Friday, August 26, 2016

"WHAT WILL IT TAKE?"



In the matter of writing, exclamation points are used for varying degrees of expressions. Sometime we mean, “look how horrible!” and other times we think, “Can you believe it!” But each exclamation point has a story to tell. Some saucy, some sticky, some plain vanilla wonderful. Sometime with exclamation points, we want to invite the attention of another to come in and enter our thoughts - a difficult proposition indeed. But what about the curly exclamation point that we call the question mark? Where does that take us? And therein lies a tale…

“What will it take?” The answer to that question is not easily available. The answer seems hidden in the last missing page of a well worn mystery novel. Conjuring up ideas of how to answer a question like that one takes skill and wading into an ocean of emotions. Indeed what would it take to fix a problem like Joe’s?

Joe, you see has a medical riddle. He carries a truant gene that seems to create the mischief in his cells. Joe is painfully aware of this for he has been told of the same after three surgeries and countless therapeutic endeavors to salvage his life. He is safe for now. Content at working his daily dose of living as a salesperson in a shoe store. He is on a constant follow up with his oncologist and each visit is marked with the growing fear of the inevitable. He has learned to avoid the downer thoughts but the fog of uncertainty keeps visiting him in times of repose. He is a truly wonderful gentleman. His once blond hair is now gone replaced by a shaved head. his physique is equally diminished after many bouts under the scalpel and chemicals. A once brawny physique, which he claimed he had, is now replaced with the scrawny shadow of the former self that I see. Yet he claims he sees life in a better light now. He walks daily, communes with nature and has a smile that would brighten any dull cloudy day. Faced with the prospects of a hazy future, he has learned the art of living and the wonders of the limits of survival that each one of us take for granted. He is working on a doctorate in psychology. He already has one in physics.

“What will it take?” he asks again. “We shall see Joe, we are working on it.”

“Sorry Sir, but Joe’s plan does not approve the PET/MRI scan without further information and a certified letter from the oncologist.” The tinny voice speaks from the Insurer never-never-land. “But I am the oncologist!”

“We still need documentation Sir.”

“We have received the documentation, but the test is still denied.” a different de-empathized voice responds a week later.


“But I certified the reasoning for the test.”

“Would you like to speak with the supervisor?”

“Sure!”

After the click and the muzak that invites frustration another click and a human voice arrives, “May I help you?”

I am looking for an approval for a PET/MRI scan based on the certified documentation I sent earlier.”

“Could you briefly explain the issue. That will help greatly.”

A ten minute explanation later, we are running in circles.

“Are you a physician?”

“No sir, I am a Registered Nurse.”

“May I speak with physician in your department.”

“Surely.” And the shifting sounds on the telephone cease momentarily and then the infernal muzak comes back to haunt.

“Hello, may I help you?”

“Are you a doctor?”

“Yes, my name is Jane Blah, Blah.”

“I am looking for an approval for a PET/MRI scan.”

“Um, I looked at the records you provided and I am sorry but based on the data, I cannot approve the test.”

“Are you an oncologist?”

“No, I am a pediatrician.”

“Do you have any training in oncology?”

“No.”

“Then how can you deny this request?”

“We have criteria for best practices based on the Choosing Wisely programs and we adhere to that. Besides, we are constantly reviewing the established criteria.”

“Oh! Okay. Do you mind giving me your full name, your position at this Insurance company and your official phone number?”

“Sure, why?

“I will send that information to my attorney and ask the patient to hire an attorney as well so that the future is not as murky for his survival or for an unnecessary litigation. While you adhere to your criteria, a patient's future is at stake that your have promised to help mitigate their financial health needs through premiums. I am sure you will prevail!” The sarcasm and irony was not lost on the receiver.

“There is no need for that!” The voice on the other end has some degree of angst now.

“There is a need for this, when you arbitrarily try to make decisions based on your esteemed guidelines without consideration of your client’s needs.”

“Let me see what I can do.”

The phone goes dead.


And therein lies a tale to ponder upon! This exclamation point has many meanings but only a few very clear expressions!

Thursday, August 11, 2016

CANCER CELL CYCLE & the CDK INHIBITORS



Interesting thing about medicine is that knowledge never seems to end. It comes in waves as brilliant folk look upon failures and success with a critical eye and not through the lens of judgment. For both adding to success and learning from failure ultimately defines progress.


We have known about the cell cycle for quite a long time. Lets look upon the cell as it divides from one into two. Such division is required for the growth and well being of the human body. Cyclins are a very Important part of Cell Division and growth!


In short a Cell must go through the cycle of acquiring various agencies of proteins and enzymes before it can divide into two. Cells are in a continuous state of growth and replication. The stages move from G1 —> S —> G2 —> M and back to —>G1

(G1 = Initial state)

(S = Synthesis phase where the cell synthesizes various needed agencies within)

(G2 = Bulking up stage and acquired various agencies)

(M = Mitosis stage or the actual act of division)

There is a G0 cell phase which is interdependent on the G1 phase. G0 cells are quiet but functional, and not surging through the cell cycle. They can recruited into the cycle when need arises.

Chemotherapeutic drugs affect the cells cycle in various stages. eg. Vinca alkaloids and Taxanes in the M phase and the Alkylating agents in the G1 - S phase etc.



We shall focus on the G1 - S Phase inhibitors where most of the mischief seems to take place.

When an external mitogenic stimulus is received, in oncogenesis (tumorogenesis) at the G1 phase, the D1 Cyclins merge with the CDK4 and CDK6 to create a D:CDK4/CDK6 complex. 

(D1 Cyclins + CDK4/CDK6 = D:CDK4/CDK6)



The D:CDK4/CDK6 complex phosphorylates the Retinoblastoma protein (pRb). pRb is a well known tumor suppressor. Thus phosphorylation of the pRb leads to its inactivation. 

The pRb has the unique characteristics of sequestering the E2F family of transcription factors. This inactivation of the pRb leads to release of the E2F family of transcription factors that drive the wayward cancer cell from the G1 through to the S phase.


Although this might seem straightforward and simplistic, let us not forget that there are various Negative feedback loops available to protect us fragile humans. These are the INK family of p16 protein which is encoded by the CDKN2A gene and the CIP/KIP family of p21 and p27 proteins. Provocation by the TGF-beta signaling mechanism via the SMAD3/4 pathway, which leads to expression of the p16 and KIP family of p21 and 27 proteins that act as suppressors of the Cyclin D1 complex formation. Some of the initiators of these negative feedback loos are basic cell senescence and the release of various molecules that trigger the cell growth cessation


The "Ts" suggest blockade and Arrows mean throughput!

The magic being that p16 binds with the CDK4 and CDK6 and prevents them from creating the D:CDK4/CDK6 complex. This binding prevents the cell from going into the next phase of the cell cycle and ultimate division.



Most of the data on the Cycle Dependent Inhibitor activity was determined in Breast Cancer research where the Estrogen Receptor positive cases became resistant to the Anti-estrogenic compounds.

Several drugs have been manufactured as CDK inhibitors. The lead one is Pablociclib, that received FDA approval in Hormone positive Breast Cancer.


Pablociclib by itself was essentially useless as a therapeutic option. But in ER+, HER2- Breast cancer cases that had developed resistance to the antiestrogens, Pablociclib when given with Letrazole there was a substantially higher PFS of 26.1 months versus 7.5 months in (PALOMA-1 trial). PALOMA-2 trial (using Pablociclib + Fulvestrant) confirmed the PALOMA-1 trial data. The dose limiting toxicity, as one might expect, is based on the Neutropenia and Diarrhea. Both organs Bone marrow and the GI tract have fairly robust cell replication. The toxicity seems to have been addressed modestly well with another D:CDK4/CDK6 Inhibitor, Abemaciclib. And Abemaciclib crosses the blood-brain barrier to impact the brain metastatic disease as well. Corroborative data are not yet available on the brain metastatic activity at present.

Lest one thinks that these Inhibitors only work on Breast Cancer, you might not know that animal trials with mice suggest otherwise. Activity is noted in the laboratory in Melanoma, Colorectal Cancer and Non Small Cell Lung Cancer as well. Trials are or will shortly be in progress to prove efficacy in the various malignancies.

The problems that still need to be addressed are whether these “Ciclibs” can be used with chemotherapeutic agents, since both impact the cell cycle dynamics. And whether the combination might reduce the effects of one another. And equally whether they can be used with the Immune check-point Inhibitors (Anti PD-1 and PD-L1) since the growth and proliferation of the T Reg cells is dependent on the Cell Cycle also.
Time, Hard work and Good Basic plus Clinical Research will tell the tale.

Meantime, we have seem to have another arrow in our quiver.

Online References:

1. http://cancerdiscovery.aacrjournals.org/content/6/4/353.full

2. https://genomebiology.biomedcentral.com/articles/10.1186/gb4184

3. http://genesdev.cshlp.org/content/13/12/1501.full

4. http://ac.els-cdn.com/0092867495903852/1-s2.0-0092867495903852-main.pdf?_tid=0e3f1db2-5d7a-11e6-b269-00000aab0f6b&acdnat=1470669128_f251eeee9fd0e65f46702003f67c90e4

Wednesday, August 3, 2016

SUMMER WEATHER FLYING

We were all at the FBO. The three of us; I was the pilot, with my my two non-pilot college friends. They wanted to go flying and it didn't matter what the weather was. Even after mentioning that it was going to be Instrument conditions, they remain unfazed. “we want to see what it feels like in the clouds in a small aircraft!” is what both grown men chimed simultaneously.

On the other hand there were these beautiful relatively still looking clouds overhead at around 2000 feet with a soft underbelly undulating to the rigors of the Appalachian mountain waves currents. The atmospheric hue was a crisp grey with a bit of a yellowish hue thrown in.


“A bit of a yellowish hue?” My mind raced back many years earlier. I had not quite hit the teens then and there we were the three friends who had promised to remain friends forever, now lost to each other in the sea of human life’s tumult. But there in the Raspberry tree bearing white raspberries in the bushels, we sat crushing the juice out of nature one raspberry at a time. Meanwhile, the yellowish hue deepened a bit, the colors intensified and just as smartly the first raindrop fell. We chose to ignore it and soon drenched in a deluge we sought shelter in the nearby friend's home. The rain it poured and poured till the streets couldn't take it anymore and let go of onrushing waves and waves of water turning gardens and lawns into shallow swimming pools.

It was the same color this day! I mentioned the weather issues and the two daredevils wanted nothing to do with that. Their reaction against my weather reading judgment was; “Dont be a Chump!” “Chicken, “ then there was the “Chicken wing walk around” and a litany of other disparagements that good friends are wont to do. So I suggested that we go have an early lunch and if the weather truly was not changing, then we could continue with our plans. They agreed as long as I paid for the lunch.


Entering the diner, I felt a raindrop on my head. Soon we were seated and I pulled out my smartphone and checked the weather. There were isolated green and yellow spots of radar images suggesting a few scattered cells in the area and one tiny green one overhead. I checked the k-index ("vertical temperature lapse rate, moisture content of the lower atmosphere, and the vertical extent of the moist layer.” - Mathematically speaking: K-INDEX K = (T850 - T500) + Td850 - (T700 - Td700) The result was not heartening to me; The K Index was listed at 36. (K values +20 indicate some potential for air mass thunderstorms. K values +40 indicate almost 100% chance for air mass thunderstorms). I quietly ordered my lunch and launched on a long conversation about other things.


No sooner had the waiter brought our food, we heard a distinct crackle of thunder and a bright light. Ah, I thought, the tiny green cell had reached out for help from the devil’s worksop. The momentary lapse in the conversation was proceeded with a call for dessert and coffee. But the coffee never came. The water broke and the heavens poured down their heavy weight of moisture into a sheet of blur outside the window. The lights in the dinner flickered and then darkness descended for us so we could see nature’s display outside. The torrents continued, the lightening flashes and the constant rumble interspersed with a loud bark from nature’s displeasure. We paid out the handwritten bill presented to us and thought about escape strategies from the diner towards our vehicles.


That we didn’t fly that day, was good thing. The tiny green blobs predictably had grown over the hour we had sat in the diner and merged together with others to create a “train effect,’ that left us helplessly running for our vehicles when we thought the rain was letting down a bit. But it didn't. Not at all!

Some summer days, it just is better sitting in a hanger, a diner or at home and wishing we were flying. That was certainly one of those days.

I often question had I not had the childhood experience, would I have launched in the air given the two major distractions mixed with insinuations of being a wimp? Given the questionable weather forecast of thunderstorm after 8 pm? I cant say. But I am glad, for the experience, to experience another one in complete ground safety.

In these lazy, hazy, crazy days of summer, when humidity is in the 60%, your shirt is sticking to your skin and the temperatures are hovering around the high eighties or higher, check the K-Index, it might save your life.

Sunday, July 24, 2016

TUMOR INFILTRATING LYMPHOCYTES (TILs)

Much to the chagrin of the astrology experts, Shakespeare had a thing to say about it, “It is not in our stars to hold our destiny but in ourselves.” So what is in ourselves that we need to look at?

Interestingly, plenty of stuff!

In the 1990s there were articles about the importance of the presence of lymphocytes infiltrating the cancerous tissue. Physicians looked at these findings and compared outcomes with and without the presence of lymphocytes. They came away with the unassailable thought that the presence of the lymphocytes had some positive impact on survival. In early stage II/III colorectal cancer for instance they were able to determine that the presence of tumor infiltrating lymphocytes (TILs) in the tumor tissues were associated with longer term survival. Curious indeed, but at that time the tools were not there to study them further.


In Melanoma for instance a similar viewpoint held that TILs helped improve a person’s chances in overcoming the disease. In Melanoma, however, the immunity issue became a singular focus for a long time. Treatments included Interferon therapy, Interleukin-2 (as well in Renal Cel cancer) therapy and Vaccination against the epitope on the melanoma cells. These treatments were quite debilitating in nature, giving symptoms of a aggressive “Flu-like syndrome” each time the patient received the IFN or IL-2. One had to get the Interferon shot daily for 30 days, then three times a week for a year. It wreaked havoc on the patient, but there were responses. People not supposed to live, survived.




Breast Cancer data also seemed to suggest the presence of TILs in the surrounding tissue of the cancer. Little evidentiary information has been gathered or experimented in this malignancy, however, since there are much better methods of treatment available for this malady.

Modern Medicine dating back five or so years has resurrected the whole TIL concept once again and it seems successfully given another kick in the pants.


Knowing that the composition of the lymphocytes is T cells, B cells, NK (Natural Killer) cells, Helper Cells, Dendritic Cells that sample the antigen and macrophages, medicine has figured out how to manipulate the immune system in those patients that have an army of these TILs lurking around the tumor tissue. Since these cells are present, it is obvious that they have sampled the antigen on the cancer cells and having done so, if one were to enhance their effect, one could gain another foothold against this scourge called “The emperor of Maladies.”



Further knowledge development from studying this cellular machinery revealed that the cancer cells have accommodated this immune onslaught quite successfully by using the cell’s own defense mechanism of cloaking their anticancer activity with a protein. This protein, the scientists realized, was preventing the immune function from destroying the tumor. From the alternate point of why, one might ask, why does the body not want to protect itself? The answer was clear, allowing a rampant immune response without any checkpoints would lead the body to “destroy” itself when attacked by a simple infection, akin to a pleasant breeze turning into a hurricane. So checks and balances needed to be present to prevent such hyperbolic activity. 

Well now having delineated the mechanisms of action the Immune brigade can be carefully turned against the cancer itself. First the presence of the TILs is an important precursor to the present thinking. The determination of the protein called PD-1 (receptor on the lymphocyte that limits its anticancer function) and PD-L1 (the receptor present on the cancer cells itself). Inhibiting the function of these receptors has resulted in a plethora of drugs armed and aimed at these two proteins (the guardians against hyperbolic responses). Once the checkpoint has been blocked the immune cells can go on to demolish the enemy (cancer). It goes without saying; the more the TILs the better the body is equipped to be helped or conversely if the disease is advanced with a large tumor burden and low to absent TILs, the lower the chances of response.


We tread slowly towards a better future and I end with Shakespeare again, “ Wisely and slow. They stumble that run fast.”


References:

Adam, S et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014 Sep 20;32(27):2959-66.

https://www.researchgate.net/profile/Claudio_Clemente/publication/14591062_Clemente_CG_Mihm_Jr_MC_Bufalino_R_Zurrida_S_Collini_P_Cascinelli_NPrognostic_value_of_tumor_infiltrating_lymphocytes_in_the_vertical_growth_phase_of_primary_cutaneous_melanoma._Cancer_77_1303-1310/links/541c00f00cf203f155b34fb0.pdf

http://www.cancernetwork.com/oncology-journal/high-dose-interleukin-2-it-still-indicated-melanoma-and-rcc-era-targeted-therapies

http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0431-3

http://jnci.oxfordjournals.org/content/108/11/djw144.short

Wednesday, July 13, 2016

HAWTHORNE EFFECT

You might wonder what this is about. And I, for starting this have a bit of concern too. But this is a story not about the author, Nathaniel Hawthorne of the House of Seven Gables, nor is it about the City in New York. It is about an effect.


Effect, you say, what about it? Actually it is a fascinating insight into the human condition. Let me trace it back to its origins. A town named Cicero in the Chicago burbs, housed a manufacturing plant called Hawthorne Works. 


The Illinois City named after the one in New York, which was named after the Roman statesman Marcus Tullius Cicero . Both the city and the Roman it was named after suffered; the city lost 5/6th of its land due to weak politicians and its manufacturing status and Cicero’s head and hands were displayed in the Rome’s Forum after his assassination for angering Julius Caesar (34 BC).

Hawthorne Works enjoyed prosperity in the early 20th century and there is where it was determined that when observation and positive interest is shown in a worker’s work, productivity goes up and vice versa. Meanwhile the display of Cicero’s body parts in the Roman Forum were of equal force preventing any further threat against Mark Antony’s reign -  a negative feedback. Funny how the ghosts in names play out the future with equal measure gained from their history.


The Hawthorne Effect has been written about and “studies” done on hand washing among physicians and nurses in an effect to reduce the potential for spreading infections. The reality goes this way…if one is being observed to do a job, one is psychologically forced to comply. Thus the rate of hand washing among the observed goes up against the unobserved. It might be called oversight in another document, but in the Hawthorne effect the simple act of observation even via cameras or other digital means conspires to inspire an individual to take action. All well and good. Good actions beget good results.

Extrapolating from this act of “observation” as an “observational interest” and giving that “interest” some term such as “value” might have an identical effect, if not profound, at least above the zero mark in a person’s productivity? Again, don't take this to the bank, because where I am going with this is a hotbed of molten lava created from fire and brimstone. You fall in, you are done! So look, Learn and Understand!

“Moon walking” back to the premise of interest and productivity we find that if an employee feels his worth by the company, he or she tries harder. The idea behind that is simple incentive, create value for the company and be rewarded with promotions and higher salary.

You with me so far? Ok, so what gives in the environment of Medical care then?

Physicians are “burnt out!” Indeed, more and more reports seem to not only suggest, but also correlate that with higher rates of suicides by physicians. The metaphor of “losing a jumbo jet filled with physicians every year.” Or if you prefer, “Losing an “entire year’s worth of medical graduates from medical school” every year. Disabling thought, isn't it?
And you must ask why? Ah there in that three lettered word is the essence of science. 

Why, indeed?

Let me posit a simpler solution; maybe in medicine, there is a negative Hawthorne Effect. with no cheerleaders for the once noble profession, only grim reapers always crying, "foul!" Maybe, physicians are being railed against in the media 365/24/7 and characterized as bad actors. So if you are a physician and work the 12 hour weary days and find the profession maligned on the television and media when you sit down at the table for dinner, something’s got to go "kerplunk!" The negative Hawthorne Effect comes to play - remember Cicero’s head and hands on display as deterrence? When every observation is a negative event, work becomes a chore, the shoulders get slumped, the days get longer, the work becomes weary, soon depressing thoughts arrive, unannounced, the devolving gyre tightens and finally the mind cannot hold.

But don't take me wrong on this, the powers that be seem to have absolutely NO interest in the Medical care of the patients, it seems. The powers that be have an interest in their own interests. For instance, The Insurers are interested in making higher and higher profits (the average Healthcare company CEO salary in 2014 was $11.7 million) and they blame the claims from the physicians and make them go through hoops of the medical Revenue Cycle to collect their reimbursement on behalf of the work completed. The government has an inverse viewpoint; to lower the costs of healthcare as a percentage of GDP (currently 17% of the GDP) and they too blame the physicians as the drivers. To that effect they have the annual CMS “Data Dumps” showing what physicians have received in payments (BTW: in 2012 out of $1.2 Trillion only $70 Billion went to pay the 850,000 physicians that translates to 5.8% of total). They also have a “Sunshine Act” displaying any gifts from pharmaceutical agencies to physicians; citing that $10 lunches invoke a severe Conflict of Interest in prescribing medications. Then there are quasi, not for profit agencies that have their hand in the pot like the ABIM, ABMS (claiming public interest as their only mantra while fleecing the physicians in millions of dollars - NAV as of 2014: $134 million), PWRS, PCORI (Reporting agencies that create pseudo-science on the go to determine efficacy of care) and other shenanigans like SGR, MACRA, MIP, APM (designed to create and maintain an ever-ascending vertical bureaucracy that deems who and how payments are to be made for service rendered). The list goes on...

You still with me?

Consider this; The physician is now a "data logger," a well-educated scribe so to speak, on the computer (EHR) and the computer spits out (based on an algorithm) a defined set of tests to order for compliance. All this cataloging is nothing more than information gleaned by and for other companies to sell data for analysis to insurers and governmental agencies to better control expenses in some cases, raise revenues in others and further the interests of all involved in their Net Asset Values. For instance CERNER an EHR computer company, for the year 2014, revenues were up 16.9% to $3.4 billion from $2.9 billion in 2013. Net income for the 2014 fourth quarter jumped 146% to $147.9 million, up from $60.1 million in the 2013 third quarter. Hmm… Judgment and Reason, need not apply when it comes to patient care anymore. Its about dollars and cents and a large public pot for any company to pull out oodles and oodles of cash. In this “One size fits all,“ for better or worse, EHR world, the actual “fit” is immaterial. So what if the helm shows, the shoulders sag on the jacket, the stitching is subpar. So what? And it will all get worse, I predict, because the non-practicing physicians who have taken on the mantle of “experts” have decided that programs such as “Choosing Wisely” and “Less is More” need to be the bully-pulpit from where to scream down into the trenches, “Do this and Not that, or else…” 

There is a pathological obsession in replicating an idea that is profoundly destabilizing and will ricochet through humanity transecting the tether that binds us all as humans. Ah "disruption" they cry and all fall down to their knees in unison to the lure of the ethereal enriching beast. The capacity to think of the whole and not always the parts in isolation can bring to view the unintended consequences; those things that go "crunch" in the long winter nights are never a part of their thought.

The Mocking Jay



So while this rant appears like a rant and maybe is, it does have the potential of the sound of a “Mocking Jay.” As the people realize what the future holds for them a band of brothers and sisters will finally say, “I’m mad as hell and I’m not going to take this anymore!” The physicians might lead on this and then as care is depleted and noticed, the rest of us will follow suit.

Monday, July 4, 2016

ASPIRIN & CANCER


Every so often a product comes along that defies augury. And yet with each passing future it provides tiny visages of it’s abilities to predict what may lie ahead. Aspirin, the old Salicylic Acid, the most used and ofttimes reviled substance comes to the fore in cancer care.



But barely so, because the pockets of the high and mighty pharmaceuticals continue to whip up a storm of this and that in small incremental advances through complex machinations of the human cellular biology, while Aspirin continues along its merry way easing the burdens of diseases unbeknownst to its takers.

Aspirin and Colorectal Cancer:

Aspirin continues on its quest to impair the mechanism of inflammation; the hallmark of most diseases such as cardiovascular and rheumatological diseases and including cancer. We will leave the heart to the cardiologists, but for now let us delve into the wayward cancer cell.



Low dose Aspirin continues to be a constant nagging positive feature in cancer prevention, much to the delight of many. The most recently studied data disclosed suggest a significant reduction of risk and death from Colorectal cancer in those using a daily dose of lo-dose Aspirin. Looking at the mechanism, it becomes clear that COX-2 inhibition may be at play here. 


The implications stem from the reduced inflammatory effect and the production of polyp formation. Since most such polyp formations precede colon cancer and with the steady stream of sequential and sometime concurrent genetic mutation is at play in the polyps. Preventing the polyp formation itself becomes the “Strike three” (in baseball analogy) against the cancer. 



Aspirin and Esophageal and Stomach Cancer:

Continuing on the gastrointestinal tract issues, there is also abundance of proof that suggests that the same lowly lo-dose Aspirin taken over 5 years also may reduce the risk of Esophageal and Stomach cancers by 30% and death from these malignancies by 35-40% (1). A meta analysis of eight studies using individual patient data showed an overall lower deaths from common cancers in those patients consuming daily Lo-Dose Aspirin (3).

Aspirin and Colon, Breast and Prostate Cancers:

Another study highlighted benefits of risk and death reduction in bowel, breast and prostate cancer patients who took Lo-Dose Aspirin by 15-20% (2).

Given such accrued overwhelming data the USPSTF added Colorectal prevention with Lo-Dose Aspirin in their Preventative Recommendations in 2015 (4).

Liquid Aspirin:

A more interesting and provocative study from Britain shows that Liquid Aspirin in the form of IP1867B when given intravenously leads to cell kill in brain tumors (Glioblastoma Multiform or GBM). The nuance from this study has significant implications in overall cancer care in the future (5). Keep your eyes peeled on this development!

So with such a preponderance of information it behooves people over the age of 45 and beyond to take Lo-Dose Aspirin (as long as no allergy or sensitivity towards gastric bleeding exists) as a cheap form of prevention. This when added to exercise and a healthy 2000 calorie diet (fruits, vegetables, legumes etc.) will keep most in good health longer.



And just for the record, don’t forget Aspirin’s effect against Cardiovascular Diseases: heart attacks and strokes!

REFERENCES:

1. Jack Cuzick, Ph.D., head, Center for Cancer Prevention, Queen Mary, University of London, England; Leonard Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society; Aug. 6, 2014, Annals of Oncology.

2. Peter C. Elwood, Gareth Morgan, Janet E. Pickering, Julieta Galante, Alison L. Weightman, Delyth Morris, Mark Kelson, Sunil Dolwani. Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality: A Systematic Review and Meta-Analyses of Published Studies. PLOS ONE, 2016; 11 (4)

3. Rothwell PM1, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW.Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011 Jan 1;377(9759):31-41. doi: 10.1016/S0140-6736(10)62110-1. Epub 2010 Dec 6. 
 
4. Chubak J, Kamineni A, Buist DS, et al. Aspirin Use for the Prevention of Colorectal Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 133. AHRQ Publication No. 15-05228-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2015 

5. http://www.dailymail.co.uk/sciencetech/article-3663188/How-liquid-aspirin-help-fight-brain-cancer-Special-version-drug-ten-times-effective-killing-cancer-cells-chemotherapy.html

Wednesday, June 29, 2016

THE SOUL of a HUMAN


Is it my misery that beckons you? Is it the pain that I suffer that invites your eyes? Is it the torment of my daily life or the once in the blue moon event that attracts your attention? Is it the muted cry of my humanness that plucks wildly at your heartstrings? Or is it the weakness of my being that encourages a look? What is it? What drives you to peer at my destiny? What makes you realign your focus? Is it empathy? Or is it to feed on my despair? Does that make you feel good about yourself? Does my misfortune make less yours? Do my cries wash your selfpity away? Am I the monster of your dreams gone ugly? Or am I the wretched soul that gives you comfort that you are not me? Where are you, at?

Or is it the art of tutoring? The fawning over tragedies that make for a resonating vibration, which has the magnetic pull since the invention of the written word. Shakespeare’s Hamlet, Macbeth and Romeo and Juliet, enjoy more recognition then comedies like Midsummer Nights Dream and Taming of the Shrew. Or is it the constant chatter of the pain of loneliness, the sense of ostracism from an inwardly turned society or just a game of the mind. Or do the far away Roman prisoners fighting for their lives idealized in movies, in the Coliseum bring forth the unholy desire to peer at a similar carnage?

Is it my fame that calls your attention? Is it my material trappings that invite your disdain? Is it my knowledge or my intellect or lack of it that triggers the belligerence? Is it the soft-spoken nature of truth that undoes your passionate anger towards success? Is it the blind rage towards the goals that I have achieved or desire? What is it? What drives you into this riveting narrow focus of hate directed towards me? Am I the monster that quashes your ego? Or am I the beacon of truth that you wish to demonize? Or is it my soul that I have carefully crafted over my lifetime to succeed that governs your wrath? What makes you greave in fits of anger directed at my visage that haunts your very being? What gives you such vehemence?

Or is it the greed and jealousy of a few that fan the flames of hate of the many, cloaking their better angels? Is it in us or is it inbred? Is it Darwinian or Lamarckian? Or is it the implied flow of human emotions festering like a sore sprinkled with salt? Where does this pain of greed originate that feeds and simultaneously bleeds us of our better self. What nerve root, what impulse, what receptors deliver and receive these poisoning emotions?

These are the questions that tear a soul apart. These questions force an inward look. These are the questions that change life. Answer them and then look at yourself. Answer them quietly in the comfort of your being and you will change – for the better. They will force you into a place where superficial comfort is not given entry. It is a lonely place, a place of horrors, of soul mutilation, of ego deflation, of ghostly demons, of the id forced beneath the murmurs of human thought. Go there and look deep and what might emerge is a pure soul. The soul of a human! The oneness of being! The solemnity of truth!

You!