Research Spotlight

Gonzalez, S. A. and R. P. Perrillo (2016). “Hepatitis b virus reactivation in the setting of cancer chemotherapy and other immunosuppressive drug therapy.” Clin Infect Dis 62 Suppl 4: S306-313.

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Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder.

Gonzalez-Stawinski, G. V. (2016). “Donor hearts: Time to look at them in a different light?” J Card Fail 22(5): 383-384.

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In this edition of The Journal of Cardiac Heart Failure, 2 papers aim to inform readers of donor groups that could be considered at the time of cardiac donation in the hope of expanding the stagnant donor pool.

Holzman, M. A., B. D. Hanus, J. W. Munz, D. P. O’Connor and M. R. Brinker (2016). “Addition of a medial locking plate to an in situ lateral locking plate results in healing of distal femoral nonunions.” Clin Orthop Relat Res 474(6): 1498-1505.

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BACKGROUND: Nonunion of the distal femur after lateral plating is associated with axial malalignment, chronic pain, loss of ambulatory function, and decreased knee ROM. The addition of a medial locking plate with autogenous bone grafting can provide greater stability to allow bone healing and may be used to achieve union in these challenging cases. QUESTIONS/PURPOSES: We wished to determine (1) the proportion of patients who achieve radiographic signs of osseous union for distal femoral nonunions with an in situ lateral plate after treatment with addition of a medial locking plate and autogenous bone grafting, and (2) the frequency and types of complications associated with this treatment. METHODS: Between 2007 and 2013, we treated 22 patients for 23 distal femoral nonunions, defined as an unhealed fracture with no radiographic signs of osseous union at a mean of 16 months (SD, 13 months) after injury. During that time, we used a treatment algorithm consisting of treatment in one or two stages. The single-stage procedure performed in 16 aseptic nonunions with a stable lateral plate involved addition of a medial locking plate and autogenous bone graft. A two-stage treatment performed in seven nonunions with lateral plate failure involved placement of a new lateral locking plate followed by addition of a medial locking plate with autogenous bone graft at least 2 months after the first procedure. Of the 22 patients treated, 20 had a median followup of 18 months (SD, 6-94 months). We defined osseous union by bridging bone on three of four cortices with absence of a radiolucent line or more than 25% cross-sectional area of bridging bone via CT. RESULTS: Twenty of the 21 nonunions attained radiographic signs of osseous union by 12 months. Six of the 20 patients experienced complications: one patient had a persistent nonunion; four patients underwent removal of symptomatic hardware; and one patient experienced skin breakdown at the bone graft harvest site. CONCLUSIONS: A very high proportion of patients achieve union when using medial locking plates to treat distal femoral nonunions after lateral plating of the original injury. Addition of bone graft, staged reconstruction, and revision of the initial lateral plate is indicated when the nonunion is associated with fatigue failure of the initial lateral plate.

Noguchi, T., Y. Toiyama, T. Kitajima, H. Imaoka, J. Hiro, S. Saigusa, K. Tanaka, Y. Inoue, Y. Mohri, S. Toden and M. Kusunoki (2016). “Mirna-503 promotes tumor progression and is associated with early recurrence and poor prognosis in human colorectal cancer.” Oncology 90(4): 221-231.

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OBJECTIVES: MicroRNA (miR)-503 is downregulated in several cancers and plays a tumor-suppressive role in carcinogenesis. However, the miR-503 expression pattern, its clinical significance and its molecular mechanism in colorectal cancer (CRC) have not been investigated. METHODS: We analyzed miR-503 expression in normal mucosa (n = 20), adenoma (n = 27) and CRC (n = 20). We quantified miR-503 expression in an independent cohort (n = 191) and investigated the clinical significance of miR-503 in CRC. CRC cell lines were transfected with anti-miR-503 to assess its function and target gene. RESULTS: miR-503 expression increased according to the adenoma-carcinoma sequence. High miR-503 expression was significantly associated with large tumor size, serosal invasion, lymphatic and venous invasion as well as lymph node metastasis. CRC patients with high miR-503 expression had significantly earlier relapse and poorer prognosis than those with low expression. miR-503 was an independent recurrence marker in stage I/II CRC. In vitro, attenuated miR-503 expression resulted in inhibition of proliferation, invasion and migration and acquisition of anoikis of CRC cells. The putative target gene (calcium-sensing receptor) was significantly upregulated after miR-503 attenuation. CONCLUSIONS: miR-503 acts as an ‘onco-miR’ in CRC. High miR-503 expression is associated with early recurrence and poor prognosis in CRC.

Smith, S. and J. Taylor (2016). “Best practices in caring for patients infected with clostridium difficile.” Crit Care Nurse 36(3): 71-72.

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The number of C difficile infections (CDIs) has doubled from 2000 to 2009, and C difficile now rivals methicillin-resistant Staphylococcus aureus as the most frequent cause of health care–associated infection in the United States.1 It is the most common cause of health care– associated diarrhea and accounts for 15% to 25% of antibiotic-associated diarrhea.2,3 Costs are estimated to be more than $1.3 billion per year.2 For many reasons, CDI has captured the interest of both insurers and the public. Beginning in 2017, the Centers for Medicare and Medicaid Services will include CDI in the reimbursement metrics for its valuebased purchasing program.1