|
|
The Medical News Report #139 August, 2023 Samuel J.LaMonte, M.D., FACS |
|
|
IMPORTANT REMINDER!!!! PLEASE READ!!! I remind you that any medical information provided in these reports is just that…information only!! Not medical advice!! I am not your doctor, and decisions about your health require consultation with your trusted personal physicians and consultants. The information I provide you is to empower you with knowledge, and I have repeatedly asked you to be the team leader for your OWN healthcare concerns. You should never act on anything you read in these reports. I have encouraged you to seek the advice of your physicians regarding health issues. Feel free to share this information with family and friends, but remind them about this being informational only. You must be proactive in our current medical environment. They can request being placed on my reports, by emailing me. samlamonte@gmail.com Don’t settle for a visit to your doctor without them giving you complete information about your illness, the options for treatment, care instructions, possible side effects to look for from medications, and plans for follow up. Be sure the prescriptions you take are accurate (pharmacies make mistakes) and always take your meds as prescribed. The more you know, the better your care will be, because your doctor will sense you are informed and expect more out of them. Always write down your questions before going for a visit. Thank you, Dr. Sam
Subjects for August: 1. Late Breaking Medical News— Will we see a drop in Medicare Drug prices in 2025?; Xylazine making fentanyl more deadly; Emergency contraception vending machines at colleges in 17 states; More info on the origin and reason for gain of function research; The summer heat extremely tough on those with dementia; CDC and “chest feeding” for transgender individuals 2. Breast Cancer Series-Part 2-treatments 4. Life’s Essential 8—higher scores extend health span
-Drop in Medicare prices in 2025? -Xylazine making fentanyl more deadly -More on Long COVID syndrome -Emergency contraception in vending machines at colleges in 17 states -More information on the origin of COVID-19 and the reason for gain of function research, and safety of the vaccine --Summer heat serious for those with dementia --CDC guidance for transgender individuals “chest feeding”
a. Will we see a drop in Medicare Drug prices in 2025???? The Inflation Reduction Act (better known as the Climate Change Act) promises that in 2025, there will begin a reduction in Medicare drug prices. President Trump attempted to lower prices with cooperation from Big Pharma, but nothing happened. Now there are promises in the above mentioned inflation act to do it beginning in 2025, which has already been pushed to 2026. Notice this is after the presidential race. When will the Congress have the guts to kick out the lobbyists who own them and change the law for Medicare and be able to negotiate prices of medication? There is a law which was created when dealing with Big Pharma and getting to negotiate drug prices for Medicaid patients but not Medicare patients. That must be reversed. Do we have a congress that has the will to stop being controlled by Big Pharma and other major corporations who get their way because of their campaign financing donations? We are the only country that does not negotiate with Big Pharma. Unfortunately, it took most of these countries to become socialist to do it….but that does not have to happen in America if we didn’t have a congress bought and sold by Big Pharma anf Big Corporations. Next month, I will describe corporatism replacing liberalism.
b. Xylazine making fentanyl more deadly! Fentanyl from across the border has killed as many as 100,000 Americans over the past year and half, and our administration just sits idly by letting it happen. How do those people sleep at night? Fentanyl comes almost exclusively from China and does our administration ask them to stop sending it? No, because our president is compromised. Now, a veterinarian tranquilizer, xylazine (called “tanq”on the street and “the zombie drug”) has been found in the street drugs to make fentanyl and other opioids to last longer and bring a lower price to the buyer. It is blackmarketed by cartels in our country, which are groups that are totally hostile to our country. The combination of these 2 drugs laced in a multitude of street drugs, even those that very young people like to abuse, is costing them their lives. This drug for animals is not approved for human use. Injected, it can cause skin to itc causing severe acratchind and rot off. Raw wounds erupt as scaly crusts of dead skin, and if untreated can lead to amputation. It has become a serious threat for the law enforcement, and it is resistant to Narcan. It is being sold on the street in flavors of lime and blueberry. When people use it, it makes them walk around like zombies, hence the nickname!
This is just one more reason parents need to protect their children from these street drugs. Where is the federal attack on these drug pushers?? The cartels??
c. More on Long COVID syndrome There is a federal advisory for those with Long COVID syndrome regarding the number of mental health conditions. Doctors need to be particularly aware of depression, anxiety, psychosis, obsessive compulsive syndrome, PTSD, fatigue, trouble sleeping, brain fog, and cognitive impairment are on the rise. COVID infections are much less common but still infecting many Americans, and the most vulnerable are still the ones most affected regardless of viral strain. Studies have shown gliosis* (of the putamen and ventral striatum, the prefrontal cortex, cingulate cortex, and hippocampus of the brain) occurs in many patients who became infected with COVID-19, and it is theorized that this inflammation of the brain may be a key factor in the increased mental crisis facing the world, well demonstrated in long COVID with the majority dealing with depressive and cognitive challenges.
*gliosis=inflammation in the key cortex cell called glial cells; the virus injures these cells by infiltrating them with products produced by the virus (cytokines, prostaglandins, reactive nitrogen species, and reactive oxygen species). These findings are from autopsy findings in those who died of COVID. Hypoxic or vascular occlusion may also play a role. Gliosis is implicated as a cause of depressive and cognitive symptoms. Will this be permanent or temporary?? PET scans can detect gliosis. It is known that some antidepressants (serotonin reuptake inhibitors—SSRIs) have some positive effects on gliosis, and further studies are necessary to improve understanding of this mechanism. There is no proof of causality between antidepressants and improvement of depression because of its effect on the glial cells of the brain. JAMA Psychiatry, May 31, 2023 Interestingly, these areas of inflammation are involved in Parkinson’s disease, which raises the question that some of these patients might be at an increased risk of this disease. Only time will tell. Suggested interventions should include group therapy, peer support groups, physical therapy, neurorehabilitation, and medication to treat anxiety and depression, speech therapy for people whose language skills have been affected, and active treatment for substance abuse. Primary Care Physicians need to be proactive in asking patients about their symptoms which may not be easy for them to discuss when suffering from psychological issues. Data is still showing about 10% of those with COVID infection will get some long term symptoms usually lasting as long as a year or more. The highest percentage of cases of long COVID occur between ages 36-50, and most are not hospitalized patients and often can occur with mild acute illness, according to studies. This might be a great reason for getting vaccinated, since this group of younger people are the least likely to get vaccines. Many of those who develop mental disorders do not have a prior history of psychological problems. Black, Latino, and Native Americans are at higher risk, and have higher rates of hospitalization, primarily because they have more underlying health issues. They have disparity issues at home, are poorer, with fewer resources. People with disabilities and those in the LGBTQI+ community are at higher risk, especially with their higher risk life style in many cases. This federal advisory stemmed from statistics from California, which might be more severe than other states. Los Angeles Times Article
17 states have colleges now with vending machines ($12.95) with emergency “night after” pills with 20 additional colleges considering allowing these “abortion” pills available to young females without seeing a doctor and being given the risk/benefits of this medication. Emergency contraceptives (Plan B One Step) prevent pregnancy when a woman has unprotected sex voluntarily or by rape.
Other options An emergency copper IUD (Paragard) can be placed within 5 days of intercourse, that are successful. If left in place will continue to provide contraception. It is 99.9% successful.
UPA is ulipristal acetate (also known as Ella), which binds to human progesterone receptor and is effective for 5 days. The mechanism of action involves inhibition or delay in follicular rupture of ovum (ovulation). LNG (Plan B)--The pill can be made of levonorgestrel (a progestin only) in a single dose (1.5 mg) or as a split dose (0.75mg followed by a second 0.75mg dose 12 hours later). This can be successful, longer than other products decreasing the chance for pregnancy for up to 5 days, but it is recommended to take within 3 days. Plan B is the product in vending machines. It is stated that Plan B is successful in 75-89% of time. If a woman takes Plan B and then has sex 2-3 days later, she should take another pill. Taking Plan B may cause an irregular period, especially if taken regularly. Doctors tend to not use this product. Short term side effects include dizziness, fatigue, headache, nausea, stomach cramps, tender breasts, and if a woman vomits shortly after the pill is ingested, she must take another one. The menstrual period may be up to 7 days late. There are no long term side effects. Any of the oral preparations must be taken within 3-5 days of having unprotected sex to have the most success. Another option is a pill combining estrogen and progestin in 2 doses plus 0.50mg levonorgesterol 12 hours later. The product in vending machines is a single dose (Plan B) How often can it be taken? Apparently as often as needed each time a woman has sex. Only one dose is necessary for each time sex occurs. If actually pregnant does it abort a fertilized ovum? Or if someone who is already pregnant for weeks and does know it, will it create issues for the fetus if the woman decides to have the baby? Hard to say, but these questions should b asked to the doctor. These are reasons seeing a doctor are important. Regular birth control pills contain both estrogen and progesterone, but higher doses.
Other forms of treatment to prevent pregnancy Birth control pills are a combination of estrogen and progesterone, which is different than tha above “night after” pills. Regular pills are taken each day, and some have a 7 day break to allow a menstrual period. There are diaphragms, sponges, IUDs (as above) cervical caps, and spermicides, “family planning method”(know when ovulation occurs and don’t have sex or have protected sex). Tubal ligation and vasectomy are permanent forms of birth control (if performed correctly). Depo-Provera shot every 3 months will prevent pregnancy. It releases progestin to prevent ovulation. Birth control patch, which releases estrogen and progesterone through the skin to prevent pregnancy. Birth control ring (Nuvring) is a flexible small ring that sits inside the vagina, which releases hormones to prevent pregnancy.
In summary, the morning after pills are safe and fairly effective but there is always a small risk of pregnancy. In Europe they are often used beyond the recommended time with success. Medical News Today
e. More on the origin of COVID-19 and the reason for “gain of function” research Current House Congressional hearings on the origin of COVID-19 continue to bring more information forward that I became privy to 2 years ago. The origin of the virus was leaked from the Wuhan labs. Dr. Fauci and his colleagues did everything to discredit that idea, pushing the concept of it showing up in a food market in Wuhan. Most scientists know that lab leaks are not uncommon and clearly the origin of the spread of COVID. Why is Dr. Fauci not being called up for contempt of court and be indicted? We are dealing with the most corrupt administration perhaps in history. Why was the virus manipulated to make it easily spread to humans, when it is well known that the bat coronavirus is hard to transmit to humans? It was stated to either develop a biodefense weapon or bioterror weapon. Regardless, the U.S. funded some of the gain of function research to develop this weapon, perhaps for a good reason, but Fauci should have admitted it and lied to a Congressional committee, which is a crime. It was just announced that funding of the Wuhan Lab has just ceased. Wow!! Just now!! Speaking of a crime….somebody tell President Biden he has 7 grandchildren, not 6! There should be no special privilege for any American, including the Biden family. No one is above the law!!
f. Summer heat extremely tough on those with dementia Those with dementia are not able to appreciate when they get overheated, and their caregivers must keep them out of the heat, especially with this summer’s triple digits. The brain center for appreciation of being overheated is impaired with people who suffer from any type of dementia. Those who wander could certainly be at risk. Hydration is the key, since that center of the brain is involved as well in those as they age, and dehydration increases the risk of heat stroke. Avoid alcohol, caffeine, and encourage drinking water, not just beverages. Dizziness, headache, nausea, rapid pulse, exhaustion, or a sudden change in behavior, are all signs of heat stroke. Keep inside in the AC, remove clothing, use cold compresses, and hydrate them immediately. If neighbors who do not have AC, give them help. Alzheimer’s Foundation of America news release, July 10, 2023
g. CDC guidance for transgenders wanting to “chest feed” The CDC has provided guidance on their website for transgender and non-binary individuals for those seeking guidance on how to “chest feed” their infants. This was pointed to females who had mastectomies, and biological males who have no milk ducts whatsoever to take hormones to grow “breasts” (without milk ducts) on how to feed their newborn infants. Many doctors are outraged that they would expose these infants to estrogen and progesterone products that the trans person is taking when the nipple will produce fluids with these hormones in them, even though there is no real milk present. Sad that the CDC has felt they need to be so policitically correct that they have added this “bad advice” under the breast feeding section on the CDC’s website. One of the medications have FDA warnings (domperidone), which can cause irregular heartbeats in the infant (not to mention in the adult). I realize everyone should be able to do what they want with their bodies, but to potentially harm an innocent infant, is beyond comprehension, when these hormones are ingested through fluids made by the male or female breast, the infant deserves better protection. The transgender issue, as in every minority issue, is politicized and weaponized to grab headlines to further separate the ideologies of our country. Association of American Physicians ans Surgeons, Dr. Jane Orient in an article in the NY Post, July 5, 2023
2. Breast Cancer Series 2023—Part 2-Treatment-medical, surgical, radiation therapy
Last month, I reported on the latest diagnostic procedures, the different types and stages of breast cancer, and the signs and symptoms of breast cancer that might be ignored. This month, I will report on the options for treatment, based on the type of breast cancer, family history, genetic markers, and the stage of the cancer. General health, other underlying medical issues, and age all play a role in determining treatment strategy. The decisions are not easy, and that is why I strongly recommend your case be presented to a tumor board of different specialists to come up with a combined decision preventing bias in large medical centers. Certainly, centers that have vast experience and talent are a must. Breast cancer tends to be more aggressive in younger women, and more common If BRCA genes are present, and an evaluation of the ovaries is critical, as there may be 50% of these women that are at risk to develop ovarian cancer sometime in their life. Women with breast implants are not at a higher risk for breast cancers usually seen, however, there is a very rare type that can occur around the implant and is a form of lymphoma (anaplastic large cell lymphoma). Texture surfaced implants are more likely to cause this rare cancer starting in the lymph nodes that can surround the implant. For mammograms, there are national standards all radiology centers follow. It should be noted that if a woman has implants, smaller cancers might be missed, therefore, following the guidelines for cancer screening is a must.
Treatment options for early stage cancers I-III These cancers are small and may be removed with breast conservative surgery (partial mastectomy), removing a zone of normal breast tissue. If the pathologist finds more extensive tumor than thought, further surgery may be required. In early stage breast cancer, there is usually no evidence of spread to other parts of the breast, to the lymph nodes or other organs, and usually no further surgery is recommended until assessment of the tumor and its extent have been analyzed. Ductal carcinoma in situ (DCIS) are considered precancerous but can definitely progress to more aggressive cancers and develop in other milk ducts. If it is initially found in more than one area, a simple mastectomy still may be considered. A simple mastectomy, means all of the breast tissue is removed, and the skin and nipple may or may not be spared. Implants may be placed at the time of surgery or delayed. DCIS means the cells of the milk ducts of the breast are involved, but usually do not spread to other parts of the breast early on, but can develop over time in different milk ducts. If it is, a simple mastectomy may be recommended or breast conserving surgery, which implies a part of the breast is removed with or without the skin, depending on the position of the cancer. However, if there are premalignant changes in the ducts throughout the breast, a simple mastectomy may be required to prevent a second cancer from developing with the option of immediate reconstruction. The nipple may be removed as well. Even with DCIS or other types early cancer, a sentinel node biopsy may be recommended, especially if the tumor is larger or the cells are aggressive. This was described last month, but essentially dye is injected into the area of the breast cancer and then armpit lymph nodes, which are normally present, are biopsied wherever the dye moves to, as the dye drains to the lymphatic vessels to the most likely lymph node(s). If the sentinel node is positive, all of the axillary (arm pit)lymph nodes must removed. If a sentinel node biopsy is not recommended, but after the surgery the tumor is more advanced than thought, a sentinel node biopsy can’t be done, and complete removal of all the armpit nodes must be performed at a second surgery. In most early stage cancers, radiation is recommended following surgery. If the woman is older or not in good health, it may not be recommended. These decisions should come from a group of doctors (most likely members of a tumor board). Choosing breast conserving surgery followed by radiation has the same cure rate as having a total mastectomy in early breast cancers with 20 year studies proving that statement, as discussed in the extensive American Cancer Society’s website. A simple mastectomy with or without reconstruction may be recommended even in larger DCIS cases as well as early cancers whose cells are more aggressive (called differentiation-mild, moderate, or poorly differentiated). If a woman has a simple mastectomy with DCIS, radiation is usually not recommended, and reconstruction can be performed immediately or later.
Types of Surgery Surgery is performed to remove the cancer in the breast and often in the lymph nodes of the axilla. Breast conserving surgery (sometimes called a lumpectomy) removes the cancer plus a zone of normal tissue to be examined for microscopic spread, and assist the doctors in futher treatments. Younger patients would like this to have reconstructive (implant) surgery to make the breast equal size. The amount of removal is dictated by the tumor(s). Note the difference in simple mastectomy and a modified radical mastectomy..it includes the axillary breast tissue. The lymph nodes may be removed as well.
Simple mastectomy with bilateral implant breast reconstruction Simple mastectomy with skin removal, both breasts
Breast reconstruction after breast conserving surgery with surgery on the other breast to create symmetry.
Mastectomy (simple or radical) implies removing all of the breast tissue including the wing of breast tissue often in the armpit. In certain cases a double mastectomy is performed in those cases who have a higher risk of a second cancer, BRCA gene mutations, etc. Sometimes the skin of the breast must be removed including the nipple opening up an option for abdominal flap reconstruction to create a mound of tissue to mimic the other breast. This can create more favorable appearances using the free flap (microvascular flaps are sutured to neighboring blood vessels so that there is no pedicle of tissue that has to be tunneled from the abdomen to the chest).
This technique also improves the abdomen appearance.
The DIEP flap reconstruction
Fat grafts can be used. Reconstruction can be performed immediately or delayed depending on a patient’s wishes and multiple medical issues based on the extent of the cancer, etc. Tatooing of skin to make a pseudo-nipple can be performed with or without skin grafts. Older women may choose to have both breasts removed when breasts are small, which is easier to perform a bilateral reconstruction, or the woman may choose to do nothing after mastectomy. Surgery for open wounds of an advanced cancer may be recommended or other organ surgeries to remove tumors causing symptoms in the brain, liver, lungs, and all organs.
Axillary node dissections are often performed at the same time to remove nodes that are positive or in cases that have a positive sentinel node.
Surgery can be guided with wire localization, MRIs, etc. in specific cases. Biopsies can be performed during surgery (frozen sections) to guide the extent of sugery and improve the chances of complete removal.
Radiation therapy Radiation is not used as an exclusive treatment in breast cancer, but can be used after a more conservative surgical removal of an early cancer. There is controversy about the benefits in early cancers, discussed above, compared to tamoxifen.
It can be used after a large cancer is removed (mastectomy) in cases when the surgical margins are close, or the tumor is 5 cm (2 inches of larger) ,and when there are many lymph nodes positive with an axillary node dissection as added insurance. It can be used to treat areas of metastases which are causing symptoms (pressure on nerves, airway, spine with pain or weakness in an extremity(s) from pressure of the espinal cord. There are two types of radiation—external beam (EBRT) or brachytherapy (seeds of radiation or some kind of device) to allow direct radiation into the area of concern. 6-7 weeks of EBRT can cover the whole or part of the breast, chest wall, arm pit (axilla) just in case there are still some cancer cells present. Radiation after a lumpectomy is called breast conservative therapy. The amount of radiation can be varied depending on the circumstances. For more information, please read the section on radiation therapy for breast cancer at www.cancer.org (the American Cancer Society). This describes various approaches. I realize that this subject is very complex, and am in no way trying to cover this subject as well as it deserves. Radiation can be used for more advanced breast cancer or to reduce the size of an advanced cancer to make it more surgically accessible. Inflammatory breast cancer can be treated plus chemotherapy and mastectomy with or without an axillary lymph node removal. It can control metastatic cancer for pain control, especially in the spine. For more details, click on www.mayoclinic.org Side effects of radiation therapy can include of numbness, pain, and lymphedema of the arm, and may require special therapy including seeing a physical therapist to assist with the swelling of the arm including a compression stocking.
Oncology-medical therapy The discussion on treating breast cancer with medications is extremely complicated and difficult to comprehend. The American Cancer Society has very detailed information and separates these cancer treatments into chemotherapy, hormone therapy targeted therapy, immunotherapy, or a combination of them. Age, menopausal status, and over health play a role for the patient and doctors to consider, as these added treatments come with risks for side effects.
A. Chemotherapy If there is evidence of aggressive tumor cells, chemotherapy may be recommended before (neoadjuvant) surgery, but also may be recommended after surgery (called adjuvant therapy) and or radiation, or both. Shrinking the tumor before surgery may allow less aggressive breast removal. It also is a test to see if a specific drug can shrink the tumor (if it does,it means it will be helpful in controlling spread if needed later…if not, another drug may be chosen to be more effective. Neoadjuvant therapy may make the cancer disappear in early cases and allow the patient to live longer and reduce the risk of recurrence. This is true in women with triple negative or HERS protein positive cancers. Neoadjuvant therapy also gives time for genetic testing to used or plan for reconstructive breast surgery. Neoadjuvant therapy is commonly used in inflammatory, HERS positive, triple negative, high grade, or larger cancers. Cancers that spread to lymph nodes usually are treated with combination treatments. Advanced or metastatic cancers can be treated to control the cancer for a time even though not curative. For women with metastatic breast cancer chemotherapy may be the mainstay of therapeutics. Specific chemo agents include the taxanes (Taxol etc.), ixebepilone, erbulin (Halaven), anthracyclines (doxorubicin, etc.), platinum drugs, venrelbine (Navelbine), capecitabine (Xeloda), Gemcitabine (Gemzar), and antibody drug conjugates-combos (Kadcyla, Enhertu, Trodelvy). All these drugs are given IV in infusion centers, which are popping up in larger cities. The chemo side effects include hair loss, nausea, nail changes, mouth ulcers (mucositis with pain), gastrointestinal symptoms, weakness, fatigue, brain fog, heart damage, and neuropathies. It also affects the bone marrow and blood system, with easy bruising and an increased risk for infections (since the patient is usually immunosupressed), which can increase the risk of leukemia. Menstrual changes and infertility may occur. If future pregnancy is an issue, taking fertility drugs may help.
B. Hormonal therapy DCIS (ductal carcinoma in situ) or other types of breast cancer cells that are hormone receptor positive (means the cells produce estrogen or progesterone) treatment. Hormone therapy is used as an adjuvant therapy (after surgery) to prevent the recurrence of the cancer. 2 out of 3 breast cancers are hormone positive!
Choice of these medications include: 1--Selective estrogen receptor modulators (tamoxifen) (toremifene only for metastatic cases) Tamoxifen is often the first choice for many women who have hormone positive cancers to be taken after primary treatment. It does increase the risk of uterine cancer. A Korean study recently reported the incidence ws 4-5X greater. Close monitoring of the uterus is necessary with possible D&Cs annually in high risk individuals.
There are other advantages to taking these meds. The American Cancer Society cites a 50% lower risk of another breast cancer in the opposite breast and less recurrence by 30-50%. Tamoxifen can be taken pre or post menopausal, but there are better choices for postmenopausal patients, (aromatase inhibitors discussed below). Tamoxifen can be used in those who are intolerant to aromatase inhibitors. How these medications are taken may vary and depend on the oncologist. Tamoxifen can be used in cases when the cancer returns or spreads.
2--Selective estrogen receptor degraders (Faslodex, Orsedu) These medications are an alternative to Tamoxifen, attach to estrogen receptors and break them down anywhere in the body (breast, adrenal, body fat where estrogen can be produced and would possibly stimulate the cancer to grow. Faslodex can be used in advanced cases when other hormones are not used or others are intolerant or quit working. This medication can be combined with other types of medications (CDK 4/6 inhibitor or P13-K inhibitor to treat metastatic cancers. Orsedu can be used to treat advanced, ER-positive, HERS negative cases when the cancer cell has an ERR1 mutation,or after failure of another choice.
3—Drugs that lower estrogen (Aromatase inhibitors)—Femara, Arimadex, Aromasin,etc. These meds lower the level of estrogen in the body to slow the growth of these cancers, most often in postmenopausal women. This will reduce production in any tissue making estrogen—breast, adrenals, and body fat. It is made with the aid of an enzyme, aromatase. Femara, Arimidex, and Aromasin are the 3 products that can be chosen from. Along with menopause symptoms, bone thinning can occur, and biphosphonated medications (Fosamax, Aconel, etc.) may be prescribed to counter the osteoporosis.
4—Ovarian suppression All these methods cause symptoms of menopause including hot flashes, night sweats, vaginal dryness, and mood swings. Late effects can increase the risk of cardiovascular disease. These anti-estrogen (progesterone) treatments remove all sources of hormone which come from not only the breast tissue but the adrenal glands and abdominal fat. Certain chemotherapy agents, surgical removal of ovaries, luteinizing hormone releasing hormone agonists—LHRH analogs, are the choices and all accomplish the same thing. The surgeon and oncologist will decide the choice with the patient.
Special Cases often common Early breast cancers deserve consideration for more conservative therapy in older women who have hormone receptor positive cancers (estrogen/progesterone), who are considering hormone suppressing medical therapy (tamoxifen) with and without radiation therapy. A study compared breast conserving surgery with and without radiation, which was performed to find out the differences in survival after 10 years in women. All had hormone suppressing therapy (tamoxfen) with or without radiation therapy. These women had tumors 3cm (1.18 inches) or smaller. Results for both groups had an 80% survival rate, but the group who didn’t have radiation as well, had a 10% higher rate of recurrence in the breast. Those who had regional recurrences (axilla) were the same in both groups. The survival was the same for both groups, regional recurrences were the same, but those who didn’t have postop radiation therapy had a 10% higher chance of a recurrence locally in the breast, even with the same survival rate. These women all had negative margins when they had surgery. A woman 65 and older must decide if that 10% higher recurrence rate is enough to accept adjuvant radiation therapy after breast conserving surgery. Radiation does have that small 10% lower risk of having a recurrence in the breast, but that is the only benefit. But radiation has its side effects too. 26% of breast cancers occur in women 65-74 and the rate is rising. NEJM, February 16, 2023 Most other types of breast cancers that are localized are treated with surgery and radiation therapy. For women with BRCA gene mutations that do not want to undergo bilateral mastectomy and removal of the ovaries and tubes, can take these anti-hormonal medications as an alternatives to prophylactic removal. Most postmenopausal women should consider taking these hormone suppressors to improve the cure rate and prevent recurrence or the development of a new breast cancer. They must accept the side effects of the hormone suppressing therapy, which prompts as many as 40% to stop.
C. Targeted therapy For HERS positive cancers While 80% of breast cancer are ER-positive (estrogen receptor positive), 15-20% of breast cancers have extra copies of a gene that makes too much of a growth promoting protein known as HERS*, which tend to be more aggressive and can spread more easily. This means that 80% of these estrogen positive cancers are HERS negative, an important distinction regarding their aggressivenss. There are drugs developed to target that protein—monoclonal antibodies, which are man made immune antibodies that attack the HERS protein. *HERS=human epidermal growth factor receptor 2 The monoclonal antibodies are Herceptin, Hylecta, Perjeta, Phesgo, Margenza and are usually taken for 6 months to a year, but it can be given indefinitely in advanced cases.
1-- Other options Another option for targeted therapy is antibody drug conjugates, which are monoclonal antibodies combined (Kadcyla, Enhertu). Another choice are kinase inhibitors (Tykerb, Nerlynx, Tukysa).
2-- Targeted therapy for estrogen positive receptor breast cancers Certain breast cancers will do better with a targeted medication added to the hormone suppression. These added medications make the anti-hormone therapy (i.e. Tamoxifen) more effective, which include a couple of different groups of targeted therapies:
a- CDK4/6 inhibitors (Ibrance, Kisquali and Vernezio) These drugs block proteins in the cell called cyclin-dependent kinases (CDKs, mostly CDK 4 and 6). It helps stop the cancer cell from growing. These drugs are approved for hormone positive cancers that are HERS negative. They can be combined with aromatase inhibitors and other drugs, and can be used in advanced or early cancers. These pills are taken once or twice a day, but can add side effects, such as low blood count and fatigue. How these drugs are used depends on specific circumstances known by the oncologists.
b- mTOR inhibitors Everolimus (Afinitor) blocks tumors from developing new blood supply that would inhibit growth. c- P13K inhibitors Alpelisib (Piqray) blocks another protein, P-13, in the cancer cell, taken orally daily, which can stop the cancer cell growth. It can be used with fulvestrant to treat postmenopausal women with advanced hormone receptor positive, HERS negative cancers with the PIK3CA gene mutation that has grown after resistance to aromatase inhibitors. 30-40% of breast cancers have this mutated gene and the doctor can have the tumor tested for it.
d- Antibody Drug Conjugate This drug is a monoclonal antibody combined with a chemo drug. The antibody helps direct the chemo agent better into the cancer cell. Trodelvy is such a drug conjugate, which is used in cases that are advanced, who have already had hormonal therapy (i.e. tamoxifen) and 2 chemo agents. These cancers are hormone positive, HERS negative. This drug is given IV weekly for 2 weeks, with one week off and restarted.
e- Targeted Therapy for BRCA gene mutation cancers This therapy is known as PARP inhibitors (Lynparza and Talzenna). The BRCA gene mutations help the DNA thrive in the cancer cells, and PARP inhibitors inhibits them. Lynparza is used in cases who have been treated with chemotherapy previously and are at high risk for recurrence, and given for one year to extend life. Both Lynparza and Talzenna can be used in metastatic cancers, who are HERS negative with the BRCA, who have already had chemo. Targeted therapy for triple negative breast cancer, that do not have hormone receptors are harder to treat. Trodelvy, an antibody drug conjugate makes chemo more effective in these cases.
f- Targeted therapy for triple negative breast cancer Triple negative cancers are those that do not have hormone receptors or HERS protein. The above named antibody conjugate (Trodelvy) can be used to drive the chemo agent into the breast cancer cell directly.
D. Immunotherapy Immune therapy are products that boost a woman’s own immune system to fight the cancer. Some immune drugs are called monoclonal antibodies and can also be called targeted therapy, as just discussed. An important function of our immune system is to protect our needed immune system while telling the lymphocytes to stimulate secretion of cytokines to attack cancer cells. To do this the immune cells that must be turned on or off must use checkpoint proteins a- PD-1 inhibitors Pembrolizumab (Keytruda) targets PD-1 proteins on the T-cells (lymphocytes) is such an immunotherapeutic that targets the PD-1 protein, and boost the body to not attack normal cells, thus allowing the body’s own immune system to fight the cancer. (If you have heard of these drugs, they are used for other cancers and other diseases). It can be used alone or with other agents (chemo—called drug conjugates) in triple negative breast cancers, to be discussed below. There are many experimental immune drugs in clinical trials are usually reserved for the more aggressive and later stage cancers, too complex to include in this discussion. Consult the American Cancer Society’s website on immunotherapy for more detailed information.
Specific challenging types of breast cancer—
Triple negative breast cancer Because these cancers don’t have hormone receptors or HERS protein, hormone therapy and drugs that target HERS don’t work. Therefore chemotherapy is the main drug therapy used. Although the chemo makes the cancer respond initially, recurrence is not uncommon. These tend to be more aggressive. Stages I-III triple negative cancers can be initially treated with surgery (mastectomy or breast conserving surgery) for early tumors, whereas if the lymph nodes are involved regardless of the size of the cancer, radiation should follow. Chemotherapy post operatively (adjuvant chemo) will likely be recommended as well.
Triple negative/BRCA+ tumors Targeted therapy olaparib (Lynparza) would also be recommended if the triple negative tumor has the BRCA gene mutation and is larger than 2 cm bur less than 5 cm. For a larger tumor chemo may be given preoperativle (neoadjuvant) to shrink the tumor and or large lymph node metastases, or with Keytruda, an immunotherapy. If the tumor is found still present in the pre-chemo case, a chemo agent, Xeloda, may be given to increase the liklihood of recurrence. The targeted drug olaparib (Lynparza) may be used in patients with the BRCA gene mutation to reduce recurrence. For Stage IV breast cancer, chemo may be used primarily (anthracyclines, capecitabine, gemcitabine or eribulin) as a single or double agent. Immunotherapy is probably going to be recommended in triple negative/BRCA gene mutation patients-pembrolizumab if the cancer cell has a particular protein called PD-L1. Antibody conjugates will be used in cases where failure of other chemo agents have occurred. Various agents will be tried if there are other gene mutations such as MSI, MMR, TMB-H, etc. Immunotherapy will be needed in recurrent triple negative cases with options to use drug conjugates. Because I have had to report on these different types of medical therapy for completeness in this section, when I discuss recurrent breast cancer next month, I will repeat some of this section.
Next month, I will discuss complications of breast cancer treatment, recurrences, 2nd breast cancers, and other aspects in Part 3 of the Breast Cancer Series.
3. Most common mood disorder--new guidelines for treating depression, suicidal depression Depression can have different symptoms: wanting to sleep, listless, anger, tantrums, anxiety intermixed with depression (bipolar), change in appetite, food cravings, insomnia (waking up after going to sleep is most common), restlessness, agitation, crying, irritability, or social isolation, lack of concentration, slowness in activity, thoughts of suicide. Weight gain (or loss), and low self-esteem, hopelessness, a feeling of helplessness, guilt ridden, non-motivated, not able to make decisions, and not enjoying life. Physical symptoms often accompany the psychological symptoms. Speaking more slowly, constipation, unexplained aches and pains, loss if libido, changes in mentstrual cycle. 21 million adult Americans suffer from major depressive disorders. In 2017, 18% of teenagers, especially girls, have experienced at least one major depressive episode in the past year, up from 8% in 2007, according to Pew Research Center. However, the latest information from the AMA from a Harvard study found that parents (20% of mothers and 15% of fathers) of these teens have the same rate of anxiety and depression. This puts a tremendous burden on families to thrive in such a negative environment with inflation ripping them apart, CRT and sex education going out of control in schools, and job security weak. AMA Morning News, June, 2023
80% of antidepressants are prescribed by primary care doctors. 20% of adults over their lifetime will suffer from depression. The majority of those treated don’t achieve remission. The pandemic caused a mark increase in depression, but rates are not falling, and with substance abuse, and suicide rising, we are facing an endemic in younger kids and their parents. Senator John Fetterman (D-Pa) was hospitalized for 6 weeks with this disorder, which followed his stroke, as others can experience after a serious neurovascular or cardiovascular event, according to the American Heart Association. He disclosed he has had depression for years, and he is representing Pennsylvania as their senator.
According to experts, it is rare for someone with depression to be in the hospital for so long, and the real question remains about his effectiveness for the future. He still struggles with understanding speech and needs a computer to read what is told him. Depression disorder is a type of mood disorder. Most depression is categorized into mild, moderate, and severe, with some experiencing psychotic symptoms. Depression used to be included under neuroses (not used now), and occasionally psychoses. If psychotic behavior is present, hospitalization may be necessary, or if suicidal attempts occur. Many severe cases are requiring electrical shock therapy and ketamine is now being used. Categories include general depression, postpartum, bipolar, and seasonal affective disorder (usually in the winter or holidays). If symptoms persist over 2 weeks, seek help. Grief is a gift While reading a daily message from Pastor Rick (Warren), he had a nice take on grief as a gift, when something happens that is painful. It is a tool to get through the transitions of life. Certainly, the teenage years are a transition period in life. Not grieving when there is an emotional trauma gets people stuck there and they may not transition through it (denial), leaving individuals in depression and anxiety. He stated that sadness is not weakness, and it requires strength to face our emotions. Without doing that, one is stuck in repression and individuals try to block painful thoughts from the mind. Seeking help is critical. To not grieve losses is a mistake. We must face our traumas and allow it to pass through, otherwise the emotion remains unresolved. Cognitive behavioral therapy can allow this transition to occur. Abusing drugs is not uncommon, and alcohol usually worsens the symptoms significantly. SSRIs ( a type of antidepressants) are the most commonly prescribed (selective serotonin reuptake inhibitors. Increasing serotonin, a neurotransmitter, in the brain relieves depression in many if they will tolerate the medication’s side effects and stay on them. This regulates nerves that affect emotion. The SSRIs block the reabsorption of serotonin to allow it to work more effectively to promote normal emotion. The doseage and actual antidepressant may need to be adjusted or changed. Patience and sticking with these meds is critical to give them time to fully work (several weeks). It has recently been found to help gliosis of parts of the brain that are fertile areas for depression to occur, and inflammatory reactions such as in COVID cases, especially Long COVID, may cause this damage to these brain cells.
A new study has reported in a study that probiotics as an adjunctive treatment to anti-depressants will reduce the symptoms of depression. It is estimated that up to 60% of patients with depression do not receive full control of their disorder requiring different antidepressants, dosage, and a second antidepressant (Rexulti, Abilify) as mentioned above. This pilot study that treated 49 females (average age 32) who had incomplete response from antidepressants taking a multistrain probiotic 4X a day for 8 weeks experienced significant improvement over the placebo group. This study is small and begs for larger clinical trials, but this is a promising study from an improvement in the gut flora without side effects (just one importance of the gut bacterial flora. JAMA Psychiatry, June 14, 2023
An alternative to SSRIs are SSNIs (serotonin and norepinephrine reuptake inhibitors), such as Cymbalta, Effexor, Pristiq, or Fetzima. Tricyclics are less used today. It is known that mild depression will respond equally from antidepressants or CBT (cognitive behavioral therapy), but with no side effects (dizziness, sleeplessness, gastrointestinal symptoms, fatigue, and sexual dysfunction). In children and the young, there is an increase in suicidal ideation. There are interactions with other drugs as well, and that must be evaluated by the doctor. It is known that aerobic exercise helps relieve depression and anxiety. Those who chose to stop the medication after a few weeks, must taper the dose, otherwise the withdrawal syndrome can occur with nausea, dizziness, uneasiness, fatigue, or lethargy. Only about 60% of those with depression will seek psychologic therapy. And a significant percent may need both antidepressants and cognitive behavioral therapy (CBT) to relieve depression satisfactorily. Stick with th treatment, and if they are not working, please discuss with the treating doctor rather than just stopping them. It takes time, and patience in its beginning for these meds to work (4-6 weeks). A second medication may also be necessary (usually mirtazapine, bupropion, or buspirone) as mentioned above, but repeated for emphasis. Close follow up is necessary especially monitoring for suicidal ideation, since 1 in 3 younger females have this problem. Medication must start with low doses and increased with time, needing at least 4-9 months, and often even longer.
Resistant depression –ECT and Ketamine For resistant cases, magnetic brain stimulation, ECT (electroconvulsive therapy) or Ketamine infusions, with inpatient care may be needed. Even hallucinogenics (psilocybin) are being used in clinical studies with success. After 3 weeks of treatment, 41% of ECT patients and 50% of ketamine patients reported 50% or greater improvement in symptoms. but ECT had more musculoskeletal side effects from the induced seizures with ECT while ketamine can caused a degree of dissociation of thought processes for a short period of time, but often a few weeks. Ketamine is given IV usually in 6 doses over 2 weeks and longer in some cases. It can be used acutely in a patient who has attempted suicide. Studies are still limited, and need to be performed under extremely controlled circumstances. Glutamine is accepted as playing a role in depression. Glutamate is one of the main excitatory neurotransmitters, which has a role in neurodevelopment, neurocognitive functions (memory learning), and neurotrophic function (nerve growth differentiation and maintenance). Ketamine is a N-methyl-D aspartate receptor inhibitor, a glutamate, which can relieve depression rapidly. The dose is far from what is used as an anesthetic agent, which I have experience in when in training doing surgery on humans and animal experiments. It is accepted that modulating the level of glutamates in the brain is the main mechanism for action in relieving depression temporarily. It also helps relieve suicidal ideation and self harm. NIH-National Library of Medicine
ECT ECT provides small electrical impulses to cause chemical changes in neurotransmitters in the brain responsible for depression. It creates a brief seizure. It has been used when antidepressants can’t be used, in pregnancy, older patients who can’t tolerate the drugs, and certainly in drug resistant depressives. Confusion, memory loss for the events around the time of treatment can occur, but can be more extensive (retrograde amnesia). Most improve in a couple of months. ECT is usually performed 2-3X a week for 3-4 weeks. Recovery is usually fairly complete within a couple of weeks (driving, working, hazardous activities). Most patients notice improvement in about 6 treatments. Patients will still need antidepressants.
ECT is used on the non-dominant hemisphere of the brain, but a seizure must occur as an end point, and if no seizure occurs, both sides of brain are given electrical stimulation. ECT requires brief general anesthesia. Ketamine is schedule III medication, and can be addictive, and causing temporary changes in perception and thinking. There is more memory decline temporarily with ECT for a few months. However, patients will return to normal memory functioning.
Results of ECT vs Ketamine therapy In this study comparing ECT and ketamine after 6 months, relapse of depressive symptoms occurred in 56% of patients of the ECT group and 34% of the ketamine group. The symptoms of memory loss from the ECT group and dissociation from the ketamine group had decreased considerably after 6 months. In addition to a dissociative state, paranoia, and other psychotic symptoms may occur temporarily. These side effects are why these more drastic treatments are limited to resistant cases. Patients who are subjected to these aggressive treatment modalities have had life changing depression, suicide attempts, and difficulty coping. Guidelines from the American College of Physicians The American Psychiatric Association
Hallucinogens (ketamine, mushrooms, LSD) are now being used for more severe cases with a short term regimen usally of 2 weeks in clinical controlled studies. Now, transcranial magnetic stimulation (TMS), which has been used for sometime for depression, and other psychiatric disorders with some success, over 4-6 weeks, however, it is too slow a process in emergency situations such as a depressive who contemplating or attempting suicide. There are no seizures with TMS with this relatively benign treatment, with only a mild headache as the side effect, and no anesthesia, which is required with ECT. TMS has been re-engineered for a 7-10 day treatment called theta burst stimulation, but can be used in just one day, using an MRI to find the exact spot the electrical pulses will work best (dorsolateral prefrontal cortex). Some were given the 18,000 pulses daily for a few days, and compared to standard shock therapy were better, according to the presentation published in Medscape by Drs. Carpenter, Strakowski, Aaronson, Nolan from a host of different medical centers including Brown, U. of Texas, Stanford, and the U. of Maryland. There is great progress being accomplished with these neuromodulatory treatments, since oral medication has a high failure rate, but should always be tried first with cognitive behavioral therapy. As depression, suicide, and mental diseases continue to escalate in our country, these types of therapies may be the future for a select group of patients about to commit suicide. Medscape, March 15, 2023
With cardiovascular disease continuing to be so common, knowing how to live is all the more important. A recent report stated that there are 8 essentail factors that will increase life span. There are factors that can’t be controlled, especially genetics and certain environmental circumstances with work that are hard to avoid. But here are the essential 8 that can be controlled: 1. Not smokng 2. Regular physical exercise 3. Healthy weight 4. Healthy sleep (7-9 hours per night) 5. Blood pressure in a healthy range (140/90 or less) 6. Blood glucose under 100mg/dl fasting 7. LDL cholesterol in normal range 100mg/dl 8. Healthy diet Life span can be expected to be 75 for males and 80 for females, although the life span overall in the past few years has dropped slightly because of obesity, heart disease, and diabetes. Those with good cardiovascular health live an additional 7 years, and women 9.5 years. This was true across all socioeconomic strata including education and income. And yet, in my medical journals, there is one article after another about the disparities of race. Today, I have to read so much about racism, because the editors of these medical journals are very liberal. JAMA Internal Medicine, Joann E. Manson, M.D., DrPH As mentioned, with more Americans gaining weight, fast food, food insecurity, and other difficulties, it is so important to know as much about factors that increase the risk of cardiovascular disease, since it continues to be the main cause of premature desth and disability in the general population, and it is increasing throughout the world. Conventional risk factors that contribute to the occurrence and worsening of cardiovascular disease have been studied and are well known including high blood pressure, high cholesterol levels, diabetes, obesity, smoking, lack of regular exercise. Despite the measures to prevent and treat these risk factors with lipid lowering drugs, antihypertensives, antiplatelet drugs, and anticoagulants, the mortality rate related to cardiovascular disease remains high. But gaps in care continue. According to the American Journal of Medicine there are other factors that have emerged and need attention. Inflammation has become a common underlying factor in many diseases that affect the entire cardiovascular system. These diseases are not curable but can be controlled with prper management. 1. Gout has always been an associated factor in creating health issues and is one of the metabolic diseases that should be added to the conventional risk factors, since diet, being overweight, hypertensive, diabetes, and high lipid levels are commonly found in these patients. High uric acid levels must be reated along with certain restrictions in diet, and behavior. 2. Rheumatoid arthritis and lupus are experiencing higher incidences are cardiovascular disease prematurely, especially coronary artery disease. 3. Inflammatory bowel disease (Crohn’s and ulcerative colitis) are becoming more common and with that increase more coronary artery disease. 4. Psoriasis is now known to increase cardiovascular disease by 50%. 5. Maternal and childhood factors have increase cardiovascular premature disease icludng gestational diabetes, pre-eclampsia, delivering a low weight baby, preterm delivery, and premature or surgical menopause. 6. Migraine headache have an associated increase risk, especially in women with aura before the onset of the headache. 7. Early life traumas have been added to the list with midlife heart attacks. 8. Transgender individuals are now experiencing increased cardiovascular events due to the hormonal manipulation required in the gender affirming care. Coronary artery disease, depression, and anxiety are common associated conditions. 9. Low socioeconomic status will always play a role along with psychological stressors, limited education, and pack of peer influence that could favor positive behavioral life styles. Air pollution in certain areas is a factor and is known to cause 9 million deaths worldwide, with 62% due to cardiovascular events. Toxic metals, aerosols, mercury containing food and water, and cadmium exposure. 10. Lifestyle factors include long working hours, skipping breakfast, long term consumption of sugar containing drinks, and major stress can complete the list. What we do about these factors requires lifelong behavioral modifications, and since doctors have little time to discuss such factors, it is our own responsibility as a person, a parent, and a responsible citizen to address them. Medscape, April 24, 2023
5. A follow up on tongue nerve stimulators to treat obstructive sleep apnea—
We now have a controlled study to give us data on the efficacy of the first electrical device (the aura 6000 THN-targeted hypoglossal nerve device) treatment for obstructive sleep apnea (OSA). This is different from the newer Inspire device, which is similar. And the news is good for moderate to severe OSA. Hypoglossal nerve stimulating lines from a pacemaker imbedded in the chest wall, just like a regular pacemaker would work. This is blue toothed to a handheld device to control it, turning it on and off, etc. It senses when a sleeping person stops breathing, and sends a small bit of current to the back of the tongue to the lingual muscles (in the Inspire device only the genioglossus muscle-the anterior tongue protruder is stimulated) to create enough tension in the tongue to force it slightly forward, as the tongue tends to fall into the back of the throat and obstruct the airway. His small amount of stimulation is just enough for a breath to get by that obstructing tongue. The THN stimulator stimulates all the lingual muscles to put tension in the entire tongue enough to allow it to anterior move off the back of the throat. The electrodes are more easily placed since all the muscles, especially the back of the tongue muscles are more stimulated. The THN device synchronizes with respiration whereas the Inspire device does not. 138 participants were studied after their device was installed. On average, after one month of the device being placed, the apnea index reduced from 53 apneic episodes per minute to 20 per hour. This is called the apneic index, which needs to be 20 or less with improved oxygen saturation from 62% compared to 42% in those who had the implant but did not have it turned on. Symptoms were greatly improved including daytime drowsiness and quality of life issues. Those who were the controls, had their stimulator turned on at 4 months, and did not have as good a response (only 40% improvement in apnea index) and 60% improvement in oxygen desaturation. Even with less improvement, the symptoms were still improved (Epworth sleepiness scale). There are differences in how the tongue muscles are stimulated, and since the THN device is newer, the way the electrical pulse are sent to the tongue may be superior, but only time will tell, with comparison of these two products. It is critical for those with large tonsils, and nasal obstruction problems be addressed if CPAP does not help or is not tolerated. Dental devices, CPAP, and surgical procedures, especially with significant weight loss, still are the recommended beginning of treatment for OSA. Therefore, even though there is significant improvement, physiological measurements must improve enough to reduce a cardiorespiratory complications of OSA. Otherwise, just feeling better is not enough!! 2 complications occurred—one with electrode displacement, and the other neck pain from an electrical cord tension. 6.5% were replaced and 72% experienced some adverse event from pain to wound complications at the time of the implant. With this study, as stated the device used for this study was the aura6000 THN( targeted hypoglossal nerve) device from ImThera Medical, not yet FDA approved, while Inspire device has had FDA approval for a decade. It includes a remote that allows the patient to control the device’s strength of stimulation and sensitivity. The authors gave the nod to the aura 6000 THN device over the Inspire device, but with refinements of these devices will improve the results with less complications. However, with a 9 year time experience for the Inspire device, it will continue to be the mainstay device. The Inspire device to be calibrated requires a drug induced sleep endoscopy to examine collape of the sides of throat which would not stiffen with these electrodes, and it proves the tongue collapses on the back of the throat for insurance to cover it, if the tongue moves off the back of the throat enough to relieve obstruction of air. The THN device will not require it. With experience, the surgeons will find which device they prefer in time, and hopefully won’t be getting financial incentives from either company. There was reported 80% satisfaction level with patients in the THN study. I am sure we will see a similar study from Inspire quite soon. Competition is everything, and obstructive sleep apnea is far just the tongue blocking the back of the throat to obstruct the airway, but has been a nemesis for surgeons until now. Medpage Today, April 6, 2023
This completes the August, 2023 report The September, 2023 report will have: 1. Breast Cancer Series-Part 3—recurrence and second cancers, etc. 2. Celebrities with unusual diseases-Part 5—Nick Jonus-type 1 diabetes, Ashton Kucher-systemic vasculitis, and Elizabeth Hasslebach-Celiac disease 3. Late breaking Medical News 4. The Coup I never knew-about the state of our country!
Enjoy the summer, even with heat or more tolerable mountain temperatures. Stay healthy and well, my friends, Dr. Sam
|
||
