In this retrospective study with 56 patients with autism spectrum disorder (ASD) and 123 controls underwent colonic manometry (CM). Key findings:
The rate of abnormal CM findings between ASD and matched controls (24% vs 20%, P = 0.78) did not differ significantly
The authors noted that higher rates of abnormal CM with duration of constipation and with soiling in children with ASD. However, “even in the minority of cases with abnormal colonic motility, chronic stool retention due to functional constipation over time likely caused impaired motility in the majority of these cases. In 6 of the 8 ASD cases with abnormal CM finding, impaired motility was isolated to the distal colon while normal motility occurred in the proximal colon.”
My take: In this highly-selected group of patients with ASD from specialized motility centers, only 2 had abnormal colonic motility affecting the entire colon. Overall, patients with ASD did NOT have higher rates of abnormal CM studies. Hence, for most children with ASD, CM has little value.
This was a very large retrospective study (with more than 90 authors) with 1433 children.
Only 40.3% of children reach adulthood with their native liver; 54.4% had their native liver at 10 years of life
“It is noteworthy that bile duct paucity was reported in only 65% of liver biopsies performed during the first 3 months of life, the period during which there are diagnostic challenges with distinguishing ALGS from syndromic BA.” Thus, with a liver biopsy, there is a significant risk of misdiagnosis
The all‐cause mortality rate was 8.5%
The total bilirubin level between 6-12 months of life had significant predictive value. In the associated editorial: “The authors reported that 79% of patients with median TB of <5.0 mg/dL..reached adulthood with their native livers, whereas only 31.6% and 18.2% of patients with median TB levels between” 5-10 and >10 mg/dL survived into adulthood with their native livers.
The editorial makes the point that this data will be helpful and ongoing studies will be needed to determine the effectiveness of novel treatments (e.g. IBAT inhibitors)
My take: This is a very useful study in understanding the long term outcomes of Alagille syndrome.
At our center, we are fortunate to work with an immune dysregulation clinic (Dr. Shanmuganathan Chandrakasan, Dr. Taylor Fitch) that helps sort out patients with inflammatory bowel disease with underlying monogenetic disorders. This is very important as specific treatments, including hematopoietic stem cell transplants (HCST), may be needed. The likelihood of an underlying monogenetic disorder is much more frequent in the VEO population. A recent talk on this topic by Taylor Fitch was given to our group. Here are some of the slides:
Generally, about 2% of those older than 6 years of age have monogenetic disorders, but it is much higher in those with severe or refractory disease.
This slide shows six major categories of immune defects.
This slide shows the high frequency of extraintestinal manifestations in patients with monogenetic disorders, particularly recurrent infections, skin/hair abnormalities, and autoimmunity. Perianal disease is also frequent in this population.
In the discussion, it was noted that DHR testing is often unreliable, especially if the specimen is not run promptly.
My take: I have had several patients with IBD/immune dysregulation, including a patient with CTLA4 and a patient with TTC7A. Making these diagnoses led to specific treatment recommendations. The patient with CTLA4 is doing well with abatacept therapy.
For those in Atlanta, a referral can be made via EPIC order and/or via contact with immune dysregulation team members. Epic order:
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
S Corlette, CH Monahan. NEJM 2022; 387: 2297-2300.
There are a lot of problems with the U.S. Healthcare system. This article focuses on healthcare coverage.
The U.S. has a patchwork system of health insurance coverage “in which people’s access to services and level of financial protection — not to mention whether they have coverage at all — varies depending on their birthplace, age, job, income, location, and health status…Many people in the United States work for employers that do not offer insurance or do not sufficiently subsidize it, making it unaffordable for lower-income workers.”
“No one would purposefully design the system we have. Unlike many of our peer countries, the United States has never had a centrally planned, cohesive system to help its citizens obtain and pay for health care services. Ours is a system built on happenstance, unintended consequences, and gap filling…”
“The United States has made sporadic efforts at creating a national system of health coverage…These efforts all foundered in the face of opposition from health insurers, the American Medical Association, and other health industry stakeholders, as well as concerns about the proposals’ costs.”
“Americans who have “good” insurance today may be surprised to learn that they, too, are vulnerable. Underinsurance is a growing problem, as fewer and fewer Americans are able to afford their share of costs. Premiums and deductibles continue to increase as health care costs rise, straining the budgets of families, employers, and state and federal governments. Unless and until policymakers curtail the power of health care monopolies to drive up costs and do more to limit health care prices across our array of public and private coverage systems, virtually everyone’s access to affordable care is at risk… the primary reason millions of Americans remain uninsured or have insurance coverage that leaves them financially exposed is the high costs in our health care system. Constraining the growth of costs while reducing inequities in access and outcomes will require new but difficult reforms.”
My take: There are no simple solutions to the high costs of our health care or to assuring adequate coverage. At every level, there are excessive costs which undermine these goals:
Hospitals charge exorbitant fees and try to monopolize markets
Insurance companies have split loyalties and often deny expensive but necessary care
Pharmaceutical companies charge as much as the market will bear even with older generics. Increasingly, newer medications are very expensive
Health care providers have no incentives to constrain costs. Even salaried physicians may feel complicit by being part of systems owned by hospitals and venture capital firms which have excessive charges.
Although deaths from Covid have slowed, the disillusionment among health workers has only increased. Recent exposés have further laid bare the structural perversity of our institutions. For instance, according to an investigation in The New York Times, ostensibly nonprofit charity hospitals have illegally saddled poor patients with debt for receiving care to which they were entitled without cost and have exploited tax incentives meant to promote care for poor communities to turn large profits. Hospitals are deliberately understaffing themselves and undercutting patient care while sitting on billions of dollars in cash reserves. Little of this is new, but doctors’ sense of our complicity in putting profits over people has grown more difficult to ignore…
And many physicians are now finding it difficult to quash the suspicion that our institutions, and much of our work inside them, primarily serve a moneymaking machine…Our health care institutions as they exist today are part of the problem rather than the solution.”
In this retrospective study with 92 patients (182 colonoscopies), the authors found “minimal variability between degree of inflammation among biopsy fragments within and among different colorectal segments in UC, suggesting that even a single biopsy would adequately reflect the inflammation of the entire colorectum.”
My take: This study suggests that taking biopsies from every segment of the colon (when it looks uniform) is usually not needed, unless the purpose is to look for dysplasia. Also, it is worth recognizing that individuals with primary sclerosing cholangitis often have greater histologic activity in the right colon.
Methods: A prospective study of pediatric patients (N=16) undergoing standard colonic motility testing that were able to consume caffeinated coffee, decaffeinated coffee, and caffeine tablet during colonic manometry (with normal response to bisacodyl)
Caffeinated coffee resulted in a higher AUC, motility index (MI), and time to HAPC compared with decaffeinated coffee (P < 0.05).
Urge to defecate, or actual bowel movement in 100% (n = 16) of patients after intraluminal bisacodyl (IB), compared to 81% (n = 13) after caffeinated coffee (CC), 56% (n= 9) after caffeine tablet (CT), and 50% (n = 8) after decaffeinated coffee (DC)
Based on AUC between T = 1 and T = 60 minutes after each agent, the response of the colon to IB was more robust, relative to other agents (P < 0.05). Both CC and DC had resulted in a higher AUC compared to CT (P < 0.05), but no significant difference between CC and DC
Caffeine is indeed a colonic stimulant; however, other components of caffeinated and non-caffeinated beverages likely induce colonic response as well
Limitation: Study population: patients required motility testing for refractory chronic constipation Therefore, they do not represent a normal population
My take: As with adult patients, coffee (both caffeinated and decaffeinated) acts as a colonic stimulant. Though, it is relatively weak compared to bisacodyl
This article discusses several conditions like Prader-Willi and pregnancy that can result in increase hunger and then elaborates on genetic tendency towards obesity in an age of abundant ultra-processed high calorie foods. Excerpts:
A famous 1990 study of identical twins born in Sweden showed that pairs who were separated at birth and adopted had weights more similar to each other than to their adoptive families…The ability to sense such fullness — and hunger — varies, the result of genetic differences in brain circuits that control appetite.
The new drugs are the first to manipulate the hormonal regulatory systems governing energy balance. The drugs simulate the action of our native GLP-1 but with longer-lasting effects, amplifying the fullness signal inside the body…At the very least, though, the way the drugs work can teach us that people who are larger did not necessarily choose to be, just as people who are smaller did not — and are not morally superior. This “isn’t a free pass, either to individuals who do have the capacity to choose better, nor does it take the heat off of food industries,” said a University of Sydney nutritional biologist, Stephen Simpson, but it’s “evidence that obesity isn’t a personal lifestyle choice.”
My take: For those who benefit from GLP-1 medications, it is important to recognize that weight gain is likely when the medications are discontinued; this indicates once treatment is started, the goal would be to use indefinitely –until something better comes along.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition