About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

CCFA IBD Update -Conference Notes (part 1)

Posted on March 24, 2013 by gutsandgrowth

I wanted to share some notes from the Atlanta CCFA “Update in Inflammatory Bowel Disease” conference which was held March 23, 2013.

The first talk by Gil Melmed reviewed immunization issues in IBD. One of the best quotes of the conference was on his first slide: “The single most important thing a [rheumatologist] can do to optimize care for a [lupus] patient is to act as their internist, yet that is the last thing most [rheumatologists] wish to or feel qualified to do.” (Wallace DJ. Lupus 2008 (17) 91-2.

While trying to manage all aspects of the health care of our patients with chronic disease is an ideal, he also noted that 20-30% of adult IBD doctors do not understand the importance of avoiding live-virus vaccines (a list of these are noted in previous blog: Protecting the most vulnerable | gutsandgrowth).

One of the take-home points from this talk for me was to avoid use of rotavirus vaccine in newborn patients if their mother is receiving Infliximab or Adalimumab. Another useful point would be to remind family members of immunosuppressed IBD patients to receive the influenza vaccine rather than the live-virus vaccine (flumist).

The second talk by Wallace Crandall focused on improving health care delivery. The best quote of the day was from his first slide: “Every system is perfectly designed to achieve exactly the results it gets.” (Donald Berwick). One of his slides that I found intriguing showed 2007 data on immunomodulator use within the first 3 months of diagnosis from 10 different centers. The rate varied from 30% to 98%. He didn’t try to answer how frequent immunomodulator use in this time period should occur but there was no valid reason for this degree of variation.

In Columbus (Ohio), he stated that they are working to transform chronic care from 15-30 minute visits every 3-6 months to a more continuous process. “Patients receive only 60% of recommended care.” With a better health care delivery system, this could be improved and potentially improve outcomes.

Another obstacle is the lack of evidence to guide decisions. Recent “ECCO” guidelines for pediatric ulcerative colitis had 48% of recommendations based on level D evidence.

The third talk by Douglas Drossman was probably the most helpful. He discussed pain management in IBD. He reviewed a lot of recent data on irritable bowel syndrome (IBS) and discussed similarities between post-infectious IBS and many patients with treated IBD.

He also discussed central pain aspects and alluded to changes in the brain that happen with chronic treatment (Pain changes brain | gutsandgrowth). He noted that antidepressants have the potential to reverse brain changes due to chronic pain but that regrowth of neurons can take a long time. As such, he noted that agents like imipramine are needed for at least one year. Use of imipramine, he noted, has been shown to improve cognitive function in mice with traumatic brain injury (J Neurotrauma 2011; 28: 995).

With regard to IBD, Dr. Drossman noted a wide variability in pain response among patients. Some who have very significant mucosal disease do not experience significant pain, likely due to downregulation of some central pathways. He outlined his treatment model for pain in IBD.

Effective communication improves clinical outcomes
Just as there is a “treatment pyramid” for IBD, with IBS the treatment pyramid ncludes the following: motility agents, antispasmodics, antidepressants, psychological intervention, and central augmentation.
With regard to antidepressants, he highlighted the differences between tricyclics, SSRIs, and SNRIs. He noted that SSRIs like citalopram, escitalopram, fluoxetine, paroxetine, and sertraline are not effective at reducing pain but can help anxiety/depression.
Tricyclic antidepressants are effective at reducing pain and are inexpensive. Side effects can include sedation, dry mouth, dizziness, and constipation. Desipramine and nortriptyline have fewer side effects.
SNRIs including duloxetine, venlafaxine, desvenlafaxine, and minacipran are effective at reducing pain and fewer side effects. However, they are considerably more expensive. Nausea, though, is not infrequent.
Psychologic treatments: cognitive behavioral, psychotherapy, hypnosis, and relaxation training. When to refer? moderate-severe symptoms, maladaptive coping (eg. “catastrophizing”), and motivated patient.
What is central augmentation? If an antidepressant is not effective, augmentation is adding an agent that may target a different brain receptor. Potential augmenters include pharmacologic and non-pharmacologic approaches. Pharmacologics could include added gabapentin, added atypical antipsychotic (e.g.. quetiapine [Ability]), added clonidine, added buspirone, or added mirtazepine (e.g. remeron). Most practitioners will need the help of a psychiatrist to manage these medications.

Public Health Casualties: Collateral Damage in the War on Terror

Posted on March 23, 2013 by gutsandgrowth

This week there is a fascinating editorial that I almost skipped because the title didn’t grab my attention: “Ensuring Public Health Neutrality” (NEJM 2013; 368: 1073-1075).

This commentary provides background by recollecting Red Cross relief flights to Biafra being shot down by the Nigerian government. “In the minds of some people, ..these attacks were justified by another clear violation of humanitarian neutrality: on at least one occasion, a plane painted with the Red Cross insignia was actually carrying weapons.”

Fast-forward to January 6, 2013. 12 deans of U.S. schools of public health sent a letter to President Obama protesting the conduct of a sham vaccination campaign as part of the hunt for Osama bin Laden. Apparently, the CIA hired a Pakistani surgeon to go house to house vaccinating children but also drawing back a little blood in the syringe in order to analyze the DNA. This ploy was not effective in the bin Laden compound as the surgeon’s team was kicked out.

So what are the consequences?

Pakistan has expelled foreign staff of the international aid agency Save the Children (Sept 2012)
Eight polio vaccination workers were killed (Dec 2012)
U.N. has suspended its polio-eradication efforts in Pakistan. Pakistan is one of three countries where polio has not been eradicated (Nigeria and Afghanistan are the other two).
This undermines vaccination in Pakistan where 150,000 children die of vaccine-preventable illness each year.

Using physicians in this manner violates the Hippocratic Oath: “Whatever house I may visit, I will come for the benefit of the sick, remaining free of all intentional injustice.”

The authors note that “although some U.S. policymakers consider immediate national security concerns a higher priority than long-term global health efforts, the CIA’s false vaccination campaign in Pakistan may cause collateral damage with profound long-term implications for national security. If every aid worker..is suspected of being a spy, the children..of the world will no longer have protection against our greatest killers.”

Public health neutrality –a different twist to think about while you are watching “Zero Dark Thirty.”

Related links:

Thiopurine Metabolite Testing -NASPGHAN Consensus Recommendations

Posted on March 22, 2013 by gutsandgrowth

The inflammatory bowel disease committee of NASPGHAN has published a review and recommendations for the use of thiopurine metabolite testing (JPGN 2013; 56: 333-40).

The effectiveness of thiopurines is reviewed with a few key points:

Cochrane reviews have shown that azathioprine and 6-mercaptopurine are effective in inducing remission in Crohn’s disease. For active disease the overall response rate has been reported as 54% compared with 33% for placebo.
For ulcerative colitis, a Cochrane analysis deemed the methodologic quality of 4 of the 6 studies as unsatisfactory and that all studies were small. “The reviewers concluded that azathioprine may be effective treatment for patients with ulcerative colitis.”

The review covers the potential adverse effects of the thiopurines: myelosuppression, pancreatitis, elevated transaminases, susceptibility to infection, and malignancy. The review suggests that the risk of non-Hodgkin lymphoma is probably increased up to 4-fold. Though, it is difficult to determine how much of the risk is truly due to the usage of thiopurines or other confounding factors. The studies about the risk of non-melenoma skin cancer are not discussed.

Other covered topics: advantages of thiopurine metabolite testing (6-thioguanine [6-TGN] and 6-methylmercaptopurine[ 6-MMP]), potential disadvantages of metabolite testing (e.g.. cost), use of genotype versus phenotype (phenotypic testing is generally preferred), thiopurine metabolism, devising target levels, use of allopurinol, and misinterpretation of metabolite testing.

Specific Consensus Recommendations:

Obtain thiopurine methyltransferase (TPMT) testing prior to initiation of thiopurines.
Avoid use of thiopurines in individuals with extremely low TPMT activity or who are homozygous recessive for TPMT activity
TPMT testing does not predict all cases of leukopenia. All individuals receiving thiopurines should have routine monitoring with CBCs. “Most adverse effects from thiopurines are not directly related to 6-TGN or 6-MMP levels.”
Metabolite testing can help determine adherence to therapy
Metabolite testing may be helpful in guiding dose adjustment and/or adding allopurinol treatment
Routine and repetitive testing of metabolites is not recommended in patients who are doing well on an acceptable thiopurine dosage.

Related blog posts:

What happens to micronutrient levels in the hospital setting?

Posted on March 21, 2013 by gutsandgrowth

When atypical labs need to be obtained, many times this is easier in the hospital setting for logistical reasons including insurance and accessibility to specialty labs. One group of labs that may be less suited for checking in the hospital, despite convenience, would be micronutrients. Many of the micronutrients can be affected by systemic inflammatory response (Am J Clin Nutr 2012; 95: 64-71). Thanks to Kipp Ellsworth for this reference (from his @PedNutritionGuy twitter feed).

Previous studies on systemic inflammatory response (SIR), as assessed by elevated C-reactive protein (CRP) concentrations, has shown that with elective surgery there are transient decreases in plasma concentrations of zinc, selenium, iron, vitamin A, vitamin E, carotenoids, riboflavin, vitamin B-6, vitamin C, and vitamin D.

This current study adds to this body of information. Between 2001-2011, 2217 whole-blood samples were taken from 1303 patients. Specific micronutrients that were studied: plasma zinc, copper, selenium, vitamins A, B-6, C, and E. For vitamin D, the authors examined 4327 samples from 3677 patients. The authors did not include manganese, thiamine or riboflavin because these are measured in erythrocytes.

For each analyte, the concentrations were separated according to 6 categories of CRP values: <5, 6-10, 11-20, 21-40, 41-80, and >80 mg/L.

Key finding: Except for copper and vitamin E, all plasma micronutrient concentrations decreased with increasing severity of acute inflammatory response. For selenium, vitamin B-6, and vitamin C, this occurred with only slight increases in CRP (5 to 10 mg/L).

The magnitude of the SIR effect on micronutrients was quite variable among patients and analytes. When CRP was >80 mg/L, analyte deficiency rate was noted to be the following:

60 % for selenium (vs. 33% with NL CRP)
48% for vitamin A (vs. 7% with NL CRP)
35% for vitamin B-6 (vs. 14% with NL CRP)
80% for vitamin C (vs. 33% with NL CRP)
88% for vitamin D (vs. 69% with NL CRP)
81% for zinc (vs. 33% with NL CRP)
9% for copper (vs. 4% with NL CRP)
16% for vitamin E (vs. 9% with NL CRP)

**The specific normal value cutoffs and more data at all CRP values are noted in Table 9 of the manuscript.

The implications from this study are clear. When micronutrient values are derived from plasma during a SIR, a false-positive diagnosis of a micronutrient deficiency is more likely. The study has several limitations and the findings may not be applicable to all types of medical conditions.

Authors conclusion: When CRP concentration is >20 mg/L (>2 mg/dL), “plasma concentrations of selenium, zinc, and vitamins A, B-6, C, and D are clinically uninterpretable.”

Related blog entries:

Predicting outcome in Pediatric Acute Liver Failure

Posted on March 20, 2013 by gutsandgrowth

In a recent study, soluble interleukin 2 receptor alpha (sIL2Rα) was identified as a marker associated with patient outcome in pediatric acute liver failure (JPGN 2013; 56: 311-5).

Because systemic inflammatory response and immune function have potential effects on the outcomes of patients with acute liver failure (ALF), the authors decided to study markers of T-cell immune activation in patients enrolled in the pediatric ALF (PALF) cohort. The PALF cohort was derived from the PALF study group which consists of 20 sites. All of the enrollees from this study were from the 17 U.S. sites.

Design: Blood was collected within 48 hours of enrollment into the PALF cohort. Blood had to received by the testing laboratory within 24 hours of collection. The final study group included 77 patients, though outcomes for two patients (who were discharged alive within 10 days of enrollment) were not known. Blood was tested for numerous markers including “CD56 bright,” perforin, Natural Killer T-cell (NKT) perforin, NK lytic activity, granzyme B, CD8, CD16, CD56 and others. Outcomes were assessed within 21 days of enrollment.

Results:

Acetaminophen was the most common identifiable reason for PALF (n=13) and all acetaminophen patients survived without liver transplantation.
Other etiologies included autoimmune marker positive-ALF (n=8), Drug-induced ALF (n=2), viral ALF (n=6), metabolic (n=7), hemophagocytic lymphohistiocytosis (HLH) (n=3), and shock/ischemia (n=3). Besides indeterminant ALF (n=27), all other diagnosis had n=1.
Age was distributed across all pediatric groups: < 5 years (n=24), 5-9 years (n=19), >9 years (n=34).
Of all the markers of T-cell immune activation, only sIL2Rα was identified as being able to discriminate between survival with native liver, liver transplantation, and death.
Of the 15 subjects with markedly elevated sIL2Rα (>5000 IU/mL), 5 (33%) survived with native liver, 2 died, and 8 underwent liver transplantation. In contrast, all 37 patients with normal sIL2Rα lived, 30 (81%) with their native livers.

Study limitations included the cross-sectional design which entailed measuring sIL2Rα at a single point in time. In addition, it is not clear whether sIL2Rα levels reflect a causal role in liver injury or a response to liver injury.

Take home message:

sIL2Rα along with traditional measures could improve the ability to predict hepatic recovery in PALF.

Related blog posts:

Anti-TNFs and Pregnancy

Posted on March 19, 2013 by gutsandgrowth

While pregnancy does not occur commonly while patients are in a pediatric gastroenterology practice, the possibility of becoming pregnant certainly influences our choice of medications. With inflammatory bowel disease (IBD), I rarely recommend methotrexate in young women due to its teratogenicity. With regard to the anti-TNF agents, there is less data available. Two recent studies add some insight into this issue.

The first study ((Clin Gastroenterol Hepatol 2013; 11: 318-21) followed 31 pregnancies in 28 women with IBD (2006-2011). 18 patients received infliximab (IFX) and 13 adalimumab (ADA). Most were receiving lower doses; only one IFX patient was receiving 10 mg/kg/dose and only two ADA patients were receiving weekly dosing. Levels of anti-TNF agents were measured from cord blood from 18 newborns (12 IFX, 6 ADA).

Results:

28 live births. 3 miscarriages (1 IFX, 2 ADA). No congenital malformations were noted.
Mean cord IFX level was 6.4 mcg/mL. A level of 2.8 mcg/mL was noted in the early discontinuation group –stopping 10 weeks prior to delivery .
Mean ADA level was 1.7 mcg/mL in five infants. One infant had an undetectable level. All mothers had stopped ADA at gestational week 22.

In the second study (Clin Gastroenterol Hepat 2013; 11: 286-92) there were 31 pregnant patients. Anti-TNF treatment: Certolizumab (CZP) (n=10), IFX (n=11), ADA (n=10). Serum levels were measured at birth in the mother, infant, and in cord blood. Then, levels were followed monthly until undetectable. Among women receiving IFX, two were receiving 10 mg/kg/dose. Women were identified through the Crohn’s Colitis Foundation of America Pregnancy IBD and Neonatal Outcomes (PIANO) Registry.

Results:

IFX was detectable for 2-7 months postpartum (median interval prior to delivery and last dose was 35 days). Median IFX level in the cord was 160% that of the mother.
ADA was detectable for at least 11 weeks in infant’s circulation (median interval prior to delivery and last dose was 5.5 weeks). Median ADA in the cord was 153% of the mother.
Median CZP in the cord was 3.9% that of the mother.
No congenital anomalies or complications were reported in any of the infants.

Bottomline from these studies:

Stopping these drugs after the second trimester lowers the level of these medications in the infant. This likely results in a lower likelihood of the infant developing an opportunistic infection but also results in a low risk for the mother of an IBD flareup. Certolizumab pegol has very low levels of placenta transfer.

Related references:

-J Am Acad Dermatol 2011; 65: 870. Death noted in infant whose mother took IFX after BCG vaccination.
-J Crohns Colitis 2011; 5: 555-8. Low levels of IFX detected in infants from nursing mothers with IBD (1/200th of the maternal level in serum 2 to 3 days after infusion).
-Clin Gastroenterol & Hep 2010; 8: 509. n=2377. Crohn dz assoc w prematurity but not birth defects.
-Gastroenterol 2003;124: 9-17. Safety of 6-MP in pregnancy. n=155, at least 1 pregnancy. No adverse effect noted.
-Clin Gastroenterol & Hepatology; 2006: 4: 1255. Infliximab crosses placenta but was not detected breastmilk.

Trends in Adolescent Bariatric Surgery

Posted on March 18, 2013 by gutsandgrowth

Despite increased numbers of obese adolescents, the number of inpatient bariatric surgery cases has plateaued (JAMA Pediatr 2013; 167: 126-32). Thanks to Ben Gold for sharing this reference.

In this retrospective cross-sectional study using an administrative dataset (Healthcare Cost and Utilization Project Kids’ Inpatient Database), the authors documented the following bariatric surgery rates:

In 2000: 0.8 per 100,000 (328 procedures)
In 2003: 2.3 per 100,000 (987 procedures)
In 2006: 2.2 per 100,000 (925 procedures)
In 2009: 2.4 per 100,000 (1009 procedures)

The other observations in this study were that procedures were predominantly performed on females (75%), the prevalence of comorbidites increased (49% in 2003 vs. 59% in 2009), and complications rates were low. 68.3% had private insurance.

Take-home points:

The number of adolescents who would qualify for bariatric surgery has increased but the rates have not changed. Why?

Societal barriers. Obesity is more common in lower socioeconomic groups with lower educational levels. Yet, the rates of bariatric procedures is the same in low-income and high-income populations.
Insurance coverage. In many states, medicaid does not cover bariatric surgery.
Physicians limiting access. After initial enthusiasm (2000-2003), published guidelines to identify appropriate patients and to highlight recommendations prior to surgery may have led to more cautious referral patterns.

Over the past decade, there are increased numbers of qualified surgeons and there has been more use of laparascopic techniques. The Roux-en-Y gastric bypass (RYGB) was the most common bariatric procedure in this population, accounting for 67.6% of cases in 2009 (60.6% were laparascopic, 7% were open). Laparascopic adjustable gastric banding (LAGB) accounted for the remaining 32.1% of cases.

Since this study relied on administrative data, there are several limitations. Billing codes may not reflect the procedures accurately. For example, ICD-9 codes for laparascopic sleeve gastrectomy were not available until 2011. Nevertheless, this study provides some insight into the trends with bariatric procedures in adolescents.

Related blog link:

Six year outcomes with bariatric surgery | gutsandgrowth

Closer to Star Trek Medicine

Posted on March 17, 2013 by gutsandgrowth

In Star Trek, Dr. Leonard McCoy used a medical tricorder to effortlessly diagnose a lot of conditions (Tricorder – Wikipedia, the free encyclopedia, Medical tricorder – Wikipedia, the free encyclopedia). While many of the newest diagnostic tests are not as portable, they share a feature of being able to diagnose a wide range of conditions quickly. These tests include imaging studies like MRI and CT, genetic microarrays, and now PCR panels to diagnose a broad array of respiratory and gastrointestinal ailments.

One of the newest is the “xTAG GPP.” With one stool sample, this Gastrointestinal Pathogen Panel (GPP) can detect at least 11 common bacteria, viral, and parasitic pathogens in about five hours. Thus, all patients with identifiable gastroenteritis illnesses can be diagnosed more quickly. The test relies on a “multiplex nucleic acid test.”

FDA News Release Jan 15, 2013 (Press Announcements > FDA permits marketing of first test that can …):

“Infectious gastroenteritis is an inflammation of the stomach and intestines caused by certain viruses, bacteria, or parasites. Common symptoms include vomiting and diarrhea, which can be more severe in infants, the elderly, and people with suppressed immune systems. Gastroenteritis can be spread easily through person-to-person contact and contaminated food, water, and surfaces.

The Centers for Disease Control and Prevention reports that between 1999 and 2007 gastroenteritis-associated deaths in the United States increased from nearly 7,000 to more than 17,000 per year. Norovirus and Clostridium difficile accounted for two-thirds of the deaths.

The xTAG Gastrointestinal Pathogen Panel (GPP), a multiplexed nucleic acid test, detects the following causes of gastroenteritis:

Bacteria

Campylobacter
Clostridium difficile (C. difficile) toxin A/B
Escherichia coli (E. coli) O157
Enterotoxigenic Escherichia coli (ETEC) LT/ST
Salmonella
Shigella
Shiga‐like Toxin producing E. coli (STEC) stx 1/stx 2

Virus

Norovirus
Rotavirus A

Parasite

Cryptosporidium
Giardia

“Tests such as the XTag GPP that can detect viruses, bacteria, and parasites from one sample at the same time can help clinicians more quickly identify and treat what’s causing gastroenteritis,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiology at the FDA’s Center for Devices and Radiological Health. “The test could also allow clinicians and public health professionals to more quickly identify and investigate the source of potential gastroenteritis outbreaks.”

The manufacturer demonstrated the performance of the xTAG GPP by collecting samples from 1,407 patients with suspected infectious gastroenteritis and comparing the xTAG GPP results to individual tests that are known to separately and reliably detect the 11 viruses, bacteria, or parasites associated with the xTAG GPP. The manufacturer also ran the test on 203 samples from patients with previously confirmed infectious gastroenteritis, and 313 additional specimens from pediatric patients with suspected infectious gastroenteritis. Results were comparable to the individual tests. Due to the risk of false positives, all positive results from the xTAG GPP need to be confirmed by additional testing (blog entry underlined for emphasis, not in original FDA release).

Luminex, Inc., of Austin, Texas, manufactures the xTAG.”

According to manufacter’s website, the test also detects Yersinia, Entamoeba histolytica, and adenovirus. It reports sensitivity of of >94% for almost all pathogens (except Salmonella which was 84%) and specificity of >94% for all of the pathogens.

NEWxTAG® Gastrointestinal Pathogen Panel (GPP) – Luminex

Related blog entries:

Copper in Cholestasis

Posted on March 16, 2013 by gutsandgrowth

More data indicate that copper levels in infants receiving parenteral nutrition are usually not affected by cholestasis (JPEN 2013; 37: 92-96).

A retrospective study reviewed all patients younger than 1 year who had copper levels measured between 1999-2009 at Riley Hospital for Children. Inclusion criteria: parenteral nutrition for at least 50% of caloric needs and cholestasis (direct bilirubin >2 mg/dL).

Key findings:

26 of 28 patients had gastrointestinal disorders. 82% were receiving standard parenteral nutrition (PN) dose of copper (20 mcg/kg/day).
Only one elevated copper level was found in a child with congenital heart disease.
46% (n=13) of cholestatic infants had low copper levels. Three of theses infants had no copper in their PN.
There was no correlation between bilirubin level and measured copper values.

Bottomline:

Measure copper values periodically in patients requiring parenteral nutrition. Most patients, even cholestatic patients, will require standard dosing but some will need less and some more.

Additional References:

-JPGN 2010; 50: 650-54. n=28. (only 2 had elevated Cu). Typical Cu supplementation in HAL did not lead to significant increase in Cu toxicity or worsening of liver disease in cholestatic infants. Study prompted by single infant who developed Cu deficiency/anemia.
-Clin Gastro & Hepatol 2004; 2: 1074. Two patients with Cu deficiency after bariatric surgery
-JPGN 2000; 31: 102-111. (review)

More options for Hepatitis C

Posted on March 15, 2013 by gutsandgrowth

As noted in numerous blog entries (see below), there has been increasing availability of new and more effective treatments for Hepatitis C virus (HCV). Two more drugs have promising results:

NEJM 2013; 368: 34-44
NEJM 2013; 368; 45-53

The first study provides encouragement with regard to sofosbuvir (previously known as GS-7977) which is a direct-acting nucleotide polymerase inhibitor targeting the NS5B polymerase.

In this open-label study, there were eight groups of patients. Of 40 previously untreated patients (genotype 2 or 3), all patients received sofosbuvir (400 mg daily) for 12 weeks. All 10 who received the study drug with ribavirin (& without interferon) and all 30 who received the study drug with ribavirin and peginterferon had a sustained virologic response (SVR) at 24 weeks. Among patients with sofosbuvir monotherapy, 6 of 10 had a SVR. Among HCV genotype 1 patients, 21 of 25 (84%) previously untreated patients had a SVR. The most common adverse effects were headache, fatigue, insomnia, rash and anemia.

The second study also was a phase 2a, open-label study for HCV genotype 1 non-cirrhotic patients using ABT-333 and ribavirin. ABT-333 is a nonnucleoside NS5B polymerase inhibitor. Results: 17 of 19 (89%) patients in group 1 (Rx with ABT-333, ribavrin, ABT-450, and ritonavir), 11 of 14 (79%) patients in group 2 (Rx with same drugs at lower doses of latter two drugs) had extended rapid virologic response. SVR was achieved in 95% and 93% respectively. Groups 1 and 2 were previously untreated. Group 3 were patients who had either a null or partial response to previous treatment achieved a 47% SVR. The most common adverse effects were abnormalities in liver function tests, headache, fatigue, insomnia, pruritus, nausea and rash.

Bottom-line:

These preliminary results suggest that Sofosbuvir is effective in all genotypes and may allow a short duration all-oral regimen. ABT-333 similarly is effective in an all oral regimen in genotype 1 patients.

Related blog posts: