Research Spotlight

Posted February 15th 2018

Early Detection of Scoliosis-What the USPSTF “I” Means for Us.

Richard Hostin M.D.

Richard Hostin M.D.

Hresko, M. T., R. M. Schwend and R. A. Hostin (2018). “Early Detection of Scoliosis-What the USPSTF “I” Means for Us.” JAMA Pediatr. Jan 9. [Epub ahead of print].

Full text of this article.

In the current issue of JAMA is the latest recommendation statement by the US Preventive Services Task Force (USPSTF), and accompanying evidence report, on the value of screening asymptomatic adolescents for adolescent idiopathic scoliosis. Since the topic was last reviewed in 2004, important new evidence has emerged that potentially supports scoliosis screening. In this update, the USPSTF changed its grade of the evidence from a “D” (discourage the use of screening programs) to an “I” (uncertainty about the balance of benefits and harms of the service).1 The recommendation highlights the high sensitivity, specificity, and predictive value and the low false-positive rate of screening programs when the Adams forward bend test is paired with scoliometer measurements and Moiré topography. It is important to recognize that a properly implemented screening program will identify potential patients who can benefit from brace treatment, possibly avoiding surgery. In addition, spinal deformity may be the presenting sign of a variety of conditions, including heritable collagen disease, neurological conditions, or skeletal dysplasia unrecognized until adolescence. Even if surgery cannot be averted, early diagnosis of progressive curves allows for surgical intervention at the most opportune time. [Excerpt from text of this commentary; no abstract available.]


Posted February 15th 2018

Perioperative THR-184 and AKI after Cardiac Surgery.

Peter McCullough M.D.

Peter McCullough M.D.

Himmelfarb, J., G. M. Chertow, P. A. McCullough, T. Mesana, A. D. Shaw, T. M. Sundt, C. Brown, D. Cortville, F. Dagenais, B. de Varennes, M. Fontes, J. Rossert and J. C. Tardif (2018). “Perioperative THR-184 and AKI after Cardiac Surgery.” J Am Soc Nephrol 29(2): 670-679.

Full text of this article.

AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%-79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%-20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients


Posted February 15th 2018

Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal cancer.

Arianne L. Theiss Ph.D.

Arianne L. Theiss Ph.D.

Han, J., D. Jackson, J. Holm, K. Turner, P. Ashcraft, X. Wang, B. Cook, E. Arning, R. M. Genta, K. Venuprasad, R. F. Souza, L. Sweetman and A. L. Theiss (2018). “Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal cancer.” Proc Natl Acad Sci U S A 115(5): 1057-1062.

Full text of this article.

d-2-hydroxyglutarate (D2HG) is produced in the tricarboxylic acid cycle and is quickly converted to alpha-ketoglutarate by d-2-hydroxyglutarate dehydrogenase (D2HGDH). In a mouse model of colitis-associated colon cancer (CAC), urine level of D2HG during colitis correlates positively with subsequent polyp counts and severity of dysplasia. The i.p. injection of D2HG results in delayed recovery from colitis and severe tumorigenesis. The colonic expression of D2HGDH is decreased in ulcerative colitis (UC) patients at baseline who progress to cancer. Hypoxia-inducible factor (Hif)-1alpha is a key regulator of D2HGDH transcription. Our study identifies urine D2HG and tissue D2HGDH expression as biomarkers to identify patients at risk for progressing from colitis to cancer. The D2HG/D2HGDH pathway provides potential therapeutic targets for the treatment of CAC.


Posted February 15th 2018

Gastric cardia lesion with abnormal volumetric laser endomicroscopy imaging result.

Vani J.A. Konda M.D.

Vani J.A. Konda M.D.

Gupta, N., V. Konda and U. D. Siddiqui (2018). “Gastric cardia lesion with abnormal volumetric laser endomicroscopy imaging result.” Gastrointest Endosc Feb; 87(2): 610-612.

Full text of this article.

A 71-year-old man with a history of epigastric pain and dyspepsia had previously been found to have Barrett’s esophagus (BE) with low-grade dysplasia. He presented to our institution for repeated EGD to thoroughly assess the Barrett’s segment. EGD showed short-segment BE with a 2-cm area of nodular, polypoid-appearing mucosa on the gastric cardia side of the gastroesophageal junction (A). The area was examined by high-definition white-light endoscopy (WLE) and narrow-band imaging (NBI) with near focus (A). Volumetric laser endomicroscopy (VLE) was also used (NVisionVLE, NinePoint Medical, Cambridge, Mass) and showed suggestive features including irregular surface (blue arrow) and atypical glands (red circle) in the area corresponding to the nodular mucosa (B). Further assessment with EUS did not reveal any obvious lesions. The lesion seen on WLE and NBI was nonspecific; however, the suggestive VLE features raised concern about malignancy, so EMR was performed of the polypoid mucosa and associated abnormal VLE area. Four hemostatic clips were placed at the site of resection because of bleeding (C). Dysplasia suspected on the basis of VLE was confirmed by a final pathologic examination, which showed cellular atypia consistent with high-grade dysplasia/intramucosal carcinoma arising from BE (D) and clear resection margins. A 3-month surveillance EGD found a small nodular area of gastric foveolar hyperplasia but no dysplasia. [Excerpt from text of this image study.]


Posted February 15th 2018

Trajectories of quality of life following breast cancer diagnosis.

Elizabeth Z. Naftalis M.D.

Elizabeth Z. Naftalis M.D.

Goyal, N. G., B. J. Levine, K. J. Van Zee, E. Naftalis and N. E. Avis (2018). “Trajectories of quality of life following breast cancer diagnosis.” Breast Cancer Res Treat. Jan 24. [Epub ahead of print].

Full text of this article.

PURPOSE: Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may show different patterns of QoL. This study sought to identify distinct QoL trajectories among BCS and to examine characteristics associated with trajectory group membership. METHODS: BCS (N = 653) completed baseline assessments within 8 months of diagnosis. QoL was assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and 6, 12, and 18 months later. Finite mixture modeling was used to determine QoL trajectories of the trial outcome index (TOI; a composite of physical well-being, functional well-being, and breast cancer-specific subscales) and emotional and social/family well-being subscales. Chi-square tests and F tests were used to examine group differences in demographic, cancer-related, and psychosocial variables. RESULTS: Unique trajectories were identified for all three subscales. Within each subscale, the majority of BCS had consistently medium or high QoL. The TOI analysis revealed only stable or improving groups, but the emotional and social/family subscales had groups that were stable, improved, or declined. Across all subscales, women in “consistently high” groups had the most favorable psychosocial characteristics. For the TOI and emotional subscales, psychosocial variables also differed significantly between women who started similarly but had differing trajectories. CONCLUSIONS: The majority of BCS report good QoL as they transition from treatment to survivorship. However, some women have persistently low QoL in each domain and some experience declines in emotional and/or social/family well-being. Psychosocial variables are consistently associated with improving and/or declining trajectories of physical/functional and emotional well-being.