<table border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td colspan="3" style="background-color: rgb(244, 242, 246);">Additional&nbsp;Signals</td>
 </tr>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">Physiological&nbsp;Signals</td>
 <td style="background-color: rgb(244, 242, 246);">Advantages</td>
 <td style="background-color: rgb(244, 242, 246);">Limitations</td>
 </tr>
 <tr>
 <td>Continuous ketone and lactate sensors</td>
 <td>Lactate increase with exercise and can differentiate moderate-intensity exercise and high-intensity exercise. 
 Ketone responds to different types of exercises. These levels ensure safety during exercise.</td>
 <td>Very limited ability to differentiate between the type of exercise, and mixed levels show a slow increase with exercise</td>
 </tr>
 <tr>
 <td>Accelerometers and heart-rate sensors coupled with lactate sensing</td>
 <td>Might have potential to inform CL on both exercise type (E.g., running, swimming or weights) and intensity (low, moderate, high or interval)</td>
 <td>Non-specificity to exercise with stress, illness, medications, dehydration, and all potential modulators</td>
 </tr>
 </tbody>
</table>

<ul>
 <li>
 Information from&nbsp;physiological signals&nbsp;like lactate, ketones, counterregulatory hormones, accelerometry, heart rate, galvaic skin response, skin temperature, and blood volume pulse could be used as potential adjunct for developing an algorithm about onset, offset and intensity of physical activity.</li>
 <li>
 Counterregulatory hormones&nbsp;can differentiate exercise intensity, however a lot of technical challenges were involved in measurement of them in real world.</li>
 <li>
 Other wearable&nbsp;sensors combining galvanic skin response, accelerometry, blood volume pulse, heart and skin temperature&nbsp;are able to classify the physical states and exercise type and could potentially differentiate exercise and physiological stress.</li>
</ul>

Additional signals

OTHER-DIABETES-TOPICS

DIABETES

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td colspan="3" style="background-color: rgb(244, 242, 246);">
 Bi-hormonal CL systems 
 (Systems delivering both Insulin and glucagon)</td>
 </tr>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">Strategies</td>
 <td style="background-color: rgb(244, 242, 246);">Advantages</td>
 <td style="background-color: rgb(244, 242, 246);">Limitations</td>
 </tr>
 <tr>
 <td>Glucagon helps in minimizing the impact of the delayed onset in insulin action by counteracting the persisting glucose-lowering effects of insulin</td>
 <td>
 <ul>
 <li>
 Bypass limitations of SC route</li>
 <li>
 Improved time-in-range</li>
 <li>
 Less hypoglycemia during excercise</li>
 </ul></td>
 <td>
 <ul>
 <li>
 Stability and cost</li>
 <li>
 Long-term safety of glucagon</li>
 <li>
 Increased complexity of the system</li>
 </ul></td>
 </tr>
 </tbody>
</table>

BI hormonal CL systems

<h2>Improved usability of existing strategies</h2>
An&nbsp;exercise button&nbsp;could be integrated into CL device activation which triggers several adaptive changes, such as:
<ul>
 <li>
 Automatic increase in glucose at a preset time</li>
 <li>
 Modifications in the algorithm so that it becomes less aggressive in minimizing rises in glucose levels and more aggressive in minimizing falls in glucose</li>
 <li>
 A function to preprogram future recurrent scheduling for exercise (date and time) which could automatically set temporary targets 90 minutes prior.</li>
</ul>

Improved usability


<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td colspan="3" style="background-color: rgb(244, 242, 246);">Development of insulin formulations and routes of delivery with more favorable pk characteristics</td>
 </tr>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">Strategies</td>
 <td style="background-color: rgb(244, 242, 246);">Advantages</td>
 <td style="background-color: rgb(244, 242, 246);">Limitations</td>
 </tr>
 <tr>
 <td>Intranasal insulin</td>
 <td>Significantly faster onset and offset in action with potential to reduce residual insulin activity associated with pre-exercise meal bolus</td>
 <td>
 <ul>
 <li>
 Not widely available</li>
 <li>
 Long-term safety is not clear</li>
 </ul></td>
 </tr>
 <tr>
 <td>Continuous intraperitoneal insulin infusion</td>
 <td>
 <ul>
 <li>
 Faster onset and offset action</li>
 <li>
 Improves HbA1c with less hypoglycemia</li>
 </ul></td>
 <td>
 <ul>
 <li>
 Invasive procedures</li>
 <li>
 Carries risk of infection and immunogenicity</li>
 </ul></td>
 </tr>
 <tr>
 <td>Intravenous (IV) CL insulin delivery models</td>
 <td>
 <ul>
 <li>
 Rapid delivery with no delay in absorption</li>
 <li>
 Would bypass limitations of SC route</li>
 </ul></td>
 <td>
 <ul>
 <li>
 Invasive</li>
 <li>
 Prone to complications such as infections, thrombosis</li>
 <li>
 Less feasible for ambulatory use</li>
 </ul></td>
 </tr>
 </tbody>
</table>

Development of Insulin

<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td colspan="3" style="background-color: rgb(244, 242, 246);">Enhanced algorithms</td>
 </tr>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">Strategies</td>
 <td style="background-color: rgb(244, 242, 246);">Advantages</td>
 <td style="background-color: rgb(244, 242, 246);">Limitations</td>
 </tr>
 <tr>
 <td>HCL systems incorporating heart rate, accelerometry along with energy expenditure and galvanic skin response</td>
 <td>For detection of physical activity and improvements in glycemic outcomes</td>
 <td>These algorithms reactive and remain subject to the slower PK of subcutaneous insulin absorption</td>
 </tr>
 <tr>
 <td>Machine learning for personalization of CL systems</td>
 <td>Recognizes habitual pattern of imminent exercises and trigger CL systems</td>
 <td>Potential risks associated with insulin dosing determined upon the basis of the probability of an event occurring</td>
 </tr>
 </tbody>
</table>

Enhanced algorithms


A series of videos that shows Prof Kausik Ray, Cardiologist and Professor of Public Health, Imperial College London, presenting the ACS Story narrative in a visually engaging way.
Please explore the 4 mini videos below to learn more on how to implement the guidelines recommendations and achieve higher clinical benefits for your patient

The first chapter talks about how to identify patients at very high CV risk.

Patient Identification

The second chapter talks through how to manage patients in alignment to the guidelines.

Treat Aggressively, Combine and Treat Early

The third chapter talks through how to optimise the ACS pathway.

Optimise Your ACS Pathway

Summary on the ACS patient journey and ESC guidelines recommendation for physician on how to manage patients efficiently.

Summary

Act Now for your ACS Patients

DYSLIPIDEMIA

Meet a Sanofi Specialist

OTHER-RARE-DISEASE-TOPICS

RARE-DISEASE

Belumosudil is the&nbsp;first and best-in-class ROCK2 inhibitor, specifically designed as an immunomodulator to target both the inflammatory and fibrotic/sclerotic manifestations of cGVHD.1

black

Belumosudil&nbsp;decreases activation of STAT3, triggering the significant&nbsp;downregulation of both Th17 and Tfh cells, leading to the&nbsp;downregulation of pro-inflammatory cytokines (IL-21, IL-17).1,4

↓&nbsp;Inflammation
Belumosudil&nbsp;increases phosphorylation of STAT5, causing the&nbsp;upregulation of Treg cells.3&nbsp;Overall, this has an&nbsp;immunomodulatory effect&nbsp;on STAT3 and STAT5 phosphorylation,&nbsp;reducing inflammation.1,4

200 mg once daily administered orally6

REZUROCK® (belumosudil) is indicated for the treatment of adult and pediatric patients 12 years and older with cGVHD after failure of at least two prior lines of systemic therapy.6

Belumosudil&nbsp;prevents the polymerization of G-actin to F-actin, including the&nbsp;downregulation of MRTF-related profibrotic gene expression.5
↓&nbsp;Fibrosis

Belumosudil&nbsp;downregulates fibrosis, as demonstrated by&nbsp;decreased collagen deposition around the bronchioles&nbsp;and the&nbsp;delayed progression of scleroderma&nbsp;in animal cGVHD models.2

Abbreviations
ROCK2:&nbsp;Rho associated coiled-coil containing protein kinase 2;&nbsp;STAT3:&nbsp;Signal transducer and activator of transcription 3;&nbsp;Th:&nbsp;&nbsp;helper cells;&nbsp;Tfh:&nbsp;T follicular helper cells;&nbsp;IL-21 :&nbsp;Interleukin-21;&nbsp;IL-17:&nbsp;Interleukin-17;&nbsp;Treg:&nbsp;Regulatory&nbsp; ;&nbsp;STAT5: Signal transducer and activator of transcription 5;&nbsp;G-actin:&nbsp;Globular protein;&nbsp;F-actin:&nbsp;Filamentous protein;&nbsp;MRTF:&nbsp;Myocardin-related transcription factor;&nbsp;cGVHD:&nbsp;Chronic graft-versus-host disease.

References

Rezurock Dosage

PAYOR

OUT-OF-TAXONOMY

cGVHD has a&nbsp;high unmet need beyond 2L, as current treatments&nbsp;inadequately address diverse manifestations&nbsp;such as fibrosis and&nbsp;do not support long-term use, resulting in&nbsp;rapid disease progression.1

Guidelines clearly state that there are&nbsp;no standard therapies for SR patients1,2,4,6, limiting these patients to the following available therapies:

Currently, there is&nbsp;no consensus&nbsp;on the&nbsp;optimal choice of agents for 3L or further lines of therapy&nbsp;as per the major guidelines1
The need to investigate&nbsp;novel therapies&nbsp;to address the&nbsp;fibrotic manifestations&nbsp;of cGVHD in 2L and 3L has been recognized7, 10
cGVHD progression is a key reason to modify or discontinue cGVHD therapy7

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(122, 0, 230); border-color: rgb(255, 255, 255);">
 1L</td>
 <td style="background-color: rgb(122, 0, 230); border-color: rgb(255, 255, 255);">
 2L</td>
 <td style="background-color: rgb(122, 0, 230); border-color: rgb(255, 255, 255);">
 3L</td>
 </tr>
 <tr>
 <td style="text-align: center; border-color: rgb(255, 255, 255);">3 to 7 months</td>
 <td style="text-align: center; border-color: rgb(255, 255, 255);">3 to 4 months</td>
 <td style="text-align: center; border-color: rgb(255, 255, 255);">4 to 5 months</td>
 </tr>
 <tr>
 <td style="text-align: center; border-color: rgb(255, 255, 255);">96%7</td>
 <td style="text-align: center; border-color: rgb(255, 255, 255);">71%7</td>
 <td style="text-align: center; border-color: rgb(255, 255, 255);">47%7</td>
 </tr>
 </tbody>
</table>

Abbreviations
1L:&nbsp;First Line;&nbsp;2L:&nbsp;Second Line;&nbsp;3L:&nbsp;Third Line;&nbsp;SR:&nbsp;Steroid-resistant;&nbsp;NCCN :&nbsp;National Comprehensive Cancer Network;&nbsp;ASH:&nbsp;American Society of Hematology;&nbsp;ANZTCT:&nbsp;Australia and New Zealand Transplant &amp; Cellular Therapies;&nbsp;EBMT: European Society for Blood and Marrow Transplantation;&nbsp;ECP:&nbsp;Extracorporeal photopheresis;&nbsp;cGVHD:&nbsp;Chronic graft-versus-host disease.

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