What You Need To Know About Low-dose Aspirin Therapy Thinking about starting daily low-dose aspirin? Discover the pros and cons, understand the guidelines, and learn why talking to your doctor first is essential. InBrief by Madeleine Beckman Edited by Richard Strongwater, MD Updated by Stu Caplen, MD Some 30-million Americans who are at least 40 years old take a small daily dose of aspirin (81 mg) in an attempt to prevent cardiovascular disease, cancer, and even dementia. Of these individuals, over 6-million Americans self-medicate with aspirin each day, taking the drug without a doctor’s recommendation. The Daily Low-Dose Asprin Therapy Argument Pro : A low daily dose of aspirin thins the blood, by keeping platelets from clumping, which can help prevent heart disease and clots that may lead to a heart attack or stroke. Con: This same low daily dose of aspirin may increase the risk of hemorrhagic stroke, gastrointestinal bleeding, and stomach-ulcer development. The use of daily low-dose aspirin therapy is a complex issue. In 2018, the results of three major clinical trials prompted the American Heart Association (AHA) and the American College of Cardiology (ACC) to change clinical practice guidelines, recommending against routine use of aspirin in people over age 70 and individuals at increased risk of bleeding with no existing cardiovascular disease (CVD). In March 2019, the AHA and the ACC recommended against routine use of low-dose aspirin in people at greater risk of bleeding (e.g., those with peptic ulcer) and in persons 70 years of age or older without either existing heart disease or history of stroke.  In addition, they recommended that adults 40 to 75 years of age being evaluated for cardiovascular disease prevention undergo a 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimation and have a clinician–patient risk discussion before starting on aspirin.  It was further recommended that aspirin be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit. In 2022, guidelines from the US Preventive Services Task Force (USPTF) recommended that the decision to initiate low-dose aspirin for the primary prevention of cardiovascular disease (CVD) in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk be an individual one. Evidence indicates that the net benefit of aspirin use in this group is small. Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. The USPTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older. Results of A Study of Cardiovascular Events in Diabetes 7.4-year trial, (ASCEND) reported that aspirin reduced serious vascular events 12% in diabetics who did not have evident cardiovascular disease at the beginning of the trial, but the risk of major bleeding events was 29% higher than the controls. They found no evidence, in the 7.4 years of the study, of any decrease in gastrointestinal cancer risk in the aspirin group. In a study of aspirin use for colorectal cancer prevention, with almost 95,000 subjects, it was reported that there was a 20% less risk of colon cancer for those subjects over 70 years of age that started aspirin before age 70, particularly those that used it for 5 years or more. There was no reduction in cancer risk in subjects who initiated aspirin at age 70 or older. The American Medical Association recommends that physicians ask patients if they are taking unprescribed daily aspirin and advise them about the benefits versus risks. Instead of taking a baby aspirin, persons not at risk should consume a heart-healthy diet, exercise regularly, control blood pressure and cholesterol (including use of a statin or other lipid-lowering medication, if indicated), quit smoking, and maintain a healthy weight. Takeaway for Patients Patients should not self-medicate with aspirin. Instead, they should consult with their physicians about starting low-dose aspirin therapy. Further, suddenly stopping low-dose aspirin therapy may have a rebound effect that could trigger a blood clot and increase the risk of a heart attack. Therefore, anyone deciding to stop self-prescribed aspirin therapy should speak with a physician before making changes that may result in serious consequences. Aspirin use in patients with heart disease is universally agreed on.  However, for primary prevention in patients without cardiac disease, the major bleeding risks that have been discovered may exceed the benefit aspirin will provide, and as such it is being recommended much less for this purpose.  Aspirin may reduce the risk of colorectal cancer if started before age 70, but it is a risk versus benefit decision that should be discussed with a physician.  Lifestyle and dietary changes, with cancer screening exams or colonoscopies, can also decrease colorectal cancer risk. Editor’s note: When a patient asks me about stopping low-dose aspirin that was started without medical consultation for primary prevention, I am reluctant to stop it, especially if the patient has at least two major cardiovascular risk factors (eg, family history for cardiovascular disease, high blood pressure, dyslipidemia, diabetes, smoking, obstructive sleep apnea, obesity). If I am in doubt, I obtain an ultrasound of the carotid arteries to determine the degree of atherosclerotic plaque and/or a coronary calcium score by computed tomography scan to help identify an additional layer of risk. References Agence France-Presse. The pros and cons of a daily aspirin: good for heart disease but it raises risk of internal bleeding . South China Morning Post Web site SCMP.com .  January 24, 2020. Accessed March 2, 2020. American Heart Association News. Avoid daily aspirin unless your doctor prescribes it, new guidelines advise. American Heart Association Web site. https://www.heart.org/en/news/2019/03/18/avoid-daily-aspirin-unless-your-doctor-prescribes-it-new-guidelines-advise . March 18, 2019. Accessed March 2, 2020. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379:1529-1539.Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJMoa1804988 Berg S. New heart-disease prevention guideline: what physicians must know. American Heart Association Web site. https://www.ama-assn.org/delivering-care/hypertension/new-heart-disease-prevention-guideline-what-physicians-must-know . March 28, 2019. Accessed March 2, 2020. Final Recommendation Statement: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication . U.S. Preventive Services Task Force Web site www.usreventitiveServiceTaskForce.org . September 2017. Accessed March 2, 2020. Grisham J. Does an aspirin a day reduce the risk of colorectal cancer?  Memorial Sloan Kettering Cancer Center Web site, www.mskcc.org  March 21, 2017. Accessed March 2, 2020. Hart RJ, Halperin JL, McBride R, et al. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses . Arch Neurol. 2000;57:326-332. Huang WY, Saver JL, Wu YL, Lin CJ, Lee M, Ovbiagele B. Frequency of intracranial hemorrhage with low-dose aspirin in individuals without symptomatic cardiovascular disease: a systematic review and meta-analysis. JAMA Neurol. 2019 [Epub ahead of print]. Mahmoud AN, Gad MM, Elgendy AY, Elgendy IY, Bavry AA. Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J. 2019;40:607-617. Mayo Clinic Staff. Daily aspirin therapy: understand the benefits and risks . Mayo Clinic Web site. www.mayoclinic.org . January 9, 2019. Accessed March 2, 2020. McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med. 2018;379:1499-1508. O'Brien CW, Juraschek SP, Wee CC. Prevalence of aspirin use for primary prevention of cardiovascular disease in the United States: results from the 2017 National Health Interview Survey. Ann Intern Med . 2019;171:596-598. Ranger GS, McKinley-Brown C, Rogerson E, Schimp-Manuel K. Aspirin use, compliance, and knowledge of anticancer effect in the community. Perm J. 2020;24: 19.116. Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA. 2019;321:277-287. Arnett DK et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. September 10, 2019. Vol 140, Issue 11, Retrieved from: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000678#d1e1164 U. S. Preventative Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication. April 26, 2022. Retrieved from: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/aspirin-to-prevent-cardiovascular-disease-preventive-medication Guo C, Ma W, Drew DA, et al. Aspirin Use and Risk of Colorectal Cancer Among Older Adults. JAMA Oncol. 2021;7(3):428–435. Retrieved from: https://jamanetwork.com/journals/jamaoncology/fullarticle/2775175 Initially posted Feb. 2020

Unveiling Ginger's Healing Powers: From Kitchen Spice to Digestive Remedy Discover the ancient origins and modern applications of ginger, a versatile spice renowned for soothing nausea, easing pain, and reducing inflammation, backed by both tradition and scientific research. Culinary Medicine by Mary B Grosvenor, MS, RD and Lori A Smolin, PhD Did your grandmother tell you to sip ginger ale when your stomach was queasy? It was good advice. Ginger, which gives ginger ale its spicy flavor, has been used for centuries in folk and traditional medicine as a remedy for digestive complaints. [1] Today it is among the most commonly used herbal medicines. [2] Ginger, a spice we enjoy in savory stir-fries and curries and in sweets like ginger breads and cookies, originated in Southeast Asia. Although often called ginger root, ginger is not actually a root, but a rhizome, which is an underground horizonal stem from which the roots grow. It can be purchased fresh in the produce section of your grocery store, or dried and ground in the spice aisle, as well as in teas, candies, and supplements. [2] Ginger contains a variety of nutrients including niacin, vitamin B6, vitamin C, iron, and potassium, but it is generally consumed in such small amounts that it does not contribute much to overall nutrient intake. However, ginger is a source of numerous phytochemicals, including gingerols and shogaols. These phytochemicals are believed to provide antinausea and antiemetic effects; they also have antioxidant and anti-inflammatory properties. [3,4] Ginger helps with nausea For over 5000 years traditional Chinese medicine has used ginger as a nausea remedy and the ancient Greeks used it as a digestive aid. Today, modern science is evaluating the effectiveness of ginger in reducing nausea and vomiting due to motion sickness, pregnancy, and chemotherapy.  A dose of 160 g of dried ginger has been shown to be effective in reducing symptoms of motion sickness; this is the equivalent to 1/8 tsp of powdered ginger, one cup of ginger tea, or a small piece of crystalized ginger. [3,5]  Ginger is a popular treatment for morning sickness -  the nausea and vomiting that frequently occur during early pregnancy. Meta-analyses have found ginger to be better than placebo at relieving the symptoms of morning sickness. [3]  While studies varied in the dosage, timing, and duration of the ginger used as a treatment for morning sickness, in general 1 gram of ginger divided into doses over the course of the day for four days was effective at reducing symptoms.  Ginger has also been used to reduce nausea and vomiting caused by many types of chemotherapy used in cancer treatment. In an analysis of seven well-controlled studies of the effectiveness of ginger at reducing symptoms, five studies showed some benefit of ginger. [3] Although more research is needed to determine the optimal dose, this evidence shows that ginger is an effective and inexpensive treatment for nausea and vomiting. Ginger for pain and inflammation Ginger has also been used in the management of pain and inflammation. [2]  For example, ginger is often used to soothe a sore throat. Ginger reduces sore throat pain and swelling due to its anti-inflammatory effects as well as to antimicrobial properties that may help fight infections that cause sore throats. [6] Ginger’s anti-inflammatory role has been investigated for its effectiveness in relieving pain from muscle overuse, osteoarthritis, migraines, and menstrual cramps showing some benefit. [2,7]  Research on ginger supplementation has shown mixed results in managing diseases involving chronic inflammation including rheumatoid arthritis, psoriasis, inflammatory bowel and neurodegenerative diseases. [2,7,8] There is also some evidence that ginger is beneficial in metabolic conditions related to chronic inflammation including type 2 diabetes and obesity. Ginger supplementation causes a slight reduction in blood glucose and blood pressure levels in adults with diabetes.[7] In obese women, ginger supplements showed a minor benefit on weight reduction and heart disease risk factors that accompany obesity. [7] Safety When consumed in food, a daily intake of up to 4 grams of ginger is categorized as GRAS (generally recognized as safe) by the U.S. Food and Drug Administration. [9] While it would be unusual to consume this amount when used as a spice, doses that exceed 4 grams can easily be consumed from crystalized ginger, ginger candies, teas, and supplements. Although the GRAS designation only applies to food, ginger supplements in this amount have been used safely in many research studies. [10]  Higher intakes may cause mild abdominal discomfort, heartburn, diarrhea, and irritation of the mouth and throat. Research studies using ginger for morning sickness have shown it to be safe for pregnant women; most studies evaluated doses of 250 mg taken four times daily for a total 1 g per day. [11] Ginger may increase the risk of bleeding so should be used with caution by those taking blood thinning medications, such as Eliquis, Coumadin, and aspirin. [6] Bottom Line This savory spice will add a kick to your recipes and also has medicinal benefits. Ginger is best known for its ability to reduce nausea and vomiting, but it also has beneficial antioxidant and anti-inflammatory properties. To reap these benefits, add it to stews, casseroles, and salad dressings, bake it into snaps and muffins, or enjoy a cup of ginger tea. Bring some crystalized ginger or ginger cookies on your next car, boat, or plane excursion to stave off motion sickness. Unfortunately, many commercial ginger ales contain very little ginger. Not sure how to cook with ginger? Try our healthy ginger, turmeric, rice recipe. References [1] Institute MS. Ginger. McCormick Science Institute. https://www.mccormickscienceinstitute.com/resources/culinary-spices/herbs-spices/ginger#:~:text=In%20Thailand%2C%20it%20is%20an [2] Ballester P, Cerdá B, Arcusa R, Marhuenda J, Yamedjeu K, Zafrilla P. Effect of Ginger on Inflammatory Diseases. Molecules. 2022;27(21):7223. doi:https://doi.org/10.3390/molecules27217223 [3] Lete I, Alluέ J. The Effectiveness of Ginger in the Prevention of Nausea and Vomiting during Pregnancy and Chemotherapy. Integrative Medicine Insights. 2016;11:11-17. doi:https://doi.org/10.4137/imi.s36273 [4] Mao QQ, Xu XY, Cao SY, et al. Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale Roscoe). Foods. 2019;8(6):185. doi:https://doi.org/10.3390/foods8060185 [5] Nunes CP, Rodrigues C, Mendel Suchmacher, et al. A Combination of Gamma-Aminobutyric Acid, Glutamic Acid, Calcium, Thiamine, Pyridoxine, and Cyanocobalamin vs Ginger Extract in the Management of Chronic Motion Sickness: A Clinical Evaluation. Current therapeutic research. 2023;99:100719-100719. doi:https://doi.org/10.1016/j.curtheres.2023.100719 [6] Ginger for Sore Throat: Benefits, Uses, and Recipe. Healthline. Published August 10, 2018. https://www.healthline.com/health/ginger-for-sore-throat#4 [7] Anh NH, Kim SJ, Long NP, et al. Ginger on Human Health: A Comprehensive Systematic Review of 109 Randomized Controlled Trials. Nutrients. 2020;12(1):157. doi:https://doi.org/10.3390/nu12010157 [8] Arcusa R, Villaño D, Marhuenda J, Cano M, Cerdà B, Zafrilla P. Potential Role of Ginger (Zingiber officinale Roscoe) in the Prevention of Neurodegenerative Diseases. Frontiers in Nutrition. 2022;9. doi:https://doi.org/10.3389/fnut.2022.809621 [9] Modi M, Modi K. Ginger Root. PubMed. Published 2021. https://www.ncbi.nlm.nih.gov/books/NBK565886/ [10]  National Center for Complementary and Integrative Health. Ginger. Published December 2020. https://www.nccih.nih.gov/health/ginger [11]  Stanisiere J, Mousset PY, Lafay S. How Safe Is Ginger Rhizome for Decreasing Nausea and Vomiting in Women during Early Pregnancy? Foods. 2018;7(4):50. doi:https://doi.org/10.3390/foods7040050

Promoting Healthy Sleep with Essential Tips and Benefits for Optimal Rest Recommendations from multiple sources to help your patient sleep better. by Kruti Vora and Rich Strongwater, M.D. Healthy sleep is essential to maintain a good quality of life and mental and physical well-being. Although people are unconscious when they sleep, their brains and bodies are active. An understanding of what biological processes occur during sleep, why sleep hygiene is important, and how sleep quality can be promoted can encourage restful sleep and refreshed daily functioning. What happens when you’re asleep? Your brain progresses through different stages of sleep that are characterized by varying brain activity. These stages can be divided into rapid eye movement (REM) sleep and non-REM sleep, which is further subdivided into three stages. Stage 1 represents the transition from wakefulness to sleep and lasts a short period of time; it is characterized by slower brain-wave activity. Stage 2 involves deeper sleep, and stage 3 refers to deepest sleep. Cycling through these stages takes 90-110 minutes; as the night progresses, the REM period takes up a larger proportion of the cycle. During REM sleep, the eyes move, and most dreaming occurs. The sleeping person has brain activity much like that during waking hours but becomes extremely relaxed or even paralyzed. Children experience higher percentages of REM sleep during a sleep cycle than do older sleepers. Why is sleep so beneficial? As the brain is cycling through sleep stages, the body uses sleep to heal and become strong. Non-REM sleep, in particular, can help rejuvenate bone, muscle, tissues, and the immune system as it helps the body release growth and sex hormones needed for proper growth and puberty. Both REM and non-REM sleep may aid memory consolidation. On the other hand, bad sleep hygiene may affect both mental and physical health and increase the risk of depression, high blood pressure, obesity, infections, and kidney disease. How can I get good sleep? The amount of sleep needed each day changes as people age. The National Institute of Health recommends that newborns sleep 16-18 hours per day, since they are growing and developing rapidly. Sleep requirements decrease as children age, dropping to 9.5 hours per night for teenagers. Adults typically require 7-9 hours per night, although the elderly may find their sleep to be lighter and more interrupted. Not only is getting enough sleep important, but the quality of the sleep must also be ensured. Sleep hygiene is a set of lifestyle habits that promote healthy sleep. Behavioral therapy to teach patients the elements of sleep hygiene is an important initial step in treating insomnia. The National Library of Medicine recommends several measures that may help improve sleep, including: keeping to a regular schedule of rising from and getting into bed (weekend sleep hours ideally should not vary excessively from weekday hours); avoiding consumption of large meals, caffeine, nicotine, and alcohol, especially later in the day; exercising regularly, but avoiding physical activity close to bedtime; sleeping in a cool environment; avoiding use of electronics before bedtime; doing something relaxing before bed, especially if you can’t fall asleep; using the bed only for sleep and sexual activity, although reading a relaxing book may help promote sleep; and going to bed when sleepy, doing something relaxing/enjoyable before bedtime. Other good sleep habits include: making your bedroom quiet, dark, and comfortable; removing your clock from sight; avoiding naps during the day (any nap should last only 30 minutes and take place in the early afternoon); avoiding frequent use of sedatives or hypnotics; spending time outdoors at the same time each day; checking medicines with a pharmacist to find out if they may affect sleep; avoiding blue light-emitting screens (eg, from cell phones) before bedtime; avoiding or limiting use of products containing nicotine before bedtime; avoiding watching violent television programs before bedtime; and avoiding working in bed. People who work shifts have a particularly difficult time obtaining restful sleep. They may try: limiting consumption of caffeine-containing products during the early part of the shift; limiting changes from one shift to another to help the body adjust; taking naps and making more sleeping time available; maintaining bright lighting in the workplace; and using light-blocking curtains and avoiding distracting sounds in the bedroom when sleeping during the day. What if I still can’t sleep well? Sometimes people have sleep disorders that cause them to have too little sleep(insomnia), inappropriate sleep (narcolepsy), or abnormal occurrences during sleep (eg, sleep apnea, restless leg syndrome, and REM sleep behavior disorder). A consultation with a physician is important if symptoms of these conditions occur or if good sleep is not obtained after the recommendations above are followed. Further treatment may produce restful sleep and productive, energetic, and active waking hours. References Cleveland Clinic. Sleep basics. Cleveland Clinic Web site. https://my.clevelandclinic.org/health/articles/12148-sleep-basics . December 7, 2020. Accessed January 31, 2021. Jermaine DM. Sleep disorders. In: Carter BL, Angaran DM, Lake KD, Raebel MA, eds. Pharmacotherapy Self-Assessment Program. 2nd ed. Psychiatry Module. Kansas City: American College of Clinical Pharmacy, 1995:139–154. National Institutes of Health; US National Library of Medicine. Healthy sleep. MedlinePlus Web site. https://medlineplus.gov/healthysleep.html . Updated November 16, 2020. Accessed January 31, 2021. National Institutes of Health; National Institute of Neurological Disorders and Stroke (NINDS). Brain basics: understanding sleep. NINDS Web site. https://www.ninds.nih.gov/Disorders/patient-caregiver-education/Understanding-sleep . August 13, 2019. Accessed January 31, 2021. Rehman A, Fry A. What is healthy sleep? Sleepfoundation.org Web site. https://www.sleepfoundation.org/sleep-hygiene/what-is-healthy-sleep . Updated January 8, 2021. Accessed January 31, 2021. Rehman A, Pacheco D. Sleep disorders. Sleepfoundation.org Web site. https://www.sleepfoundation.org/sleep-disorders . Updated December 1, 2020. Accessed January 31, 2021. #PatientHandouts

Understanding Frank's Sign and Its Link to Heart Disease InBrief by Richard Strongwater, MD Frank's sign is defined as a deep wrinkle or crease (usually single or double on the same earlobe) that extends diagonally from the tragus toward the posterior border of the earlobe. It may occur unilaterally or bilaterally. Earlobe crease (ELC) sign has been associated with an increased risk for coronary artery disease (CAD). The prevalence of ELC increases with age and in patients with CAD. ELC and CAD may be associated with the loss of elastin and elastic fiber in skin and arteries. Many studies support the association of CAD with ELC. The presence of a persistent earlobe crease should prompt careful assessment of the patient's risk factors for heart disease and stroke. References Kirkham N, Murrells T, Melcher DH, Morrison EA. Diagonal earlobe creases and fatalcardiovascular disease: a necropsy study.Brit HeartJ.1989;61:361–364. Gulsin GS, Clement KD, Anglim N. Frank’s sign as a marker of coronary arteryatherosclerosis.J Cardiol Clin Res.2014;2:1032.

Stem cell transplants - autologous and allogenic Oncology Terms FibonacciMD Compendium Autologous | Allogenic InBrief Written by: Anurag Saraf, MD, Nirmala Saraf, MD, and Nancy Mills MD The first successful bone marrow transplant was performed in 1957 by Dr. E. Donnall Thomas in a patient with acute leukemia. For his research Dr. Thomas subsequently won the Nobel Prize in physiology and medicine. The success of this transplant was in part due to the fact that it was a “syngeneic transplant”. The donor was the patient’s monozygotic twin! (7) Traditionally, stem-cell transplants had been collected through the bone marrow, and therefore were referred to as "bone marrow transplant". However, today most transplants can be collected through pheresis of the peripheral blood using CD34 as a differentiating marker or from cord blood; therefore the name hematopoietic stem cell transplant is now more appropriate. Hematopoietic stem cell transplant involves the administration of healthy hematopoietic stem cells to patients with dysfunctional bone marrow (from disease) or with depleted bone marrow (either by disease or by purposeful high-dose chemotherapy or total body irradiation)(6). Indications for hematopoietic stem cell transplant might include malignancies (including multiple myeloma, Hodgkin and Non-Hodgkin lymphomas, acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, chronic lymphocytic leukemia, myelofibrosis and polycythemia vera), other solid tumor malignancies (including testicular tumors refractory to chemotherapy) and non-malignant diseases including aplastic anemia, severe combined deficiency syndrome, thalassemia, sickle cell anemia and possibly autoimmune disorders such as progressive multiple sclerosis, systemic sclerosis and systemic lupus erythematosus. (6) Autologous Hematopoietic Stem Cell Transplant AKA Auto HSCT Auto SCT Autologous Hematopoietic Stem Cell Transplant Autologous HSCT Autologous SCT Autologous Stem Cell Transplant Autologous Hematopoietic Stem Cell Transplant (Auto HSCT) involves an induction therapy to eradicate a patient’s hematopoietic system and then rescue it with their own stem cells. It is used in the setting of blood cancers (e.g. leukemia, lymphoma), as well as some autoimmune conditions. Auto HSCT should be differentiated from Allogeneic HSCT, which involves transplanting a donor’s stem cells, rather than the patient's own stem cells, after hematopoietic ablation. Efficacy of Auto HSCT on the disease process is thought to be primarily from the induction therapy. High-dose chemotherapy and/or radiation therapy is used to eradicate as many malignant cells as possible, including microscopic and resistant cells. Higher dose therapy can be used because the bone marrow will be rescued with autologous stem cells. This is different from Allo HSCT which has the second effect of the Graft-versus-leukemia (GVL) effect, where any microscopic and/or resistant disease after myeloablation can continue to be attacked by donor immune system, an effect seen even weeks to months after transplant. Auto HSCT has no GVL effect, and the primary treatment effect is from the induction therapy. Advantages of Auto HSCT over Allo HSCT include patients not having to find a donor and not experiencing graft-versus-host disease. Elderly and frail patients who cannot tolerate the myeloablative procedure are not considered good candidates for Auto HSCT. Allogeneic Hematopoietic Stem Cell Transplant AKA allo allo transplant allogeneic hematopoietic stem cell transplant allogeneic stem cell transplant allo-HSCT allo-SCT HSCT Allogeneic hematopoietic stem cell transplant (allo-HSCT) involves the transplantation of stem cells from a healthy person into the body of a patient who has undergone induction chemotherapy or radiation therapy (myeloablation therapy, reduced-intensity conditioning therapy) to treat blood cancers (leukemia, lymphoma) and some autoimmune conditions. Allo-HSCT is different than autologous HSCT, which involves transplanting the patient’s own cells after chemotherapy and radiation. Allo-HSCT is believed to have two effects on disease. First, the myeloablation itself eradicates the malignancy. Second, the donor transplant has some graft-versus-leukemia (GVL) effect, in which any microscopic and/or resistant disease after myeloablation can continue to be attacked; this effect can remain even weeks to months after transplant. For certain diseases, particularly certain leukemias, the GVL effect may be the strongest, so patients can get less intensive induction protocols (often called reduced-intensity conditioning therapy or non-myeloablation induction therapy), particularly elderly patients who cannot tolerate myeloablation that well. In contrast, auto-HSCT has no GVL effect, and the primary treatment effect comes only from the induction therapy; however, patients do not have to be concerned about finding a donor or experiencing graft-versus-host disease (GVHD). Allo-HSCT given at transplant is for rescue of hematopoietic function after induction therapy; it allows patients to engraft bone marrow stem cells and produce normal hematopoietic function. Complications of Allo-HSCT GVHD, in which transplanted cells attack the host's organs, is a major complication of allo-HSCT. It is particularly prevalent in the gastrointestinal tract, skin, and eyes. Treatment often involves immunosuppression (either with a chronic course of steroids or other immunomodulators [e.g., tacrolimus]). Acute GVHD is seen within the first weeks to months after transplant, whereas chronic GVHD can last for several years afterwards. Patients undergoing auto-HSCT do not develop GVHD. Oncology definitions in the FibonacciCOMPENDIUM Autologous Stem Cell Transplant Allogenic Hematopoietic Stem Cell Transplant #InBrief #Oncology #FibonacciCOMPENDIUM Sources: 1. Leukemia & Lymphoma Society 2019. "AUTOLOGOUS STEM CELL TRANSPLANTATION". (https://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/autologous-stem-cell-transplantation) 2. MSKCC 2019. "Autologous Transplantation". (https://www.mskcc.org/cancer-care/diagnosis-treatment/cancer-treatments/blood-stem-cell-transplantation/autologous) 3. Allogeneic stem cell transplantation. Leukemia & Lymphoma Society Web site. https://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/allogeneic-stem-cell-transplantation. Accessed August 21, 2019. 4. Autologous vs. allogenic stem cell transplants: what’s the difference? Insight from Dana Farber Cancer Institute Web site. https://blog.dana-farber.org/insight/2017/03/autologous-vs-allogenic-stem-cell-transplants-whats-the-difference/. March 6, 2017. Accessed August 21, 2019. 5. Sengsayadeth S, Savani BN, Blaise D, Malard M, Nagler A, Mohty M. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. Haematologica. 2015;100:859-869. 6. Khaddour K, Hana C, Mewawalla P. Hematopoietic Stem Cell Transplantation. StatPearls. Last Update: June 27, 2022. 7. Thomas ED, Lochte HL, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957 Sep 12;257(11):491-6. [PubMed]

Spondylolisthesis Causes, Locations, and Why It's Unique to Humans. InBrief Spondylolisthesis is a slip, or transverse subluxation, of one vertebral body on an adjacent vertebral body. The most common location for spondylolisthesis is an anterior slip of the L5 vertebral body on the sacrum. The next most common location is L4 on L5. Spondylolisthesis is unique to humans due to erect posture placing great loads at the lower lumbar spine. more about spondylolisthesis in our Compendium. More about this orthopaedic medical term, in our FibonacciMD APP medical Compendium. Log-in with your email to see more of the definition, diagnostic evaluation, staging and further stratifications, treatment of, complications, prognosis, and more. www.FibonacciMD.app / spondylolisthesis

Advancing Spinal Cord Regeneration - Recent Breakthroughs and Future Directions Explore recent therapeutic successes and the latest insights into spinal cord biology that are bridging the gap in regenerative medicine. Discover how innovative treatments, from cell therapies to molecular interventions, offer hope for restoring movement in paralyzed individuals. InBrief by Zachary A. Knecht, PhD Although made a cliché by TV medical dramas, “you’ll never walk again” remains a harsh reality for victims of spinal-cord injury (SCI). In a split second, victims can go from moving normally to being permanently paralyzed and often requiring aid just to breathe. Our resilient bodies routinely mend broken bones and seal wounds, yet the ability of the body to recover from so devastating an injury has long been beyond our reach. Regenerating damaged tissue of the central nervous system and restoring function in SCI patients is a goal that has captivated medical science for over 100 years. Now, recent therapeutic successes and insights into the underlying biology of the spinal cord have closed the gap between the field of regenerative medicine and restoring movement in paralyzed people. In 2014, Derek Fidyka, a Polish man rendered paralyzed from the chest down in a 2010 knife attack, miraculously regained the partial use of his legs. His remarkable recovery resulted from a groundbreaking treatment that transplanted specialized cells called olfactory ensheathing cells (OECs) from the patient’s olfactory bulb, a small structure found in the front of the brain. These cells normally guide bundles of nerve fibers to form new synaptic connections between nerve cells.[1] Nerve fibers were taken from Mr. Fidyka’s ankle and implanted into the injured area of the spinal cord; a culture of OECs was injected above and below the area. Eventually, the two cut ends of the spinal cord fused, and Mr. Fidyka regained some movement and feeling in his legs, allowing him to walk, drive, and resume a few functions we normally take for granted. Although Mr. Fidyka’s recovery is historic, OEC transfer itself does not represent a cure for SCI. Many experts still disagree about the long-term effectiveness of the OEC transplant. The results of most studies show that OEC transfer can improve motor function, but the degree of improvement and long-term outcomes vary greatly and can sometimes worsen SCI-associated pain.[2] Despite early success, the uncertainty of OEC transfer highlights the challenges inherent to treating SCI- the spinal cord is a dauntingly complex structure composed of many different types of cells, and its injuries vary greatly from patient to patient. The mechanisms that allow regeneration differ from one part of the spinal cord to the next. Thus, the location, severity, and time since the injury are all important considerations in finding new ways to repair the damage.[3] Luckily, these insights are now being applied to a new generation of promising treatments that can be divided roughly into the broad categories of “cell therapies” and “molecular therapies.” Cell therapies use types of stem cells alone or with growth factors to induce the growth of new functional connections between nerve cells.4 Stem cells can be cultured from fetal tissue or taken directly from the patient’s body, as is done in OEC transfer. Molecular therapies, on the other hand, seek to encourage regeneration by directly altering the biologic environment of the injury site, which often has scar tissue, growth inhibitors, and other factors that can prevent regeneration and return to normal function.3 Molecular therapies include compounds that degrade scar tissue and soak up growth inhibitors with sponge-like artificial receptors.4 Specially designed biomaterials with unique physical and electrical properties can act as scaffolds to help guide regrowth of tissue, facilitate the delivery of stem cells, and even directly stimulate the growth of new nerves.[4,5] The road to advancing treatments for SCI remains long, but anyone paying attention to the field has plenty of reasons to feel hopeful. A growing understanding of the spinal cord’s biology presents opportunities for innovation and enhancement of current therapies. The story of Mr. Fidyka is a rare one, but few successes are infinitely better than none. Mr. Fidyka’s story and the tireless efforts of countless research teams provide much needed hope for both SCI patients and the medical professionals and researchers who strive to help them walk again. References Tabakow P, Raisman G, Fortuna W, et al. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. 2014;23: 1631–1655. Nakhjavan-Shahraki B , Yousefifard M , Rahimi-Movaghar V, et al. Transplantation of olfactory ensheathing cells on functional recovery and neuropathic pain after spinal cord injury; systematic review and meta-analysis. Sci Rep. 2018;8:325. Sofroniew MV. Dissecting spinal cord regeneration. Nature. 2018;557:343–350. Dalamagkas K , Tsintou M , Seifalian A , Seifalian AM . Translational regenerative therapies for chronic spinal cord injury. Int J Mol Sci. 2018;19(6). pii: E1776. Theodore N , Hlubek R, Danielson J , Neff K , Vaickus L , Ulich TR , Ropper AE . First human implantation of a bioresorbable polymer scaffold for acute traumatic spinal cord injury: a clinical pilot study for safety and feasibility. Neurosurgery. 2016;79:E305-E312.

Challenging Conventions: Rethinking Opioid Prescribing in Chronic Pain Management The scope of the opioid problem is immense. Taking a second look after attending an International Conference on Opioids. InBrief by Christopher King, NP At the beginning of June 2019, I attended the International Conference on Opioids (ICOO) held at Harvard Medical School in Boston, Massachusetts. I believed that I was fairly well informed about the opioid crisis in this country, and I hoped to learn enough to give chronic-pain patients better rationales for denying opioid prescriptions. I was sure that information shared at the conference would support two important positions: some of these drugs often are not indicated for chronic pain, and overprescribing may have dire consequences. However, information shared during some of the presentations made me question the rigidity of my beliefs. The scope of the problem is immense. From 1990-2012, opioid prescriptions in the United States increased from under 1 million to over 255 million. This is the equivalent of 81.3 opioid prescriptions for every 100 people living in this country. Although I was aware of more prescriptions being written after pain was considered “the fifth vital sign,” I found these numbers to be mind-boggling. This spike in prescriptions may have resulted from the aggressive marketing of opioid pain medications by pharmaceutical companies, which certainly engaged in some predatory practices. However, they also offered a solution to a growing problem. One in five patients in the United States suffers from chronic pain, which causes some functional loss that may be quantified by quality-of-life measures ranging from ability to work to quality of sleep. Many of my patients have been prescribed opioids for years to manage chronic pain resulting from lower-back trauma, failed back surgeries, complex regional pain syndrome, contractures and spasms resulting from paralysis, arthritis, diabetic neuropathy, and many other causes. Since 2011-2012, opioid prescriptions largely have been declining because of a national epidemic that has claimed tens of thousands of lives. In 2016, the US Centers for Disease Control and Prevention (CDC) released the CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016, which highlights a strategy to reduce excessive prescriptions. This guideline is a decent framework for the primary-care practitioner seeking to provide competent care for patients suffering from chronic pain. The most salient point for practitioners is to tread carefully when prescribing these drugs. Treating chronic pain without opioids is obviously the ideal; when this is not possible, risks must be weighed against benefits, and patients should be informed of the inherent risks of long-term opioid use. Unfortunately, the interpretation of this guideline has created some unintended consequences. The major concern of these guidelines appears to advise prescribers to avoid any medication regimen that exceeds 90 morphine milligram equivalents (MME). It is common to see new patients trying to establish care after being discharged from another practice for failure to reduce their opioid dosage according to the CDC guidelines. Many patients who have been stable for years on their opioid dosage insist that a radical dose reduction will precipitate acute pain, withdrawal, and anxiety, with all having negative impacts on day-to-day living. The message in healthcare is clear—whereas practitioners hunker down to follow” standards of care,” real people who have built productive lives are destabilized by arbitrarily imposed limits imposed to mitigate only some risk. The misapplication of the 90 MME became clear when I listened to a lecture by JeffreyFudin, PharmD, FCCP, FASHP, FFSMB, who addressed the problems in developing public policy when shared definitions of variables are lacking. MMEs are difficult to calculate for many drugs (eg, fentanyl, methadone). Dosages of these drugs cannot be reliably and consistently converted into morphine equivalents. Further, equianalgesic conversion calculators and tables are meant to help measure analgesic effect, nottoxicity. I had not considered this important point before this conference, and I began to see problems that had not occurred to me before. How can limited dosing to a target be recommended when those measurements are misapplied and misinterpreted with unreliable data? In June 2019, the authors of the CDC guidelines published a statement in the New England Journal of Medicine acknowledging problems in how guidelines have been interpreted and applied. The statement refers to “the inflexible application” of the 90MME limit and the need for more research to determine how to best decrease high-dose opioids in patients given long-term treatment. Logically, a rapid decrease and/or discontinuation of these medications will cause deleterious physical effects and possibly precipitate abuse of other substances and/or other behaviors, thereby increasing the risk of morbidity and mortality. Chronic pain remains one of the primary reasons Americans seek medical attention. Some 100-million Americans suffer from pain lasting over 3 months. Left inadequately treated, chronic pain may adversely affect multiple body functions, including the immune, endocrine, and cardiovascular systems. In addition, it may also impact depression, substance abuse, and suicide. These statistics are not as well documented as overdose deaths; in 2017, however, there were 47,173 suicide deaths and 17,029 deaths related to prescription opioid use. Reports from the US Food and Drug Administration have indicated that patients forced to taper down on medication doses or discontinue medications completely report “serious withdrawal symptoms, uncontrolled pain, psychological distress, and suicide.” Healthcare professionals who treat chronic pain have been making this case to policymakers for some time, and the CDC’s recent statement published in the New England Journal of Medicine seems to corroborate these concerns. Participating in the ICOO challenged me to think differently about safe opioid prescribing. In the past, I believed that eliminating opioid prescriptions for all indications except for palliative care and severe acute pain seemed reasonable. Unfortunately, this mindset fails to deal with the complex nature of the opioid crisis. Failure to adequately treat chronic pain has repercussions every bit as deadly and debilitating as the consequences of addiction. The CDC guidelines should not be applied as a standard of care. At the end of the day, I am a patient advocate and ally who strives to see my patients as individuals and treat them accordingly. It is still my goal to not over prescribe any medication. However, I realize that the opioid crisis is a very complex problem that may be successfully fought with a more thoughtful, nuanced approach. ABOUT THE AUTHOR Christopher King, NP Christopher's nursing experience after undergrad was primarily working in Emergency medicine in Central and Coastal Maine. In 2014 Christopher went back to school for his Master's Degree and graduated in 2016 from the University of Southern Maine with his MSN. Currently, Christopher works for New England Sport and Spine in Manchester ME. When not working Christopher enjoys the Maine outdoors with his wife, children, and 2 dogs. Sources Centers for Disease Control and Prevention (CDC), National Center for Injury Prevention and Control, Division of Unintentional Injury Prevention. US Opioid Prescribing Rate Maps. CDC Web site. https://www.cdc.gov/drugoverdose/maps/rxrate-maps.html. October 3, 2018. Accessed July 2, 2019. Dahlhamer J, Lucas J, Zelaya C, et al. Prevalence of chronic pain and high-impact chronic pain among adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;14;67:1001-1006. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. CDC Web site. www.cdc.gov March 18, 2016. Accessed July 2, 2019. Dowell D, Haegerich T, Chou R. Perspective: No shortcuts to safer opioid prescribing. N Engl J Med. 2019;380:2285-2287. Rosenblum A, Marsch LA, Joseph H, Portenoy RK. Opioids and the treatment of chronic pain: controversies, current status, and future directions. Exp Clin Psychopharmacol. 2008;16:405–416. Schatman ME, Peppin JF, Fudin J. The CDC guideline: the three amigos wade into the fray. Presented at: International Conference on Opioids; June 9, 2019; Boston, Massachusetts. http://opioidconference.org/uploads/1_8_3_FUDIN_The_Three_Amigos_Wade_into_the_Fray.pdf. Accessed July 2, 2019. US Food and Drug Administration (FDA). FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering. FDA Web site. https://www.fda.gov/drugs/drug-safety-and-availability/fda-identifies-harm-reported-sudden-discontinuation-opioid-pain-medicines-and-requires-label-changes. April 9, 2019. Accessed July 2, 2019.

Sleuthing Out Added Sugars article Culinary Medicine by Lori A Smolin, PhD and Mary B Grosvenor, MS, RD Sugar seduces our taste buds, whether you spoon it into coffee or sprinkle it onto cereal, it adds the sweetness that we crave. Sugar also provides a quick source of energy for our muscles and our brains. But adding too much sugar to your diet can contribute to the risk of obesity and other chronic disorders. Avoiding sugar, however; is not easy. For example, if you stop at Starbucks for a morning Frappuccino, snack on a granola bar, and then have a sugared soft drink with lunch you have consumed over 100 grams of what are called added sugars, more than double the maximum recommended for the entire day. How can we identify added sugars in our diets and why are health professionals trying to get us to eat less of them? Natural vs Added Sugars Many of the foods we enjoy are inherently sweet. Apples, pears, strawberries, watermelon, and even asparagus, and peas, contain the sugar fructose and milk contains lactose, also known as milk sugar. These sugars are natural components of fruits, vegetables, and milk so are not considered added sugars.  The sugar we consume in these foods comes along with the vitamins, minerals, protein, fiber, and phytochemicals found in the original source. In contrast, added sugars have been separated from their natural plant sources, often sugar beets or sugar cane, and then added to foods to increase sweetness as well to improve texture and extend shelf life. Americans consume about 60 pounds of added sugars per person per year.[1] Most of this is consumed in processed foods; 74% of processed packaged foods contain added sugars.[2]  Over half of the added sugars in the American diet come from sugar-sweetened beverages, such as soft drinks, sports drinks, fruit drinks, energy drinks, sweet tea, and sweetened coffee drinks.[3] Although added sugars are nutritionally and chemically identical to the sugars that occur naturally in foods, they do not come with other nutrients; they only contribute calories to the foods to which they are added. Added Sugars and Health Diets high in added sugars have been implicated as a risk factor for some of the major chronic diseases in the United States, including obesity, diabetes, and cardiovascular disease (CVD) as well as fatty liver disease, dental caries, and some cancers.[4]  Because so much of the added sugars in our diet come from beverages, much of the research on added sugars and health has examined the relationship between sugar-sweetened beverage intake and disease. All added sugars add calories to our diets, which contribute to weight gain, but sugar-sweetened beverage consumption is a particular risk for obesity. This is because liquids are not as satiating as solid foods so the calories we consume in liquids are not compensated for by reductions in calorie intake from other foods. Also, the rapid absorption of the sugar in these beverages causes spikes in blood glucose and insulin that could increase hunger.[5] Meta-analyses find a positive correlation between sugar-sweetened beverage intake and obesity and when sugar-sweetened beverages are added to participants diets they gain weight.[6]  In contrast, replacing sugar-sweetened beverages with non-caloric beverages reduces body weight among study participants.[7] Most sugar-sweetened beverages are sweetened with high-fructose corn syrup. This sweetener tastes sweeter than sucrose (table sugar) so manufacturers can use less to achieve the same degree of sweetness. A high intake of fructose is believed to be a particular risk for chronic disease. One reason is that fructose is broken down in the liver where it is used to synthesize fat, contributing to fat storage in the liver and the abdominal region.[8] Excess fat in the liver can lead to non-alcoholic fatty liver disease.[4] Greater amounts of abdominal fat increase the risk of diabetes and CVD. [6] The risk of diabetes is correlated with sugar-sweetened beverage intake. Part of this increased risk is due to weight gain, but factors independent of obesity also play a role. [9]   Sugar-sweetened beverage consumption is also associated with a higher risk of CVD.[10] Weight gain and diabetes increase the risk of CVD, but added sugars also impact other CVD risk factors; higher intakes increase serum triglycerides, total cholesterol, LDL cholesterol, and blood pressure. [11] Sleuthing Out Added Sugars Reducing your intake of added sugars requires knowing where they are coming from in your diet. A teaspoon of sugar tipped into your coffee is an obvious source of added sugar. And sugar-sweetened beverages, cakes, candy, and cookies are foods we recognize as high in added sugars, but other sources are not so apparent. For example, low-fat fruit yogurt, which we think of as a healthy choice, often contains 13 grams of added sugars. Foods we don’t think of as sweet, such as pasta sauces, canned soups, and baked beans can also provide significant amounts; a serving of canned baked beans has more than 10 grams of added sugars. Even condiments like ketchup, salad dressing, and barbecue sauce add sugar to our diets. To identify food products that are high in added sugars look at the Nutrition Facts panel on your food label. It lists the grams of total sugars in a serving, which is the sum of naturally occurring sugars and added sugars and includes a separate listing for added sugars, both in grams and as as a %Daily Value. The %Daily Value is the amount of added sugars in a serving of the food as a percentage of the amount recommended (less than 50 grams) for a 2000-Calorie diet. So, if a serving of a food has 20% of the Daily Value for added sugars it provides 20% of the 50-gram maximum recommended per day. Make sure to also check the serving size. If the serving size on the Nutrition Facts label on your box of cookies is 2 cookies and you eat four, you are eating twice the amount of added sugars listed on the label. The ingredient list can also help identify the added sugars in processed foods, but you may not see the word “sugar”. Only sucrose can be listed as sugar in ingredient lists and there are many other forms of sugar that are added to food products (See table). Since ingredients are listed in order of prominence by weight, the closer to the front of the list a sweetener appears, the more of it by weight is in the product. In a product that contains more than one sweetener, together they may account for a larger proportion of the products weight than you would judge from their place on the list. Reducing Added Sugars in Your Diet The Dietary Guidelines for Americans recommend that people 2 years of age and older consume less than 10% of calories from added sugars. [12]  For a 2000-Calorie diet this is less than 200 Calories from added sugars (about 50 grams), which is the equivalent of about 12 teaspoons per day. Children younger than 2 years should not be given any foods or beverages with added sugars. Currently 60% of Americans exceed the 12 teaspoon per day limit, consuming an average of 17 teaspoons of added sugars per day. [13] For most of us, cutting down on added sugars should start by replacing sugar-sweetened beverages with water. A 12-ounce can of soda contains about 10 teaspoons of sugar; sweet teas, juice drinks, and coffee drinks have about the same amount. If you want more flavor than plain water offers, try adding lemon or lime juice to your water or choose a sugar-free commercial seltzer drink. Desserts are another major source of added sugars; replace some or all of your desserts with fruit. If you choose canned or frozen fruit, check the label to be sure it doesn’t contain added sugars. Reading labels can help you limit the added sugars from foods we don’t consider sweets such as sauces and condiments.  But you don’t have to skip the ketchup or make your own sugar-free spaghetti sauce, just keep track of how much added sugar you are consuming. You can still enjoy some sweet while avoiding the bitter consequences of added sugars by keeping your total below the 50-gram limit. References [1] US Department of Agriculture, Agricultural Research Service. Food Patterns Equivalents Intakes from Food: Mean Amounts Consumed per Individual, What We Eat in America, NHANES 2017–2018. https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/FPED/tables_1-4_FPED_1718.pdf [2] Ng SW, Slining MM, Popkin BM. Use of Caloric and Noncaloric Sweeteners in US Consumer Packaged Foods, 2005-2009. Journal of the Academy of Nutrition and Dietetics. 2012;112(11):1828-1834.e6. doi:https://doi.org/10.1016/j.jand.2012.07.009 ‌ [3] Lee SH, Zhao L, Park S, et al. High Added Sugars Intake among US Adults: Characteristics, Eating Occasions, and Top Sources, 2015–2018. Nutrients. 2023;15(2):265. doi:https://doi.org/10.3390/nu15020265 ‌ [4] Huang Y, Chen Z, Chen B, et al. Dietary sugar consumption and health: umbrella review. BMJ. 2023;381:e071609. doi:https://doi.org/10.1136/bmj-2022-071609 ‌ [5] Ludwig DS, Ebbeling CB. The Carbohydrate-Insulin Model of Obesity. JAMA Internal Medicine. 2018;178(8):1098. doi:https://doi.org/10.1001/jamainternmed.2018.2933 ‌ [6] Malik VS, Hu FB. The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases. Nature Reviews Endocrinology. 2022;18(4):205-218. doi:https://doi.org/10.1038/s41574-021-00627-6 [7] Ebbeling CB, Feldman HA, Steltz SK, Quinn NL, Robinson LM, Ludwig DS. Effects of Sugar‐Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial. Journal of the American Heart Association. 2020;9(15). doi:https://doi.org/10.1161/jaha.119.015668 [8]Hannou SA, Haslam DE, McKeown NM, Herman MA. Fructose metabolism and metabolic disease. J Clin Invest. 2018 Feb 1;128(2):545-555. doi: 10.1172/JCI96702. [9] Imamura F, O’Connor L, Ye Z, et al. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ. 2015;351:h3576. doi:https://doi.org/10.1136/bmj.h3576 [10] Yin J, Zhu Y, Malik V, Li X, Peng X, Zhang FF, Shan Z, Liu L. Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages and Risk of Cardiovascular Disease: A Meta-Analysis and Systematic Review. Adv Nutr. 2021 Feb 1;12(1):89-101. doi: 10.1093/advances/nmaa084. [11] Te Morenga, L. A., Howatson, A. J., Jones, R. M. Mann, J. Dietary sugars and cardiometabolic risk: systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids. Am. J. Clin. Nutr. 100, 65–79 (2014). [12] U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. https://www.dietaryguidelines.gov ‌ [13] CDC. Be Smart About Sugar. Healthy Weight and Growth. Published May 13, 2024. https://www.cdc.gov/healthy-weight-growth/be-sugar-smart/index.html

F or the Patient with Hyperkalemia (elevated potassium in blood) Includes our Hyperkalemia Patient Handout with a Low Potassium Diet By Kruti Vora and Michael Butman, M.D. Background Potassium is amongst the most important electrolytes in the human body. It is primarily located in the intracellular space and plays a vital role in virtually all cellular functions; it is involved in the heartbeat, muscle contraction and nerve conduction. Due to the vital role potassium plays, it is tightly regulated by the kidneys. Potassium levels may be affected by certain medications, gastrointestinal disorders, hormonal disorders, kidney disease and other conditions. When this occurs, it may require patients to modify their dietary intake of potassium to help prevent it from rising to levels that are dangerously high or from dropping to levels that are dangerously low. How are potassium levels measured? Potassium levels can be measured through a small sample of venous blood. The concentration of potassium in the serum of the blood is typically 3.7 to 5.2 mEq/L. Potassium levels that are lower than 2.5 mEq/L or greater than 6.0 mEq/L can be dangerous. Potassium can also be measured in blood plasma (the liquid portion of blood left over after blood cells and white cells are removed). It is typically slightly lower than that measured in the serum. Conditions that can cause low potassium levels (hypokalemia) are typically due to a lack of intake or excessive losses. A lack of intake is typically seen in eating disorders such as anorexia or bulimia. Excessive losses are typically seen in gastrointestinal disorders that are associated with diarrheal illnesses or vomiting. Hereditary disorders affecting the kidneys’ ability to reabsorb potassium may cause excessive losses as well. Hyperaldosteronism, a disorder of the adrenal gland which results in excessive production of the hormone aldosterone will directly affect the kidneys ability to retain potassium and result in low potassium levels in the blood. Many medications such as diuretics, antibiotics, laxatives, and insulin may do the same. High potassium, known as hyperkalemia, is most often due to the kidneys’ inability to excrete potassium. This can be due to diseases that damage the kidneys directly or indirectly by either compromising the blood flow to the kidneys or preventing the excretion of urine produced by the kidneys. When the kidney function is compromised it is known as acute or chronic kidney disease. Chronic kidney disease is most often caused by diabetes and hypertension, but can be caused by antibiotics, NSAIDs, medications such as ACE- inhibitors or angiotensin II blockers, dehydration, and kidney stones. Thus, any diseases that affect the kidneys’ ability to excrete potassium may, by extension, affect potassium levels in the blood. Potassium levels can also be falsely elevated (factitious hyperkalemia or pseudohyperkalemia). This can occur when potassium is released by damaged blood cells within a sample of blood, a process known as hemolysis. Since the vast majority of potassium is found in the body is inside of cells, hemolysis can release excess potassium and artifactually elevate the concentration of potassium in a sample. Hemolysis may occur at any point during the collection, transportation, handling, storage, and processing of the blood sample. Certain diseases may also predispose to pseudohyperkalemia. These include high platelet counts (thrombocytosis), cancers of the white blood due to the fragility of the cell membranes, being asplenic (having had your spleen removed), or due to a genetic condition called familial pseudohyperkalemia. What happens if my potassium is too high or low? If potassium levels are too high or low, a variety of bodily functions may be dysregulated. The heart may beat in an abnormal rhythm or stop functioning altogether. Patients may also have fatigue, weakness, muscle cramps, and numbness or paralysis. What is a low potassium diet? Patients with chronic kidney disease or other renal insufficiency may not be able to excrete excess potassium in the urine. As a result, patients may need to follow a low potassium diet to keep their potassium levels within a safe and normal range. The typical amount of dietary potassium required for patients with normal renal function and potassium excretion is . . . Please Click Here to print the full Patient Handout on Hyperkalemia for those with hyperkalemia from the APP. References High potassium (hyperkalemia) When to see a doctor. (2018, January 11). Retrieved from https://www.mayoclinic.org/symptoms/hyperkalemia/basics/when-to-see-doctor/sym-20050776 Low potassium (hypokalemia). (2020, July 11). Retrieved from https://www.mayoclinic.org/symptoms/low-potassium/basics/definition/sym-20050632 Lewis, J. L., By, Lewis, J. L., & Last full review/revision Apr 2020| Content last modified Apr 2020. (n.d.). Overview of Potassium's Role in the Body - Hormonal and Metabolic Disorders. Retrieved from https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/electrolyte-balance/overview-of-potassium-s-role-in-the-body Potassium Test. (2020, August 19). Retrieved from https://www.ucsfhealth.org/medical-tests/003484 Office of Dietary Supplements - Potassium. (n.d.). Retrieved from https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/ Guideline: Potassium intake for adults and children. (2012). Retrieved from https://www.who.int/nutrition/publications/guidelines/potassium_intake_printversion.pdf Appendix 10. Food Sources of Potassium. (n.d.). Retrieved from https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/appendix-10/ Lowering your potassium levels. (2017, June). Retrieved from https://renal.org/wp-content/uploads/2017/06/KCUK-Potassium_web.pdf Patient education: Low-potassium diet (Beyond the Basics). (2019, October 15). Retrieved from https://www.uptodate.com/contents/low-potassium-diet-beyond-the-basics#H5 Asirvatham, J., Bjornson, L., & Moses, V. (2013). Errors in potassium measurement: A laboratory perspective for the clinician. North American Journal of Medical Sciences, 5(4), 255. doi:10.4103/1947-2714.110426 LEARN MORE SCIENCE Click here to use our Online CME, Groundbreaking Medical Search Compendium or Annotate your EMR, PDFs, and docs on FibonacciMD.app .

References for CME Article " The Conundrum of Subclinical Hypothyroidism " References [1] Thyroid hormone, Cleveland Clinic. Last reviewed 02/15/2022. Retrieved from: https://my.clevelandclinic.org/health/articles/22391-thyroid-hormone [2] Peeters RP, Visser TJ. Metabolism of Thyroid Hormone. [Updated 2017 Jan 1]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com , Inc.; 2000. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK285545/ [3] Peeters RP. Subclinical Hypothyroidism. NEJM. 2017;376:2556-65. Retrieved from: https://www.nejm.org/doi/10.1056/NEJMcp1611144 [4] Stott DJ et al. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med 2017; 376:2534-2544. June 29, 2017. Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJMoa1603825 [5] Azim S, Nasr C. MD Subclinical hypothyroidism: When to treat. Cleveland Clinic Journal of Medicine February 2019, 86 (2) 101-110. Retrieved from: https://www.ccjm.org/content/86/2/101 [6] Adlin V. Subclinical Hypothyroidism: Deciding When to Treat. Am Fam Physician. 1998 Feb 15;57(4):776-780. Retrieved from: https://www.aafp.org/afp/1998/0215/p776.html [7] Misiunas A. Peripheral neuropathy in subclinical hypothyroidism. Thyroid. 1995 Aug;5(4):283-6. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/7488869/ [8] Penza P. Painful neuropathy in subclinical hypothyroidism: clinical and neuropathological recovery after hormone replacement therapy. Neurol Sci. 2009 Apr;30(2):149-51. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/19214379/ [9] Allam MA. Prevalence and Clinical Significance of Subclinical Hypothyroidism in Diabetic Peripheral Neuropathy. Int J Gen Med. 2021;14:7755-7761. Retrieved from: https://www.dovepress.com/getfile.php?fileID=75583 [10] Reshdat, Sara. Relationship between subclinical hypothyroidism and distal-symmetric diabetic polyneuropathy in type 2 diabetes mellitus referred to Kosar Hospital in Semnan and related indicators in 2019–2020, Journal of Family Medicine and Primary Care: April 2022 - Volume 11 - Issue 4 - p 1361-1368. Retrieved from: https://journals.lww.com/jfmpc/Fulltext/2022/04000/Relationship_between_subclinical_hypothyroidism.22.aspx [11] Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365-1374. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923470/ [12] Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040-1049. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884576/ [13] Chaker, Layal et al. “Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.” The Journal of clinical endocrinology and metabolism vol. 100,6 (2015): 2181-91. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454799/ [14] Krassas GE, Rivkees SA, Kiess W (eds): Diseases of the Thyroid in Childhood and Adolescence. Pediatr Adolesc Med. Basel, Karger, 2007, vol 11, pp 80–103. Retrieved from: https://www.karger.com/WebMaterial/ShowFile/894088 [15] Garber JR et al. American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012 Nov-Dec;18(6):988-1028. 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AI-Enhanced Portable MRI Prototype Offers Promise for Wider Availability Medical News In an article published in May 2024, researchers describe the development of a whole-body ultra-low field MRI scanner prototype that does not need the typical radiofrequency and magnetic shielding cages used in current MRIs, can run on standard household current, and is portable.  Current MRIs use 1.5 to 3 Teslas, a measure of magnetic strength, while the new ultra-low field MRI uses only 0.05 Teslas.  However, the image quality of ultra-low field MRI is inferior to standard MRI.  To try to correct this, the authors used artificial intelligence, deep learning–based methods that integrated image reconstruction and super-resolution images. The authors reported that they were able to remarkably improve the image clarity and quality of ultra-low field MRIs done on volunteers. Comments: This ultra-low field MRI scanner prototype, or one like it, may be a game changer.  If it is commercially feasible, produces quality images, as it is potentially portable might allow point-of-care MRI in areas such as intensive care units.  It would also be quieter, done in a more open environment, and possibly allow more people to have MRIs who currently cannot because of metal in their bodies or inserted medical devices.  It could allow a wider availability to MRI technology around the world, as it would also be much less expensive than current MRIs.  Despite inferior imaging clarity compared to standard MRIs, the development of artificial intelligence and deep learning with neural networks appear to significantly improve ultra-low field MRI image quality to potentially make it a viable option. Resources: ZhaoY et al. Whole-body magnetic resonance imaging at 0.05 Tesla. Science. 10 May 2024. Vol 384, Issue 6696. https://www.science.org/doi/10.1126/science.adm7168