U.S. Space Force 1st Lt. Stephen Pitre, 1st Range Operations Squadron range engineer, wears an Inspiration4 patch on his uniform in support of the Inspiration4 launch Sept. 15, 2021, inside the Morrell Operations Center at Cape Canaveral Space Force Station, Florida. Pitre was part of a team of Guardians, Department of Defense civilians and U.S. Coast Guardsmen who supported the launch. The MOC supports every space launch from CCSFS and Kennedy Space Center. (U.S. Space Force photo by Tech. Sgt. James Hodgman)
By Waqas Haque, MD
Peer Reviewed
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.
Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia [1]
While glucocorticoids have been first-line treatment for immune thrombocytopenia (ITP) for decades, there are numerous drawbacks including relapse and variable response rates. As such, the FLIGHT trial – an open-label, multicenter RCT in the United Kingdom – compared standard of care (glucocorticoid) to combined glucocorticoid and mycophenolate mofetil therapy in a one-to-one ratio. Mycophenolate is a relatively inexpensive therapy that inhibits autoreactive T and B cells, and has shown promise for refractory ITP. The primary outcomes of efficacy were treatment failure (platelets less than 30e9/L) and the time it took to initiate a second-line treatment. Secondary outcomes included response rates, side effects, occurrence of bleeding, and subjective quality of life measures. A total of 120 patients with ITP were followed for 2 years. The combined therapy group had fewer treatment failures than the glucocorticoid-only group (22% vs. 44%, p=0.008). Surprisingly, while both groups had no difference in major adverse effects (bleeding or treatment side effects such as infection), patients in the combined therapy group reported worse quality-of-life outcomes (fatigue, physical function) than the steroid-only group. The combined therapy group also resulted in a lower risk of refractory or relapsed disease. Combined therapy should be considered for patients deisiring early disease control and for whom a steroid-only regimen is not predicted to succeed, but should be a shared decision with the patient given the higher risk of fatigue and impaired physical function with such a regimen.
MRI-Targeted or Standard Biopsy in Prostate Cancer Screening [2]
The overdiagnosis of prostate cancer by prostate-specific antigen (PSA) screening can potentially be addressed by utilizing MRI with targeted biopsies. In STHLM3-MRI – a population-focused noninferiority trial – 1,532 men aged 50 to 74 with a PSA of at least 3 ng/mL were randomly assigned to a standard biopsy (control group, n=603) or to MRI with subsequent biopsy for suspicious imaging results (experimental group, n=929) in a 2-to-3 ratio. With respect to the primary outcome of diagnosing clinically-significant prostate cancer (Gleason score of at least 7), 21% of participants in the experimental group were diagnosed compared to 18% in the control group (noninferiority p-value < 0.001). For the secondary outcomes of detecting clinically-insignificant cancer (Gleason score of 6), a significant reduction of the experimental group was diagnosed (4% versus 12%). The results of this study suggests that a first-stage screening MRI helps detect more concerning prostate cancers while finding fewer clinically insignificant cancers. While the trial findings are not fully generalizable (it was conducted in Stockholm, Sweden with an organized team of radiologists and pathologists on board), it does offer a promising solution to the overdiagnosis and overtreatment of prostate cancer.
Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis [3]
It is well-known that cardiovascular risk factors and disease increase an individual’s risk for severe presentation of COVID-19. It is also well-known that statins have numerous cardioprotective, anti-inflammatory, and immunomodulatory benefits in patients with significant ASCVD risk [4]. The authors performed a meta-analysis of 22 studies that compared statin users (who typically have high cardiovascular risk) and non-statin users diagnosed with COVID-19 infection. In the 10 collective studies (n = 41,807) reporting mortality hazard ratios (HR) for statin users versus non-users, the adjusted HR was 0.65 (95% CI, 0.53 to 0.81). In the other 12 studies (n = 72,881 with a weighted age of 65, 54% men, 66% with hypertension, 43% with diabetes, and 30% on a statin) reporting adjusted odds ratios, the pooled estimate for mortality was 0.65 (95% CI, 0.55 to 0.78). This meta-analysis is limited by the observational, retrospective nature of the studies it includes. Nevertheless, the association of statin use with a one-third reduction in COVID-19 mortality in a higher-risk population has important implications for improving management of this new disease, and represents an area of evolving research.
Minicuts:
This RCT of 400 SIRS-positive ICU patients randomized patients to either a low-normal (8 to 12 kPa, n = 205) or high-normal (14 to 18 kPa, n=195) oxygenation range, where an FiO2 of 0.60 was applied only if clinically necessary. The study found no significant difference in the reduction of organ dysfunction or duration of mechanical ventilation between both groups.
WellSpan Health’s integrated system of 170 outpatient clinics and 8 hospitals adopted a system-wide, team-based advance care planning (ACP) system during the pandemic response. Even adjusting for ‘LACE’ factors (LACE – Length of stay, Acuity, Comorbidities, and Emergency department visits in the preceding 6 months), consistent systemwide promotion and facilitation of ACP prior to hospitalization led to a reduction in undesired interventions (16% reduction in ICU utilization) and 25% less medical spending.
While trastuzumab (Herceptin) targets the extracellular domain in HER2-positive breast cancer, it is associated with cardiac toxicity (also called “Heart-ceptin” in board exam fodder), and is also expensive, making it necessary to re-evaluate its efficacy. A meta-analysis of seven randomized trials totalling 864 patients enrolled between 2000 and 2005 found that the addition of trastuzumab to chemotherapy in early-stage, HER2-positive breast cancer is associated with decreased recurrence and mortality by a third regardless of tumor or patient attributes. Thus, while trastuzumab does carry a risk of cardiotoxicity and is expensive, its utilization remains a cornerstone of effective therapy in HER-2 positive breast cancer therapy.
Dr. Waqas Haque is an intern in the Internal Medicine residency at NYU Langone Health.
Peer reviewed by Dr. Alexandria Imperato, chief resident at NYU Langone Health.
Image courtesy of Wikimedia Commons, source: U.S. Space Force photo by Tech. Sgt. James Hodgman,
[[File:Inspiration4 Launch (210915-X-YM354-1013).jpg|Inspiration4_Launch_(210915-X-YM354-1013)]]
References:
[1] Bradbury CA, Pell J, Hill Q, Bagot C, Cooper N, Ingram J, Breheny K, Kandiyali R, Rayment R, Evans G, Talks K, Thomas I, Greenwood R. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. N Engl J Med. 2021 Sep 2;385(10):885-895. doi: 10.1056/NEJMoa2100596. PMID: 34469646.
[2] Eklund M, Jäderling F, Discacciati A, Bergman M, Annerstedt M, Aly M, Glaessgen A, Carlsson S, Grönberg H, Nordström T; STHLM3 consortium. MRI-Targeted or Standard Biopsy in Prostate Cancer Screening. N Engl J Med. 2021 Sep 2;385(10):908-920. doi: 10.1056/NEJMoa2100852. Epub 2021 Jul 9. PMID: 34237810.
[3] Kollias A, Kyriakoulis KG, Kyriakoulis IG, Nitsotolis T, Poulakou G, Stergiou GS, Syrigos K. Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis. Atherosclerosis. 2021 Aug;330:114-121. doi: 10.1016/j.atherosclerosis.2021.06.911. Epub 2021 Jun 25. PMID: 34243953; PMCID: PMC8233054.
[4] Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004 Jun 15;109(23 Suppl 1):III39-43. doi: 10.1161/01.CIR.0000131517.20177.5a. PMID: 15198965.
[5] Gelissen H, de Grooth HJ, Smulders Y, Wils EJ, de Ruijter W, Vink R, Smit B, Röttgering J, Atmowihardjo L, Girbes A, Elbers P, Tuinman PR, Oudemans-van Straaten H, de Man A. Effect of Low-Normal vs High-Normal Oxygenation Targets on Organ Dysfunction in Critically Ill Patients: A Randomized Clinical Trial. JAMA. 2021 Aug 31. doi: 10.1001/jama.2021.13011. Epub ahead of print. PMID: 34463696.
[6] Bhatia V, Geidner R, Mirchandani K, Huang Y, Warraich HJ. Systemwide Advance Care Planning During the Covid-19 Pandemic: The Impact on Patient Outcomes and Cost. NEJM Catalyst Innovations in Care Delivery 2021; 09. doi: https://doi.org/10.1056/CAT.21.0188
[7] Early Breast Cancer Trialists’ Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol. 2021 Aug;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6. PMID: 34339645; PMCID: PMC8324484.