case lid, and / or - The battery charge level.

[0120] The server 53, which receives information from the sensors in the housing 51 and data and measurements from the perfusion machine 50, stores these values ​​and processes them to make a prediction of the evolution of at least part of these values ​​and to assist the decision-making of those responsible for the transport and transplantation of the graft 12.

[0121] In a preferred variant (not shown), a box 23 is associated with the graft in the transport case 54 of the perfusion machine 50. The box 51 thus receives data from the central unit of the perfusion machine 50 and from the box 23. This variant has, in particular, the advantage of providing redundancy in the measurement of the graft's temperature, which improves the reliability of the device.

[0122] Figures 8 and 9 show an example of a sequence of steps 160 performed jointly by the unit 51 and the server 53 during graft transport. In step 161, the geographical origin and destination of the graft are stored. These are, for example, the geographical coordinates of the hospitals, with a radius of proximity, for example, ten kilometers. In step 162, the contact details (email addresses and telephone numbers) of those responsible for transport and transplantation are stored. In step 163, the graft 12 is inserted into the transport container 14 or 54. The unit 51 thus receives data from the central processing unit of the perfusion machine 50 and / or from the unit 23 inserted into the container 14 or 54.In the case where the unit is integrated or associated with a perfusion machine 50, the unit 51 and the central unit of this perfusion machine are connected, for example via USB connectors 52.

[0123] In step 164, it is determined whether the transport case is part of a perfusion machine based on the presence of communication with that machine. If the result is negative, in step 165, the units 23 and 24 are paired. If the result is positive, or following step 165, in step 166, unit 51 performs an initial reading of the physiological and geographic location data captured by the device's sensors and, optionally, by the sensors of the perfusion machine (see list above). The operating data of the perfusion machine 50 (see list above) can also be read. by box 51 during this step.

[0124] During step 167, a prediction of the temporal evolution of the values ​​of the captured or received data is performed. To this end, machine learning is implemented based on the values ​​observed during previous transports of similar grafts. This learning is preferentially performed by server 53. This predicted evolution represents the graft's capacity to be transplanted at the destination hospital, as a function of the transport duration.

[0125] During step 168, based on the data collected and the predictions of its evolution, one or more routes for the graft are proposed, for example by road, plane, train, etc. Traffic conditions, scheduled train or plane timetables, or the availability of private flights may also be taken into account for this step. A transport manager then selects a route for the graft.

[0126] In step 169, it is determined whether the graft has left the starting perimeter, based on its geographical location. If not, step 169 is repeated. Conversely, if the graft has left the starting perimeter, in step 170, the operating mode is activated, i.e., the transport itself. In step 171, the physiological data, geographical location, and, if applicable, the operating status of the perfusion machine are read again. In step 172, the geographical location is determined. In step 173, it is determined whether the graft is near an airport. If not, during step 174, the captured data is communicated to server 19 or 53. If the graft is near an airport or following step 174, during step 175, it is determined whether the temperature of the graft is above a limit value.If so, during step 176, a local alert is triggered for the person responsible for transporting the graft, informing them of this event. Following either step 175 or 176, during step 177, it is determined whether the light level inside the transport container exceeds a limit value. If so, during step 178, a local alert similar to alert 176 is triggered. Following either step 177 or 178, during step 179, it is determined whether the humidity level inside the transport container exceeds a limit value. If so, during step 180 a local alert similar to alert 176 is triggered. Following either step 179 or 180, during step 181, it is determined whether the graft has experienced a shock exceeding a certain threshold. If so, during step 182 a local alert similar to alert 176 is triggered.Following one of steps 181 and 182, during step 183, it is determined whether any of the other physiological parameters of the graft are outside an interval bounded by two limit values. If so, during step 184 a local alert is triggered. similar to alert 176. Following one of steps 183 and 184, during a step 185, it is determined whether the geographical trajectory of the graft is normal, that is to say on a path close to the path selected at the end of step 168. If not, a local alert similar to alert 176 is triggered.

[0127] In step 187, an estimate is made of the graft's speed and the time remaining before its arrival at its destination. In step 188, it is determined whether the graft is immobile. If so, the frequency of data transmission to server 19 or 53 is slowed down in step 189. If not, or after step 189, in step 190, a new prediction is made regarding the temporal evolution of the graft's physiological parameters, its condition upon arrival at its destination, and its suitability for transplantation. The person responsible for transporting the graft and the destination hospital are informed if any of the predicted values ​​fall outside an acceptable range.

[0128] During step 191, it is determined whether the graft enters the destination perimeter. If not, it is returned to step 171. Conversely, if the graft has entered the destination perimeter, during step 192, the lock is unlocked and then, during step 193, a message is sent to the destination hospital to inform it of the estimated time of arrival of the graft.

[0129] As can be understood from the preceding description, the implementation of the invention allows for the prediction of changes in the graft's condition based on measured or received data and machine learning based on similar data collected during previous transports. These predictions assist decision-making by those responsible for transport and transplantation.

[0130] Other predictions can also be made for the purpose of other decision-making. In particular, these decisions concern the instructions to be applied to the perfusion machine, the possible immediate intervention on the graft in the event of decannulation, the possibility of continuing the transplantation procedure, the choice of the recipient patient, and the decision to keep the patient hospitalized longer after transplantation.

[0131] Figure 10 represents steps which can, in whole or in part, be combined with the steps described above in Figures 5, 6, 8 and 9. During a step 201, the collection of dated data during and / or following transplantation in the patient's body continues. For example, the duration of the transplant operation, the date of the patient's discharge from the hospital, complications during the operation or in the following days, the date of the patient's return to a hospital, the date of a new transplant and the date of the patient's death, can be recorded.

[0132] In step 202, machine learning is performed on the transport data and the data collected in step 201. This provides a database of collected data and a system capable of making predictions of evolution. of this data and the delays and complications described above, depending on data captured or read during a new graft transport and / or during and following the transplant.

[0133] During step 203, a score is determined for the initial state of the graft, prior to its transport. The evaluation of this score is taught in document PCT / FR2020 / 050437. This score is representative of the graft's ability to be implanted in the recipient patient's body.

[0134] During a step 204, the evolution of this score until arrival at destination is determined according to transport data (data collected or read, estimated remaining time before arrival at destination, ...), based on machine learning.

[0135] During a step 205, a condition of the recipient patient is determined, for example by entering his age, sex, weight, any pathologies, treatments pending transplantation.

[0136] During a step 206, a prediction of graft success, a prediction of potential complications and of the delays described above are performed, based on machine learning.

[0137] This score and these predictions relating to the recipient patient can be transmitted to the receiving hospital to assist in its decision to prepare the patient for transplantation or to forgo the transplant. Indeed, a low initial score, followed by transport lasting longer than initially planned, should lead to a decision on whether to proceed with the planned transplant and, possibly, to choose another recipient. The implementation of the present invention makes it possible to document this decision with assessments of the recipient's length of stay in the hospital, the time before their subsequent return to a hospital, the need for a new transplant, their life expectancy after transplantation, etc.

[0138] In the event of decannulation, detected during step 207 by the perfusion machine, the device of the invention can display to the person in charge and transmit to the hospital, predictions of the evolution of the score and / or physiological parameters until arrival at the destination hospital according to different scenarios: maintaining the graft is maintained as is, i.e., without feeding or with partial feeding, or this feeding is restored. These predictions are made, displayed, and transmitted during step 20. An informed decision can thus be made regarding the choice of: - Maintain the graft without blood supply or other inputs, or - Open the transport container 54, and restore the graft's supply, even at the risk of compromising sterility during this ongoing procedure. transportation.

[0139] The implementation of the present invention also makes it possible to provide information to the person in charge of transport for the purpose of potentially modifying transport conditions. For example, the glucose level and the predicted evolution of this level are determined and displayed to this person in charge and transmitted to the destination hospital during step 209, for several scenarios of instructions. This person in charge can then decide whether to modify the operating instructions of the infusion machine to increase or decrease this glucose level.

[0140] The implementation of the present invention also makes it possible, during transport and based on predictions of physiological values ​​upon arrival at the hospital, to improve the condition of the graft, for example by defatting a liver graft, using known techniques. To this end, steatosis can be measured during graft harvesting, for example by implementing the instructions in document PCT / FR2020 / 050437, and then assessed and predicted for arrival at the destination, based on several operating settings of the perfusion machine 50. The person responsible for transport or transplantation can thus choose operating settings for this machine 50 to optimize the condition of the graft upon arrival at the destination.

[0141] During step 210, the device makes a prediction of improvement in the graft score based on instruction scenarios applied to the perfusion machine. During step 211, these predictions are displayed locally and transmitted to the destination hospital.

[0142] Optionally, a camera is positioned with a light source inside the box 54 to perform successive evaluations of graft steatosis (or another parameter having visible consequences on the surface of the graft), during a step 212.

[0143] For all prediction display steps based on different scenarios of operating setpoint values ​​of the perfusion machine described above, alternatively, the device selects one of these scenarios based on the result of at least one of these predictions and applies to the perfusion machine at least one setpoint value that it represents.

[0144] Finally, machine learning makes it possible to explore new relationships between values ​​of transport conditions or physiological parameters of the graft during its collection or transport and the results of the transplant in terms of time expressed above and quality of life of the patient.

[0145] The implementation of the invention thus allows for the valorization of data (parameters) retrieved by a perfusion machine (which can assist in the decision-making of the person responsible for transport or transplantation). By retrieving the captured data The perfusion machine allows for a prediction of how these data will evolve. The device can then advise on the optimal organ transport route based on changing parameters and environmental conditions. Furthermore, the device can recommend actions to be taken during transport based on measured or predicted data.

Claims

Demands

1. Graft monitoring device, characterized in that it comprises: - a means (51, 52) for communicating with a central unit of a mobile perfusion machine (50) comprising a container (54) for transporting the graft under perfusion, this means of communication being configured to receive from this central unit, physiological parameter values ​​of a graft during transport, including at least the temperature of the graft and - a means (53) for making predictions of the evolution of physiological parameter values ​​during the transport of the graft, the prediction means being configured to make at least one prediction of physiological parameter values ​​for the time of arrival of the graft at its implantation site in the body of a recipient patient.

2. Device according to claim 1, which further comprises a means of remote communication of at least one prediction of the evolution of at least one physiological parameter of the graft.

3. Device (10) according to any one of claims 1 or 2, further comprising a housing having at least one temperature sensor configured to accompany the graft inside a transport case of the perfusion machine and provide the temperature inside the transport case.

4. Device (10) according to any one of claims 1 to 3, wherein the prediction means is based on machine learning based on physiological parameter values ​​obtained during previous transports.

5. A device according to any one of claims 1 to 4, which includes a means for geolocating and evaluating the time of arrival of the graft at its implantation site in the body of the recipient patient.

6. Device according to any one of claims 1 to 5, wherein the prediction realization means is configured to propose at least one path of the graft.

7. Device according to any one of claims 1 to 6, wherein the means for making predictions is configured to make predictions of the evolution of physiological parameters of the graft according to several scenarios of evolution of operating instructions of the transport box and display of these predictions.

8. Device (10) according to claim 3 or any one of claims 4 to 7 when they depend on claim 3, wherein the housing (11, 23, 24) further comprises a means (31, 36) for measuring the distance between the geographical position of the housing and at least one first predetermined geographical position and a control means (31) configured to control one of two operating modes of the device as a function of each measured distance, between: - an operating mode in which the housing transmits its geographical position regularly, when each distance is greater than a first predetermined distance limit value and - an operating mode in which the communication means is inhibited, when at least one measured distance is less than said first predetermined distance limit value.

9. Device (10) according to claim 3, claim 8 or any one of claims 4 to 7 when they depend on claim 3, wherein the housing (11, 23, 24) further comprises an oximeter configured to measure the oxygen available in the graft and / or the oxygen consumption of the graft and a control means (31) configured to trigger a remote alert when the available oxygen falls below a predetermined seventh value and / or when the oxygen consumption of the graft falls below a predetermined oximetry limit value.

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