The Effect of Presurgical and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats: A Pilot Study.

PURPOSE: Our previous rodent studies demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. Histologically, we found that topical tacrolimus was correlated with increased vascular growth in areas more susceptible to ischemic damage. The purpose of this study was to investigate the potential benefits of pretreatment with tacrolimus. By applying tacrolimus in advance of raising the dorsal skin flaps, we hoped to increase vascularity and thus increase the overall viability of the flaps. METHODS: Twenty Sprague-Dawley rats were initially randomized to 4 groups based on timing of tacrolimus treatment (presurgical/postsurgical treatment): control/control (C/C), control/tacrolimus (C/T), tacrolimus/control (T/C), and tacrolimus/tacrolimus (T/T). Treatments consisted of 0.2 g of the control (topical petroleum jelly) and 0.1% topical tacrolimus to the rat dorsum twice per day. After 7 days of presurgical treatment, a cranially based dorsal skin flap measuring 3 × 10 cm was created. Two rats perished during surgery and were excluded for further analysis. Each rat was treated for a further 7 days and sacrificed. Two blinded reviewers marked the total skin flap area as well as areas of viable tissue, reversible ischemia, and full-thickness necrosis. Percentage areas were calculated using Fiji/ImageJ, and statistical analysis was performed in R. RESULTS: The average viable areas for C/C, C/T, T/C, and T/T were 31.4%, 31.9%, 35.6%, and 22.6%, respectively. The average reversible ischemic area for C/C, C/T, T/C, and T/T was 53.1%, 54.0%, 54.1%, and 71.5%, respectively. The average necrotic area for C/C, C/T, T/C, and T/T was 15.4%, 14.0%, 10.2%, and 5.9%, respectively. For areas of reversible ischemia, T/T arm had higher areas compared with C/T (P = 0.004) and T/C (P = 0.044). There was no significance between treatment arms for areas of viable and necrotic tissue. CONCLUSIONS: We observed higher areas of reversible ischemia for continuous tacrolimus treatment compared with only pre-tacrolimus application or post-tacrolimus application. This suggests that tacrolimus application before and after surgical insult may be associated with improved ischemic survival of the skin. Although we did not observe decreased areas of necrosis for tacrolimus treatment compared with control, this was likely due to the limited number of rats available in each arm to reach significance. Further study is needed to fully elucidate the encouraging trends that were observed.

The Effect of Topical Tacrolimus on Pedicled Flap Survival.

PURPOSE: Skin necrosis is a known postoperative complication of mastectomies. The pathophysiology of tissue necrosis involves lymphatic congestion, followed by venous congestion and ultimately arterial insufficiency. Recent mouse model studies have shown topical tacrolimus to increase growth of lymphatic collateral vessels and decrease lymphedema, potentially obviating the cycle of necrosis and increasing skin survival. The purpose of this study was to investigate the effect of topical tacrolimus on skin flap necrosis in a rat model. METHODS: A cranially based dorsal skin flap measuring 3 × 10 cm was raised and reinset on 22 Sprague-Dawley rats. They were then randomized to either the control (topical petroleum jelly) or the treatment (topical 0.1% tacrolimus) arm. In addition, 0.2 g of either ointment was spread over the flap and then covered with an occlusive dressing. Dressings were changed daily with reapplication of both the topical ointment and occlusive dressing. The rats were sacrificed 7 days postoperatively; areas of viable tissue, reversible ischemia, and full thickness necrosis were measured with Fiji software, and comparative analysis was performed with GraphPad statistical software. RESULTS: The average area of the dorsal flaps in the control and tacrolimus groups was 22.5 and 23.9 cm, respectively. In the control cohort, the average viable area was 42.4%, the average reversible ischemia area was 43.6%, and the average necrotic area was 13.9%. In the tacrolimus cohort, the average viable area was 31.5%, the average reversible ischemia area was 59.3%, and the average necrotic area was 9.2%. Total necrotic area was significantly lower in rats receiving topical tacrolimus as compared with controls (P = 0.015). Furthermore, the ratios of necrotic to reversible ischemia and necrotic to viable tissue were significantly lower in the tacrolimus group as compared with controls (P = 0.003, P = 0.015). There was one incidence of wound dehiscence secondary to rodent self-removal of dressings and suture that required reoperation and reinset. CONCLUSIONS: Topical tacrolimus was associated with significantly less full thickness necrosis as compared with topical.

Retained Temporary Epicardial Pacing Wires: A Systematic Review and Treatment Algorithm.

INTRODUCTION: Temporary epicardial pacing wires (TEPW) are used in the immediate postoperative cardiac surgery period for the identification, diagnosis, and treatment of acute arrhythmias. They are usually removed before discharge, but are sometimes clipped and left to retract into the skin and are thus retained. Rare complications from these retained wires have been documented in numerous case reports. We describe a case of a 57-year-old man with chronically draining wounds due to infected retained pacing wires. This case prompted a systematic review of these patients to delineate complications and to create a novel treatment algorithm. METHODS: The authors conducted a systematic review of MEDLINE, Embase, and the Cochrane Library databases and retrieved relevant, English-language articles published between 1986 and 2018. Two reviewers critically appraised the studies that met inclusion and exclusion criteria. RESULTS: Thirty-one articles met inclusion criteria with a total of 35 patients included. The existing articles represent either level IV or level V evidence. Mean ± SD time of presentation from initial TEPW placement was 4.9 ± 5.9 years, with a range of 1 month to 24 years and 77% of patients were symptomatic. The TEPW wire migration occurred in 74% of patients, with invasion into vasculature, visceral organs, and subcutaneous tissue. Most of the patients who underwent wire removal had complete recovery. The relevant literature suggests that there is a wide range of complications, and migration is more often associated with need for surgical intervention. CONCLUSIONS: In patients with severe symptoms or evidence of migration, surgical intervention and removal should be strongly considered to prevent potentially deadly complications. We propose an algorithm to minimize these complications based on a literature analysis in accordance with PRISMA guidelines.

Course Offerings in the Fourth Year of Medical School: How U.S. Medical Schools Are Preparing Students for Internship.

The fourth year of medical school remains controversial, despite efforts to reform it. A committee from the Clerkship Directors in Internal Medicine and the Association of Program Directors in Internal Medicine examined transitions from medical school to internship with the goal of better academic advising for students. In 2013 and 2014, the committee examined published literature and the Web sites of 136 Liaison Committee on Medical Education-accredited schools for information on current course offerings for the fourth year of medical school. The authors summarized temporal trends and outcomes when available.Subinternships were required by 122 (90%) of the 136 schools and allow students to experience the intern's role. Capstone courses are increasingly used to fill curricular gaps. Revisiting basic sciences in fourth-year rotations helps to reinforce concepts from earlier years. Many schools require rotations in specific settings, like emergency departments, intensive care units, or ambulatory clinics. A growing number of schools require participation in research, including during the fourth year. Students traditionally take fourth-year clinical electives to improve skills, both within their chosen specialties and in other disciplines. Some students work with underserved populations or seek experiences that will be henceforth unavailable, whereas others use electives to "audition" at desired residency sites. Fourth-year requirements vary considerably among medical schools, reflecting different missions and varied student needs. Few objective outcomes data exist to guide students' choices. Nevertheless, both medical students and educators value the fourth year of medical school and feel it can fill diverse functions in preparing for residency.