Research Spotlight

Ramani, A., G. Testa, Y. Ghouri, E. C. Koon, M. Di Salvo, G. J. McKenna, J. Bayer, A. M. Warren, A. Wall and L. Johannesson (2019). “DUETS (Dallas UtErus Transplant Study):Complete report of 6-month and initial 2-year outcomes following open donor hysterectomy.” Clin Transplant Nov 22. [Epub ahead of print].

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INTRODUCTION: Uterus transplantation has shown success in treating women with uterine-factor infertility who want to carry their own pregnancy. METHODS: We report the medical, sexual, and psychological outcomes of our first cohort of 13 living-donor hysterectomies. As we have transitioned from open to robotically assisted hysterectomy, this report represents the complete series of open-donor hysterectomies at our center, all with >/=6-month postoperative outcomes. RESULTS: The open donor hysterectomy had a median of a 6.5-hour surgical time, 0.8 L estimated blood loss, 6-day hospital stay, and 28-day sick leave. Three donors had a grade III or IV complications, one reported new-onset psychological symptoms, and 9 experienced transient sexual discomfort. All complications were addressed and resolved, and all donors returned to their presurgical social and physical activities. CONCLUSION: Since uterus transplantation is not life-saving or life-extending, the risks in living uterus donation must be weighed against the benefit of giving another woman the opportunity to give birth to her own child. This report provides data to support more detailed informed consent regarding the medical, psychological, and sexual complications of open living donor hysterectomy and allows for further evaluation of the ethical acceptability of this procedure.

Raju, B. and P. A. McCullough (2019). “Circulating plasma dipeptidyl dipeptidase 3 and the prognosis of cardiogenic shock.” Eur J Heart Fail Nov 28. [Epub ahead of print].

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The current management of cardiogenic shock after acute myocardial infarction (AMI) focuses on early revascularization, optimizing cardiac filling pressures, and inotropic or mechanical circulatory support (MCS). These interventions target two pathophysiologic processes underlying cardiogenic shock; myocardial ischaemia and low cardiac output. Despite advances in MCS and percutaneous coronary intervention that address both these mechanisms, in‐hospital mortality for cardiogenic shock remains high (27–51%). There are no approved in vitro diagnostic assays for the prognosis of cardiogenic shock. Over the past two decades the medical community has gained more knowledge about the myriad of other processes involved in the pathophysiology of cardiogenic shock and AMI. Biological pathways that affect systemic inflammation, neurohormonal modulation, and extracellular matrix remodelling are all altered in cardiogenic shock. Multiple studies have demonstrated the marked change in inflammatory markers and downstream mediators after myocardial infarction. Vasopressin and angiotensin II levels increase in the setting of cardiogenic shock, altering fluid and salt homeostasis. Alterations of the renin–angiotensin system also affects extracellular remodelling pathways. Understanding the downstream regulatory pathways associated with cardiogenic shock may allow for better prognostication, risk stratification, and targets for future therapies. Circulating plasma dipeptidyl dipeptidase 3 (cDPP3) is a protease that is ubiquitous in many organ systems throughout the human body. Although DPP3 has been identified and isolated as far back as 1967, its haemodynamic and cardiovascular relevance have only come to light more recently. cDPP3 has been implicated in pathophysiologic processes such as inflammation, blood pressure regulation, and pain modulation. Concentrations of cDDP3 have been found to be elevated in septic and cardiogenic shock. In vitro testing shows that cDPP3 is involved in angiotensin II regulation. In animal models cDPP3 inhibited angiotensin II‐induced hypertension, cardiac fibrosis, and hypertrophy. Animal studies have also shown cDPP3 significantly affects cardiac contractility and with a negative inotropic effect. Thus, cDPP3 clearly plays a role in cardiovascular physiology but the practical application of this knowledge is not yet clear. In the present issue of the Journal, Takagi et al. attempt to delineate a clinical role for DPP3 and confirm the relationship between cDPP3 and clinical outcomes measured in patients with ST‐ elevation myocardial infarction (STEMI) and cardiogenic shock from the OptimaCC trial. (Excerpt from text of this commentary on the article by K. Takagi et al., “Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial” which appears in the same issue.)

Nakase-Richardson, R., D. J. Schwartz, L. Drasher-Phillips, J. M. Ketchum, K. Calero, M. N. Dahdah, K. R. Monden, K. Bell, U. Magalang, J. Hoffman, J. Whyte, J. Bogner and J. M. Zeitzer (2019). “Comparative Effectiveness of Sleep Apnea Screening Instruments During Inpatient Rehabilitation Following Moderate to Severe TBI.” Arch Phys Med Rehabil Nov 6. [Epub ahead of print].

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OBJECTIVE: To determine the diagnostic sensitivity and specificity and comparative effectiveness of traditional sleep apnea screening tools in traumatic brain injury (TBI) neurorehabilitation admissions. DESIGN: Prospective diagnostic comparative effectiveness trial of sleep apnea screening tools relative to the gold standard, attended Level 1 polysomnography including encephalography. SETTING: Six TBI Model System Inpatient Rehabilitation Centers PARTICIPANTS: Between 05/2017 and 02/2019, 452 of 896 screened were eligible for the trial with 348 consented (78% consented). Additional screening left 263 eligible for and completing polysomnography with final analyses completed on 248. INTERVENTION: Not applicable. MAIN OUTCOME: Area Under the Curve (AUC) of screening tools relative to total apnea hypopnea index>/=15 (AHI, moderate to severe apnea) measured at a median of 47 days post-TBI (IQR 29-47). RESULTS: The Berlin high risk score (ROC-AUC=0.63) was inferior to the MAPI (ROC-AUC = 0.7802) (p=.0211, CI: 0.0181, 0.2233) and STOPBANG (ROC-AUC = 0.7852) (p=.0006, CI: 0.0629, 0.2302); both of which had comparable AUC (p=.7245, CI: -0.0472, 0.0678). Findings were similar for AHI>/=30 (severe apnea); however, no differences across scales was observed at AHI>5. The pattern was similar across TBI severity subgroups except for post-traumatic amnesia (PTA) status wherein the MAPI outperformed the Berlin and STOPBANG. Youden’s Index to determine risk yielded lower sensitivities but higher specificities relative to non-TBI samples. CONCLUSION: This study is the first to provide clinicians with data to support a choice for which sleep apnea screening tools are more effective during inpatient rehabilitation for TBI (STOPBANG, MAPI vs Berlin) to help reduce comorbidity and possibly improve neurologic outcome.

Palomaki, G. E., C. Bupp, A. R. Gregg, M. E. Norton, D. Oglesbee and R. G. Best (2019). “Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).” Genet Med Nov 8. [Epub ahead of print].

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Open neural tube defects (ONTDs) include open spina bifida (OSB) and anencephaly. These defects are caused by incomplete closure of the neural tube at about 4 weeks of pregnancy. Levels of early second-trimester maternal serum (ms) alpha-fetoprotein (AFP) are sufficiently elevated in affected pregnancies to be used as a population-based screening test. The basic screening methodology was described in the late 1970s and screening programs were active a few years later. By identifying pregnancies with the highest msAFP levels, about 80% of OSB and 95% of anencephaly can be identified as early as 16 weeks gestation. The interpretation of msAFP levels is complicated by the need to consider multiple factors such as gestational age, maternal weight, maternal race, multiple gestations, and more. Testing for AFP and acetylcholinesterase in amniotic fluid and/or identification of the lesion by targeted ultrasound is considered diagnostic of ONTD. When a diagnosis is made, options include termination, surgery after delivery, or in utero surgery, depending on factors such as location and size of the defect, and the presence of any additional anomalies. Screening for ONTD should be performed as part of a comprehensive program linking primary obstetrical care providers, laboratorians, and high-risk clinicians.

Neal, M. D., E. E. Moore, M. Walsh, S. Thomas, R. A. Callcut, L. Z. Kornblith, M. Schreiber, A. P. Ekeh, A. J. Singer, L. Lottenberg, M. Foreman, S. Evans, R. D. Winfield, M. D. Goodman, C. Freeman, D. Milia, N. Saillant, J. Hartmann and H. E. Achneck (2019). “A Comparison Between the TEG(R) 6s and TEG(R) 5000 Analyzers to Assess Coagulation in Trauma Patients.” J Trauma Acute Care Surg Nov 11. [Epub ahead of print].

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BACKGROUND: Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG(R) 5000 system is widely used for viscoelastic testing. However, the TEG(R) 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG(R) 6s system for use in trauma patients. METHODS: Multicenter noninvasive observational study for method comparison conducted at 12 US Level I and II trauma centers. Agreement between the TEG(R) 6s and TEG(R) 5000 systems was examined using CK.R, CFF.MA, CK.LY30, CRT.MA and CK.MA parameters in adults meeting full or limited trauma team criteria. Blood was drawn less-than-or-equal-to 1hr after admission. Assays were repeated in duplicate. Reliability (TEG(R) 5000 vs. TEG(R) 6s analyzers) and repeatability (inter-device comparison) was quantified. Linear regression was used to define the relationship between TEG(R) 6s and TEG(R) 5000 devices. RESULTS: A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ss) and linear correlation estimates (p) were as follows: CK.R (ss=1.05,p=0.9), CFF.MA (ss=0.99,p=0.95), CK.LY30 (ss=1.01,p=0.91), CRT.MA (TEG(R) 6s) vs. CK.MA (TEG(R) 5000) (ss=1.06,p=0.86) as well as vs. CRT.MA (TEG(R) 5000) (ss=0.93,p=0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG(R) 6s vs. TEG(R) 5000, particularly for CFF.MA and CK.LY30. CONCLUSIONS: The TEG(R) 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG(R) 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG(R) 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE: Level II-Diagnostic test.