With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.
During vigorous exercise, skeletal muscle experiences low oxygen levels, which forces cells into anaerobic glycolysis, generating lactate as a byproduct. Lactate is then shunted to the liver, where it is converted back to glucose that can be used by muscle and other cells, in a loop known as the Cori Cycle .
Researchers have discovered a new link between the Cori Cycle and the microbiome of elite runners. They recruited athletes who ran the 2015 Boston Marathon, along with sedentary controls, and sequenced stool samples collected for one week before and one week after the marathon. Bacteria of the genus Veillonella became more abundant after the marathon, an exciting result given that members of this genus can metabolize lactate into short-chain fatty acids, acetate, and propionate . Researchers next demonstrated that introducing Veillonella into mice boosted their maximum running times without affecting serum lactate levels. Surprisingly, rectal introduction of propionate also boosted exercise performance, suggesting that the effect of Veillonella might be secondary to byproducts of lactate metabolism.
While it remains unclear whether byproducts of bacterial lactate metabolism can boost athletic performance in humans, the observation that the microbiome of athletes changes as a result of intense exercise highlights yet another dynamic and potentially symbiotic relationship between humans and their microbiome.
Breast cancer is more aggressive and has a poorer prognosis among premenopausal women; however, most trials that validated the efficacy of current hormonal treatments excluded premenopausal women . Cyclin-dependent kinases 4 and 6 (CDK4/6) are thought to promote cell-cycle progression and tumor growth, and to play a role in resistance to endocrine therapy in hormone-receptor-positive breast cancer. Ribociclib is a small molecule inhibitor of CDK4/6 that, when combined with endocrine therapy, has been shown to prolong progression-free survival in postmenopausal women with hormone-receptor-positive metastatic breast cancer [6-10].
In this planned interim analysis of the MONALEESA-7 trial, 672 premenopausal and perimenopausal women were randomly assigned to receive either ribociclib or placebo, in addition to endocrine therapy. Estimated survival at 42 months was 70.2% in the ribociclib group (95% CI 63.5-76%) and 46% in the placebo group (32-58.9%). Neutropenia was a notable adverse effect seen in 63.5% of patients receiving ribociclib, and 4.5% in the placebo group.
The impressive effect size of ribociclib in prolonging survival suggests that CDK4/6 inhibitors could become a standard therapy for breast cancer in young and premenopausal women. Furthermore, the trial suggests that women who undergo chemically-induced menopause as part of breast cancer treatment respond similarly to women who underwent menopause naturally and should be included in future clinical trials .
Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis 
After an unprovoked venous thromboembolism (VTE), patients are started on prolonged anticoagulation therapy to avoid life-threatening recurrences, but it remains unclear just how prolonged that therapy should be, especially in light of the risk of bleeding.
Researchers compiled data from prior studies that followed patients with unprovoked VTEs after stopping anticoagulation therapy. Among patients that discontinued therapy after at least 3 months, the cumulative incidence of VTE recurrence was 10.3% (95% CI 8.6-12.1%) at 1 year and 36% (28-45%) at 10 years. The fatality rate secondary to a recurrent VTE was 3.8% (95 CI 2.0-6.1%), with a cumulative risk of 1.5% after 10 years. In contrast, the cumulative risk of death due to bleeding while on anticoagulation was 1.32%, suggesting a minor benefit in mortality from prolonged anticoagulation. When data was subdivided by gender and site of initial VTE, men had a higher rate of VTE recurrence at 10 years (41%; 95% CI 28-56%) than women (29%; 20-38%).
While this study provides useful data for counseling patients regarding their individual risk when stopping anticoagulation therapy, it is incomplete without risk stratification based on age. The risk of a massive bleed secondary to anticoagulation increases with age , making such an analysis a significant omission.
Antibiotic treatment for urinary tract infections (UTIs) is often initiated prior to having culture data and sensitivities available. This practice can result in selection of an ineffective antibiotic and contribute to resistance.
Investigators in Israel developed a machine-learning algorithm that outperformed physicians at selecting effective antibiotics for treating UTIs. The authors compiled a 10-year longitudinal set of patient data, with over 700,000 community-acquired UTIs and 5,000,000 corresponding antibiotic purchases. They uncovered strong correlations between antibiotic resistance and patients’ antibiotic purchase history, along with demographic factors such as age, gender, and residence in retirement homes. Factoring in that information, their resultant algorithm was able to choose an effective antibiotic about 95% of the time, with physicians doing so 91.5% of the time.
While this study illustrates how machine learning can improve clinical decision making, it also highlights the need for obtaining culture data before antibiotic therapy. The algorithm did still select an inappropriate antibiotic agent in a significant number of cases — a reminder that culture data remains our biggest ally against antibiotic resistance.
Chinese clinicians have used acupuncture in combination with pharmacologic antianginal agents and Chinese traditional medicine to treat chronic, stable angina and prevent major cardiovascular events. This study — the largest randomized, multicenter clinical trial to date — demonstrated that properly performed acupuncture, along with pharmacologic therapy, reduced the frequency of patient-reported anginal events by 5.63 attacks (95% CI, 3.99-7.27; P < .001) during a 4-week period, when compared to antianginal meds alone.
Vena cava filters are widely used in trauma centers to prevent fatal pulmonary embolisms in patients for whom prophylactic anticoagulation is contraindicated. This randomized, controlled trial found that early filter placement within 72 hours of hospitalization did not lower the incidence of symptomatic pulmonary embolism or death within 90 days, relative to no filter. However, vena cava filters may still be effective in reducing risk among patients who cannot be anticoagulated after 7 days of hospitalization.
While many hospitals use rapid response teams (RRTs) to improve survival among in-hospital cardiac arrests, this study found that hospitals with better outcomes had RRTs staffed by dedicated team members, and had empowered nurses to activate RRTs without fear of reprisal. In contrast, hospitals that performed poorly had RRTs composed of clinicians with competing clinical responsibilities, and who had less communication with nurses about ongoing patient care.
Diabetic retinopathy (DR) is characterized by microvascular damage to the retina that leads to vision loss, but this study suggests that neuronal damage actually precedes microvascular changes. Authors followed 101 patients with type 2 diabetes (T2DM) and 63 healthy individuals for 3 years. They found that T2DM accelerates the aging-associated reduction of peripapillary retinal nerve fiber layer thickness, regardless of whether DR is present or not.
Dr. Luis Martinez-Velazquez is a resident physician at NYU Langone Health
Peer reviewed by Christian Torres, MD, chief resident, internal medicine, NYU School of Medicine
Image courtesy of Wikipedia
- Scheiman J, Luber JM, Chavkin TA, et al. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat Med. 2019;25(7):1104-1109. https://www.nature.com/articles/s41591-019-0485-4
- Melkonian EA, Schury MP. Physiology, Gluconeogenesis. StatPearls. Treasure Island (FL)2019. https://www.ncbi.nlm.nih.gov/books/NBK541119/
- Ng SK, Hamilton IR. Carbon dioxide fixation by Veillonella parvula M 4 and its relation to propionic acid formation. Can J Microbiol. 1973;19(6):715-723. https://www.nrcresearchpress.com/doi/abs/10.1139/m73-116 – .XUNAnS2ZNBw
- Im SA, Lu YS, Bardia A, et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019;381(4):307-316. https://www.nejm.org/doi/full/10.1056/NEJMoa1903765
- Rugo HS. Achieving Improved Survival Outcomes in Advanced Breast Cancer. N Engl J Med. 2019;381(4):371-372. https://www.nejm.org/doi/full/10.1056/NEJMoa1903765
- Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016;375(20):1925-1936. https://www.nejm.org/doi/full/10.1056/NEJMoa1607303
- Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541-1547. https://academic.oup.com/annonc/article/29/7/1541/4989216
- Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019;5:5. https://www.nature.com/articles/s41523-018-0097-z
- Rugo HS, Finn RS, Dieras V, et al. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat. 2019;174(3):719-729. https://doi.org/10.1007/s10549-018-05125-4
- Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30292-4/fulltext
- Khan F, Rahman A, Carrier M, et al. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ. 2019;366:l4363. https://www.bmj.com/content/366/bmj.l4363
- Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. https://journal.chestnet.org/article/S0012-3692(10)60585-5/fulltext
- Yelin I, Snitser O, Novich G, et al. Personal clinical history predicts antibiotic resistance of urinary tract infections. Nat Med. 2019;25(7):1143-1152. https://www.nature.com/articles/s41591-019-0503-6
- Zhao L, Li D, Zheng H, et al. Acupuncture as Adjunctive Therapy for Chronic Stable Angina: A Randomized Clinical Trial. JAMA Internal Medicine. 2019. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2739058
- Ho KM, Rao S, Honeybul S, et al. A Multicenter Trial of Vena Cava Filters in Severely Injured Patients. N Engl J Med. 2019;381(4):328-337. https://www.nejm.org/doi/full/10.1056/NEJMoa1806515
- Dukes K, Bunch JL, Chan PS, et al. Assessment of Rapid Response Teams at Top-Performing Hospitals for In-Hospital Cardiac Arrest. JAMA Intern Med. 2019. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2739059
- Lim HB, Shin YI, Lee MW, Park GS, Kim JY. Longitudinal Changes in the Peripapillary Retinal Nerve Fiber Layer Thickness of Patients With Type 2 Diabetes. JAMA Ophthalmol. 2019. https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2739235