How is your calcium?

How is your calcium? Is it good or bad? Does it help you or hurt you? Where is it? Evaluating calcium in humans is a lot like evaluating a piece of real estate: It is all about location, location, location.

First, the good places: More than 99% is in teeth, bones, or blood and intra- and extracellular fluid.

Then, the bad places: soft tissues; kidneys and urinary tract; artery and vein walls; tumors; female breasts; or as part of resolving necrosis or cellular degeneration.

How does it get there? Calcium in, calcium out. Calcium in: maybe a supplement of 1000 mg/day orally for an adult. Calcium out: via urine and feces, with the retained calcium being managed by spectacular metabolic homeostasis. It is a very delicate balance.

One of the ways that calcium appears in seemingly unwanted locations is called “dystrophic calcification,” and its presence seems relatively inert.

Can you move calcium around in the body? Maybe not moving individual calcium moieties from place to place, but can you regulate how much of what kind of calcium is in any one place at any one time?

Like the Blind Man and the Elephant: Point of View Matters

  • The nutritionists would say: This is all about diet.
  • The endocrinologists would say…a lot; they really know this field.
  • The imagers would say: I love calcium; it gives me so many fun things to look at, measure, and analyze to try to predict importance.
  • The urologists would say: I can take care of your stones. We will flush them out or pluck them out or shake them into small pieces with the lithotripter. And by the way, here is your $30,000 bill.
  • The mammographers and breast surgeons would say: If I did not have calcium flecks to find in the mammogram, I might have a really hard time justifying biopsies.
  • The procedural interventionists would say: Send me your calcified arteries; I have a stent for you.
  • Big pharma would say: We have lots of drugs.
  • The outlier chelationists would say: We can give you some IV infusions to get rid of all that bad stuff.

As a pathologist, I have cut—or, more accurately, sawed—a whole lot of bones, healthy and diseased. It is really good to have a lot of calcium as hydroxyapatite there, in the bone. I have cut up a lot of kidneys destroyed by stones obstructing the urinary tract. Calcium can be really bad to have there. I have longitudinally opened or perpendicularly transected many hundreds of large and small arteries; many normal, many diseased by narrowing; many occluded by atherosclerotic plaque, intraplaque hemorrhage, cholesterol, thrombus (acute, evolving, organized, or recanalized), and calcified; sometimes very thick, hard, brittle, even rigid; and especially in arteries of hearts, brains, necks, chests, bellies, legs. Bad.

But which came first: the chicken or the egg? Was the vascular wall calcium an instigating progenitor, a fellow traveler as simple dystrophy, a part of the inflammatory pathogenesis, or a culminating bony add-on for advanced atherosclerosis? Those are really good questions.

Here’s the new stuff. A large volume of alternative literature has been hyping vitamin K2 as active in preventing or treating arterial calcification for years. But serious science now seems to be backing that up. The relationship of vitamin D, vitamin K2, and calcium may hold a real key to a better understanding of harmful arterial calcification. Check it out; keep an open mind;

A novel promising biomarker for monitoring and prognosis of heart failure patients

In this regard it is noteworthy to mention ST2 which is a widely accepted biomarker for prognosis and risk stratification of heart failure patients and is highly specific to the cardiac tissue. sST2 protein is independent of traditional factors, such as age and BMI, which usually affect levels of NT-proBNP

ST2 (for growth Stimulation expressed gene 2; also known as IL1RL1, or Interleukin 1 Receptor-Like 1) is a member of the interleukin 1 receptor family. The ST2 protein has two isoforms directly implicated in the progression of cardiac disease: a soluble form (referred to as soluble ST2
or sST2) and a membrane-bound receptor form (referred to as the ST2 receptor or ST2L).

The ligand for ST2 is the cytokine Interleukin-33(IL-33). Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, such as an ischemic event, elicits a cardioprotective effect resulting in preservedcardiacfunction.

This cardioprotective IL-33 signal is counter-balanced by the level of soluble ST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of soluble ST2, leading to cellular death and tissue fibrosis, reduced cardiac function, and increasing the rate of disease progression.

Multiple published studies have demonstrated that the level of ST2 in blood can help a physician better predict a patient’s prognosis, and thus make better treatment decisions than solely employing clinical parameters and existing laboratory assays.

ST2: An overview of clinical utility

The ideal clinical situation for using ST2 is for prognostication, risk stratification and mortality prediction of a patient with acute decompensated HF. sST2 has been considered as a possible biomarker in dyspnoeic patients with and without acute destabilized HF referred to the emergency department. Notably high levels of ST2 are seen in chronic HF patients. Determining ST2 plasma levels in chronic HF patients can drive therapy decision making and predictions of clinical outcomes. A combination of ST2 with other well established markers like NPs, troponins and CRP can further augment the prognosis and risk stratification in HF patients. Patients with ST2 >35 ng/ml have a 2.8x higher risk of adverse outcomes within 30 days than patients with low ST2 concentrations. The relative risk of adverse events in patients with ST2 > 35ng/ml persists at a level of at least 1.8 for a follow up period of 4 years. Patients with a greater decrease in sST2 during serial monitoring (baseline & week 2) have better outcomes at one year than patients with smaller change in sST2, independent of NT-proBNP concentration.

ST2: The regulatory status and endorsement by guidelines

The American College of Cardiology Foundation/American Heart Association Task Force jointly released its expanded clinical practice guideline for the management of patients with heart failure and has identified ST2 “not only predictive of hospitalization and death in patients with HF [heart failure] but also additive to natriuretic peptide levels in its prognostic value.” In 2011, the US FDA had also provided its approval to the use of presage ST2 as a biomarker for prognosis of chronic heart failure.

Sperm can carry the Ebola virus for at least 82 days

Sperm can carry the Ebola virus for at least 82 days, the World Health Organization has said, urging men recovering from the disease to use condoms for three months after the onset of symptoms.

“Because of the potential to transmit the virus sexually during this time, they should maintain good personal hygiene after masturbation, and either abstain from sex (including oral sex) for three months after onset of symptoms, or use condoms if abstinence is not possible,” the WHO said in a statement.

In four studies, on a total of 43 patients, three men who had recovered from Ebola still had the live virus in their semen 40 days, 61 days and 82 days respectively after the onset of symptoms.

The WHO said that no case of sexual transmission of Ebola had been documented, and that it was unclear whether semen that tests positive for Ebola is actually infectious.

The four studies were carried out in different countries, with the first dating back more than 30 years.

Microtransplant – Read on

Nineteen-year-old Neena (name changed) was suffering from acute blood cancer or acute myeloid leukaemia. Her disease slipped into a life-threatening stage even after two cycles of chemotherapy. She did not have a human leukocyte antigen, or HLA matched related or unrelated donor for a stem cell transplant, the standard procedure for such medical situations.

It was then a team of specialists led by Dr. Neeraj Sidharth, Head of Bone and Marrow Transplant programme at the Kochi-based Amrita Institute of Medical Sciences decided to try, a relatively new treatment protocol, for the first time in India, to save Neena’s life called ‘Microtransplant’, which involves normal chemotherapy followed by infusion of intentionally mismatched cells.

This unique procedure is based on immunological killing of leukemic cells. The result was a success and Neena can possibly spring back to her normal life, though long-term data on a larger number of patients are required to validate the medical procedure.

“Worldwide cellular therapy has been done in a more sophisticated and costly manner in select centres at North America. Natural Killer Cell or NK cell therapy and CAR T-cell therapy – engineering patient’s immune cells to treat their cancers, however, is limited by its availability in only a handful of centres. What we attempted was similar to what has been already tried in Israel and China and published in reputed scientific journals,” said Dr. Sidharth, who was guided by experts in the field from John Hopkins Hospital, Baltimore, United States and from China.

Unlike normal treatment for acute blood cancer, this procedure does not require heavy dose of chemotherapy, followed by infusion of matched stem cells to replace the patient’s stem cells. Microtransplant is cost effective – one fifth of the cost of standard treatment available and the patient needs to be hospitalised for just three weeks.

This therapy probably works best when the disease gets reduced immediately after chemotherapy and before normal cells recover. Mostly, it has been tried in some acute leukaemia and melodysplastic syndromes where standard treatment options like a stem cell transplant is either unavailable or considered too toxic. Chances of disease relapsing seem to be significantly lesser compared to standard chemotherapy extrapolating from the long term published data available from China.

The success of the treatment is a major breakthrough and opens up a window of opportunity for those select patients with relapsed and refractory leukemia and standard stem cell transplant is not considered and option for various reasons, said Dr. Sidharth