Casey T. Kraft

Trauma-induced heterotopic bone formation and the role of the immune system: A review.

ABSTRACT Extremity trauma, spinal cord injuries, head injuries, and burn injuries place patients at high risk of pathologic extraskeletal bone formation. This heterotopic bone causes severe pain, deformities, and joint contractures. The immune system has been increasingly implicated in this debilitating condition. This review summarizes the various roles immune cells and inflammation play in the formation of ectopic bone and highlights potential areas of future investigation and treatment. Cell types in both the innate and adaptive immune system such as neutrophils, macrophages, mast cells, B cells, and T cells have all been implicated as having a role in ectopic bone formation through various mechanisms. Many of these cell types are promising areas of therapeutic investigation for potential treatment. The immune system has also been known to also influence osteoclastogenesis, which is heavily involved in ectopic bone formation. Chronic inflammation is also known to have an inhibitory role in the formation of ectopic bone, whereas acute inflammation is necessary for ectopic bone formation.

Defining the relationship between patient decisions to undergo breast reconstruction and contralateral prophylactic mastectomy

Background: Recent studies suggest that the decisions to undergo breast reconstruction and contralateral prophylactic mastectomy are closely related. In this article, the relationship between method of reconstruction and decision to undergo contralateral prophylactic mastectomy is described. Recent trends in contralateral use in the context of literature questioning its oncologic benefit are also evaluated. Methods: Female patients with unilateral breast cancer were identified and data extracted from the Surveillance, Epidemiology, and End Results database from 2000 through 2010. Logistic regression analyses were performed to study the relationship between having contralateral prophylactic mastectomy and key demographic, oncologic, and reconstructive factors among women with unilateral breast cancer. Results: A total of 157,042 patients with unilateral breast cancer were included. The contralateral prophylactic mastectomy rate increased from 7.7 percent to 28.3 percent during the study period, and the proportion of reconstructed patients who underwent contralateral prophylactic mastectomy increased from 19 percent to 46 percent. Reconstruction was associated with higher odds of contralateral prophylactic mastectomy (OR, 2.79; 95 percent CI, 2.70 to 2.88; p < 0.0001). Among women who had reconstruction, implant-based reconstruction was associated with significantly higher odds of contralateral prophylactic mastectomy than autologous tissue reconstruction (OR, 1.38; p < 0.0001). Conclusions: This study confirms that reconstruction and the decision to undergo contralateral prophylactic mastectomy are closely related, with implant reconstruction dominating in these patients. Given the close relationship between reconstruction and the choice for contralateral prophylactic mastectomy, plastic surgeons should play an active role in educating patients to avoid decisions made based on inaccurate information. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Efficacy of Staged Excision With Permanent Section Margin Control for Cutaneous Head and Neck Melanoma

Importance Melanoma arising in chronically photodamaged skin, especially on the head and neck, is often characterized by poorly defined clinical margins and unpredictable occult extension. Staged excision techniques have been described to treat these challenging melanomas. Objective To investigate the local recurrence rates and margin to clearance end points using staged excision with comprehensive hematoxylin-eosin–stained permanent section margin control. Design, Setting, and Participants In this observational cohort study performed from October 8, 1997, to December 31, 2006, with a median follow-up of 9.3 years, 806 patients with melanoma on the head and neck, where clinical occult extension is common, were studied at an academic medical center. Interventions Staged excision with comprehensive hematoxylin-eosin–stained permanent section margin control commonly known as the square technique. Main Outcomes and Measures Local recurrence rates and margin to clearance end points. Results A total of 806 patients (276 women [34.2%]; 805 white [99.9%]) with a median age at the time of first staged excision procedure of 65 years (range, 20-94 years) participated in the study. The estimated local recurrence rates were 1.4% at 5 years, 1.8% at 7.5 years, and 2.2% at 10 years. For each 50-mm2 increase in the size of the clinical lesion, there was a 9% increase in the rate of local recurrence (hazard ratio, 1.09; 95% CI, 1.02-1.15; P = .02). The mean (SD) margin from lesion to clearance for melanoma in situ was 9.3 (5.1) mm compared with 13.7 (5.9) mm for invasive melanoma. For melanoma in situ, margins were clear after 5 mm or less in 232 excisions (41.1%) and after 10 mm or less in 420 excisions (74.5%). For invasive melanoma, margins were clear after 5 mm or less in 8 excisions (3.0%) and after 10 mm or less in 141 excisions (52.2%). Conclusions and Relevance Staged excision with comprehensive permanent section margin control of melanomas arising in chronically sun-damaged skin on the head and neck has favorable recurrence rates when melanoma margins are difficult to assess, and recurrence rates are high with traditional techniques.

Integration of Pulse Trains in Humans and Guinea Pigs with Cochlear Implants

Temporal integration (TI; threshold versus stimulus duration) functions and multipulse integration (MPI; threshold versus pulse rate) functions were measured behaviorally in guinea pigs and humans with cochlear implants. Thresholds decreased with stimulus duration at a fixed pulse rate and with pulse rate at a fixed stimulus duration. The rates of threshold decrease (slopes) of the TI and MPI functions were not statistically different between the guinea pig and human subject groups. A characteristic of the integration functions that the two groups shared was that the slopes of the TI functions were similar in magnitude to slopes of the MPI function only at low pulse rates (< approximately 300 pulses per second). This is consistent with the notion that the TI functions and the MPI functions at the low rates are mediated by a mechanism of long-term integration described in the statistical “multiple looks” model. Histological analysis of the guinea pig cochleae suggested that the slopes of both the MPI and the TI functions were dependent on sensory and neural health near the stimulated regions. The strongest predictor for spiral ganglion cell densities measured near the stimulation sites was the slope of the MPI functions below 1,000 pps. Several mechanisms may be considered to account for the association of shallow integration functions with poor sensory and neural status. These mechanisms are related to abnormal across-fiber synchronization, increased refractoriness and adaptation with impaired neural function, and steep growth of neural excitation with current level associated with neural pathology. The slope of the integration functions can potentially be used as a non-invasive measure for identifying stimulation sites with poor neural health and selecting those sites for removal or rehabilitation, but these applications remain to be tested.

Risk Indicators for Congenital and Delayed-Onset Hearing Loss

Objective To evaluate risk indicators for congenital and delayed onset hearing loss in a cohort of newborns who underwent newborn hearing screening, and to evaluate the impact of use of the Joint Committee on Infant Hearing (JCIH) recommendations on requirements for ongoing monitoring of infants identified as at risk for hearing loss. Patients and Methods Cohort of 26,341 newborns entered in a prospectively collected database as part of the University of Michigan Universal Newborn Hearing Screening program, with 90 patients identified. Logistic regression analysis was used to evaluate putative risk indicators for congenital and delayed onset hearing loss. An estimate of the cost burden of ongoing monitoring imposed by the use of differing risk indicators was performed. Results After controlling for the impact of other risk indicators, intensive care unit length of stay greater than 5 days and exposure to loop diuretics are not associated with an increased risk of congenital or delayed onset hearing loss. Inclusion of these risk indicators as a requirement for ongoing audiologic monitoring results in a high monitoring cost per additional case identified. Discussion This study confirms that the majority of the risk indicators currently recommended by the JCIH are effective at identifying infants at increased risk of congenital and delayed onset hearing loss. However, use of neonatal intensive care unit length of stay greater than 5 days and exposure to ototoxic medications are associated with small gains in the number of infants correctly identified as at risk of hearing loss. Further evaluation of the utility of these risk indicators, preferably with a diversity of patient population and healthcare settings, is warranted.

Differences between Breast Conservation-Eligible Patients and Unilateral Mastectomy Patients in Choosing Contralateral Prophylactic Mastectomies

There has been an increasing use of bilateral mastectomy (BM) for breast cancer. We sought to examine our trends among breast conservation (BCT) candidates and women recommended for unilateral mastectomy (UM). Our prospective breast cancer database was queried for women with a first‐time, unilateral breast cancer. Patient and histologic factors and surgical treatment, including reconstruction, were evaluated. A detailed chart review was performed among patients from two representative time periods as to the reasons the patient underwent mastectomy. We identified 3,892 women between 2000 and 2012 of whom 60% underwent BCT, 1092 (28%) had UM and 12% underwent BM. BM rose from 4% in 2000 to a high of 19% in 2011, increasing around 2002 for women <40. BCT was less likely with decreasing age (p < 0.0001), lobular histology (p < 0.0001), higher stage (p < 0.0001) and decreasing BMI (p < 0.0001). Among mastectomy patients, contralateral mastectomy was associated with decreasing age (p < 0.0001), Caucasian race (p < 0.0001), and lower stage (p = 0.005). Over time, indications for mastectomy decreased while patients deemed BCT‐eligible opting for UM or BM increased dramatically. Increases in the use of BM are in large part among women who were otherwise BCT‐eligible. Factors associated with BM use are different for BCT‐eligible patients and those recommended for UM. A better understanding of the factors driving individual patient choices is needed.

Back Grafting the Split-Thickness Skin Graft Donor Site.

Split-thickness skin grafting is a useful method of wound repair in burn and reconstructive operations. However, skin grafts require a donor site injury that creates a secondary wound at risk for delayed wound healing. Though in young healthy patients such donor sites have minimal risk, patients with risk factors for delayed wound healing are more challenging. We present a method for graft donor site management that offers an alternative to healing by secondary intention for patients with higher risk of poor wound healing. In those patients considered to be at high risk for donor site healing complications, we chose to treat the donor site with a split-thickness skin graft, or “graft back” procedure. An additional graft is taken adjacent to the initial donor site, and meshed 4:1 to cover both donor sites at once. Out of the 17 patients who received this procedure, 1 patient had a complication from the procedure that did not require an operation, and all patients appear to have good functional and cosmetic outcomes. No patients had any graft loss or graft infection. Histologic analysis showed complete epithelialization of the back-grafted area. The graft back method converts an open wound to a covered wound and may result in decreased wound healing time, improved cosmetic outcomes, and fewer complications, particularly in patients where wound healing is a concern. Importantly, it seems to have minimal morbidity. More detailed prospective studies are needed to ensure no additional risk is incurred by this procedure.

SPECT/CT in the Evaluation of Frostbite

Frostbite remains a challenging clinical scenario with multiple treatment algorithms and variable results. Currently, frostbite management often follows a conservative approach with rewarming followed by wound care and delayed amputation. We review seven patients where single-photon emission computed tomography (SPECT) fused with conventional computed tomography was used to evaluate tissue viability for earlier directed debridement and limb salvage. The goal of this report is to evaluate SPECT/CT as an appropriate modality for the screening of necrotic bone for earlier amputation in patients with frostbite. We retrospectively analyzed the records of seven patients (19 extremities) with frostbite who received SPECT/CT scans to evaluate deep tissue necrosis before digit amputation. All patients who presented within the first 24 hr following their injury without contraindications were initially treated with tissue plasminogen activator. Three patients met criteria and were treated with tissue plasminogen activator. Of the seven patients analyzed, none required revision amputation beyond the level predicted on SPECT/CT scan. No patients had viable tissue distal to the most distal extent of bone perfusion. In six of the patients, the SPECT/CT scan led to more distal amputation with proximal debridement of soft tissues thus maintaining extremity length. Frostbite remains a challenging clinical scenario for which there are a wide number of clinical algorithms. SPECT/CT appears to be valuable in the evaluation of frostbite to determine the need for amputation. Fusion of the nuclear images with the CT allows for more exact delineation of the level of amputation than a bone scan alone.