Percentage of U.S. residents with up-to-date screening for colorectal cancer remains at 60% - what options, other than colonoscopy, do we have?

From the NEJM:

The percentage of U.S. residents with up-to-date screening for colorectal cancer has not increased appreciably since 2010 and remains at approximately 60%. To achieve the highest level of adherence to colorectal cancer screening, it may be best to provide participants a choice, because the “best” strategy is the one that they will adhere to consistently.

The NEJM reviews all the options in this table:

http://blogs.nejm.org/now/wp-content/uploads/sites/6/2017/01/nejmcp1512286_t2.jpeg

Full article is here:

Screening for Colorectal Neoplasia - Now@NEJM http://buff.ly/2ikfKA0

Overcoming Colonoscopy Fears with Educational Videos by EMMI

From Dartmouth-Hitchcock: patient education and engagement video by EMMI Solutions can decrease anxiety before a colonoscopy, decrease dosage of sedatives during the procedure and shorten recovery time after the procedure.

Emmi(TM), stands for Expectation Management and Medical Information, and was originally developed by physicians with the goal to educate patients and decrease malpractice risk specifically in surgical patients. As of February 2016, there are 4 published studies about EMMI in PubMed:

http://www.ncbi.nlm.nih.gov/pubmed/26210560
http://www.ncbi.nlm.nih.gov/pubmed/26101988
http://www.ncbi.nlm.nih.gov/pubmed/21245476
http://www.ncbi.nlm.nih.gov/pubmed/19606763

Do you have any experience with EMMI?

Watch the Dartmouth-Hitchcock video below:



Here is the standard "Preparing for a Colonoscopy" video by Dartmouth-Hitchcock:



References:

http://www.dartmouth-hitchcock.org/news/newsdetail/64940/

Highly effective HCV treatment: once daily oral Sofosbuvir/Velpatasvir

The hepatitis C virus (HCV), a single-stranded RNA virus of the family Flaviviridae with six major genotypes, infects up to 150 million people worldwide. Chronic hepatitis C virus infection causes progressive liver fibrosis, which can lead to cirrhosis and hepatocellular carcinoma. There is now an effective oral regimen. New research findings are summarized in this short video from NEJM:



This is a ribavirin-free single-tablet regimen. There 2 medications in the single tablet:

- Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase approved for the treatment of HCV in combination with a variety of other agents, including NS5A inhibitors, ribavirin, and peginterferon–ribavirin.

- Velpatasvir is a new pangenotypic HCV NS5A inhibitor with antiviral activity against HCV replicons in genotypes 1 through 6.

The rate of sustained virologic response among patients receiving sofosbuvir–velpatasvir was 99%.

See the NEJM article, "Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection":
http://www.nejm.org/doi/full/10.1056/NEJMoa1512610#t=abstract

"Gluten sensitivity" may be caused by FODMAPs in everyday foods: Fructose in fruit, Lactose in milk, Galactans in beans, Polyols in chewing gum

FODMAPs is an acronym for fermentable oligosaccharides, disaccharides, monosaccharides and polyols. FODMAPs are sugars that draw water into the intestinal tract. They may be poorly digested or absorbed, and become fodder for colonic bacteria that produce gas and can cause abdominal distress.

FODMAPs are FLF-GP:

- Fructose: A sugar found in many fruits (hence the name), for example, apples, pears, watermelon, mangoes, grapes, blueberries, tomatoes and tomato concentrate, and all dried fruits; vegetables like sugar-snap peas, sweet peppers and pickles; honey; agave; and jams, dressings and drinks made with high-fructose corn syrup.

- Lactose: Sugar in milk from cows, goats and sheep, present in ice cream, soft cheeses, sour cream and custard.

- Fructans: Soluble fiber found in bananas, garlic, onions, leeks, artichokes, asparagus, beets, wheat and rye.

- Galactans: Complex sugars prominent in dried peas and beans, soybeans, soy milk, broccoli, cabbage and brussels sprouts.

- Polyols: Sugar alcohols (sweeteners) isomalt, mannitol, sorbitol and xylitol, present in stone fruits like avocado, cherries, peaches, plums and apricots.

People with irritable bowel syndrome (IBS) or gluten sensitivity often find that their symptoms lessen or disappear when avoiding foods rich in FODMAPs; however, it can take 6-8 weeks on a low-FODMAPs diet to see a significant improvement.

References:

When Gluten Sensitivity Isn't Celiac Disease - NYTimes.com http://nyti.ms/1EmXFDl
Celiac disease and nonceliac gluten sensitivity - 2017 review in Annals of Allergy, Asthma & Immunology http://buff.ly/2pI2x61

Irritable Bowel Syndrome (IBS) - DW video

Professor Hubert Mönnikes talks about why people with IBS are often mislabeled as hypochondriacs, and how to best treat the symptoms.



Are Dietary FODMAPs a Cause of Irritable Bowel Syndrome? (Fermentable, Oligo-, Di-, Monosaccharides, And Polyols).

IBS symptoms improved with a diet low in short-chain carbohydrates (FODMAPs - fructose, lactose, polyol sweeteners) http://buff.ly/1fdzBWJ -- A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome - the evidence supports its use as a first-line therapy http://buff.ly/1Ch3scU

DOWNLOAD the Handout  Stanford University: Low FODMAP Diet Handout

References:

A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome - supports its use as a first-line therapy http://buff.ly/1Ch3scU

Inflammatory Bowel Disease (IBD) - DocMikeEvans animation video

Dr. Mike Evans is founder of the Health Design Lab at the Li Ka Shing Knowledge Institute, an Associate Professor of Family Medicine and Public Health at the University of Toronto, and a staff physician at St. Michael's Hospital.

Written and Narrated by Dr. Mike Evans.

Pancreatic Cancer - 2014 update from Am Fam Physician

Pancreatic cancer remains the fourth leading cause of cancer-related deaths in the United States.

Risk factors include:

- family history
- smoking
- chronic pancreatitis
- obesity
- diabetes mellitus
- heavy alcohol use
- possible dietary factors

Symptoms

Because more than two-thirds of adenocarcinomas occur in the head of the pancreas, abdominal pain, jaundice, pruritus, dark urine, and acholic stools may be presenting symptoms.

Diagnosis

In symptomatic patients, the serum tumor marker cancer antigen 19-9 can be used to confirm the diagnosis and to predict prognosis and recurrence after resection.

Pancreas protocol computed tomography is considered standard for the diagnosis and staging of pancreatic cancer.

Treatment

Surgery

Although surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinomas, less than 20% of surgical candidates survive five years. The decision on resectability requires multidisciplinary consultation. Pancreatic resections should be performed at institutions that complete at least 15 of the surgeries annually.

Chemotherapy

Postoperatively, use of gemcitabine or fluorouracil/leucovorin as adjuvant chemotherapy improves overall survival by several months. However, more than 80% of patients present with disease that is not surgically resectable. For patients with locally advanced or metastatic disease, chemoradiotherapy with gemcitabine or irinotecan provides clinical benefit and modest survival improvement.

Palliative care

Palliation should address pain control, biliary and gastric outlet obstruction, malnutrition, thromboembolic disease, and depression.

Jon Lord, the keyboardist of the pioneering British hard-rock band Deep Purple, died of pancreatic cancer in 2012 and at age 71. Here is David Coverdale's eulogy for Jon Lord: David Coverdale remembers his first meetings with Jon Lord - supporting Deep Purple, joining Deep Purple and rehearsing for the Burn album:



References:

Diagnosis and Management of Pancreatic Cancer. De La Cruz MS1, Young AP2, Ruffin MT2. Am Fam Physician. 2014 Apr 15;89(8):626-632.
http://www.ncbi.nlm.nih.gov/pubmed/24784121

Jon Lord, Keyboardist With Deep Purple, Dies at 71. NYTimes http://buff.ly/1kC6iOD

Image source: Wikipedia, public domain.

Constipation - Mayo Clinic patient education video series

Constipation: Causes and Symptoms - Mayo Clinic - YouTube http://buff.ly/1pUrfdV



Constipation: Dietary and Behavior Modifications - Mayo Clinic - YouTube http://buff.ly/Sq8lNv



Constipation: Lifestyle Modifications - Mayo Clinic - YouTube http://buff.ly/1pUrsO9



Constipation and the Colon - Mayo Clinic - YouTube http://buff.ly/Sq8pg8

What is Gluten? AsapSCIENCE video

From Jimmy Kimmel Live: "Some people can't eat gluten for medical reasons, but a lot of people in Los Angeles don't eat gluten because someone in their yoga class told them not to. Jimmy wondered how many of these people even know what gluten is, so we sent a camera crew out to a popular exercise spot here in LA and asked people who are gluten-free a simple question: "What is gluten?"



Gluten free diets have become widespread over the past few years, from people with celiac disease, who have a true medical reason for avoiding gluten, to people who mistakenly believe it will help them stay healthy or lose weight. There is also a group of people in the middle of the spectrum: those who haven’t been formally diagnosed with celiac disease, but suffer from similar symptoms and believe their bodies are sensitive to gluten nonetheless.

Stefano Guandalini, MD recently answered a few questions on the topic at the UChicago Science Life blog: The existence of non-celiac gluten sensitivity, as it’s called, has been under debate recently in the medical community. In December, researchers from Australia published a study in which people who didn’t have celiac disease but self-reported sensitivity to gluten were placed on diets containing low or high amounts of gluten, or a placebo. Those on the placebo diet–meaning no gluten at all–still reported a worsening of their symptoms. The culprit, researchers believe, may not be gluten at all, but instead a combination of carbohydrates and sugars known as FODMAPs, which are often found in gluten-containing foods.

Read the full interview here: Does Non-Celiac Gluten Sensitivity Exist? | UChicago Science Life http://buff.ly/1tDshbG

Autoimmune hepatitis - 2013 Lancet review

In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity.

Autoimmune hepatitis can present in acute or chronic forms.

Remission is achievable in up to 85% of cases. For the remaining patients, immunosuppression is an option.

Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma.

References:

Autoimmune hepatitis: The Lancet http://bit.ly/1aApnxp

Hepatitis A

Excerpts from a recent review in Am Fam Physician:

Hepatitis A is a common viral illness worldwide. It incidence in the U.S. has diminished as a result of immunization.

How is Hepatitis A transmitted?

Hepatitis A virus is transmitted through fecal-oral contamination, and there are occasional outbreaks through food sources.

What are the symptoms of Hepatitis A?

Young children are usually asymptomatic, although the likelihood of symptoms tends to increase with age.

What is the prognosis of Hepatitis A?

Most patients recover within 2 months of infection. However, 10-15% of patients will experience a relapse in the first 6 months. Hepatitis A virus does not usually result in chronic infection or chronic liver disease.

What is the treatment for Hepatitis A?

Supportive care is the mainstay of treatment, for example, PO and IV fluids if nausea and vomiting are severe, etc.

How to prevent Hepatitis A?

The CDC recommends routine vaccination of all children 12-23 months of age, as well as certain vulnerable populations.

What to do if you have just been exposed to Hepatitis A?

Hepatitis A vaccine is also recommended for most cases of postexposure prophylaxis. Immunoglobulin is an acceptable alternative.

References:

Hepatitis A. Matheny SC, Kingery JE. Am Fam Physician. 2012 Dec 1;86(11):1027-34.

There are patients with "gluten sensitivity" in whom neither allergic nor autoimmune mechanisms can be identified

There are 3 main forms of gluten reactions:

- allergic (wheat allergy)
- autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia)
- possibly immune-mediated (gluten sensitivity) ("non-celiac gluten sensitivity" or NCGS). We need to be extremely cautious in calling somebody gluten sensitive. It may be sensitivity to FODMAPs instead. It could have nothing to do with gluten at all. http://buff.ly/1k2UjNW -- Fodmaps are sugars that draw water into GI tract (fermentable oligosaccharides, disaccharides, monosacch, polyols) http://buff.ly/1CQpQcc

Celiac disease is the most common genetically based food intolerance (1% prevalence among general population) (JAMA 2014, http://buff.ly/1cJWgFy).

From BMJ:

It is now becoming clear that, besides those with celiac disease or wheat allergy, there are patients with gluten sensitivity in whom neither allergic nor autoimmune mechanisms can be identified. It has been estimated that, for every person with celiac disease, there should be at least six or seven people with non-celiac gluten sensitivity. Gluten sensitivity may therefore affect 6-10% of the general population.

Patients with gluten sensitivity have negative immuno-allergy tests to wheat and negative celiac disease serology; normal endoscopy and biopsy; clinical symptoms that can overlap with those of celiac disease, irritable bowel syndrome, and wheat allergy; and they show a resolution of symptoms when started on a gluten-free diet.

Currently there are no laboratory biomarkers specific for gluten sensitivity, and the diagnosis is based on exclusion criteria; elimination of gluten-containing foods from the diet followed by an open challenge is most often used to establish whether health improves with the elimination or reduction of gluten from the patient’s diet.

New nomenclature and classifications are proposed (see the figures below).



"Fibromyalgia of the gut"

Some physician have labeled "gluten sensitivity" "fibromyalgia of the gut" to reflect the presence of symptoms in the absence of pathological findings. The BMJ editor-in-chief reflected on these doubts in an editorial: Gluten sensitivity: real or not?.

Since there are no biomarkers, gluten sensitivity is the ultimate diagnosis of exclusion. The worldwide shift to the Mediterranean diet may explain the rising prevalence of gluten sensitivity. The has been an “explosion of requests” for serological testing for celiac disease since 2007.

3 million Americans are living with celiac disease

Celiac disease, an immune system reaction to gluten in the diet, is four times as common today as it was 50 years ago. Lack of awareness of celiac could be contributing to a delay of up to 11 years in diagnosis of adults in North America (http://goo.gl/sy778).

This is an informative and beautifully designed video by the University of Chicago Celiac Disease Center. It looks like an infographic made into video - have a look:



New classification is being proposed for gluten-related disorders: celiac disease; dermatitis herpetiformis; gluten ataxia; wheat allergy; gluten sensitivity. WSJ, 2012.

Recent studies support the existence of the new condition nonceliac gluten sensitivity which is defined as symptoms with negative celiac antibodies and biopsy (http://goo.gl/57IlB).

References:

Non-coeliac gluten sensitivity | BMJ, 2012.

Gluten sensitivity: real or not? | BMJ http://buff.ly/ZgKgK1

Does gluten sensitivity in the absence of coeliac disease exist? | BMJ http://buff.ly/RvC7zg

New nomenclature and classification of gluten-related disorders - http://www.biomedcentral.com/1741-7015/10/13/figure/F1

Algorithm for the differential diagnosis of gluten-related disorders, including celiac disease, gluten sensitivity and wheat allergy - http://www.biomedcentral.com/1741-7015/10/13/figure/F4

Spectrum of gluten-related disorders: consensus on new nomenclature and classification. Anna Sapone et al. BMC Medicine 2012, 10:13 doi:10.1186/1741-7015-10-13.

Image source: Colon (anatomy), Wikipedia, public domain.

Disclaimer: I am an Assistant Professor of Medicine and Pediatrics at University of Chicago.

Comments from Google Plus:

Neil Mehta: thanks for sharing this. Besides the content itself, Really like this type of articles where a patient can write about medical lessons learned. 


Howard Luks: That's me :-) thanks for sharing this! My GI guy will see it in the AM 

Pancreatic Auto Islet Transplantation with Total Pancreatectomy - Johns Hopkins Video

Animation explaining the pancreatic auto islet transplantation process with complete removal of the pancreas to treat pancreatitis:

Only 60% of the eligible U.S. population gets screened for colon cancer

Only 61% of the eligible population in the USA gets screened for this common cancer, according to The Lancet.

Here are some excerpts from the new guidance for colorectal cancer screening by the American College of Physicians (ACP):

- colorectal cancer screening should start at the age of 50 years for people at average risk, and at 40 years (or 10 years before the age of the youngest case of colorectal cancer in a family) for people at high risk

- stool-based tests, flexible sigmoidoscopy, and optical colonoscopy are all acceptable screening options for people at average risk

- the gold standard—optical colonoscopy—is recommended for people at high risk

- screening should be stopped for adults aged over 75 years or who have a life expectancy of less than 10 years

Colorectal cancer screening can lead to harmful outcomes such as perforation, bleeding, and false-negative results.

10 Questions You Need to Ask About Colonoscopy

From The NYTimes:

1. Why is effective bowel preparation important?
2. How can I maximize my chance of an effective bowel preparation?
3. Are there certain medications I should stop taking before colonoscopy?
4. Are all colonoscopists equally effective at finding polyps and cancers during colonoscopy?
5. How can I be sure that my colonoscopist will do a careful examination?
6. How can I reduce the risk of a complication during colonoscopy?
7. Should I try colonoscopy without sedation?
8. If I undergo sedation, should it be given by an anesthesiologist?
9. Do all colonoscopists follow the same rules to determine when my colonoscopy should be repeated?
10. Why aren’t the problems with the delivery of colonoscopy already solved?

Questions # 1, 2, 3, 6, 7 are very important, question # 10 probably not so much.

17% of U.S. hospitals now provide virtual colonoscopy


Medicare does not currently reimburse routine screening with virtual colonoscopy, but it does cover evaluations with "regular" colonoscopy.

References:

New guidance for colorectal cancer screening. The Lancet, Volume 379, Issue 9820, Page 978, 17 March 2012.
Virtual Colonoscopy Gains in Popularity. Is It Right for You? TIME.
Colonoscopy Developer Dies at 94 - NYTimes http://goo.gl/iBnOp - Dr. Wolff was unconventional and surely made headlines in his day.
When President Obama underwent his first-ever colon cancer screening last year, he chose virtual colonoscopy. USA Today.
Cleveland Clinic Colorectal Cancer Risk Assessment Tool. Get your score in 2 minutes (free).
Image source: Colon (anatomy), Wikipedia, public domain.

Spectrum of gluten-related disorders: consensus on new nomenclature and classification

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals.

Celiac disease is the most common genetically based food intolerance (1% prevalence among general population) (JAMA 2014, http://buff.ly/1cJWgFy).

In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide.

Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010.

This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns.

This review summarized the current knowledge about the 3 main forms of gluten reactions:

- allergic (wheat allergy)
- autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia)
- possibly immune-mediated (gluten sensitivity) ("non-celiac gluten sensitivity" or NCGS)

New nomenclature and classifications are proposed (see the figures below).



Key figures:

New nomenclature and classification of gluten-related disorders - http://www.biomedcentral.com/1741-7015/10/13/figure/F1

Algorithm for the differential diagnosis of gluten-related disorders, including celiac disease, gluten sensitivity and wheat allergy - http://www.biomedcentral.com/1741-7015/10/13/figure/F4

3 million Americans are living with celiac disease

Celiac disease, an immune system reaction to gluten in the diet, is four times as common today as it was 50 years ago. Lack of awareness of celiac could be contributing to a delay of up to 11 years in diagnosis of adults in North America (http://goo.gl/sy778).

This is an informative and beautifully designed video by the University of Chicago Celiac Disease Center. It looks like an infographic made into video - have a look:



New classification is being proposed for gluten-related disorders: celiac disease; dermatitis herpetiformis; gluten ataxia; wheat allergy; gluten sensitivity. WSJ, 2012.

Recent studies support the existence of the new condition nonceliac gluten sensitivity which is defined as symptoms with negative celiac antibodies and biopsy (http://goo.gl/57IlB).

References:

Spectrum of gluten-related disorders: consensus on new nomenclature and classification. Anna Sapone et al. BMC Medicine 2012, 10:13 doi:10.1186/1741-7015-10-13.
Image source: Colon (anatomy), Wikipedia, public domain.
Disclaimer: I am an Assistant Professor of Medicine and Pediatrics at University of Chicago.
Non-coeliac gluten sensitivity | BMJ http://bit.ly/SlOTNO

Comments from Twitter:

Karen Price @brookmanknight: reflects well what we see in clinical practice, though haven't seen or dx'd too much derm herpetiformis.

Crohn's disease - 2011 review

Crohn's disease is a chronic inflammatory condition affecting the GI tract at any point from the mouth to the rectum.

Symptoms and signs may consist of:

- diarrhea
- abdominal pain
- fever
- weight loss
- abdominal masses
- anemia

Extraintestinal manifestations of Crohn's disease include:

- osteoporosis
- inflammatory arthropathies
- scleritis
- nephrolithiasis
- cholelithiasis
- erythema nodosum

Laboratory findings

Acute phase reactants, such as CRP and ESR, are often increased with inflammation and may correlate with disease activity.

Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status.

Procedures often used to diagnose Crohn's disease:

- colonoscopy with ileoscopy
- capsule endoscopy
- computed tomography (CT) enterography
- small bowel follow-through

Diagnostic tools for extraintestinal manifestations or complications (e.g., abscess, perforation):

- ultrasonography
- computed axial tomography (CT)
- scintigraphy
- MRI

Medical management

Mesalamine products are used for mild to moderate colonic disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment.

Patients with moderate to severe Crohn's disease are treated with:

- corticosteroids
- azathioprine
- 6-mercaptopurine
- anti-tumor necrosis factor agents (e.g., infliximab, adalimumab)

References

Diagnosis and management of Crohn's disease. Wilkins T, Jarvis K, Patel J. Am Fam Physician. 2011 Dec 15;84(12):1365-75.

Image source: Colon (anatomy), Wikipedia, public domain.

Cirrhosis - 2011 update from Am Fam Physician

Cirrhosis is the 12th leading cause of death in the United States. The mortality rate is 9.7 per 100,000 persons.

The most common causes of cirrhosis are:

- alcohol abuse
- viral hepatitis
- nonalcoholic fatty liver disease is emerging as an increasingly important cause

Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every 6-12 months.

Causes of hepatic encephalopathy include:

- constipation
- infection
- gastrointestinal bleeding
- some medications
- electrolyte imbalances
- noncompliance with medical therapy

Treatment

Lactulose and rifaximin are aimed at reducing serum ammonia levels.

Ascites should be treated initially with salt restriction and diuresis. Physicians should be vigilant for spontaneous bacterial peritonitis.

Patients with acute GI bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours.

Prevention

Mechanisms to reduce the incidence of cirrhosis:

- treat alcohol abuse
- screen for viral hepatitis
- control risk factors for nonalcoholic fatty liver disease

Cirrhosis: Phil's story (video):



From NHSChoices: Many people enjoy a drink in the pub after work without realising how social drinking can damage health. Phil didn't realise the harm his alcohol intake was doing until he was diagnosed with cirrhosis of the liver. He talks about his experience and the shock he felt at being diagnosed.

References

Cirrhosis: diagnosis, management, and prevention. Starr SP, Raines D. Am Fam Physician. 2011 Dec 15;84(12):1353-9.

Cirrhosis - JAMA Patient Page, 2012.

Chronic Diarrhea - Diagnostic Evaluation

Chronic diarrhea is defined as a decrease in stool consistency (loose BM) for more than 4 weeks (Am Fam Physician, 2011).

It can be divided into 3 categories:

- watery
- fatty (malabsorption)
- inflammatory

Watery diarrhea

Watery diarrhea may be subdivided into:

- osmotic
- secretory
- functional, e.g. IBS

Watery diarrhea includes irritable bowel syndrome (IBS), which is the most common cause of functional diarrhea. Another example of watery diarrhea is microscopic colitis, which is a secretory diarrhea affecting older persons.

Laxative-induced diarrhea is often osmotic.

Malabsorptive diarrhea

Malabsorptive diarrhea is characterized by excess gas, steatorrhea, or weight loss. Giardiasis is a classic infectious example of malabsorptive diarrhea.

Celiac disease (gluten-sensitive enteropathy) is also malabsorptive, and typically results in weight loss and iron deficiency anemia.

Inflammatory diarrhea

Inflammatory diarrhea, such as ulcerative colitis (UC) or Crohn disease, is characterized by blood and pus in the stool and an elevated fecal calprotectin level.

Invasive bacteria and parasites also produce inflammation. Infections caused by Clostridium difficile (C. diff.) subsequent to antibiotic use have become increasingly common and virulent.


Image source: Escherichia coli, Wikipedia, public domain.

Not all chronic diarrhea is strictly watery, malabsorptive, or inflammatory, because some categories overlap.

References:

Evaluation of Chronic Diarrhea. Juckett G, Trivedi R. Am Fam Physician. 2011 Nov 15;84(10):1119-1126.
Skin patch vaccine to prevent travelers' diarrhea
Image source: Colon (anatomy), Wikipedia, public domain.

How to investigate mildly elevated liver transaminase levels

Mild elevations in the liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST) are commonly found in asymptomatic patients.

The most common cause is nonalcoholic fatty liver disease (sometimes called nonalcoholic steatohepatitis or NASH), which can affect up to 30% of the U.S. population.

Other common liver causes include:

- alcoholic liver disease
- medication-associated liver injury
- viral hepatitis (hepatitis B and C)
- hemochromatosis



Pale stool and dark urine (click to enlarge the images). This is an example of "obstructive" jaundice with the classic constellation of tea-colored urine and clay-colored stool.

Less common liver causes include:

- alpha-1-antitrypsin deficiency (AAT)
- autoimmune hepatitis
- Wilson disease

Extrahepatic conditions can also cause elevated liver transaminase levels:

- thyroid disorders
- celiac disease
- hemolysis
- muscle disorders

Initial testing should include:

- fasting lipid profile (FLP)
- measurement of glucose
- serum iron and ferritin; total iron-binding capacity (TIBC)
- hepatitis B surface antigen and hepatitis C virus antibody

If above test results are normal, a trial of lifestyle modification is appropriate.

Additional testing may include:

- ultrasonography (USG) of liver
- alpha-1-antitrypsin (AAT) and ceruloplasmin
- serum protein electrophoresis (SPEP)
- antinuclear antibody (ANA), smooth muscle antibody (ASMA), and liver/kidney microsomal antibody type

GI evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for more than 6 months.

References:

Causes and evaluation of mildly elevated liver transaminase levels. Oh RC, Hustead TR. Am Fam Physician. 2011 Nov 1;84(9):1003-8.

Linaclotide for treatment of constipation - minimally absorbed peptide agonist of guanylate cyclase C receptor

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. It consists of 14 amino acids. The sequence is:

H–Cys1–Cys2–Glu3–Tyr4–Cys5–Cys6–Asn7–Pro8–Ala9–Cys10–Thr11–Gly12–Cys13–Tyr14–OH

Two randomized, 12-week trials included 1,300 patients with chronic constipation (NEJM, 2011). Patients received either placebo or linaclotide once daily for 12 weeks.

The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in linaclotide groups.

Linaclotide reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks of linaclotide in chronic constipation.

References:

Two Randomized Trials of Linaclotide for Chronic Constipation. N Engl J Med 2011; 365:527-536August 11, 2011.

Image source: Colon (anatomy), Wikipedia, public domain.