Episode 25: Early diagnosis and personalization in medicine

00:00:10: Welcome to another episode of PhD Billion Beyond The Lab.

00:00:14: Today we will explore the topic of early diagnosis and personalization in medicine, a field that is becoming increasingly central.

00:00:25: In this episode, together with Elisa, Lorenzo, Giovanni and myself we will look at the topic from different research perspectives showing how biomedical innovation can help us move a one-size fits all approach towards more precise individualized and patient centered medicine.

00:00:42: Let's begin!

00:00:51: And let me introduce Elisa's project that takes us into the fascinating connection between a nervous system and an immune system, exploring how this planktonic anti-inflammatory reflex could open new paths toward more precise and personalized therapies.

00:01:07: We're going to explore our fascinating biological mechanism which highlights close relationship with the nervous system or immune system – the inflammatory weakness.

00:01:17: Whenever a virus of a bacterium enters your body, the immune system is first line of defense!

00:01:23: salide immune cells detect these pathogens through receptors known as tolact receptor.

00:01:29: Once activated, this receptors trigger inflammation a critical process that helps eliminate harmful microorganisms and protect the body from infection.

00:01:39: however while it is essential for fighting disease excessive or prolonged inflammation can damage healthy tissue and contribute to a wide range of chronic illnesses.

00:01:50: For this reason, the body has evolved sophisticated mechanisms to keep inflammation under control.

00:01:57: One of these is known as Diplomatary Reflex a nervous reflex that consists too many two main components A sensory pathway that detects changes in your body and send information through brain The central nervous system where the brain processes disinformation and activates an error response And the effector pathway that generates the response.

00:02:20: this response is mediated by splanthilic anti-inflammatory pathway.

00:02:25: This pathway is composed of sympathetic nerves that connect the central nervous system with server organs, involving immune relations such as liver, spleen, lung, lungs or digestive tract.

00:02:38: For the past decade researchers have demonstrated that these pathways plays a crucial role in controlling inflammation.

00:02:46: In animal studies when splan headache nerves are surgically severed The inflammatory response becomes significantly stronger.

00:02:54: Specifically, there is an increase in the production of tumor necrosis factor alpha TNF a major pro-inflammatory cytokines and a decrease in interlucentenine, an important anti-inflammatories cytokine.

00:03:08: More recent research have revealed that the sphagnic antiflamatory pathway appears to regulate these two cytokins through separated mechanisms.

00:03:18: Sympathetic fibers are that innervate the adrenal gland are primarily responsible for increasing interlocking time production.

00:03:25: Why?

00:03:26: Fibers that project to the spleen and other abdominal organs, are mainly responsible for suppressing the TNS production.

00:03:34: When these sympathetic nerves become activated they release several secret nailing molecules.

00:03:40: Among them most important are noradrenaline and neuropyde called Y. At the same time adrenaline releases adrenally into the bloodstream.

00:03:49: These molecules are believed to communicate directly with the immune cells.

00:03:54: Narodrenaline and adrenaline exert a half-act mainly through beta two adrenergy receptor, known as Beta Two Adrenaline Receptor while MPY acts primarily through MPYone receptor.

00:04:08: The research group at an University of Bologna is based on these premises.

00:04:15: The goal of the study is to determine whether beta-II adrenoreceptor and MPY-I receptor are responsible for merely the anti-inflammatory effect on the splunknet antiframatory.

00:04:26: In this study, researchers studied four groups of mice – a well tied group, a Beta II Adrenal Receptor knockout group, an MPY I receptor knock out group ,and double knocked out

00:04:39: group

00:04:39: .

00:04:40: The mice will be exposed at scores to an immune challenge, use lipopolysacal common known as LPS.

00:04:50: A component of the odor membrane of non-gram negative bacteria and it is widely used in research to induce a controlled inflammatory response.

00:05:06: Why does this research important?

00:05:09: This is associated with abnormal immune responses becoming increasingly common worldwide.

00:05:15: These include chronic inflammatory conditions such as arbremotorid arthritis, inflammatory bowel disease and many other other resources in which excessive inflammation contributes to tissue damage and disease progression.

00:05:31: Understanding how the nervous system naturally controls inflammation could provide valuable insight for development of a new therapeutic approach.

00:05:40: Rather than simply suppressing symptoms, fewer treatments might be designed to target the narrow pathways that regulate immune activity.

00:05:49: At the same time a better understanding of these mechanisms could also be beneficial in situations where the immune system is too weak and needs to be announced such as due to certain infection or state-of-the-art immune suppression.

00:06:04: In conclusion, this project represents an important example of fundamental research aimed at understanding how the nervous immune system communicates.

00:06:13: Although its mediate goal is to cover biological mechanisms underlining inflammatory effects, the knowledge gain could ultimately contribute to the development of innovative treatments for a wide range of inflammatory and immune-related diseases.

00:06:30: studying how nerves and immune cells work together could reveal one of the most intricate and important communication effects in a body.

00:06:40: And that would be key to future advance in my study.

00:06:54: Now let's move from biological regulatory pathways, two diagnosis.

00:06:59: Lorenzo Schwarz brings us to another key challenge in personalized medicine, identifying high-risk patients earlier before disease progression becomes clinically evident.

00:07:11: Hello everyone

00:07:12: my name is

00:07:12: Lorenz Solani.

00:07:13: I'm a PhD candidate in biochemical and neuromotor sciences at the University of Bologna.

00:07:19: today i would like to present my research project which focuses on improving the surveillance.

00:07:26: Hepatocellular carcinoma is the most common primary liver cancer and represents a major global health challenge.

00:07:38: In fact, it accounts for about ninety percent of all primary liver cancers And this one of the leading causes or cancer related death were wild.

00:07:48: Most cases develop in patients with underlying cirrhosis A chronic condition characterized by progressive liver fibrosis an impaired liver function.

00:07:57: One of the major problems with HCC is that it's usually asymptomatic in its early stages.

00:08:04: As a result, many patients are diagnosed only when the diseases already advanced and treatment options are limited.

00:08:11: Current surveillance programs generally recommend liver ultrasound sometimes combined with alpha-fatal protein measurement every six months for all patients considered at risk.

00:08:22: However not all patient with cirrhosis have same risks of developing liver cancer.

00:08:28: Moreover, this risk can change over time depending on several factors such as the underlying liver disease treatment response lifestyle modifications and disease progression.

00:08:39: Therefore one side's fit all surveillance strategy may not be most effective approach.

00:08:47: The overall aim of my PhD is to identify novel criteria that can help personalize surveillance strategies, allowing us better identify patients at highest risk and potentially improve early cancer detection.

00:09:03: My project is structured into four main tasks.

00:09:06: the first task focuses on understanding how the epidemiology of liver cancer.

00:09:14: Historically, hepatitis B and hepatitis C infections were the main causes of cirrhosis in HCC.

00:09:21: Thanks to vaccination programs and highly effective antiviral therapies The burden on viral liver disease is decreasing.

00:09:29: At that same time we are observing a rapid increase in metabolic dysfunction associated with satotic liver diseases known as meso-D and alkyl related liver disease or ALD Using the Italian liver cancer Thalica database, one of the largest multi-center databases in Europe.

00:09:46: I will investigate how these epidemiological changes are influencing the incidents and occur...and the recurrence of HCC.

00:09:55: In parallel i will conduct a perspective study in patients with non virus erosies to identify clinical subgroups that may benefit from personalized surveillance strategies.

00:10:06: The second task examines the impact of removing the underlying cause of liver disease on liver cancer recurrence.

00:10:14: For example, in patients with hepatitis C modern antiviral therapies can completely eradicate a virus.

00:10:21: however it is not still fully understood how viral eradication affects long-term risk of HCC recurrence after curative treatments such as surgical resection or ablation.

00:10:34: Through analysis of the Italica database, I will evaluate whether successful antiviral treatment modifies recurrence patterns and whether these patients behave differently from individuals with non-viral liver diseases such as muscle D or alkyl related liver disease.

00:10:50: The third task focuses on a concept known has recompensation.

00:10:55: Traditionally decompensated cirrhosis was considered an irreversible condition.

00:11:00: More recent evidence suggests that some patients can partially recover from liver function if the underlying cause is effectively treated.

00:11:11: This process is called recompensation, in collaboration with the Medical University of Vienna where I worked on my residency final dissertation i will investigate our zoological treatment and recompensation influence prognosis in patients with HCC.

00:11:27: The goal is to identify patients whose liver function can improve and understand how this affects survival in clinical outcomes.

00:11:35: Finally, the fourth task explores the role of Alcon's consumption patterns.

00:11:40: frailty and immune dysfunctional development of liver cancer.

00:11:44: Impatience with alcohol-related liver disease factors such as the amount of alcohol consumed, long term abstinence, physical frailty and sarcopenia may significantly influence cancer risk and disease progression.

00:11:58: Additionally I will study specific immune markers including PD-I and CTLA-IV which are involved in immune regulation that may contribute to liver casinos' illnesses.

00:12:09: By integrated clinical, behavioral and biological data the ultimate objective is to develop predictive models capable of stratifying patients according their individual risk.

00:12:20: In conclusion my research aims contribute a more personalized approach to liver cancer surveillance By better understanding how epidemiological changes, ethylogical treatments disease dynamics and biological markers influence cancer risk.

00:12:35: we hope to identify patients who require more intensive monitoring while reducing a necessary procedure in lower-risk individuals.

00:12:43: Ultimately this could lead to an earlier diagnosis of more effective treatment and improved outcomes for patients living with cirrhosis.

00:12:51: Thank you for listening!

00:12:54: highlighted how clinical and biological risk factors can be combined to personalize surveillance, and improve early cancer detection.

00:13:03: From this perspective of individualized prediction we now move from my project where the same logic of personalization is applied to surgery defining patient-specific alignment targets in adoration spinal deformity correction.

00:13:25: My PhD project focuses on adolescent spinal deformities and in particular, how we can make spinal surgery more precise & personalized.

00:13:34: To explain the idea let me start from a simple concept.

00:13:38: When we look at person's side The spine is not straight.

00:13:42: It has physiological curves.

00:13:44: The thoracic spine is normally kyphotic And the lumbar spine is normaly lordotic has its physiological version, in other words it's societal orientation.

00:13:55: These curves are not random.

00:13:57: they're part of a complex balance that allow us to stand walk and use as little energy as possible.

00:14:05: In adolatian spinel deformities the spine is typically described as three dimensional deformity involving vertebral translation rotation and west deformity.

00:14:18: The deformity is not limited to the coronal plane, but it also involves transverse and sagittal plane.

00:14:25: Surgeons have traditionally focused mainly on the coronial plane meaning the frontal x-ray where we measure the cob angle and on actual plane meaning vertebral rotation and rib hump.

00:14:36: these are very important because they largely determine the visible deformity.

00:14:41: however The sagittal plane, the side view of the spine has often been underestimated.

00:14:47: This is a problem because sagittale alignment is strongly related to how the spine works over time.

00:14:53: If the spine is corrected in the frontal plane but remains poorly balanced from the site ,the patient may develop persistent compensatory mechanism back pain and early degenerative changes in the infused segment.

00:15:08: This is especially important in adolescence because these patients are often operated between eleven and eighteen years of age, And ideally the surgical correction should last for the rest of their lives.

00:15:20: So this question not only can we correct a curve but also can we leave patient with spine as closed to his or her physiological alignment?

00:15:32: And that's where research gap begins!

00:15:35: In adult spinal deformity surgery Surgeons already use several tools and formulas to define SUZET alignment targets.

00:15:43: These targets help in planning the operation, reducing risk of mechanical complication within a short period after surgery typically two years.

00:15:53: But adolescents are not simply small adults, and at the moment we do not have clear adolescent-specific sagittal alignment targets.

00:16:02: This means that in many cases we cannot precisely define what the ideal sagittale profile should be for a specific young patient.

00:16:11: Without this information it is difficult to plan the correction before surgery And also difficult to judge after surgery whether the sagittales result is truly physiological.

00:16:22: The main idea of my PhD project is to fill this research gap by defining normative sagittal alignment targets in healthy adolescence, and then using these targets to improve personalized preoperative planning in Adolescent spinal deformity surgery.

00:16:38: the first step is to start from healthy subjects.

00:16:41: we collected biplanned standing full spine X-ray of adolescent without Spinal or Lower Lymphatology.

00:16:48: The goal was to understand what normal sagittal alignment looks like in this age group.

00:16:54: We focused first on the relationship between pelvic incidence and sacral slope.

00:16:59: Pelvic incidence, or PI is a morphological parameter.

00:17:03: In simple terms it describes shape of pelvis And sacral's slope, or SS, describe how inclined upper part of the sacrum.

00:17:14: These two parameters are important because the pelvis acts like a foundation of the spine.

00:17:20: If we want to understand ideal orientation, then we need to understand the ideal pelvic version.

00:17:26: In first paper on this project we analyzed relationship between PI and SS in healthy adolescence.

00:17:32: We tested different mathematical models including linear polynomial and logarithmic models And also tested A-to-derived model.

00:17:41: The key finding was that models developed from adult population are less reliable when applied to an adolescent and tend to underestimate sacral slope.

00:17:50: From a practical point of view, the most useful result for this paper is simple formula Ideal Sacral Slope Equals Point Sixty-One.

00:17:59: Multiplied by PI plus eleven.

00:18:02: This formula can help the surgeon estimate the ideal pelvic version of an adulation patient, and in other words it gives us a first personalized target where the pelvis would probably be if the patient did not have compensatory mechanisms related to spinal deformity.

00:18:20: But this first result also raises second important question Can we always consider PI stable during growth?

00:18:29: In our second study, based on the one hundred and sixty-six patient with serial full spinaxase we found that PI significantly increased during growth from about forty five degrees to about forty eight degrees.

00:18:42: But this increase was mainly observed in very skeletal immature patients especially before and around the closure of the trieradiate cartilage.

00:18:52: This means when planning treatment for a growing patient should not only ask What is the pelvic incidence today?

00:18:59: We should ask how likely it is to change during remaining growth.

00:19:05: And after these first two steps, The project will expand to other sagittal element targets.

00:19:11: The next objectives are to define adolescent-specific relationship between PI and lumbar lordosis, thoracic kyphosis, global spinopelvic balance & deposition of transition point between spinal curves.

00:19:27: of the project is to build a more complete map of physiological societal alignment in adolescence.

00:19:33: The projects will then move from description, application and targets developed for healthy adolescents will be externally validated and implemented into standardised digital preparative planning protocol.

00:19:46: This protocol would first be tested on retrospective cases to evaluate its feasibility.

00:19:53: In the prospective phase it will be applied to patient undergoing surgical correction of AIS, comparing the planned sagittal alignment with the actual postoperative result.

00:20:05: in summary my PhD project tries to bring the logic of precision medicine into Adolescent spinal deformity surgery.

00:20:13: The idea is to move from a general correction of the deformity To a patient specific reconstruction of physiological sagittale alignment.

00:20:22: for me The most fascinating aspect is that this project starts from a very simple clinical question.

00:20:28: What's normal for these patients?

00:20:33: And how can we make surgery not only corrective, but also durable in the whole life of young people like us?

00:20:48: We now move to Giovanni's Project which explores another important aspect of spinal surgery and shows how research continues to improve outcomes for patient with spinal disorders.

00:20:59: Imagine your spine like the frame of a building.

00:21:03: If you fix the ground floor but make it too stiff, The floor right above can collapse from extra stress.

00:21:11: That's what happens in the spine surgery And its' problem behind my PhD project.

00:21:18: Welcome to this episode.

00:21:20: Let start with the background.

00:21:22: As people get older more and more of them develop spying deformity the spine curves or shifts out of alignment.

00:21:33: This is very common after age sixty five and it can seriously affect quality life, most patients with this

00:21:42: problem

00:21:44: eventually need surgery but this surgery is tough.

00:21:49: Complications happen in about thirty-five percent cases.

00:21:54: Patients are often elderly with an older health problems.

00:21:59: So, a long operation with lot of blood loss has even more risk.

00:22:05: Beside these infections the most common complications are mechanical.

00:22:11: Scuse, Camelouser, Rose Brack and the vertebra just above the surgeon can fail.

00:22:20: This is called PJK & PJF.

00:22:23: Think off it as the floor above giving away.

00:22:28: Why does this happen?

00:22:30: Standard open surgery uses a screw in almost every vertebra, which makes the construct very rigid.

00:22:39: That rigid puts a lot of stress on the vertebra right above it The one without protection.

00:22:49: This is why doctors are now exploring minimally invasive techniques fewer screws less muscle damage and more flexibly exactly where it's in its most, in the upper back.

00:23:05: And that is a gap I want to fill!

00:23:07: The idea behind these minimally invasive techniques sounds great but we still don't have strong clinical evidence.

00:23:16: Real patients' proper comparison Proving that they actually lived the fewer complications.

00:23:25: my project aimed at providing that evidence.

00:23:29: Here is the method I have chosen.

00:23:31: I want to test a minimally invasive bridging technique instead of placing a screw in every vertebra We use fascia rot that run from the lower spine Where we correct the main curve all The way up today upper back held by just two or three pairs of screws.

00:23:54: think off a bridge.

00:23:55: Instead of supporting every single point, you anchor it firmly at just a few spots and let the rest flex naturally.

00:24:06: This means less muscle damage, a shorter operation... And this is my main hypothesis, fewer mechanical complications like PJK & PJF.

00:24:16: I also build a lab model using cadaver spines to physically measure and confirms that this technique really does reduce cells compared to the traditional rigid one.

00:24:30: Now I will let the project work, i compare two groups of patients One treated with a traditional open surgery ,one with minimum invasive techniques.

00:24:40: All patients get careful correction in their spine alignment Guided by imaging and planning software.

00:24:48: I followed them before surgery And they are at six and three months checking closely from complication.

00:24:57: As for the timeline, The first three months

00:25:01: are

00:25:01: for reviewing the literature and getting ethical approval.

00:25:11: From month six to eight.

00:25:14: I collected data and performed surgery.

00:25:19: So where could this lead?

00:25:22: if my hypothesis is right?

00:25:24: This research would give surgeons a safer less invasive option for treating spine deformity in odors with fewer serious complications, fewer repeated surgeries and better outcomes for patients who are often already fragile.

00:25:43: And the lab model I built could help other researchers improve this technique even further.

00:25:50: And with that, we wrap up today's episode.

00:25:53: Thank you for joining us on this journey!

00:25:55: Staying tuned for more episodes of Ph.D.

00:25:58: BM Beyond the Lab Until next time.