Research Spotlight

McCullough, P. A., A. Afzal and P. Kale (2016). “Goal-directed heart failure care in patients with chronic kidney disease and end-stage renal disease.” JACC Heart Fail 4(8): 662-663.

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Investigators have long recognized that renal function and cardiac performance are integrally linked through hemodynamic, neural, humoral, cell signaling, proteomic, and metabolomic pathways (1). Among risk factors for the development of heart failure (HF), chronic kidney disease (CKD) is the most powerful because it contributes to the three fundamental mechanisms of left ventricular failure: 1) pressure overload; 2) volume overload; and 3) cardiomyopathy (2). When CKD progresses to end-stage renal disease (ESRD), these three mechanisms driving HF become more difficult to control because patients undergoing dialysis have on average higher blood pressures; poor volume control only partially addressed by thrice weekly hemodialysis in most cases; and a well-described form of cardiomyopathy characterized by severe left ventricular hypertrophy, marked cardiac fibrosis, reduced capillary density, and calcific deposits on the mitral and aortic valves (3).

Packer, M. (2016). “The room where it happens: A skeptic’s analysis of the new heart failure guidelines.” J Card Fail: 2016 Jul [Epub ahead of print].

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New heart failure guidelines have been issued during the past several months, both in the US and in Europe, in response to recent advances in and the approval of new drugs for the treatment of heart failure. Although guidelines documents are often viewed as authoritative and purely evidence-based, there are replete with meaningful (and inexplicable) inconsistencies, which derive from a review of the same body of scientific data by different groups. This satirical review highlights several examples of the entertaining foolishness of recent guideline documents in the good-natured hope that physicians will understand what the guidelines are, and more importantly, what they are not. Specifically, this paper describes the emergence of a new non-existent disease; the strange battle between two bradycardic drugs (digoxin and ivabradine); the confusion that reigns over the positioning and dosing of inhibitors of the renin-angiotensin system; and the special recommendations that have been issued for certain special populations. As Otto von Bismarck remarked, guideline deliberations are like sausages; it is better not to see them being made. Yet, even after they are ready for public view, we should be cautious. Practitioners who rely on them for clinical decision-making engage in an unnecessary form of self-deception; those who read them literally and adhere to them strictly do not practice evidence-based medicine; and those who delve into them in a search for the truth are destined to be disappointed.

Perez, D. E., L. M. Wolford, E. Schneiderman, R. Movahed, C. Bourland and E. P. Gutierrez (2016). “Does unilateral temporomandibular total joint reconstruction result in contralateral joint pain and dysfunction?” J Oral Maxillofac Surg 74(8): 1539-1547.

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PURPOSE: The purpose of this study was to evaluate patients requiring unilateral total temporomandibular joint (TMJ) reconstruction and the risk for development of postsurgical contralateral TMJ pain and dysfunction over time requiring subsequent contralateral total joint reconstruction. Long-term subjective and objective outcomes of unilateral TMJ reconstruction also were evaluated. MATERIALS AND METHODS: Seventy patients underwent unilateral total joint reconstruction using a patient-fitted total joint prosthesis from a single private practice from 1990 through 2012. The inclusion criteria were 1) unilateral TMJ reconstruction with TMJ Concepts or Techmedica patient-fitted total joint prosthesis; 2) operation performed by 1 surgeon (L.M.W.); 3) minimum 12-month follow-up; and 4) adequate records. There were no specific exclusion criteria. The primary outcome variable was to evaluate the effects of unilateral TMJ reconstruction with a total joint prosthesis on the contralateral TMJ relative to development of pain and dysfunction requiring subsequent contralateral reconstruction with a total joint prosthesis. Secondary outcome variables for all patients included TMJ pain, facial pain, headaches, diet, disability, quality of life, maximum incisal opening (MIO), and lateral excursion movements after unilateral TMJ reconstruction with the patient-fitted total joint prosthesis. Student t test and Wilcoxon test were used for statistical analyses, with a P value less than .01 for statistical significance. RESULTS: Sixty-one of 70 patients (87%) met the inclusion criteria (47 women [77%] and 14 men [23%]; average age, 38 yr; age range, 11 to 69 yr; average follow-up, 44 months; range, 12 to 215 months). Eight of 61 patients (13%) subsequently required contralateral TMJ reconstruction with a total joint prosthesis related to contralateral pain, dysfunction, and arthritis, but all 8 (8 of 27 [29.6%]) had previous contralateral TMJ disc repositioning surgery. For the secondary outcomes, TMJ pain decreased 63%, jaw function improved 61%, facial pain decreased 59%, headaches decreased 57%, diet improved 52%, disability decreased 58.5%, and MIO increased from 31.4 to 38.8 mm (mean change, 7.4 mm). All subjective factors and MIO showed statistically significant improvements at longest follow-up (P < .01). CONCLUSIONS: Patients requiring unilateral TMJ reconstruction with a patient-fitted total joint prosthesis have a strong probability of improving their clinical condition and do not require bilateral reconstruction if the contralateral TMJ is healthy. Patients with previous or concomitant contralateral TMJ surgery (articular disc repositioning) have an approximately 30% chance of requiring a total joint prosthesis in the future.

Peterson, D. E., J. A. O’Shaughnessy, H. S. Rugo, S. Elad, M. M. Schubert, C. T. Viet, C. Campbell-Baird, J. Hronek, V. Seery, J. Divers, J. Glaspy, B. L. Schmidt and T. F. Meiller (2016). “Oral mucosal injury caused by mammalian target of rapamycin inhibitors: Emerging perspectives on pathobiology and impact on clinical practice.” Cancer Med 5(8): 1897-1907.

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In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop.

Sapisochin, G., M. Facciuto, L. Rubbia-Brandt, J. Marti, N. Mehta, F. Yao, E. Vibert, D. Cherqui, D. R. Grant, R. Hernandez-Alejandro, C. Dale, A. Cucchetti, A. Pinna, S. Hwang, S. Lee, V. Agopian, R. Busuttil, S. Rizvi, J. Heimbach, M. Montenovo, J. Reyes, M. Cesaretti, O. Soubrane, T. Reichman, J. Seal, P. Tw Kim, G. Klintmalm, C. Sposito, V. Mazzaferro, P. Dutkowski, P. A. Clavien, C. Toso, P. Majno, N. Kneteman, C. Saunders and J. Bruix (2016). “Liver transplantation for “very early” intrahepatic cholangiocarcinoma. International retrospective study supporting a prospective assessment.” Hepatology: 2016 Aug [Epub ahead of print].

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The presence of an intrahepatic cholangiocarcinoma (iCCA) on a cirrhotic liver is a contraindication for liver transplantation (LT) in most centers worldwide. Recent investigations have shown that “very early” iCCA (single tumors 2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and HCC and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the “very early” iCCA group and 33/48 (69%) the “advanced” group. There were no significant differences between groups in the preoperative characteristics. At explant, the median size of the largest tumor was larger in the “advanced” group [3.1 (2.5 – 4.4) vs. 1.6 (1.5 – 1.8)]. After a median follow-up of 35 (13.5 – 76.4) months, the 1-, 3- and 5-years cumulative risk of recurrence was 7%, 18% and 18% in the very early iCCA group vs. 30%, 47% and 61% in the advanced iCCA group, p=0.01. The 1-, 3- and 5-years actuarial survival was 93%, 84% and 65% in the very early iCCA group vs. 79%, 50% and 45% in the advanced iCCA group, p=0.02. CONCLUSION: Cirrhotic patients with very early iCCA may become candidates for LT. A prospective multicenter clinical trial is needed to further confirm these results.