Research Spotlight

Posted April 15th 2016

Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection.

Karina Reyner M.D.

Karina Reyner, M.D.

Reyner, K., A. C. Heffner and C. H. Karvetski (2016). “Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection.” Am J Emerg Med 34(4): 694-696.

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OBJECTIVE: Urinary tract infection (UTI) is a common cause of severe sepsis, and anatomic urologic obstruction is a recognized factor for complicated disease. We aimed to identify the incidence of urinary obstruction complicating acute septic shock and determine the characteristics and outcomes of this group. METHODS: Patients prospectively enrolled in a sepsis treatment pathway registry between October 2013 and July 2014 were reviewed for the diagnosis of UTI. Standardized medical record review was performed to confirm sepsis due to UTI and determine clinical variables including the presence of anatomic urinary obstruction. Patients with septic shock due to UTI with obstruction were compared with those without obstruction. The primary outcomes were incidence of urinary obstruction and hospital mortality. RESULTS: Among 1084 registry enrollees, 209 (19.2%) met inclusion criteria for the study. Acute anatomic obstruction was identified in 22 (10.5%) patients. Hospital mortality in patients with obstruction was 27.3% compared with 11.2% in patients without obstruction (absolute difference of 16.1%; P = .03; 95% confidence interval [CI], 1.2%-30.9%). Hospital length of stay among survivors was 12.8 days compared with 8.3 days (absolute difference of 4.5 days; P = .04; 95% CI, 0.2-8.8 days). History of urinary stone disease was independently associated with obstruction (odds ratio, 5.6; 95% CI, 2.2-14.3). CONCLUSIONS: Approximately 1 in 10 patients presenting with septic shock due to a urinary source is complicated by anatomic urinary obstruction. These patients have significantly higher mortality compared with patients without obstruction. Early imaging of patients with septic shock due to suspected urinary source should be considered to identify obstruction requiring emergency intervention.

Posted March 15th 2016

Belatacept and Long-Term Outcomes in Kidney Transplantation.

Kim M. Rice M.D.

Kim M. Rice, M.D.

Vincenti, F., L. Rostaing, J. Grinyo, K. Rice, S. Steinberg, L. Gaite, M. C. Moal, G. A. Mondragon-Ramirez, J. Kothari, M. S. Polinsky, H. U. Meier-Kriesche, S. Munier and C. P. Larsen (2016). “Belatacept and Long-Term Outcomes in Kidney Transplantation.” N Engl J Med 374(4): 333-343.

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BACKGROUND: In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. METHODS: We randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). RESULTS: A total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. CONCLUSIONS: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; number, NCT00256750.).

Posted March 15th 2016

Improving Treatment of Uncomplicated Diverticulitis: The Old Appendicitis.

James W. Fleshman M.D.

James W. Fleshman, M.D.

Fleshman, J. (2016). “Improving Treatment of Uncomplicated Diverticulitis: The Old Appendicitis.” JAMA Surg. Feb 10. [Epub ahead of print]

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We continue to struggle with the perfect definition of the indication for an elective operation in the patient with diverticulitis. Simianu et al,1 in their review of the MarketScan Commercial Claims and Encounters Database, have attempted to determine the influences that drive early and late operation on patients with diverticulitis. The group from University of Washington, Swedish Hospital of Seattle, and Virginia Mason Clinic hypothesized that patients commonly undergo early (<3 episodes) elective resection for diverticulitis, especially when the patient is young and responsible for the cost of the operation, which is done laparoscopically, and the preceding episodes have been frequent over a short period. Simianu et al concluded that none of these factors influenced the decision to operate and at least 50% of patients had early operations. The database is a commercial insurance administrative database with all of the limitations of an administrative database. Since these are insured, non–immune-compromised patients with uncomplicated disease, there is an element of selection and bias. The clinical data that normally influence the timing of an operation are not available (computed tomography, white blood cell count, vital signs). In an interesting twist, the definition of an incident of diverticulitis included the use of antibiotics as an outpatient or an inpatient in combination with the code for diverticulitis or the prescription of ciprofloxacin and metronidazole, in combination, in a patient with a previous episode of diverticulitis. This should have increased the number of episodes beyond the 2 cases that have historically been used as an indication for an operation. It did not. There are, therefore, surgeons who persist in operating immediately for more than 1 episode of diverticulitis. This is reminiscent of the way we treated diverticulitis in past years. Why have we not seen an improvement in the consistency of patterns of elective operation? Can we have surgeons who hold fiercely onto autonomy? Why have surgeons in the southern part of the United States continued to operate early on patients with uncomplicated diverticulitis when the patients are not noticeably different from the patients elsewhere? If capitated patients are the least likely to have early operation of the insured patients from the multiple insurance plans represented in this database, it would seem that protocols and peer review are working to reduce unnecessary operations in these patients. There was also an association between open operations and early operation. Could this indicate that resistance to change is contributing to the problem? Older surgeons who have not adopted laparoscopic techniques may also be holding on to the outdated thoughts toward diverticulitis. Assuming that not all patients who underwent operation for early diverticulitis would have eventually have required operation, there is a possibility that we, as surgeons concerned with population health, could reduce the cost of care for these patients by prescribing bulk fiber and encouraging a healthy diet high in vegetables, all of which may help to avoid another episode of diverticulitis. There should never be a financial reason for operating on an early case of diverticulitis. Chronic malignant smoldering diverticulitis, that has caused stricturing and resulted in a difficult operation to remove the disease, usually develops after many more than 3 episodes of diverticulitis. It is my opinion that this should not be considered an excuse for early operation on uncomplicated diverticulitis. Patients usually have symptoms that point to the development of severe disease, such as chronic rather than intermittent pain, incomplete resolution of fever and leukocytosis, and partial obstructive symptoms with each episode. As Simianu et al mentioned in their article,1 time between episodes may be a significant influence on this progression as well. The concerned, informed, and ethical surgeon will adhere to the recommendations proposed by almost all of the national surgical societies to improve the care for patients with diverticulitis and avoid operation on early uncomplicated diverticulitis. This review did not indicate whether there is a difference between academic, major metropolitan community, and small community hospitals in their treatment of diverticulitis. The mobility of patients in search of health care should allow the appropriate care of uncomplicated diverticulitis as the public is better educated in the modern method of treating diverticulitis. As with all interesting studies, there are always more questions than answers at the end of the study. The authors acknowledge that the next step should be a focused prospective approach to answering the number of questions raised from their article. (Excerpt from text.)

Posted March 15th 2016

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

Robert G. Mennel M.D.

Robert G. Mennel, M.D.

Harris, L. N., N. Ismaila, L. M. McShane, F. Andre, D. E. Collyar, A. M. Gonzalez-Angulo, E. H. Hammond, N. M. Kuderer, M. C. Liu, R. G. Mennel, C. van Poznak, R. C. Bast and D. F. Hayes (2016). “Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.” J Clin Oncol. Feb 8. [Epub ahead of print]

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PURPOSE: To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. METHODS: A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. RECOMMENDATIONS: In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.

Posted March 15th 2016

Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.

William C. Roberts M.D.

William C. Roberts, M.D.

Roberts, W. C., S. A. Hall, J. M. Ko, P. A. McCullough and B. Lima (2016). “Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.” Am J Cardiol 117(5): 878-879.

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Described are findings in a 70-year-old man who had heart transplantation 4 years after treatment with a left ventricular assist device, and surgical closure of his previously replaced aortic valve. The result was a totally nonfunctioning left ventricle resulting in severe atrophy.