Research Spotlight

Posted December 15th 2018

Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome.

Veeral N. Tolia M.D.

Veeral N. Tolia M.D.

Tolia, V. N., K. Murthy, M. M. Bennett, R. G. Greenberg, D. K. Benjamin, P. B. Smith and R. H. Clark (2018). “Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome.” J Pediatr 203: 185-189.

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OBJECTIVE: To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome (NAS) admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: From the Pediatrix Clinical Data Warehouse database, we identified all infants born at >/=36 weeks of gestation between 2011 and 2015 who were diagnosed with NAS (International Classification of Diseases, Ninth Revision code 779.5) and treated with methadone or morphine in the first 7 days of life. We used multivariable Cox proportional hazards regression analysis to quantify the association between initial treatment and LOS after adjusting for maternal age, maternal race/ethnicity, maternal drug use, maternal smoking, gestational age, small for gestational age status, inborn status, and discharge year. RESULTS: We identified a total of 7667 eligible infants, including 1187 treated with methadone (15%) and 6480 treated with morphine (85%). Birth weight, gestational age, and sex were similar in the 2 groups. Methadone treatment was associated with a 22% shorter median LOS (18 days [IQR, 11-30 days] vs 23 days [IQR, 16-33]; P < .001) and a 19% shorter median NICU stay (17 days [IQR, 10-29 days] vs 21 days [IQR, 14-36 days]; P < .001). After adjustment, methadone was associated with a shorter LOS (hazard ratio for discharge, 1.24; 95% CI, 1.11-1.37; P < .001) CONCLUSION: Among infants born at >/=36 weeks of gestation with NAS, initial methadone treatment was associated with a shorter LOS compared with morphine treatment. Future prospective comparative effectiveness trials to treat infants with NAS are needed to verify this observation.


Posted December 15th 2018

MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review.

Ajay Goel Ph.D.

Ajay Goel Ph.D.

Toiyama, Y., Y. Okugawa, J. Fleshman, C. Richard Boland and A. Goel (2018). “MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review.” Biochim Biophys Acta Rev Cancer 1870(2): 274-282.

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Emerging evidence has demonstrated the feasibility of circulating miRNAs as robust non-invasive biomarkers for the diagnosis in colorectal cancer. The use of circulating miRNAs for the early detection of colorectal cancer (CRC) is of particular interest as it can offer a potential complementary approach to screening colonoscopy. However, the development of circulating miRNAs as “liquid biopsy” biomarkers for development into clinical screening tests has been hampered by several issues. In this article, we summarize the status of this field for the clinical utilization of miRNA biomarkers as liquid biopsies in colorectal cancer (CRC) and discuss their applications as screening tests for patients with colorectal adenoma (CRA) and CRC. Herein, we undertook a systematic search for citations in PubMed and the Cochrane Database from January 1, 2002 through December 31, 2017 as electronic sources for this study. All published studies were screened with no restriction on language, date, or country. We used database-specific combinations of the following index terms and text words, including: microRNA, colorectal cancer, serum, plasma, and exosomes. Based upon these searches, we summarize the progress and salient features of the current state of knowledge of miRNA diagnostic biomarkers in CRC, and focuses on the articles that attempt to optimize ideal methodologies to further advance their as liquid biopsies for clinical use. We conclude that the field of noncoding RNAs, particularly for the clinical use of miRNAs as liquid biopsy assays is maturing rapidly, and it is highly promising that these genomic signatures will likely be developed into clinically-viable tests for the early detection and clinical management of patients with colorectal cancer in the not so distant future.


Posted December 15th 2018

Magnitude and impact of multiple chronic conditions with advancing age in older adults hospitalized with acute myocardial infarction.

Hoa L. Nguyen M.D.

Hoa L. Nguyen M.D.

Tisminetzky, M., H. L. Nguyen, J. H. Gurwitz, D. McManus, J. Gore, S. Singh, J. Yarzebski and R. J. Goldberg (2018). “Magnitude and impact of multiple chronic conditions with advancing age in older adults hospitalized with acute myocardial infarction.” Int J Cardiol 272: 341-345.

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BACKGROUND: To examine age-specific differences in the frequency and impact of cardiac and non-cardiac conditions among patients aged 65years and older hospitalized with acute myocardial infarction (AMI). METHODS: Study population consisted of 3863 adults hospitalized with AMI at 11 medical centers in central Massachusetts on a biennial basis between 2001 and 2011. The presence of 11 chronic conditions (five cardiac and six non-cardiac) was based on the review of hospital medical records. RESULTS: Participants’ median age was 79years, 49% were men, and had an average of three chronic conditions (average of cardiac conditions: 2.6 and average of non-cardiac conditions: 1.0). Approximately one in every two patients presented with two or more cardiac related conditions whereas one in every three patients presented with two or more non-cardiac related conditions. The most prevalent chronic conditions in our study population were hypertension, diabetes, heart failure, chronic kidney disease, and peripheral vascular disease. Patients across all age groups with a greater number of previously diagnosed cardiac or non-cardiac conditions were at higher risk for developing important clinical complications or dying during hospitalization as compared to those with 0-1 condition. CONCLUSIONS: The prevalence of multimorbidity among older adults hospitalized with AMI is high and associated with worse outcomes that should be considered in the management of this vulnerable population.


Posted December 15th 2018

Correspondence: Future direction of uterine transplantation.

Giuliano Testa M.D.

Giuliano Testa M.D.

Testa, G. and L. Johannesson (2018). “Correspondence: Future direction of uterine transplantation.” Curr Opin Organ Transplant Dec 3. [Epub ahead of print].

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We would like to direct your attention to a statement written in the article “Current status and future direction of uterus transplantation” authored by Dr. Mats Brannstrom and published in Current Opinion in Organ Transplantation, October 2018. In the Section, “Live Donor Uterus Transplantation: Results”, it is stated that “Although the case proved to be successful, it has to be pointed out that bilateral use of utero-ovarian veins will necessitate donor oophorectomy and this will lead to premature menopause, with may lead to increase morbidity in this 32-year-old altruistic donor.” This statement is incorrect. In the publication announcing the first live birth after uterus transplantation in the United States, G. Testa et al. American Journal of Transplantion, May 2018, we clearly specified that “The utero ovarian veins were identified as they run closely to the fallopian and dissected free from the ovary. The ovaries were left in situ.” This donor surgical technique has been used routinely by us. In fact, the second mother to give birth in our programme also received a uterus transplant in which the venous outflow was based exclusively on the utero-ovarian vein segment and who donor did not require and oophorectomy. We thank you for the attention given to reporting the correct information. (Excerpt from text of this correspondence; no abstract available.)


Posted December 15th 2018

Systematic review of the real-world evidence of adalimumab safety in psoriasis registries.

Alan M. Menter M.D.

Alan M. Menter M.D.

Strober, B., J. Crowley, R. G. Langley, K. Gordon, A. Menter, C. Leonardi, D. Arikan and W. C. Valdecantos (2018). “Systematic review of the real-world evidence of adalimumab safety in psoriasis registries.” J Eur Acad Dermatol Venereol 32(12): 2126-2133.

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Long-term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real-world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practice. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, EMBASE, EMBASE Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient-years [PY]) of adverse events (AEs), serious AEs (SAEs) and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n = 10; no safety data, n = 2; no on-treatment data, n = 1; not English, n = 1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N = 6059). Rates of infections (7.7-14.7/100PY) and serious infections (<0.6-2.0/100PY) were reported in four studies. Cardiovascular-related events were reported in three studies: