Anion gap not great for lactic acidosis

Interesting study from 1990 showing that anion gap is not sensitive as a screening for lactic acidosis in a critically ill patients

May-Thurner syndrome

50 yo female with no prior medical history p/w left lower extremity swelling. She is found to have a DVT extending from the external iliac to the posterior tibial vein, big clot! 

The radiologist thought it could be due to compression of iliac vein between the spine and iliac artery => May-Thurner syndrome.

What to do about that? 

A case report and review of literature suggests that:

"Endovascular therapy is the current mainstay of treatment for May-Thurner syndrome. Review of the current literature supports treatment via catheter-directed thrombolysis followed by stent placement with good early results."

A review from Annals of Vascular Surgery suggest:

"Treatment is based on the clinical presentation and includes staged thrombolysis with/without prophylactic retrievable inferior vena cava filter placement, followed by angioplasty/stenting of the left iliac vein in MTS patients with extensive DVT"

Weight loss and exercise in diabetes - Look AHEAD Trial

I just saw dr Anne Peters talking on Medscape why the Look AHEAD trial was stopped:

http://www.medscape.com/viewarticle/772429?src=mp&spon=38

As a reminder, the trial failed to show over a period of 11 years that modest weight loss and exercise can decrease CV events and death in patients with type 2 DM. There were some benefits however, like less OSA and urinary incontinence, slower decline in mobility in overweight adults.  Further analysis of data from the trial are still underway. In general there were few CV events in both groups.

It seems like another thing taken for granted in medicine is not that clear-cut when tested under the scrutiny of a RCT or is it? What is important to note, patients in the control group did not gain weight and actually lost some weight (1%), also in general the groups were fairly well-controlled in terms of their diabetes (A1c 7.3%) and lipids (LDL 112 mg/dL) comparing to a significant number of patients we see. Should the population studied be different? If somebody starts with an A1c of 7.3% and with weight loss and exercise is able to get it down to lets say 6.9%, do we think it make a difference in her CV outcomes.

What also is noticeable is the amount of weight loss the intervention group was able to achieve with this considerable amount of help - 8.6% in the first year, which was not sustained and stayed at about 5% for the rest of the study. Losing weight is very hard!

Does this patient have a chronic wound infection?

Another article from JAMA series of articles on the rational clinical examination:

JAMA, February 8, 2012 - vol. 307, No. 6

The only proven indicator on history was INCREASING PAIN, however lack of it did not rule out infection.

Other symptoms and signs, which are commonly used, were not helpful in making the diagnosis, i.e.
- Erythema
- Edema
- Heat
- Foul odor
- Discolored granulation tissue
- Serous exudate
- Purulent exudate
- Sanguinous exudate
- Delayed healing
- Wound breakdown
- Pocketing

Classic signs of wound infection, evaluated in isolation from the clinical context and other findings, are not particularly helpful in diagnosing infection in a chronic wound (LR 0.8-2.3). Available studies suggest that the character of wound fluid exudates is most likely not useful as predictor of infection when the reference standard is a deep tissue biopsy culture.

What is interesting, when IDSA criteria for diagnosing infected diabetic foot ulcers were studied, they were found to lack utility (Se and Sp 50%), which turned out to be both surprising and dissapointing, it highlights the difficulty of making the diagnosis.

Non-invasive test that appeared promising - quantitive swab culture with Levine technique - swab is rotated an area of 1x1 cm for 5 seconds with sufficient pressure to extract fluid from within the wound tissue. Positive test made infection more likely, negative test made it less likely.

Get up and go

Screening test for fall risk in the elderly.

Should be performed in around 10 seconds if you ask the patient to walk 3 meters.

Nice chart to document results.

Iron (1) - Physiology

NEJM January 26, 2011 - two articles on iron pathophysiology, one on iron overload the other on minihepcidins. It motivated me to review iron physiology.

Iron physiology:

How much iron do we have? ~4 grams


Absorption in duodenum 1-2mg/day, transport by transferrin, utilization by BM and muscle, storage as ferritin in liver and reticuloendothelial cells (ferritin can be oxidized to hemosiderin), loss mainly by sloughed mucosal cells.

Iron store regulation is achieved by regulating iron absorption, there are no physiological means of iron excretion!

Iron absorption:


Bioavailability: heme > Fe 2+ > Fe 3+ 

Why heme is better absorbed? Different mechanism.


What form of iron is absorbed?

Iron is rapidly oxidized in physiologic pH, low pH slows this process.

Most dietary iron is turned into it's ferric form (Fe 3+), which is insoluble. Ferric iron is reduced by an enteral brush border enzyme to ferrous (Fe 2+) so the DMT-1 can transport it into the cell. Low gastric pH and vitamin C facilitate this process by slowing iron oxidation.

Where? Duodenal enterocytes

How? DMT-1 which stands for divalent metal transporter-1, so a lot of divalent metal get in this way and can compete with iron. Examples? Lead, copper,
cobalt, zinc, strontium, cadmium

What next? Iron stays in the cell as ferritin or gets out transfered by ferroportin

What helps ferroportin?

Hephaestin, a copper-dependent enzyme, oxidizes iron back into ferric form to help iron efflux from the cell; it is found mainly in the intestinal villi;


Two key proteins in iron physiology:


1. Ferroportin - transporter, which transports iron out of cells;

2. Hepcidin - liver peptide, binds to ferroportin stimulating its internalization and lysosome degradation

How do we lose iron? Sloughing of enterocytes. How does iron know to get into enterocytes to be lost?

High hepcidin -> low ferroportin -> iron stays in entrocytes -> epithelium sloughed -> iron loss

So iron never gets out of the enterocytes in the first place!

Iron transport


Why iron cannot be free? It's dangerous! Free radical production by the Fenton's reaction.

Fe²⁺ + H₂O₂ ----> Fe³⁺ + .OH + OH^-

Fe³⁺ + H₂O₂ ----> Fe²⁺ + .OOH + H⁺

It is bound to transferrin.

Utilization

1. BM -> erythroid precursors -> hemoglobin

2. Muscle -> myoglobin

Storage

1. Liver -> hepatocytes and Kupffer cells (reticuloendothelial cells)

2. Reticuloendothelial system 

So where in our bodies is most of the iron contained?

Tricky question... in circulating RBC's (~1800 mg), almost half.

Sputum in bronchitis

COPD exacerbation is defined by:
- increase in cough
- increase in dyspnea
- change in sputum quality/quantity

Recent study confirms the correlation between sputum color and the presence of potentially pathogenic bacteria. Especially yellow or green sputum was more predictive than sputum purulence or dyspnea in acute exacerbations.

Currently when do we use abx?

 All three above-mentioned criteria.

When we use two criteria, one has to be change in sputum.