Acute Pancreatitis: Clinical Report from NASPGHAN

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There are no surprises in a recent clinical report on acute pancreatitis (M Abu-El-Haija et al. JPGN 2018: 66: 159-76) from NASPGHAN.

Here are a few of the points:

  • The authors recommend ultrasound for initial imaging and checking liver enzymes, GGT, calcium and triglycerides.
  • For fluids, they indicate that in adults there is evidence suggesting that lactated ringer’s (LR) is likely preferable to normal saline.  In children, on presentation, “if evidence of hemodynamic compromise, a bolus of 10 to 20 mL/kg” of crystalloid is recommended followed by “1.5 to 2 times maintenance IV fluids.”
  • For pain management not responding to acetaminophen or NSAIDs, “IV morphine or other opioids should be used.”
  • They recommend early oral/enteral nutrition (within 48 to 72 hours of presentation).
  • They recommend against prophylactic antibiotics in severe acute pancreatitis.
  • They recommend against probiotics, anti-proteases, and antioxidant therapy.
  • For fluid collections that need drainage or necrosectomy, nonsurgical approaches are favored.
  • Acute biliary pancreatitis, “Cholecystectomy safely can and should be performed before discharge in cases of mild uncomplicated acute biliary pancreatitis.”

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American Ingenuity!!

Cancer due to Overweight/Obesity

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The increasing risk of cancer due to overweight and obesity has been reported by the Centers for Disease Control and Prevention in recent MMWR report (CB Steele et al. MMWR 2017; 66: 1052-8)  Vital Signs: Trends in Incidence of Cancers Associated with Overweight and Obesity — United States, 2005–2014

Key points:

  • Overweight and obesity are associated with increased risk of at least 13 different types of cancer.
  • Overweight- and obesity-related cancers accounted for 40% of all cancers diagnosed in 2014.
  • The incidence of overweight- and obesity-related cancers (excluding colorectal cancer) increased significantly among persons aged 20–74 years during 2005–2014, mirroring increases of obesity observed since 1960.
  • The findings emphasize the importance of intensifying nationwide efforts to prevent and treat overweight and obesity.

My take: While the medical risks related to overweight/obesity generally are attributed to worsened cardiovascular disease, this study adds information regarding the increased risks of some types of cancer as well.

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Colorectal Cancer: Of Mice and Microbiota

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A recent study (SH Wong et al. Gastroenterol 2017; 153: 1621-33) highlights the potential role of the microbiota and colorectal cancer (CRC).

In this study, the stool from either patients with CRC or control patients was gavaged into mice twice a week for 5 weeks.  One group of mice  had received azoxymethane (AOM) which induces neoplasia and the other group were germ-free mice.  Extensive studies involving immunohistochemistry, expresssion microarray, quantitative polymerase chain reaction, immunoblot, and flow cytometry.

Key findings:

  • Conventional, AOM-treated mice who received gavage from patients with CRC had significantly higher proportions of high-grade dysplasia (P<.05) and macroscopic polyps (P<.01)
  • Among the germ-free mice fed with stool from patients with CRC, there was a higher proportion of proliferating Ki-67-positve cells
  • These findings correlated with more dysbiosis in the mice who received stool from patients with CRC and with upregulation of genes involved in cell proliferation, stemness, apoptosis, angiogenesis, and invasiveness

“This study provides evidence that the fecal microbiota from patients with CRC can promote tumorigenesis in germ-free mice and mice given a carcinogen.”

My take: This study shows that microbiota clearly influence the risk of CRC.  I infer from this study that this could explain the potential healthy roles of diets with more fruits and vegetables, that promote healthier microbiota as well as the potential detrimental role of diets with more processed meats.

Related study: L Liu et al. Association between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor Gastroenterol 2017; 153 1517-30.  Using two databases from 2 prospective cohorts with followup of 124,433 participants, inflammatory diets had a higher risk of a colorectal cancer subtype.

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Bright Angel Trail

Screening for Bile Acid Synthesis Disorders

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A recent study (AA Al-Hussaini et al. JPGN 2017; 65: 613-20) showed that serum (total) bile acids is effective in screening for bile acid synthesis disorders. In this prospective study from Saudi Arabia, with 626 patients and 450 with infantile cholestasis, the authors identified bile acid synthetic disorder (BASD) in 2.7% of infantile cholestasis patients.  Among the 15 cases, 11 were due to 3β-hydroxyl-Δ5-C27 steroid oxidoreductase dehydrogenase deficiency (HSD3B7).  In these conditions, serum bile acids are low or normal (< 10  μmol/L) in the setting of cholestasis; most cholestatic conditions have elevated bile acids. In addition, all of their patients with bile acid synthetic disorders had a normal or low GGT.

Cholic acid is the “only effective therapy” for bile acid synthetic disorders.  It has a high cost of “$31,000 yer year in Europe” (50 mg per day).

My take: While the authors provide a diagnostic algorithm (figure 3) for diagnosis of bile acid synthetic disorders, this will likely change with the emergence of genetic screening panel.  At this time, in infants/children with cholestasis along with a normal/low GGT and normal/low serum bile acids, one should check urine for fast atom bombardment mass spectrometry.

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Bright Angel Trail, Grand Canyon

 

Modern Malady: Text Neck

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In every age, our bodies need to adapt to new challenges.  Apparently, in this age, we need to solve another problem induced by texting, “Text Neck.”

NY Times: Keep Your Head Up: How Smartphone Addiction Kills Manners and Moods

Here’s an excerpt:

The average human head weighs between 10 and 12 pounds, and when we bend our neck to text or check Facebook, the gravitational pull on our head and the stress on our neck increases to as much as 60 pounds of pressure. That common position, pervasive among everyone from paupers to presidents, leads to incremental loss of the curve of the cervical spine. “Text neck” is becoming a medical issue that countless people suffer from, and the way we hang our heads has other health risks, too, according to a report published last year in The Spine Journal.

Posture has been proven to affect mood, behavior and memory, and frequent slouching can make us depressed…

And the remedy can be ridiculously simple: Just sit up.

My take: Smartphone use increases the risk of many health problems besides “Text Neck” including car accidents.  Their use also contributes to missing social cues, including placing those in front of you behind those who interrupt conversations with texts and phone calls.

Iron Metabolism Improves after Anti-TNF Therapy for Crohn’s Disease

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A previous study has shown that low vitamin D levels improved with anti-TNF therapy for Crohn’s disease in the absence of supplemental vitamin D.  Similarly, a recent study (MA Atkinson, MB Leonare, R Herskovitz, RN Baldassano, MR Denburg. JPGN 2018; 66: 90-4) showed improvement in iron metabolism with anti-TNF therapy.

In 40 children and adolescents with Crohn’s disease, the authors measured serum hepcidin-25 and hemoglobin at baseline and then 10 weeks after anti-TNF therapy.

Key findings:

  • Median hepcidin concentrations decreased (27.9–>23.2 ng/mL) and mean hemoglobin increased (10.6–>10.9).
  • Disease activity and markers of inflammation also decreased.

My take: This study shows that improvement in inflammation is associated with meaningful improvement in anemia.  However, most patients will need additional treatment for anemia, particularly as anemia may be related to blood loss in addition to anemia of chronic disease/inflammation.

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Second-Line Treatments for Autoimmune Hepatitis

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A recent retrospective study (C Efe et al. Clin Gastroenterol Hepatol 2017; 15: 1950-6) examined both mycophenolate mofetil (MMF, n=121) and tacrolimus (TAC, n=80) as second-line therapies for autoimmnue hepatitis with a median followup of 62 months. Patients were divided into two groups. The first group (n=108) had a complete response to steroids/azathioprine but had side effects.  The second group (n=93) were nonresponders to steroids/azathioprine. Overall, the cohort examined patients as young as 7 years and as old as 76 years.

Key findings:

  • No significant difference in complete response noted in 69.4% of MMF-treated compared with 72.4% in TAC-treated patients.
  • In group 1 patients (responders to azathioprine), MMF and TAC maintained biochemical remission in 91.9% and 94.1% respectively.
  • In group 2 (prior nonresponders), TAC-treated patients had a complete response rate of 56.5% compared with 34% for MMF-treated patients (P=.029).
  • Liver-related deaths and transplantation occurred with similar rates: MMF 13.2% compared with TAC 10.3%.  With each treatment, 10 patients withdrew from treatment due to side effects.

My take: In this study, both agents were effective in those who changed due to side effects.  However, tacrolimus-treated patients had a higher response among prior nonresponders.

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Bright Angel Trail, Grand Canyon

 

Glecaprevir-Pibrentasvir for Hepatitis C Infections

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Before discussing one of the newest therapies for Hepatitis C, I wanted to give a shout out to Barbara McElhanon who along with Joanna Lomas-Mevers provided a quick update to our group on their important research to improve the management of encopresis in children with autism spectrum disorders.

Last August, the FDA announced approval of glecaprevir-pibrentasvir as a pangenomic treatment for Hepatitis C (From blog: Eight Week Pangenomic HCV Treatment Approved).

However, it is only in this past two weeks that some of the data from two large randomized, open-label, multicenter trials have been published: Z Zeuzem et al. NEJM 2018; 378: 354-69.  In total, 1208 patients were treated in the “ENDURANCE-1” and “ENDRUANCE-3” trials.

Key findings:

  • For genotype 1-infected patients, glecaprevir-pibrentasvir resulted in a sustained virologic response rate (at week 12) of 99.1% in the 8-week group and 99.7% in the 12-week group.
  • For genotype 3, glecaprevir-pibrentasvir resulted in a sustained virologic response rate (at week 12) of 95% with both 8-week and 12-week treatment.  A comparison group of sofosbuvir-daclatasvir (12 week treatment) resulted in a sustained virologic response rate (at week 12) of 97%.
  • Serious adverse events were rare.  There were three patients who died during the post-treatment period: two from heroin overdoses and one from ethanol intoxication/methadone toxicity.  Headache and fatigue were the most common reported adverse events.
  • There were no relapses among HCV-1-infected patients who were treated for 8 weeks

In addition to these studies, “recent phase 3 trials have shown that an 8-week regimen of glecaprevir-pibrentasvir in patients without cirrhosis” yielded response of 98% for genotype 2 and 93% for genotypes 4, 5, and 6.

My take: These studies indicate that glecaprevir-pibrentasvir is an effective 8-week therapy for patients with HCV infection.  Despite this terrific advance, unless we find a way to address the opioid crisis which is triggering an HCV epidemic, I am not optimistic that there will be an improvement in the number of individuals with HCV infection.

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Opioid Epidemic Affecting HCV Infection in Adolescents (as well as adults)

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SA Barritt et al. J Pediatr 2018; 192: 159-64. Increasing Prevalence of Hepatitis C among Hospitalized Children Is Associated with an Increase in Substance Abuse

Background:  “After a sustained decline in new HCV cases, in recent years there has been a significant increase in HCV incidence in adults in many areas, primarily associated with the use and abuse of intravenous heroin and prescription opioids.” This study examines this trend in adolescents.

From abstract:

Study design

We examined hospitalizations in children using the Kids’ Inpatient Database, a part of the Healthcare Cost and Utilization Project. We identified cases using the International Classification of Diseases, 9th edition, codes for HCV infection during 2006, 2009, and 2012. Nonparametric tests for trend were used to calculate trend statistics.

Results

From 2006 to 2012 nationally, the number of hospitalizations of children with HCV increased 37% (2.69 to 3.69 per 10 000 admissions; P < .001). The mean age of children hospitalized was 17.6 years (95% CI, 17.4-17.8). HCV cases among those 19-20 years of age represented 68% of the total HCV diagnoses, with a 54% increase over the years sampled (P < .001 for trend). The burden of HCV in children was highest in whites, those in the lowest income quartile, and in the Northeast and Southern regions of the US (all P < .0001). The prevalence of substance use among children with HCV increased from 25% in 2006 to 41% in 2012 (P < .001).

Conclusion

The increases of HCV in hospitalized children are largely in teenagers, highly associated with substance abuse, and concentrated in Northeast and Southern states. These results strongly suggest that public health efforts to prevent and treat HCV will also need to include adolescents.

My take: Despite the availability of highly effective therapy for hepatitis C, the opioid epidemic undermines any prospect for eliminating hepatitis C infections.

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