Research Spotlight

Posted May 15th 2019

Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.

Robert Rahimi, M.D.

Robert Rahimi, M.D.

Alsahhar, J. S. and R. S. Rahimi (2019). “Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.” Curr Opin Gastroenterol 35(3): 145-154.

Full text of this article.

PURPOSE OF REVIEW: Hepatic encephalopathy is one of the most debilitating clinical manifestations of cirrhosis and associated with increased morbidity and mortality. Treatment modalities available include the nonabsorbable disaccharides (lactulose) and the nonabsorbable antibiotics (rifaximin). RECENT FINDINGS: Newer therapeutic targets under evaluation include ammonia scavengers (ornithine phenylacetate) and modulation of gut microbiota (fecal microbiota transplantation). SUMMARY: This review will focus on the pathophysiology of hepatic encephalopathy along with an update on therapeutic targets under investigation.


Posted May 15th 2019

Perceptions of a Culturally Targeted Hispanic Kidney Transplant Program: A Mixed Methods Study.

Richard M. Ruiz M.D.

Richard M. Ruiz M.D.

Alhalel, N., N. O. Francone, A. M. Salazar, S. Primeaux, R. Ruiz, J. C. Caicedo and E. Gordon (2019). “Perceptions of a Culturally Targeted Hispanic Kidney Transplant Program: A Mixed Methods Study.” Clin Transplant Apr 29: e13577. [Epub ahead of print].

Full text of this article.

Disproportionately fewer waitlisted Hispanics receive living donor kidney transplants (LDKTs) compared to non-Hispanic whites. Northwestern Medicine’s((R)) culturally targeted Hispanic Kidney Transplant Program (HKTP) is associated with a significant increase in LDKTs among Hispanics. This multi-site study assessed potential kidney recipients’ and donors’ and/or family members’ perceptions of HKTP’s cultural components through semi-structured interviews and validated surveys. Qualitative thematic analysis and descriptive statistics were performed. Thirty-six individuals participated (62% participation rate) comprising 21 potential recipients and 15 potential donors/family (mean age: 51 years, 50% female, 72% preferred Spanish). Participants felt confident about the educational information because a transplant physician delivered the education, and viewed the group format as effective. Participants felt that education sessions addressed myths about transplantation shared by Hispanics. Primary use of Spanish enhanced participants’ understanding of transplantation. While few knew about living donation before attending the HKTP, most were ‘more in favor of’ kidney transplantation (97%) and living donation (97%) afterwards. Few reported learning about the HKTP from outreach staff and suggested leveraging community leaders to promote HKTP awareness. Our findings suggest the HKTP’s cultural components were viewed favorably, and positively influenced perceptions of kidney transplantation and living donation, which may help reduce transplant disparities in Hispanics.


Posted May 15th 2019

Outcomes of preterm infants conceived with in vitro fertilization.

Monica M. Bennett Ph.D.

Monica M. Bennett Ph.D.

Ahmad, K. A., M. M. Bennett, P. Rayburn, C. A. Combs, R. H. Clark and V. N. Tolia (2019). “Outcomes of preterm infants conceived with in vitro fertilization.” J Perinatol 39(5): 717-722.

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OBJECTIVES: To determine if there is increased risk of prematurity-related complications for in vitro fertilization (IVF)-conceived preterm infants compared to matched controls. STUDY DESIGN: Cohort study of 23-34 weeks’ preterm infants from 329 US NICUs discharged from 2009 to 2016. Each IVF patient was matched to three controls. RESULTS: We identified 6,756 IVF-conceived preterm infants who were matched with 20,268 controls. IVF-conceived infants had no increase in non-respiratory morbidities but had significantly higher rates of bronchopulmonary dysplasia (8.4% vs 7%, p < 0.001) and significantly greater exposure to common chronic respiratory medications. CONCLUSIONS: In this large cohort of IVF-conceived preterm infants we found similar outcomes to controls with the exception of bronchopulmonary dysplasia and respiratory medication exposure. Further research is needed to explore the influence of in vitro fertilization on the development of neonatal respiratory disease.


Posted May 15th 2019

Cirrhosis and the Acute Kidney Injury/Chronic Kidney Disease Continuum: The Path Chosen Matters.

Sumeet K. Asrani M.D.

Sumeet K. Asrani M.D.

Agbim, U. and S. K. Asrani (2019). “Cirrhosis and the Acute Kidney Injury/Chronic Kidney Disease Continuum: The Path Chosen Matters.” Clin Gastroenterol Hepatol Apr 17. [Epub ahead of print].

Full text of this article.

The study [Cullaro G., Verna E.C., and Lai J.C.: Association between renal function pattern and mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 2019] notably raised several important issues. First, renal dysfunction is exceedingly common and the temporal dimension of where the patient lies on the AKI/CKD continuum may matter. Although a mathematical model such as the MELD or MELD-Na may attempt to summarize AKI, CKD, or AKI/CKD by a singular serum creatine concentration or its surrogates, these may be 3 separate entities, each with their own trajectory. A young cirrhotic patient with a MELD score of 25 and a serum creatinine concentration of 2 mg/dL driven by AKI owing to volume depletion may have a different trajectory than an older cirrhotic patient with a similar MELD but volume depletion complicating underlying CKD. Overall, AKI exerts a greater influence in risk of mortality on CKD than it does on those with normal renal function. Intuitively thinking, this makes sense because any insult, whether small or large, on an otherwise diseased kidney can drive cirrhotics in an unfavorable direction. This is relevant given the increasing prevalence of CKD in this population, necessitating favorable strategies to avoid or mitigate further renal injury, thereby minimizing the potential for waitlist mortality. Hence, mechanisms and chronicity of renal dysfunction may be important even before an eventual transplant. Second, this study emphasized the need to measure renal function effectively. All serum creatinine–based equations overestimate GFR in the presence of renal dysfunction. Furthermore, several equations assume a stable GFR, which is not often the case in cirrhotic patients on the waiting list. Risk stratification remains paramount, requiring continual enhancement of tools. Several biomarkers, in addition to patient characteristics, currently are being evaluated to assess renal function. The operationalization of AKI, particularly in cirrhosis, has been problematic throughout the literature, and it will be necessary to formalize a consistent definition to measure the real effect of renal dysfunction. Furthermore, AKI represents a heterogeneous entity with a multitude of phenotypes (hypovolemic nephropathy, vasogenic nephropathy, acute tubular necrosis, hepatorenal syndrome), as does CKD, and it is unclear in this analysis how any particular AKI phenotypic insult influences risk. Finally, the study highlighted the importance of extrahepatic factors in determining mortality on the waitlist. Although in all comers, a mathematical model such as the MELD-Na score may be able to predict that a registrant with a higher MELD-Na score has an increased risk of mortality than someone with a lower MELD-Na score (e.g., score of 40 vs 6), the ability of any statistical model to parse out differences in patients with similar MELD scores is difficult. The presence of comorbid conditions, malnutrition and sarcopenia, infections, critical illness, and now pattern of renal dysfunction, all may play a role. (Excerpt from text of editorial, article in press, not paginated.)


Posted April 15th 2019

Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients.

Michael J. Mack M.D.

Michael J. Mack M.D.

Mack, M. J., M. B. Leon, V. H. Thourani, R. Makkar, S. K. Kodali, M. Russo, S. R. Kapadia, S. C. Malaisrie, D. J. Cohen, P. Pibarot, J. Leipsic, R. T. Hahn, P. Blanke, M. R. Williams, J. M. McCabe, D. L. Brown, V. Babaliaros, S. Goldman, W. Y. Szeto, P. Genereux, A. Pershad, S. J. Pocock, M. C. Alu, J. G. Webb and C. R. Smith (2019). “Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients.” N Engl J Med Mar 17. [Epub ahead of print].

Full text of this article.

BACKGROUND: Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk. METHODS: We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery. The primary end point was a composite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population. RESULTS: At 71 centers, 1000 patients underwent randomization. The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan-Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, -6.6 percentage points; 95% confidence interval [CI], -10.8 to -2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P = 0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P = 0.02) and in lower rates of death or stroke (P = 0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe paravalvular regurgitation. CONCLUSIONS: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).