Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White community. Each newly published article features the researcher, the abstract, and link to the full text. For information on including your own research, please contact John Fullinwider, john.fullinwider@baylorhealth.edu. 214-828-8989.


Posted January 15th 2019

Transcatheter Mitral-Valve Repair in Patients with Heart Failure.

Michael J. Mack M.D.

Michael J. Mack M.D.

Stone, G. W., J. Lindenfeld, W. T. Abraham, S. Kar, D. S. Lim, J. M. Mishell, B. Whisenant, P. A. Grayburn, M. Rinaldi, S. R. Kapadia, V. Rajagopal, I. J. Sarembock, A. Brieke, S. O. Marx, D. J. Cohen, N. J. Weissman and M. J. Mack (2018). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure.” N Engl J Med 379(24): 2307-2318.

Full text of this article.

BACKGROUND: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes. METHODS: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%. RESULTS: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001). CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).


Posted January 15th 2019

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.

Andrew L. Masica M.D.

Andrew L. Masica M.D.

Girard, T. D., M. C. Exline, S. S. Carson, C. L. Hough, P. Rock, M. N. Gong, I. S. Douglas, A. Malhotra, R. L. Owens, D. J. Feinstein, B. Khan, M. A. Pisani, R. C. Hyzy, G. A. Schmidt, W. D. Schweickert, R. D. Hite, D. L. Bowton, A. L. Masica, J. L. Thompson, R. Chandrasekhar, B. T. Pun, C. Strength, L. M. Boehm, J. C. Jackson, P. P. Pandharipande, N. E. Brummel, C. G. Hughes, M. B. Patel, J. L. Stollings, G. R. Bernard, R. S. Dittus and E. W. Ely (2018). “Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.” N Engl J Med 379(26): 2506-2516.

Full text of this article.

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).


Posted January 15th 2019

A CD4(+) T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.

Virginia Pascual M.D.

Virginia Pascual M.D.

Caielli, S., D. T. Veiga, P. Balasubramanian, S. Athale, B. Domic, E. Murat, R. Banchereau, Z. Xu, M. Chandra, C. H. Chung, L. Walters, J. Baisch, T. Wright, M. Punaro, L. Nassi, K. Stewart, J. Fuller, D. Ucar, H. Ueno, J. Zhou, J. Banchereau and V. Pascual (2019). “A CD4(+) T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.” Nature Medicine 25(1): 75-81.

Full text of this article.

Understanding the mechanisms underlying autoantibody development will accelerate therapeutic target identification in autoimmune diseases such as systemic lupus erythematosus (SLE)(1). Follicular helper T cells (TFH cells) have long been implicated in SLE pathogenesis. Yet a fraction of autoantibodies in individuals with SLE are unmutated, supporting that autoreactive B cells also differentiate outside germinal centers(2). Here, we describe a CXCR5(-)CXCR3(+) programmed death 1 (PD1)(hi)CD4(+) helper T cell population distinct from TFH cells and expanded in both SLE blood and the tubulointerstitial areas of individuals with proliferative lupus nephritis. These cells produce interleukin-10 (IL-10) and accumulate mitochondrial reactive oxygen species as the result of reverse electron transport fueled by succinate. Furthermore, they provide B cell help, independently of IL-21, through IL-10 and succinate. Similar cells are generated in vitro upon priming naive CD4(+) T cells with plasmacytoid dendritic cells activated with oxidized mitochondrial DNA, a distinct class of interferogenic toll-like receptor 9 ligand(3). Targeting this pathway might blunt the initiation and/or perpetuation of extrafollicular humoral responses in SLE.


Posted January 15th 2019

Minimally Invasive Oncologic Surgery, Part I.

James W. Fleshman M.D.

James W. Fleshman M.D.

Conrad, C. and J. W. Fleshman (2019). “Minimally Invasive Oncologic Surgery, Part I.” Surg Oncol Clin N Am 28(1): xv-xvii.

Full text of this article.

Modern cancer surgery has the unique and unprecedented capacity to go beyond technical aspects of removing the tumor, focusing simultaneously on the cancer’s biology and its morbidity. For example, while Halsted’s radical mastectomy certainly helped many patients suffering from breast cancer, later attempts to reduce the morbidity in the context of progress in oncologic management led to a significant reduction of morbidity. Similarly, once surgeons such as Codivilla (1898), Kausch (1912), and Whipple (1935) pioneered the complex operation of a pancreaticoduodenectomy, attempts to perform the operation less invasively led to Gagner and Pomp reporting the first laparoscopic pancreaticoduodenectomy in 1994. In parallel, after the first successful liver resection by the German surgeon Langenbuch in 1888 (the specimen showed normal liver), the eagerness of performing liver surgery according to anatomic principles resulted in post-1950 reports of selective anatomic liver resection by Honjo (Japan), Lortat-Jacob (France), and Ton That Tung (Vietnam). Then, minimally invasive liver resection was introduced in the 1990s. Like many daring innovations, early attempts to develop minimally invasive surgery have not always drawn praise, or even approval. For example, after Semm performed the first laparoscopic appendectomy from the gynecological clinic of Kiel in 1981, the president of the German Surgical Society wrote to the Board of Directors of the German Gynecological Society requesting suspension of Semm from medical practice. Stories of such challenging environments are numerous and well known, and the ability of surgeons to push through those have paved the way for the exciting time in cancer surgery we live in today. This historic time includes standardizing minimally invasive operations and augmenting its potential by injecting high-tech applications, such as augmented reality or fluorescent-guided surgery. This issue of Surgical Oncology Clinics of North America on Minimally Invasive Cancer Management, written by experts from around the world, provides an up-to-date overview on the tremendous progress that has been made in this field. In my role as Editor, I was fortunate to learn about the frontiers of our field from the editorial process and from scientific exchange with the contributing authors. Reviewing the beautiful and concise articles summarizing the tremendous progress in the field of minimally invasive cancer surgery takes me back to early days in my career, at the threshold of committing to surgery as my specialty. Some of my professors discouraged me, envisioning that cancer surgery would have been completely replaced by the progress in systemic therapies by now. Reality has proven the opposite, where the efficacy of systemic therapies has allowed surgical interventions against cancer to become more aggressive and effective. I am humbled and honored to contribute to the community of minimally invasive surgeons who hope to help their patients’ battles by skillfully trading morbidity for radical oncologic surgery, maximizing the time and quality of a patient’s life with their loved ones. (Excerpt from the introduction to a special issue of Surgical Oncology Clinics of North America, 28:1.)


Posted January 15th 2019

Non-Radiographic Severity Measurement of Pectus Excavatum.

Nathan A. Vaughan, M.D.

Nathan A. Vaughan, M.D.

Bliss, D. P., Jr., N. A. Vaughan, R. M. Walk, J. A. Naiditch, A. A. Kane and R. R. Hallac (2019). “Non-Radiographic Severity Measurement of Pectus Excavatum.” J Surg Res 233: 376-380.

Full text of this article.

BACKGROUND: To avoid the radiation exposure of CT imaging and the expense of CT or MRI studies, we sought to develop a non-radiographic severity measurement of pectus excavatum based on 3D photogrammetric imaging. METHODS: Over 28 mo, ten consecutive patient volunteers with pectus excavatum underwent 3D stereophotogrammetric imaging. The surface width to surface depth ratio (Surface Lengths Pectus Index), the chest deformity’s surface area to total chest surface area (Pectus Surface Area Ratio), and the chest deformity’s volume to total chest volume (Pectus Volume Ratio) were calculated. Simple linear regression analysis compared the Surface Lengths Pectus Index, Pectus Surface Area Ratio, and Pectus Volume Ratio calculations each to the corresponding known CT pectus index. RESULTS: The correlation between CT pectus index versus Surface Lengths Pectus Index yielded an R-squared value of 0.7637 and a P value of 0.0013. A CT pectus index of 3.4 or greater (eight patients) corresponded to a Surface Lengths Pectus Index of 1.86 or greater (six patients). The CT pectus index versus Pectus Surface Area Ratio (R-squared = 0.4627, P = 0.0305) and the CT pectus index versus the Pectus Volume Ratio (R-squared = 0.3048, P = 0.0990) demonstrated less correlation. CONCLUSION: Surface Lengths Pectus Index corresponds to the CT pectus index and may be adequate to determine severity of pectus excavatum in some patients.