Naser's Medical Education

What are Disorders of Gut-Brain Interaction (DGBI)?

DGBIs are a group of chronic functional gastrointestinal disorders. That means that they are not structural or organic in nature, meaning that there is no visible or structural abnormality in the gastrointestinal tract. Instead, the symptoms are believed to arise from a complex interplay between the gut and the brain, involving things such as altered gut motility, increased sensitivity to pain, and the brain processing of those signals from the gut. They are characterized by a wide range of symptoms related to digestion and bowel function but lack visible disease in testing.

Key Aspects of DGBIs:

Functional, Not Structural: This is the core of the definition. In DGBIs, standard medical tests (like endoscopies, imaging) don't reveal any identifiable abnormalities in the digestive system. The issue isn't with the anatomy or tissue itself but rather the functionality and communication within the system.

Gut-Brain Axis Dysfunction: The symptoms are thought to be due to disruptions in the gut-brain axis (or "microbiome-gut-brain axis"), a complex two-way communication network linking the brain and the gastrointestinal tract.

Varied Symptoms: DGBIs can present with a range of symptoms, including:

Abdominal pain (can be recurrent, chronic, or intermittent)

Bloating

Gas

Changes in bowel habits (constipation, diarrhea, or alternating patterns)

Nausea

Vomiting

Feeling of incomplete bowel movement

Common in Children: DGBIs are quite common in children and adolescents.

Not a Single Disease: DGBI is an umbrella term encompassing various specific conditions, such as:

Irritable Bowel Syndrome (IBS): The most well-known example of a DGBI.

Functional Abdominal Pain (FAP): Chronic or recurring abdominal pain without a structural cause.

Functional Dyspepsia (FD): Upper abdominal discomfort without ulcers or other identifiable pathology.

Functional Constipation: Constipation without a clear underlying organic reason.

Cyclic Vomiting Syndrome: Episodes of severe nausea and vomiting.

Diagnosis: Diagnosis often relies on detailed symptom evaluation, clinical history, and ruling out other conditions with standard medical testing (ex. endoscopies, imaging, and biopsies). The "Rome criteria" are commonly used to standardize diagnostic criteria for these conditions.

Why is DGBI Relevant in the "Practice Points" about H. pylori?

DGBI is More Likely than H. pylori in Recurrent Abdominal Pain (No Alarm Symptoms): The text explicitly states that if a child has recurrent abdominal pain without accompanying "alarm" signs (like weight loss, vomiting, blood in stool, fevers, etc.), they are much more likely to have a DGBI than an issue arising directly from H. pylori.

H. pylori Eradication is Not Helpful: The guidelines note that in cases of recurrent abdominal pain that fit the DGBI description, even if H. pylori is found in testing, its eradication is not likely to improve their symptoms unless there are also ulcers or erosions, and, therefore, should not be the standard of care.

Avoid Unnecessary Testing and Anxiety: Because testing for H. pylori when DGBI is suspected is not likely to benefit the patient, the guidelines discourage testing. A positive result can lead to unnecessary anxiety, treatments, and procedures.

In summary, DGBIs represent a group of functional gastrointestinal disorders arising from complex communication issues between the brain and gut. It's important to understand that H. pylori and DGBI are different entities. In children with recurrent abdominal pain, it's crucial to consider DGBIs as the more probable cause (when no alarming symptoms are present) and to avoid unnecessary H. pylori testing and treatment in these cases. The "practice points" highlight the need for a nuanced and targeted approach when dealing with pediatric gastrointestinal complaints.

H. pylori Does Not Usually Cause Symptoms in Children Without Underlying Issues: The current understanding is that H. pylori infection alone doesn't typically lead to noticeable symptoms in children unless there are pre-existing conditions like peptic ulcers (PUD) or erosions in the stomach or duodenum.

"Test and Treat" Strategy Not Recommended: Due to the above, routinely performing noninvasive tests for H. pylori infection is not advised. There's no strong scientific backing for a "test and treat" approach in children without symptoms and/or underlying conditions.

Recurrent Abdominal Pain Likely Due to DGBI: Children experiencing recurrent abdominal pain without accompanying "alarm" signs or symptoms (as categorized by Rome criteria 11) are more likely to have a Disorders of Gut-Brain Interaction (DGBI), which is not directly related to H. pylori.

H. pylori Eradication Not Helpful for Recurrent Abdominal Pain (Without Ulcers): If endoscopy reveals no ulcers or erosions in children with recurrent abdominal pain, eradicating H. pylori has not been proven to alleviate symptoms. Therefore, H. pylori treatment in this scenario is not favored over standard care for DGBI.

Avoid Unnecessary Testing in DGBI Cases: Routine noninvasive H. pylori testing in children with suspected DGBI should be avoided. A positive result can lead to undue anxiety for the child and family, and may prompt an unneeded endoscopy.

Biopsies Should Be Taken During Endoscopy with Visible Issues: When erosions, ulcers, or scarring are observed during an upper endoscopy, biopsies are recommended to identify the presence of H. pylori.

H. pylori is Treatable but Not Only Cause: H. pylori is only one of several possible reasons for erosions, ulceration in children. While it is a treatable condition, it is not the sole underlying cause of such gastrointestinal issues in kids.

H. pylori Eradication Prevents Ulcer Recurrence: If H. pylori is present and treated, it can help prevent ulcer recurrence in children.

Biopsies Should Guide Treatment: When performing endoscopy, biopsies for H. pylori diagnosis should only be done if the plan is to treat the infection upon confirmation. There is no need to biopsy for H. pylori if you are not going to treat.

Detailed Breakdown:

No Routine Testing:

The central point is that simply having H. pylori infection doesn't mean a child will experience symptoms.

Noninvasive tests are deemed unnecessary if PUD or erosions aren't present.

This contradicts a "find and eradicate" approach, suggesting that overtreatment may occur using that method.

DGBI and H. Pylori:

Children with non-alarm abdominal pain more often have DGBI.

The cause of DGBI is independent of H. pylori presence.

Eradication is NOT Standard Care for Recurrent Abdominal Pain:

It’s crucial to understand that if no damage (ulcers, erosions) is visible on endoscopy, clearing H. pylori is not a standard recommendation.

The treatment is not shown to improve symptoms.

Avoid Anxiety with Testing:

Testing for H. pylori in children suspected to have DGBI is not generally recommended due to the possibility of anxiety and more medical procedures.

The recommendation implies a “do no harm” approach and consideration of cost/benefit.

Biopsy when Problems are Seen:

Biopsies during an upper endoscopy are important if erosions, ulcers, or scarring are present.

These are key for diagnosing H. pylori in a patient that may require treatment.

Treatable and a Common Cause:

H. pylori is noted to be only one of multiple possibilities causing erosions/ulcerations in children.

Eradicating H. pylori can treat these conditions and prevent future ulceration.

Diagnosis Should Lead to Action:

Biopsy for diagnosis of H. pylori is unnecessary if treatment is not going to follow.

There is no point in diagnosis unless a treatment is going to be offered.

Oxygen toxicity
Oxygen gas can be toxic at elevated partial pressures, leading to convulsions and other health problems. Oxygen toxicity usually begins to occur at partial pressures more than 50 kilopascals (kPa), equal to about 50% oxygen composition at standard pressure or 2.5 times the normal sea-level O 2 partial pressure of about 21 kPa. This is not a problem except for patients on mechanical ventilators, since gas supplied through oxygen masks in medical applications is typically composed of only 30–50% O2 by volume (about 30 kPa at standard pressure). At one time, premature babies were placed in incubators containing O2-rich air, but this practice was discontinued after some babies were blinded by the oxygen content being too high.
Breathing pure O2 in space applications, such as in some modern space suits, or in early spacecraft such as Apollo, causes no damage due to the low total pressures used. In the case of spacesuits, the O2 partial pressure in the breathing gas is, in general, about 30 kPa (1.4 times normal), and the resulting O2 partial pressure in the astronaut's arterial blood is only marginally more than normal sea-level O2 partial pressure.
Oxygen toxicity to the lungs and central nervous system can also occur in deep scuba diving and surface-supplied diving. Prolonged breathing of an air mixture with an O2 partial pressure more than 60 kPa can eventually lead to permanent pulmonary fibrosis. Exposure to an O2 partial pressure greater than 160 kPa (about 1.6 atm) may lead to convulsions (normally fatal for divers). Acute oxygen toxicity (causing seizures, its most feared effect for divers) can occur by breathing an air mixture with 21% O2 at 66 m (217 ft) or more of depth; the same thing can occur by breathing 100% O2 at only 6 m (20 ft).

Delgocitinib, a janus kinase (JAK) inhibitor, is being developed by Japan Tobacco for the treatment of autoimmune disorders and hypersensitivity, including inflammatory skin conditions. The JAK family of tyrosine kinases plays an important role in mediating the biological effects of several inflammatory cytokines, e.g. IL-4, IL-13 and IL-31, which are elevated in patients with atopic dermatitis. Delgocitinib inhibits all members of the JAK family [JAK1, JAK2, JAK3 and tyrosine kinase 2]. Topical delgocitinib (Corectim®) is approved in Japan for the treatment of atopic dermatitis.

Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases.

Janus kinase (JAK) inhibitors :
1. Abrocitinib
2. Baricitinib
3. Delgocitinib
4. Fedratinib
5. Filgotinib
6. Oclacitinib
7. Pacritinib
8. Peficitinib
9. Ruxolitinib
10. Tofacitinib
11. Upadacitinib

Always look at lebrikizumab-lbkz injection solution before injecting it. Check that the expiration date has not passed and that the liquid is clear and colorless or pale yellow or brown. Do not use a syringe if it is expired or if the liquid is cloudy, discolored or contains large or colored particles.

EBGLYSS = lebrikizumab-lbkz
EBGLYSS is a prescription medicine used to treat adults and children 12 years of age and older who weigh at least 88 pounds (40kg) with moderate-to-severe eczema (atopic dermatitis) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. EBGLYSS can be used with or without topical corticosteroids.
It is not known if EBGLYSS is safe and effective in children less than 12 years of age or in children 12 years to less than 18 years of age who weigh less than 88 pounds (40 kg).
is now approved for adults and children 12 years or older who have moderate-to-severe atopic dermatitis. Atopic dermatitis, or eczema, is characterized by itchy skin most often located on the arms or behind the knees, but which can appear anywhere.
Lebrikizumab-lbkz injection is used to treat moderate to severe atopic dermatitis (a type of eczema; a skin disease that causes the skin to be dry and itchy and to sometimes develop red, scaly rashes) in adults and children age 12 years and older who cannot use topical medications for their condition or who have not responded to topical medications. Lebrikizumab-lbkz is in a class of medications called interleukin-13 receptor inhibitors. It works by blocking the activity of interleukin-13, a substance in the body that causes inflammation.
How should this medicine be used?
Lebrikizumab-lbkz injection comes as a solution (liquid) to be injected subcutaneously (under the skin). It is usually given as two injections every 2 weeks for the first two doses, followed by once injection every 2 weeks after the first two doses for 16 weeks, and then may be continued as one injection every 4 weeks after that. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use lebrikizumab-lbkz injection exactly as directed. Do not inject more or less of it or inject it more often than prescribed by your doctor.
You may receive your first dose of lebrikizumab-lbkz injection in your doctor's office. After that, you may be able to inject the medication yourself at home or have a friend or relative perform the injections. If you will be injecting lebrikizumab-lbkz injection subcutaneously by yourself at home or having a friend or relative inject the medication for you, your doctor will show you or the person who will be injecting the medication how to inject it. Read the written instructions for use that come with lebrikizumab-lbkz injection before you inject the medication.
Lebrikizumab-lbkz injection comes in prefilled syringes and prefilled pens. Use each syringe and pen only once and inject all the solution in the syringe or pen. Do not reuse lebrikizumab-lbkz pre-filled syringes and do not recap the syringes after use. Dispose of used syringes and pens in a puncture-resistant container. Talk to your doctor or pharmacist about how to dispose of the puncture-resistant container.
You can inject lebrikizumab-lbkz injection on the front of your thighs (upper leg), at least 2 inches above your knee and 2 inches below your groin, or abdomen (stomach) except your navel (belly button) and the area 2 inches (5 centimeters) around it. If someone else is giving you the injection, the back of the upper arm may also be used. To reduce the chances of soreness or redness, use a different injection site for each injection. Do not inject the medication into damaged, bruised, scarred or tender skin.
If you are using a prefilled syringe or prefilled pen that has been refrigerated, place the syringe or pen on a flat surface without removing the needle cap and allow it warm to room temperature for 45 minutes before you are ready to inject the medication. Do not try to warm the medication by heating it in a microwave, placing it in hot water, or through any other method.
Do not shake a syringe or pen that contains lebrikizumab-lbkz injection.