
We are seeing big changes in heart care with new, less invasive options. Minimally invasive cardiac surgery (MICS) is now a choice for many. It means patients can recover faster and spend less time in the hospital.
Studies from 2020 to 2025 show MICS works as well as, or even better than, traditional surgery. This new way of doing heart surgery is making big procedures like triple bypass surgery less scary for patients.
Key Takeaways
- Minimally invasive cardiac surgery offers a less invasive alternative to traditional open-heart surgery.
- MICS results in shorter hospital stays and quicker recovery times for patients.
- Recent studies show MICS delivers similar or better outcomes than conventional CABG.
- Advancements in MICS are changing the approach to complex cardiac procedures.
- Patients can expect improved outcomes with less invasive cardiac surgery options.
Understanding Traditional Open-Heart Surgery

Open-heart surgery has several key steps that have been improved over time. It’s a complex process that needs a deep understanding of the heart and surgery.
The Conventional Approach to Cardiac Surgery
The surgery starts with a sternotomy. This is when the surgeon makes an incision in the sternum to reach the heart. It gives a clear view of the heart and its surroundings.
Sternotomy and Cardiopulmonary Bypass
After opening the sternum, the patient is connected to a cardiopulmonary bypass (CPB) machine. This machine takes over the heart and lung functions. It circulates blood, allowing the surgeon to work on a stopped heart.
- The CPB machine oxygenates the blood and removes carbon dioxide.
- It makes the surgical area bloodless, improving visibility and precision.
- The machine can adjust the blood’s temperature to support the surgery.
Limitations and Risks of Open Procedures
Traditional open-heart surgery is effective but comes with risks and limitations. Some of these include:
- Surgical Trauma: The large incision and sternotomy can cause significant tissue damage and trauma.
- Recovery Time: Patients often need long hospital stays and recovery periods.
- Infection Risk: The large incision increases the risk of surgical site infections.
- Bleeding Complications: The use of CPB can lead to bleeding complications and the need for blood transfusions.
Understanding these aspects of traditional open-heart surgery is key for surgeons and patients. It helps them decide the best cardiac care approach.
What is Triple Bypass Surgery and Its Conventional Approach
Triple bypass surgery is a lifesaving option when three major coronary arteries are blocked. It creates new paths for blood to reach the heart. This surgery is key in treating coronary artery disease, affecting millions globally.
Definition and Indications
Triple bypass surgery, or coronary artery bypass grafting (CABG), bypasses three coronary arteries with grafts. These grafts come from the patient’s veins or arteries. It’s needed when three major arteries are blocked, leading to heart attacks and angina.
Doctors consider surgery after trying other treatments. The decision depends on symptoms, disease extent, and overall health.
Traditional Surgical Technique
The traditional method opens the breastbone to access the heart. The patient is connected to a heart-lung machine during surgery.
- The surgeon takes grafts from the leg or chest.
- These grafts bypass blocked arteries, restoring blood flow.
- The procedure requires careful technique to attach grafts correctly.
Recovery Timeline and Challenges
Recovery from triple bypass surgery is long. Patients are watched closely in the ICU before moving to a regular room. The stay usually lasts 7-10 days.
Challenges include managing pain, regaining strength, and rehabilitating the chest and leg. Cardiac rehabilitation helps improve heart health and physical condition.
Key recovery milestones include:
- Returning home and starting light activities in a few weeks.
- Increasing physical activity over 2-3 months.
- Reaching full recovery, including work and normal activities, in 3-6 months.
While triple bypass surgery saves lives, it comes with risks. Complications include infection, bleeding, and anesthesia reactions. Knowing these risks and the recovery process is vital for patients and their families.
The Evolution of Cardiac Surgery: Moving Toward Less Invasive Approaches
Cardiac surgery has changed a lot over time. It has moved from big, open-heart surgeries to smaller, less invasive ones. This change has made surgeries safer and less painful for patients.
Historical Development of Cardiac Surgical Techniques
The history of cardiac surgery is filled with new ideas and improvements. The first open-heart surgery was done in the 1950s. It started a new chapter in heart care.
Over the years, doctors looked for better ways to do heart surgery. They introduced cardiopulmonary bypass (CPB) to work on a stopped heart. But CPB had its own risks, leading to the search for safer methods.
The Push for Reduced Surgical Trauma
Doctors have always wanted to make surgeries less harmful. They’ve worked hard to find ways to do this. This led to the creation of new, less invasive techniques.
These new methods help patients heal faster and with less pain. An Expert said,
“The goal of modern cardiac surgery is to achieve the best possible outcomes with the least amount of trauma to the patient.”
Patient-Centered Outcomes Driving Innovation
Now, doctors focus more on what patients want. They aim for better quality of life and less recovery time. This change has led to more personalized care and less invasive surgeries.
Today, we see a big push for minimally invasive direct coronary artery bypass (MIDCAB) and other new procedures. These methods are safer and can lead to better long-term results. By focusing on what patients need, we’re making cardiac care better.
Overview of Minimally Invasive Cardiac Surgery (MICS)
Cardiac surgery has evolved to include minimally invasive cardiac surgery (MICS). This method reduces tissue damage and speeds up recovery. MICS is now a key option for many patients needing surgery.
Definition and Key Principles
Minimally invasive cardiac surgery uses smaller incisions to cause less tissue damage. It aims to reduce recovery time and achieve results similar to or better than traditional surgery.
Key Principles of MICS:
- Smaller incisions to reduce tissue damage
- Less use of cardiopulmonary bypass when possible
- Minimized disruption of the chest cavity
- Reduced risk of complications and infections
Types of MICS Procedures
MICS includes various procedures for different heart conditions. Some common ones are:
|
Procedure |
Description |
Benefits |
|---|---|---|
|
Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) |
A technique used to bypass blocked coronary arteries without the need for cardiopulmonary bypass. |
Reduces trauma, less bleeding, and quicker recovery. |
|
Port-Access Cardiac Surgery |
A method that allows for cardiac surgery through small ports in the chest. |
Less invasive, reduced scarring, and shorter hospital stay. |
|
Endoscopic Vessel Harvesting |
A technique used to harvest vessels for bypass grafting using endoscopic methods. |
Less invasive, reduced risk of wound complications. |
Candidate Selection Criteria
Not every patient is right for MICS. We look at the patient’s anatomy, the complexity of their heart condition, and their overall health. Each patient is evaluated individually to see if MICS is the best choice.
The decision to undergo MICS is made after a thorough evaluation, considering factors such as the patient’s cardiac anatomy, previous surgeries, and comorbid conditions.
By choosing the right candidates and tailoring MICS to their needs, we can improve outcomes and enhance their quality of life.
Minimally Invasive Direct Coronary Artery Bypass (MIDCAB)
MIDCAB surgery is a new way to do coronary artery bypass grafting. It uses smaller incisions to reduce trauma. This method is popular because it can cut down on recovery time and risks of traditional open-heart surgery.
Procedure Details
The MIDCAB procedure makes small chest incisions to reach the heart. It doesn’t need a big chest cut or a heart-lung machine. Surgeons use special tools to graft on a beating heart.
Key Steps in MIDCAB:
- Small thoracotomy to access the heart
- Use of stabilizing devices to immobilize the area of the heart where the graft is being performed
- Bypass grafting using arterial or venous grafts
- Closure of the incision with sutures or staples
Advantages
MIDCAB has many benefits. It causes less trauma, less pain, and shorter hospital stays. It also avoids heart-lung machine risks.
Comparative Advantages:
|
Aspect |
MIDCAB |
Traditional CABG |
|---|---|---|
|
Surgical Incision |
Small thoracotomy |
Sternotomy |
|
Cardiopulmonary Bypass |
Not required |
Required |
|
Recovery Time |
Shorter |
Longer |
Limitations
MIDCAB is not for everyone. It needs skilled surgeons and is for patients with single or double-vessel disease.
In conclusion, MIDCAB is a big step forward in heart surgery. It’s a less invasive option than traditional CABG. While it has its limits, its benefits make it a good choice for some patients.
Less Invasive Alternatives for Triple Bypass Surgery Patients
The world of triple bypass surgery is changing. New, less invasive methods are now available. These options help patients recover faster and feel less pain.
Endoscopic Vessel Harvesting
Endoscopic vessel harvesting is a big step forward in cardiac surgery. It uses a small camera and tools to take blood vessels for grafting. This method cuts down on wound problems and speeds up healing.
A study in the Journal of Thoracic and Cardiovascular Surgery shows it lowers wound infections. A top cardiac surgeon calls it a game-changer. It means less pain and quicker recovery for patients.
Small Thoracotomy Approaches
Small thoracotomy is another option for triple bypass patients. It involves smaller cuts between the ribs, not a big chest opening. This leads to less pain and a shorter hospital stay. Special tools and techniques are used to do the grafting through these small cuts.
- Reduced postoperative pain
- Shorter hospital stay
- Less risk of wound complications
Hybrid Revascularization Options
Hybrid revascularization mixes surgery and catheter-based methods. It does a minimally invasive bypass and PCI together. This way, patients recover faster and face less risk. It’s great for those with complex heart disease.
A leading cardiologist says it’s a personalized way to treat heart disease. It combines surgery and interventional techniques for better results.
In summary, new options for triple bypass surgery are making cardiac care better. Techniques like endoscopic vessel harvesting, small thoracotomy, and hybrid revascularization offer more personalized and less invasive treatments.
Robotic-Assisted Cardiac Surgery: The Cutting Edge
Robotic technology has led to big changes in cardiac surgery. Now, we see a big shift in how surgeries are done. Robotic systems are playing a key role in this change.
Robotic Systems Used in Cardiac Procedures
The da Vinci Surgical System is the top choice for cardiac surgery. It gives surgeons better vision, precision, and control. This means surgeries can be done with less harm to the patient.
The da Vinci system has a surgeon’s console, a cart with instruments, and a 3D vision system. This setup helps surgeons do complex tasks more easily and accurately.
Procedure Types and Applications
Robotic cardiac surgery includes many procedures. These include CABG, mitral valve repair, and closing atrial septal defects. The choice depends on the patient’s needs and the surgeon’s skills.
As technology gets better and surgeons learn more, robotic surgery is growing. It’s important for hospitals to invest in training and the right equipment for these new procedures.
Precision Benefits and Learning Curve
Robotic cardiac surgery offers better precision. The robotic systems allow for finer movements and more detailed work. This could lead to better results for patients.
But, there’s a learning curve for using robotic systems. Surgeons need special training to use them well. This training is key for getting the most out of robotic surgery and keeping patients safe.
As we keep improving robotic cardiac surgery, we’ll likely see better results for patients. The challenge is to use this technology wisely. We need to balance its benefits with the need for thorough training and careful patient selection.
Transcatheter Procedures as Alternatives to Open Surgery
Transcatheter procedures have changed cardiac care by giving new ways to treat heart issues. These methods are less invasive and can help patients recover faster.
Transcatheter Aortic Valve Implantation (TAVI)
Transcatheter Aortic Valve Implantation, or TAVI, is a new way to treat severe aortic stenosis. TAVI is a less invasive option compared to traditional surgery. It involves placing a new valve through a catheter in the femoral artery.
This method has shown great results, improving symptoms and quality of life for many patients. TAVI reduces risks and hospital stays but requires careful patient selection.
Transcatheter Mitral Valve Repair
Transcatheter mitral valve repair treats mitral regurgitation by fixing the valve with a catheter. The MitraClip system is a well-known example of this technology. It has helped many patients worldwide.
This method avoids open-heart surgery and reduces complications. It’s great for patients at high risk or with complex anatomy.
Other Catheter-Based Interventions
There are also other catheter-based interventions for valvular diseases. These include treatments for pulmonary and tricuspid valves. The field of structural heart disease interventions is rapidly evolving.
These advancements offer more treatment options for cardiac patients. They allow for more personalized care and could improve outcomes. As research continues, we’ll see more improvements in these techniques.
The ELANA Heart Bypass System: Surgery on a Beating Heart
A new method in heart surgery is the ELANA Heart Bypass System. It makes sutureless connections during surgery on a beating heart. This system is changing heart surgery by cutting down on the need for a heart-lung machine and lessening surgical damage.
Technology and Sutureless Connections
The ELANA Heart Bypass System uses advanced tech for sutureless anastomoses. These are connections between blood vessels. A special device makes these connections fast and precise, without stitches. This makes the surgery simpler and could lower the chance of problems.
With sutureless connections, the ELANA system makes surgery easier. It might also help patients by reducing the chance of leaks or narrowing at the connection site.
Benefits of Operating on a Beating Heart
Doing surgery on a beating heart, or off-pump surgery, has many benefits. It avoids the use of a heart-lung machine. This can lower the risk of bleeding, inflammation, and brain problems.
Beating heart surgery also causes less harm to the patient. This could mean shorter hospital stays and faster recovery times. It’s also good for patients at high risk for traditional surgery complications.
Current Status and Availability
The ELANA Heart Bypass System is being used in many heart surgery centers worldwide. Its availability can change based on where you are and the hospital. It’s a big step forward in heart surgery.
Like any new tech, the ELANA system is being closely watched. It needs more studies and approvals. But, it looks very promising for better heart surgery results by being less invasive and more effective.
Clinical Outcomes: 2020-2025 Studies on MICS vs. Traditional CABG
Studies from 2020 to 2025 have compared Minimally Invasive Cardiac Surgery (MICS) and traditional Coronary Artery Bypass Grafting (CABG). These studies are key to improving cardiac surgery. They help us understand which method is better for patients.
Short-term Results Comparison
MICS often leads to less morbidity and shorter hospital stays than traditional CABG. A 2022 study in the Journal of Thoracic and Cardiovascular Surgery found MICS patients had fewer complications. They also needed less intensive care.
MICS offers many benefits in the short term. These include less surgical trauma, less pain, and faster recovery. These advantages make the patient’s immediate recovery better.
Long-term Effectiveness Data
Long-term data on MICS versus traditional CABG is also promising. Research shows MICS graft patency rates are as good as, or better than, traditional CABG. A 2023 study found MICS patients had high graft patency rates for five years.
Long-term survival for MICS patients is encouraging. The reduced trauma and stress of MICS may lead to better survival rates.
Graft Patency and Survival Rates
Graft patency is key to CABG success. Studies show MICS achieves high graft patency rates. This is thanks to the precision of minimally invasive techniques.
Survival rates after CABG depend on graft patency, patient health, and care after surgery. Recent studies suggest MICS patients have similar, or better, survival rates than traditional CABG patients.
Quality of Life Measures
Quality of life after surgery is important for patients and doctors. MICS is linked to improved quality of life in both the short and long term. This is due to less pain, fewer complications, and quicker recovery.
Research shows MICS patients are more satisfied and have a better quality of life than traditional CABG patients. This is because MICS causes less tissue damage and trauma.
Recovery Benefits: Up to 40% Shorter Hospital Stays
Patients who have less invasive cardiac surgery often see big benefits. These benefits touch many parts of their recovery.
Hospital Stay Duration Comparisons
One key benefit is shorter hospital stays. Studies show that patients with minimally invasive surgery stay less time than those with open-heart surgery.
|
Surgery Type |
Average Hospital Stay |
|---|---|
|
Less Invasive Cardiac Surgery |
5-7 days |
|
Traditional Open-Heart Surgery |
8-12 days |
Reduced Surgical Trauma Effects
Less invasive cardiac surgery means less trauma. This leads to quicker healing and less pain. It’s because of smaller cuts and less touching of the heart and tissues.
Lower Infection and Bleeding Rates
Smaller cuts mean a lower chance of infection and bleeding. This makes surgery safer and improves patient results.
Return to Daily Activities Timeline
Patients get back to their daily lives faster with less invasive surgery. While times vary, many are back in a few weeks.
- Return to light activities: 1-2 weeks
- Return to moderate activities: 3-4 weeks
- Return to strenuous activities: 6-8 weeks
The recovery benefits of less invasive cardiac surgery are clear. It’s a good choice for many patients.
Cost Considerations: Traditional vs. Minimally Invasive Options
When thinking about cardiac surgery, the cost of traditional versus minimally invasive options is key. It’s important to look at both the upfront costs and the long-term effects on your wallet.
Initial Procedure Costs
The cost of cardiac surgery can change a lot based on the method. Traditional surgeries might cost more because you stay in the hospital longer. On the other hand, minimally invasive surgeries might cost more upfront but you could leave the hospital sooner.
- Operating room costs
- Surgeon fees
- Anesthesia costs
- Hospital stay expenses
- Post-operative care costs
Minimally invasive surgeries might save on hospital and care costs after surgery. But, the total cost can depend on how complex the surgery is and if special equipment is needed.
Long-term Economic Impact
The long-term effects on your wallet are also important. Minimally invasive surgeries often mean you can get back to work and life faster. This can save you money and help the economy too.
“The economic benefits of minimally invasive cardiac surgery extend beyond the immediate healthcare costs, impacting overall productivity and quality of life.”
A Cardiac Surgeon
Research shows that minimally invasive surgeries might lead to fewer complications. This could mean less need for extra medical care and lower costs.
Insurance Coverage Considerations
It’s important to know what your insurance covers when it comes to cardiac surgery. Different plans might cover traditional or minimally invasive surgeries differently.
- Check if your insurance plan covers the specific procedure you’re considering
- Understand any out-of-pocket expenses you may incur
- Inquire about coverage for pre-operative and post-operative care
- Ask about any additional costs associated with the procedure, such as rehabilitation or follow-up appointments
We suggest talking to your doctor and insurance company about what’s covered. This will help you understand the costs better.
Patient Selection: Who Qualifies for Less Invasive Alternatives?
Choosing the right patients for less invasive heart surgery is complex. We look at many factors to see if these procedures are right for them.
Anatomical Considerations
The shape and size of a patient’s heart matter a lot. We check the size and location of heart structures and any unusual shapes. For example, some patients might not fit certain less invasive methods because of their heart size or blockages.
Comorbidity Factors
Other health issues also play a big role. Things like diabetes, high blood pressure, and lung problems can affect how well a patient does after surgery. We look at the patient’s overall health to see how these issues might impact their choice of surgery.
Age and Frailty Assessment
Age and how frail a patient is also matter. Older or frailer patients might do better with less invasive surgery because it’s less stressful. But we also check if they can handle the surgery.
Previous Cardiac Surgery Impact
Patients who have had heart surgery before need careful thought. We look at the type of surgery they had, if there are scar tissues, and their current heart shape. This helps us figure out if less invasive surgery is safe and right for them.
By looking at all these factors, we can find the best candidates for less invasive heart surgery. This can lead to better results and happier patients.
The Future of Cardiac Surgery: Emerging Technologies
New technologies are changing cardiac surgery, bringing hope to patients everywhere. Medical innovation is pushing limits, leading to breakthroughs in the field.
Artificial Intelligence in Surgical Planning
Artificial intelligence (AI) is making a big impact in cardiac surgery, mainly in planning. AI looks at lots of data to help surgeons choose the best plan. This could make surgeries more precise and better for patients.
AI can spot the best candidates for less invasive surgeries and predict problems. It also helps with graft placement in CABG. AI is set to be a key player in cardiac surgery’s future.
Next-Generation Robotic Systems
Robotic-assisted cardiac surgery is promising, and new systems are coming. These systems offer better dexterity, clearer views, and more precision. They make it possible to do complex surgeries with small incisions.
Combining advanced robotics with AI and machine learning will make surgeons even better. These advancements will lead to more accurate and safe surgeries. We’ll see more complex repairs and reconstructions in the future.
Bioengineered Vessels and Tissues
Research on bioengineered vessels and tissues is exciting. Scientists aim to create grafts and substitutes for surgery. This could reduce the need for traditional grafts and improve results.
Bioengineered vessels might last longer, have less rejection risk, and grow. This area is new but very promising for cardiac surgery.
These emerging technologies will greatly impact cardiac surgery. They promise better precision, shorter recovery times, and better patient results. These innovations will shape the future of cardiac care.
Making an Informed Decision: Questions to Ask Your Cardiac Surgeon
When you’re facing cardiac surgery, knowing what to expect is key. It’s important to understand your condition, the surgery options, and your surgeon’s experience. We’ll help you ask the right questions to get the best care.
Understanding Your Specific Condition
To make good choices, you need to know about your heart condition. Here are some questions to ask your surgeon:
- What is the exact nature of my cardiac condition?
- What are the possible risks and complications with my condition?
- How will my condition affect my daily life if untreated?
- Are there non-surgical treatments for my condition?
Knowing your condition is the first step. It’s vital to have a clear understanding of your diagnosis and what the future might hold.
Evaluating Surgical Alternatives
After understanding your condition, look into the surgery options. Ask these questions:
- What surgical options are there for my condition?
- What are the benefits and risks of each surgery option?
- Are there less invasive surgery options available?
- How will the surgery affect my recovery time and results?
Looking into the surgery options helps you know what to expect. This way, you can make a better choice for your treatment.
Surgeon Experience and Hospital Volume
Your surgeon’s experience and the hospital’s volume are important. You might ask:
- How many times has my surgeon done this procedure?
- What are the success and complication rates for my surgeon’s past patients?
- How does the hospital’s cardiac surgery volume affect my care and results?
- Are there extra support staff or services for me during recovery?
Choosing a surgeon with the right experience and a hospital with a lot of cardiac surgeries can greatly improve your outcomes and recovery.
By asking these questions and understanding your condition, the surgery options, and your surgeon’s experience, you can make a well-informed choice about your cardiac surgery. We’re here to support you every step of the way.
Conclusion
The field of cardiac surgery is changing fast. New, less invasive methods are coming up. These methods offer many benefits to patients. Traditional open-heart surgery is now joined by new, better ways. These new methods cut down on surgery damage. They help patients recover faster and do better overall. We’re seeing a big change in cardiac surgery. Now, we have MIDCAB, robotic surgery, and other new procedures. These changes are making care better and giving more options for complex heart problems. As cardiac surgery keeps changing, less invasive methods will be key. These new ways will help make care better for everyone. Healthcare will focus more on what patients need, improving lives all over the world.
FAQ
What is a triple bypass surgery?
Triple bypass surgery is a procedure to treat heart disease. It involves bypassing blocked arteries with grafts. These grafts usually come from the patient’s own veins or arteries.
What are the less invasive alternatives to open-heart surgery?
There are several alternatives to open-heart surgery. These include Minimally Invasive Cardiac Surgery (MICS), robotic-assisted cardiac surgery, and transcatheter procedures. Examples include Transcatheter Aortic Valve Implantation (TAVI) and hybrid revascularization options.
What is Minimally Invasive Direct Coronary Artery Bypass (MIDCAB)?
MIDCAB is a type of MICS. It involves bypassing coronary arteries through smaller incisions. This approach is less invasive and doesn’t always require cardiopulmonary bypass.
How long is the recovery time for triple bypass surgery?
Recovery times for triple bypass surgery vary. Patients usually spend several days in the hospital. They then take weeks to months to fully recover at home. Less invasive options might have shorter recovery times.
What are the benefits of robotic-assisted cardiac surgery?
Robotic-assisted cardiac surgery offers many benefits. It allows for precise surgery with smaller incisions. This reduces trauma to the patient and the risk of complications. It also might lead to shorter recovery times compared to traditional surgery.
What is the ELANA Heart Bypass System?
The ELANA Heart Bypass System is a new technology. It enables sutureless connections for coronary artery bypass grafting on a beating heart. This could make CABG procedures simpler and safer.
Are there any cost differences between traditional and minimally invasive cardiac surgery?
Cardiac surgery costs vary based on the procedure, location, and insurance. Minimally invasive procedures might have higher initial costs due to technology. But, they can reduce long-term healthcare costs by minimizing complications and shortening recovery times.
How do I know if I’m a candidate for less invasive cardiac surgery?
Suitability for less invasive cardiac surgery depends on several factors. These include the cardiac condition, anatomical considerations, comorbidities, age, and frailty assessment. A cardiac surgeon will evaluate these to determine the best surgical approach.
What questions should I ask my cardiac surgeon?
When talking to a cardiac surgeon, ask about your condition, surgical alternatives, and the surgeon’s experience. Also, ask about hospital volume and what to expect during recovery. This helps make an informed decision.
What is the future of cardiac surgery?
Cardiac surgery’s future looks promising. Emerging technologies like artificial intelligence and next-generation robotic systems will improve precision and safety. Bioengineered vessels and tissues will also enhance surgical outcomes.
How dangerous is triple bypass heart surgery?
Triple bypass heart surgery carries risks and complications. But, advancements in techniques have improved outcomes. Discussing the risks and benefits with a cardiac surgeon is essential.
What are the clinical outcomes of MICS compared to traditional CABG?
Studies from 2020 to 2025 show MICS can offer better outcomes than traditional CABG. MICS may have higher graft patency rates, survival rates, and quality of life. It also has the advantage of being less invasive.
References
National Center for Biotechnology Information. Evidence-Based Medical Insight. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC12734057/