Neutrophil-to-lymphocyte ratios as a predictor of death from melanoma in patients with NONmetastatic disease

I've talked about Neutrophil-to-lymphocyte ratios before as prognostic predictor of a response to ipi/yervoy, noting that having an "....elevated absolute neutrophil counts as well as elevated neutrophil-to-lymphocyte ratios did not bode well for the 720 melanoma patients treated with ipi in this study.  The risk for progression and death was even greater when both of those values were increased.  This report is consistent with the findings from the initial, smaller study of  214 melanoma patients treated with ipi in which:  "Patients with baseline NLR (neutrophil-to-lymphocyte ratio) less than 5, had a significantly improved progression free survival and overall survival compared to those with a NLR equal or greater than 5."

Here's the link to both those reports:  Neutrophils as a prognostic predictor in patients treated with ipi/Yervoy

In this study, from different authors, the NLR is used as a biomarker in folks with NONmetastatic melanoma to predict potential for disease-specific death....

Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma. Davis, Langan, Panageas, Postow, et al. Ann Surg Oncol. 2017 Mar 16.

Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma.

Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray's test was used to examine the effect of NLR on melanoma disease-specific death (DOD). Multivariable competing risks regression models assessed associated factors.

Data on 1431 patients with high-risk, nonmetastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (greater/= to 3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index, and more advanced nodal status. On multivariate analysis, high NLR (greater/= to 3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion, and positive nodal status were all independently associated with worse DOD.


NLR is a readily available blood test that was independently associated with DOD in patients with high-risk, nonmetastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

If this is so, then following these simple lab values may be super important in whether Stage III peeps should choose adjuvant treatment or not.  - c

BRAF/MEK rechallenge in folks who have had that treatment before

For those with BRAF positive melanoma who were treated with BRAF/MEK, perhaps went on to other things...but now are still in need of treatment...a rechallenge with BRAF/MEK can still offer some hope.   Here is the report:

Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAFV600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Schreuer, Jansen, Planken, et al. Lancet Oncol. 2017 Mar 3.

Patients with BRAF^V600-mutant melanoma benefit from treatment with the combination of BRAF and MEK inhibitors, but resistance and disease progression develops in most patients. Preclinical studies and case studies have indicated that acquired resistance to BRAF inhibition can be reversible. We aimed to assess the anti-tumour activity of rechallenge with BRAF plus MEK inhibition in a prospective clinical trial.

In this open-label, single arm, dual-centre, phase 2 academic study in Belgium, patients aged 18 years or older with BRAFV600-mutant melanoma who had previously progressed on BRAF inhibitors (with or without MEK inhibitors) and were off-treatment for at least 12 weeks, were treated with dabrafenib 150 mg orally twice per day plus trametinib 2 mg orally once per day. The primary endpoint was the proportion of patients with investigator-assessed overall response at any time (defined as complete response or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed on two occasions, at least 28 days after the first response was recorded). Analyses were done in the intention-to-treat population. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT02296996.

Between April 5, 2014, and Feb 2, 2016, 25 patients were enrolled and initiated treatment in our study. A partial response was documented in eight (32%) of 25 patients (six patients had progressed on previous treatment with dabrafenib plus trametinib and two patients had progressed on previous BRAF inhibitor monotherapy). Stable disease was noted in ten patients (40%). Rechallenge with dabrafenib plus trametinib was well tolerated. There were no unexpected or grade 4 or 5 treatment-related adverse events. Grade 3 adverse events occurred in two patients (8%; panniculitis [n=1] and pyrexia [n=1]). Serious adverse events which occurred on study were one patient with an Addison crisis triggered by grade 2 pyrexia symptoms that resolved after discontinuation of dabrafenib and trametinib. No patients died as a result of study treatment.

Rechallenge with dabrafenib plus trametinib showed anti-tumour activity in patients who had previously progressed on BRAF inhibitors and as such, rechallenge represents a potential new treatment option for these patients.

Blessings one and all - c

Side effects of immunotherapy - Part 8

In the ongoing saga...see the previous post:  Side effects of immunotherapy - Part 7

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Behling, Kaes, Munzel, et al. Melanoma Res. 2017 Apr;27.

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

Two cases of clinical myasthenia gravis associated with pembrolizumab use in responding melanoma patients. Nguyen, Kuo, Budiman, Christie. Melanoma Res. 2017 April.

Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients. One case is in an 81-year-old man and the second case in an 86-year-old woman, both with BRAF-negative metastatic melanoma receiving pembrolizumab. These two cases of ocular only associated myasthenic syndrome appeared 7 and 11 weeks after the initiation of pembrolizumab. We conclude that the condition is most likely associated with pembrolizumab as symptoms started after treatment with pembrolizumab, neither patient had other evidence of neurological cause for presentation, and symptoms also improved rapidly with administration of steroids. Both patients showed good oncological response to anti-PD1 treatment and one patient successfully continued to receive ongoing treatment with no further complications.

PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis. Wu, Hong, Zhang, et al. Lancet Oncol. 2017 Mar 3.

Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% for all-grade and 1.53% for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types.

Autoimmune limbic encephalitis with anti-contactin-associated protein-like 2 antibody secondary to pembrolizumab therapy. Brown, Hissaria, Hsieh, et al. J Neuroimmunol. 2017 Apr 15.

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma.

Acute symptomatic hypocalcemia from immune checkpoint therapy-induced hypoparathyroidism. Win, Thein, Qdaisat, and Yeung. Am J Emerg Med. 2017 Feb 27.

Ipilimumab (a monoclonal antibody against CTLA-4) and nivolumab (a humanized antibody against PD-1) target these immune checkpoint pathways and are used for treatment of melanoma and an increasing number of other cancers. However, they may cause immune-related adverse effects (IRAEs). Although many endocrinopathies are known to be IRAEs, primary hypoparathyroidism with severe hypocalcemia has never been reported. This is the first case of hypoparathyroidism as an IRAE presenting to an Emergency Department with acute hypocalcemia.  A 73-year-old man with metastatic melanoma presented to the Emergency Department for the chief complaints of imbalance, general muscle weakness, abdominal pain and tingling in extremities. He had wide spread metastasis, and begun immunotherapy with concurrent ipilimumab and nivolumab 1.5months ago. At presentation, he had ataxia, paresthesia in the hands and feet, and abdominal cramping. Magnetic resonance imaging of the brain was unremarkable. He was found to be hypocalcemic with undetectable plasma parathyroid hormone. He was admitted for treatment of symptomatic hypocalcemia and was diagnosed with primary hypoparathyroidism. Shortly afterwards, he had thyrotoxicosis manifesting as tachycardia and anxiety, followed by development of primary hypothyroidism. At 4months after the Emergency Department visit, his parathyroid function and thyroid function had not recovered, and required continued thyroid hormone replacement and calcium and vitamin D treatment for hypocalcemia.  Primary hypoparathyroidism caused by ipilimumab and nivolumab may acute manifest with severe symptomatic hypocalcemia. Emergency care providers should be aware of hypoparathyroidism as a new IRAE in this new era of immuno-oncology.

Be safe.  Be aware.  Seek help if you think you need it!  Hang tough, ratties!  Hang tough!  - c

What tangled 'paths' we weave: Nilotinib for KIT mutated melanoma and Buparlisib for the PI3K pathway in melanoma brain mets

Melanoma mutations can be confusing to say the least.  This diagram helps a bit:

Here's credit and an explanation:  Melanoma Pathways....A Melanoma Molecular Disease Model

NRAS and KIT mutated patients have not had the luxury of good responses to immunotherapy and targeted therapies currently being utilized in melanoma.  But, now there's this:

Efficacy and Safety of Nilotinib in Patients With KIT-Mutated Metastatic or Inoperable Melanoma: Final Results From the Global, Single-Arm, Phase II TEAM Trial. Guo, Carcjal, Drummer,..., Hodi. Ann Oncol. 2017 Mar 6. 

The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT -mutated advanced melanoma without prior KIT inhibitor treatment.

Forty-two patients with KIT -mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT -mutated melanomas. Thirteen patients were randomized to DTIC prior to the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors.

ORR was 26.2%, sufficient to reject the null hypothesis (ORR less than or = to 10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease, 10 (23.8%) had progressive disease, and 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, 4 with an L576P mutation. The median progression-free survival and overall survival were 4.2 months and 18.0 months, respectively. Three of 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib.

Nilotinib activity in patients with advanced KIT -mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.  

42 patients is not a ton.  26.2% ORR...with all of those being partial responses is not fabulous...but it is definitely SOMETHING!!!  Hey, I was over the moon when ipi was approved with its 15% response rate!!!  

And ~ if you refer to the chart above again...you will see the PI3K pathway....

Here is an initial post re the PI3K pathway in relation to brain mets by Dr. Davies:  PI3K/AKT - a pathway with potential for treating melanoma brain mets

And now there's this mousie medicine....

PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo. Niessner, Schmitz, Tabatabai, et al. Clin Cancer Res. 2016 Dec 1.

Great advances have recently been made in treating patients with metastatic melanoma. However, existing therapies are less effective on cerebral than extracerebral metastases. This highlights the potential role of the brain environment on tumor progression and drug resistance and underlines the need for "brain-specific" therapies. We previously showed that the PI3K-AKT survival pathway is hyperactivated in brain but not extracerebral melanoma metastases and that astrocyte-conditioned medium activates AKT in melanoma cells in vitro We therefore tested the PI3K inhibitor buparlisib as an antitumor agent for melanoma brain metastases.

Buparlisib inhibited AKT activity, decreased proliferation, and induced apoptosis in metastatic melanoma cell lines and short-term brain melanoma cells, irrespective of their BRAF and NRAS mutation status. In addition, buparlisib inhibited hyperactivated AKT and induced apoptosis in melanoma cells that were stimulated with astrocyte-conditioned medium. The growth of tumors induced by injecting human BRAF- and NRAS-mutant metastatic melanoma cells into the brain of mice was significantly inhibited by buparlisib.

These results emphasize the value of targeting the PI3K pathway as a strategy to develop drugs for melanoma brain metastases.

This last is certainly in its baby steps...  But, hey!  On these paths, any steps at all are a needed start!!
(However, there are many PI3K inhibitors in studies for other cancers - Buparlisib [drug noted above] and Alpelisib [for breast cancer], Duvelisib [hematologic malignancies], TGR1202 [follicular lymphoma].)

Thanks, mousies.  Hang tough, ratties!  - c

Circulating DNA predicts response to anti-PD1

One more thing I have been yelling about for years!!!  Medicine now has the technology to determine all sorts of things via a simple blood draw. Circulating tiny bits of tumor DNA floating through our blood can tell docs what type of tumor we have, predict response to a given treatment and let us know how the treatment is working.  Here is a link to years of posts:  Circulating DNA in melanoma treatment from 2014 til now!!

Now there's this:

Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Lee, Long, Boyd, et al. Ann Oncol. 2017 Jan 24. 

Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information.

We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab.

ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance. RECIST response was 72% (26/36) in Group A (undetectable ctDNA at baseline), 77% (17/22) in Group B (elevated ctDNA at baseline but undetectable within 12 weeks of therapy) and 6% (1/18) in Group C (elevated ctDNA at baseline and remained elevated during treatment). The median PFS was not reached in groups A and B and was 2.7 months for Group C. The median OS was not reached for Groups A and B and was 9.2 months for Group C . The poor outcome measures associated with Group C remained significant in multivariate analysis adjusted for LDH, performance status, tumour stage and disease volume. The predictive value for ctDNA for response was confirmed in a separate validation cohort.

Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS. Patients who had a persistently elevated ctDNA on therapy had a poor prognosis, and this may guide combination and sequencing of subsequent therapies.

Clearly, per the results of this study, patients did best when their circulating tumor DNA became undetectable under treatment.  Conversely, as one might suspect, when ctDNA remained elevated despite treatment, folks did less well...even when researchers controlled for known prognostic indicators like LDH, disease volume, etc.

We KNOW these facts.  We HAVE the technical ability.  WHY is this not standard of care??

Hang in there, ratties.  love, c

Chaotic Cookery! - From Someone Else's Table: Turkey Legs Confit

Duck legs confit in Sarlat, France. Roast lamb that was basically a confit in Spain (pic below). Turkey leg confit in Chicago at the Purple Pig.  Now......Turkey Legs Confit.....at home in TN!!!

For my attempt I basically adapted a Bon Appetit recipe for Chicken Leg Confit.

Turkey Leg Confit:  Salt and pepper two turkey legs.  Place in a baking dish in which the legs fit with as little extra space as possible. Cut 1 bulb of garlic in half.  Quarter 2 shallots.  Leave paper on all and tuck them in between and around the legs.  Toss in thyme sprigs.  Come close to covering the legs with olive oil.  Cover and place in oven at 275 for 3 hours.  Then, uncover and cook for 30 more minutes.  This can be done as much as 2 days before serving.  And....don't fret about all the oil.  You will not have oily legs and the flavored oil can be used in more roasted bird, with roasted potatoes or other veggies.

Prepped and ready for the oven.

First step done!

Ready to eat!!!

Once your are ready to serve.  Remove the legs from their oil bath.  Place on oven safe tray or pan and roast at 425 for about 15 - 20 minutes until browned and skin crisp.

So yummy and easy!  What an elevation for lowly legs.  And....about those sides....

B's Spicy Roasted Potatoes with Cool Yogurt Dipping Sauce - from Williams-Sonoma's New Flavors for Vegetables

Cut about 3 pounds of peeled russet potatoes (any kind really) into bite sized pieces and toss with 2 T Harissa (B decreases the amount for my whimpy self), 1/4 t cayenne, 1 T sesame seeds, and 1 t salt.  Meanwhile, heat a roasting pan with about 1/4 c oil (in this case we used the oil the turkey legs were cooked in!!) drizzled in the bottom.  Once it is hot, carefully add the potatoes and toss them to coat in the oil.  Arrange the potatoes in a single layer.  Roast until the potato pieces are nicely browned, 25-30 minutes.  Flip over and roast until tender and browned and crisp outside, about 15 minutes longer.

While roasting - mix up a yogurt sauce with 1 cup Greek yogurt, 1/2 bunch fresh copped mint (or parsley or dried herbs), and juice from 1/2 lemon.  Season with salt and pepper.

For this dinner, I also sauteed some chard with the roasted scallions and some of the garlic and oil from the turkey legs.

So yummy....Try it!  Turkey legs influenced by tables in Spain and France....not to mention Chicago!!!  You can never go wrong eating and cooking - From Someone Else's Table! - c

Think Obama Care vs Trump Care is just partisan bickering? NOPE! It is all about LIFE and HEALTH for you and those you love!

I know, I know!!!!  There is absolutely no greater mood killing, depressing and dismaying topic to discuss than insurance or politics!  And, in this context...we have both!!!  In the words of the Tweeter-in-chief, "SAD!!!!" Still, Obama Care vs Trump Care is too important to ignore!  So....here we go....

This is an amazing video that breaks it DOWN!!!

Ezra Klein: The perverse reality of the Republican health care bill

This is a particularly telling interview from NPR of an ex-insurance exec ~ and you know how much I love those vultures!!!

Insurance Industry Worried By GOP Plan To Replace Obamacare, Consultant Says

And who always suffers the most when folks who think the "bottom line" matters more than people, call the shots?  The poorest, sickest, oldest, youngest - our most vulnerable:

From The Atlantic: The Silent Victims of the GOP Health-Care Proposal “Children are the largest single group of beneficiaries on Medicaid—and they don't vote.”

If you think "Obama Care" didn't help you and yours because you have private insurance, you have a lot to rethink!!!

The ACA forced insurance companies to abandon lifetime caps!  Grand totals paid out by insurance plans, no matter that a family has paid into them for years, but ended all future payments for your dad, because after he had ONE significant surgery he maxed out his policy (never mind that he had never used it before)!  Or, your baby was no longer covered by your family plan because she stayed a few nights in the NICU right after birth. Before the ACA, that was it! No more payments.  No more coverage, you were done - UNTIL the ACA changed that horrific policy and made insurance companies play fair!

The ACA forced insurance companies to stop discrimination against those of us with pre-existing conditions.  And if you think melanoma and cancer were the only "pre-existing" diagnoses that allowed insurance companies to charge you more or not sell you insurance at all...at any price...well, that's not true.  Children with a history of a broken leg at age 4, which healed perfectly, found themselves uncovered at all or just not "that leg" should, heaven forbid it suffer an injury in an accident, football game, or develop a sarcoma.  And folks with high blood pressure, diabetes, or  a heart attack...well, they could just forget it.

The ACA stopped insurance companies from taking Americans' hard earned money for junk plans that didn't pay anything when they needed well check ups for their kids, vaccines, pap smears, mamograms, basic care when sick with a cold, flu, pneumonia, asthma...I could go on.  Those plans were a big surprise when folks tried to use them to attain basic healthcare. They were deemed illegal by the ACA.

The ACA expanded medicaid in the states willing to accept the help to cover our working poor and children.

The ACA did NOT cause your insurance rates to go up!!  Insurance company execs did that...with the approval of state legislatures. Executives who make 15-20 million dollars a year for their amazing management skills.  THEY decided they needed even more....at our expense!!!

The ACA allowed children up to the age of 26 to stay on their family's plans.

The ACA is not perfect.  There are many ways in which it could be improved.  So why don't we??? Cause here's the deal...

HEALTH: AMERICA'S HUMAN INFRASTRUCTURE

The health of our nation, physical and mental, is the vital living human infrastructure of our society. That infrastructure is absolutely essential for everything else. It includes everyone from the infant to the elder. It encompasses all parts of life: birth, childhood, adulthood, old age and death. It is what and how we eat and drink. It is the air we breathe. Procreation, pain, suffering, joy and fulfillment are all rooted in our health. The health of our nation is sacred and shared. The health of one literally affects the health of all. Wisely, health is enshrined in our Declaration of Independence: Life, Liberty and the Pursuit of Happiness. It is life, that comes first as a necessary condition and the right to health care is the concrete embodiment of that right to life. There are those who are blind to the communal nature of health. They deny health care as a right, seeing it only as a privilege for the few with resources. A privilege restricted to those whom they consider innocent, powerful or wealthy enough to save from disease, suffering and death. We must fight for the right to our health care and our lives. All of us are innocent enough, powerful enough, rich and deserving enough to have the same opportunities for healthcare. So, we join the struggle for our health with the United States Congress. It is the struggle for and of our lives and those we love. It is also the struggle for the survival and spirit of the United States. We will not lose because we cannot lose.   (Just a little op-ed written by me and B)

Indeed, the health of our neighbors, friends and family - our fellow AMERICANS - is our most essential infrastructure.  The health of our nation is the well from which all else springs.

I believe in all Americans.  I believe that healthcare is a right ~ one that belongs to all of us ~ those is the prime of health with lots of money, as well as those who are less fortunate and perhaps more in need.  No matter where you fall on that scale today....it is a fluid place.  One minute you are gainfully employed with bountiful health, the next you are facing a life threatening illness, too ill to work (NOT too lazy!!!).  But, thanks to science and the generous spirit of your fellow Americans....you can cross the bridge to health and productivity once more.  YES, WE CAN do that for each other!  And....we should. 

Much love, les