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Bodnar LM, Rouse DJ, Momirova V, Peaceman AM, Sciscione A, Spong CY, Varner MW, Malone FD, Iams JD, Mercer BM, Thorp JM, Sorokin Y, Carpenter MW, Lo J, Ramin SM, Harper M, .
Obstet Gynecol. 2013 Jun 5. [Epub ahead of print]
PMID: 23743453
OBJECTIVE:: To assess whether there was an independent association between maternal 25-hydroxyvitamin D concentrations at 24-28 weeks of gestation and preterm birth in a multicenter U.S. cohort of twin pregnancies. METHODS:: Serum samples from women who participated in a clinical trial of 17 α-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestations (2004-2006) were assayed for 25-hydroxyvitamin D concentrations using liquid chromatography tandem mass spectrometry (n=211). Gestational age was determined early in pregnancy using a rigorous algorithm. Preterm birth was defined as delivery of the first twin or death of either twin at less than 35 weeks of gestation. RESULTS:: The mean serum 25-hydroxyvitamin D concentration was 82.7 nmol/L (standard deviation 31.5); 40.3% of women had concentrations less than 75 nmol/L. Preterm birth at less than 35 weeks of gestation occurred in 49.4% of women with 25-hydroxyvitamin D concentrations less than 75 nmol/L compared with 26.2% among those with concentrations of 75 nmol/L or more (P<.001). After adjustment for maternal race and ethnicity, study site, parity, prepregnancy body mass index, season, marital status, education, gestational age at blood sampling, smoking status, and 17 α-hydroxyprogesterone caproate treatment, maternal 25-hydroxyvitamin D concentration of 75 nmol/L or more was associated with a 60% reduction in the odds of preterm birth compared with concentrations less than 75 nmol/L (adjusted odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.8). A similar protective association was observed when studying preterm birth at less than 32 weeks of gestation (OR 0.2, 95% CI 0.1-0.6) and after confounder adjustment. CONCLUSIONS:: Late second-trimester maternal 25-hydroxyvitamin D concentrations less than 75 nmol/L are associated with an increase in the risk of preterm birth in this cohort of twin pregnancies. LEVEL OF EVIDENCE:: II.
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Dawson PA.
Cell Metab. 2013 Jun 4;17(6):816-8.
PMID: 23747242
Hypercholesterolemia is a major cause of cardiovascular disease and can be treated by targeting bile acid and cholesterol metabolism. Vergnes et al. (2013) now identify Diet1 as a novel regulator of fibroblast growth factor 15/19 production and bile acid biosynthesis.
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Smith KE, Dickert E.
Clin Toxicol (Phila). 2013 Jun 4. [Epub ahead of print]
PMID: 23731371
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Strowd RE, Reynolds P.
Neurology. 2013 Jun 4;80(23):e244-6.
PMID: 23733556
Mentoring is deeply rooted in medical practice. More than just a role model, a mentor is invested in the development of the mentee, providing personal and professional support, guidance, and the means for advancement. Mentoring is vital at all levels of medical training and plays an important role in the development of academicians. Increasing clinical demands, the competitive research environment, numerous administrative pressures, and the relative undervaluing of mentoring for faculty promotion have created challenges to resident mentoring. A greater emphasis on promoting mentoring opportunities for residents is needed at many levels.
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Buchanan CF, Voigt EE, Szot CS, Freeman JW, Vlachos PP, Rylander MN.
Tissue Eng Part C Methods. 2013 Jun 4. [Epub ahead of print]
PMID: 23730946
Hyper-permeable tumor vessels are responsible for elevated interstitial fluid pressure and altered flow patterns within the tumor microenvironment. These aberrant hydrodynamic stresses may enhance tumor development by stimulating angiogenic activity of endothelial cells lining the tumor vasculature. However, it is currently not known to what extent shear forces affect endothelial organization or paracrine signaling during tumor angiogenesis. The objective of this study is to develop a three-dimensional (3D), in vitro microfluidic tumor vascular model for co-culture of tumor and endothelial cells under varying flow shear stress conditions. A central microchannel embedded within a collagen hydrogel functions as a single neovessel through which tumor-relevant hydrodynamic stresses are introduced and quantified using micro-particle image velocimetry (μ-PIV). This is the first use of μ-PIV in a tumor representative, 3D collagen matrix comprised of cylindrical microchannels, rather than planar geometries, to experimentally measure flow velocity and shear stress. Results demonstrate that endothelial cells develop a confluent endothelium on the microchannel lumen that maintains integrity under physiological flow shear stresses. Furthermore, this system provides downstream molecular analysis capability, as demonstrated by qRT-PCR, in which tumor cells significantly increase expression of pro-angiogenic genes in response to co-culture with endothelial cells under low flow conditions. This work demonstrates that the microfluidic in vitro cell culture model can withstand a range of physiological flow rates and permit quantitative measurement of wall shear stress at the fluid-collagen interface using μ-PIV optical flow diagnostics; ultimately serving as a versatile platform for elucidating the role of fluid forces on tumor-endothelial cross-talk.
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Vishwas MS, Whitlow CT, Haq IU.
BMJ Case Rep. 2013;2013()
PMID: 23737577
Typical causes of internuclear ophthalmoplegia (INO) include arterial infarcts, demyelinating conditions, inflammation and trauma. We here report the unique case of a 33-year-old man with INO of the right eye caused by infarction of the right midbrain, confirmed by diffusion-weighted MRI. At presentation he displayed impaired adduction of the right eye with normal movement of the left. CT angiogram revealed an underlying developmental venous anomaly (DVA), raising the concern of venous infarction. His symptoms improved with aggressive management of blood pressure and risk factors. The patient had vascular risk factors-smoking, hypertension and dyslipidaemia-and we theorise that the hyalinised and inelastic walls of our patient's DVA were more vulnerable to the thrombogenic effects of his risk factors, predisposing him to this event. Venous infarcts owing to DVA are rare. To our knowledge INO secondary to venous infarct has not been reported, and should be considered in the differential of such cases.
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Ferris MJ, Calipari ES, Melchior JR, Roberts DC, España RA, Jones SR.
Eur J Neurosci. 2013 Jun 3. [Epub ahead of print]
PMID: 23725404
There is great interest in outlining biological factors and behavioral characteristics that either predispose or predict vulnerability to substance use disorders. Response to an inescapable novel environment has been shown to predict a "drug-use-prone" phenotype that is defined by rapid acquisition of cocaine self-administration. Here, we showed that response to novelty can also predict the neurochemical and behavioral effects of acute and repeated cocaine in rats. We used cocaine self-administration under a fixed-ratio 1 schedule followed by fast-scan cyclic voltammetry in brain slices to measure subsecond dopamine (DA) release and uptake parameters in drug-use-prone and -resistant phenotypes. Despite no significant differences in stimulated release and uptake, animals with high responses to a novel environment had DA transporters that were more sensitive to cocaine-induced uptake inhibition, which corresponded to greater locomotor activating effects of cocaine. These animals also acquired cocaine self-administration more rapidly and, after 5 days of extended access cocaine self-administration, high-responding animals showed robust tolerance to DA uptake inhibition by cocaine. The effects of cocaine remained unchanged in animals with low novelty responses. Similarly, the rate of acquisition was negatively correlated with DA uptake inhibition by cocaine after self-administration. Thus, we showed that tolerance to the cocaine-induced inhibition of DA uptake coexists with a behavioral phenotype that is defined by increased preoccupation with cocaine as measured by rapid acquisition and early high intake.
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Guo F, Ma Y, Kadegowda AK, Xie P, Liu G, Liu X, Miao H, Ou J, Su X, Zheng Z, Xue B, Shi H, Yu L.
J Lipid Res. 2013 Jun 3. [Epub ahead of print]
PMID: 23733885
Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver disease (NAFLD), such as steatohepatitis, fibrosis and cirrhosis. Mutations in human comparative gene identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets accumulated in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared to CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-SMA, Col1α1, TNF-α and IL-1β. In conclusion: CGI-58 deficiency in liver directly causes not only heapatic steatosis but also steatohepatitis and fibrosis.
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Demissie DE, Kaplan SL, Romero JR, Leake JA, Barson WJ, Halasa NB, Byington CL, Shetty AK, Tan TQ, Hoffman JA, Lin PL, Edwards KM, Mason EO, Cooperstock MS.
Pediatr Infect Dis J. 2013 Jun 3. [Epub ahead of print]
PMID: 23736141
BACKGROUND:: Invasive meningococcal infections can be devastating. Substantial endotoxemia releases mature and immature neutrophils. Endothelial margination of mature neutrophils may increase the immature to total neutrophil ratio. These changes have not been previously well-described in invasive meningococcal disease. METHODS:: Using 2001-2011 data from the US Multicenter Meningococcal Surveillance Study, the diagnostic sensitivity and clinical correlates of white blood cell count (WBC), absolute neutrophil count (ANC), immature neutrophil count (INC), and immature-to-total neutrophil ratio (ITR) were evaluated alone and in combination at the time of diagnosis of invasive meningococcal disease. RESULTS:: 216 patients were evaluated: meningococcemia (65), meningitis (145), and other foci (6). ANC ≤ 1000/mm or ≥ 10,000/mm was present in 137 (63%), INC ≥ 500/mm in 170 (79%), and ITR ≥0.20 in 139 (64%). One or more of these 3 criteria were met in 204/216 (94%). Results were similar for meningococcemia and meningitis subgroups. All 13 cases with mildest disease met one or more of the 3 criteria. Eight children presented with absolute neutrophil counts <1000/mm: three of them died and a fourth required partial amputation in all four limbs. CONCLUSIONS:: Invasive meningococcal disease is characterized by striking abnormalities in absolute neutrophil count, immature neutrophil count, and/or immature-to-total neutrophil ratio. Neutropenia was associated with a poor prognosis. Notably, without immature neutrophil counts, 37% of cases would have been missed. Automated methods not measuring immature WBCs should be avoided when assessing febrile children. Serious infection should be considered when counts meet any of the three criteria.
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Luersen K, Dabade TS, West CE, Davis SA, Feldman SR.
J Dermatolog Treat. 2013 Jun 2. [Epub ahead of print]
PMID: 23688185
Background: Use of phototherapy in the United States declined during the 1990s, largely due to unfavorable economic incentives. The trends in phototherapy since then are not well characterized. Methods: We analyzed the National Ambulatory Medical Care Survey (NAMCS) data on quantity of phototherapy visits and associated diagnoses and payment sources. Trends were assessed by linear regression. Results: There were an estimated 230 000 outpatient phototherapy visits per year, with an increasing trend over time (p = 0.03). Dermatologists managed 87% of the visits. Leading diagnoses associated with phototherapy included psoriasis (25%), dermatitis NOS (6%), vitiligo (6%), other dyschromia (6%), and actinic keratosis (5%). Conclusions: Use of phototherapy for psoriasis has remained relatively low up to 2010. However, phototherapy may be becoming more frequent for conditions other than psoriasis.
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Beeman SM, Kemper AR, Madigan ML, Duma SM.
Accid Anal Prev. 2013 Jun ;55():34-47.
PMID: 23507433
Despite improvements in vehicle design and safety technologies, frontal automotive collisions continue to result in a substantial number of injuries and fatalities each year. Although a considerable amount of research has been performed on PMHSs and ATDs, matched dynamic whole-body frontal testing with PMHSs and the current ATD aimed at quantifying both kinetic and kinematic data in a single controlled study is lacking in the literature. Therefore, a total of 4 dynamic matched frontal sled tests were performed with three male PMHSs and a Hybrid III 50th percentile male ATD (28.6g, Δv=40 kph). Each subject was restrained using a 4 kN load limiting, driver-side, 3-point seatbelt. Belt force was measured for the lap belt and shoulder belt. Reaction forces were measured at the seat pan, seat back, independent foot plates, and steering column. Linear head acceleration, angular head acceleration, and pelvic acceleration were measured for all subjects. Acceleration of C7, T7, T12, both femurs, and both tibias were also measured for the PMHSs. A Vicon motion analysis system, consisting of 12 MX-T20 2 megapixel cameras, was used to quantify subject 3D motion (±1 mm) at a rate of 1 kHz. Excursions of select anatomical regions were normalized to their respective initial positions and compared by test condition and between subject types. Notable discrepancies were observed in the responses of the PMHSs and the ATD. The reaction forces and belt loading for the ATD, particularly foot plate, seat back, steering column, and lap belt forces, were not in agreement with those of the PMHSs. The forward excursions of the ATD were consistently within those of the PMHSs with the exception of the left upper extremity. This could potentially be due to the known limitations of the Hybrid III ATD shoulder and chest. The results presented herein demonstrate that there are some limitations to the current Hybrid III ATD under the loading conditions evaluated in the current study. Overall, this study presents a comprehensive data set of belt forces, reaction forces, accelerations, and bilateral displacement data that can be used to evaluate the performance of ATDs and validate computational models.
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Cox AJ, Lehtinen AB, Xu J, Langefeld CD, Freedman BI, Carr JJ, Bowden DW.
Acta Diabetol. 2013 Jun ;50(3):391-9.
PMID: 23161441
Selenoprotein S (SelS) has previously been associated with a range of inflammatory markers, particularly in the context of cardiovascular disease (CVD). The aim of this study was to examine the role of SELS genetic variants in risk for subclinical CVD and mortality in individuals with type 2 diabetes mellitus (T2DM). The association between 10 polymorphisms tagging SELS and coronary (CAC), carotid (CarCP) and abdominal aortic calcified plaque, carotid intima media thickness and other known CVD risk factors was examined in 1220 European Americans from the family-based Diabetes Heart Study. The strongest evidence of association for SELS SNPs was observed for CarCP; rs28665122 (5' region; β = 0.329, p = 0.044), rs4965814 (intron 5; β = 0.329, p = 0.036), rs28628459 (3' region; β = 0.331, p = 0.039) and rs7178239 (downstream; β = 0.375, p = 0.016) were all associated. In addition, rs12917258 (intron 5) was associated with CAC (β = -0.230, p = 0.032), and rs4965814, rs28628459 and rs9806366 were all associated with self-reported history of prior CVD (p = 0.020-0.043). These results suggest a potential role for the SELS region in the development subclinical CVD in this sample enriched for T2DM. Further understanding the mechanisms underpinning these relationships may prove important in predicting and managing CVD complications in T2DM.
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Allen BC, Chen MY, Childs DD, Zagoria RJ.
AJR Am J Roentgenol. 2013 Jun ;200(6):1365-9.
PMID: 23701077
OBJECTIVE. The purpose of this article is to determine whether percutaneous radiofrequency ablation (RFA) is effective and safe for the treatment of cystic renal neoplasms. MATERIALS AND METHODS. This is a retrospective review of imaging-guided RFA of Bosniak III and IV cysts from one institution. Thirty-eight subjects (19 men and 19 women; mean age, 71 years; age range, 46-95 years) underwent RFA of 40 cystic neoplasms (Bosniak III, n = 25; Bosniak IV, n = 15). Percutaneous biopsy was performed in 90% (36/40) of lesions. For patients with imaging follow-up of at least 1 year (n = 21), the mean duration of surveillance was 2.8 years (range, 1-6.5 years). The electronic medical record was reviewed for complications related to the procedure. Estimated glomerular filtration rate (GFR) was measured before RFA and at the last follow-up visit more than 6 months after the RFA session. RESULTS. According to percutaneous biopsy, 61.1% (22/36) of lesions were malignant, and 38.9% (14/36) of biopsies were inconclusive. There was no local tumor progression, and no subjects developed metastatic disease. One subject developed a new solid renal mass during the course of follow-up. Minor complications occurred in 5.3% (2/38) of ablations and included dysuria and mild hydronephrosis related to a blood clot in the ureter. There was one major complication (2.6%), a case of flash pulmonary edema. On average, estimated GFR decreased by 2.5 mL/min/1.73 m(2). CONCLUSION. Imaging-guided RFA is an effective and safe treatment of Bosniak III and IV cystic renal neoplasms with outcomes comparable to those of surgical therapies.
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Al-Dabagh A, Davis SA, Kinney MA, Huang K, Feldman SR.
Am J Clin Dermatol. 2013 Jun ;14(3):155-61.
PMID: 23575550
Methotrexate (MTX) is an effective treatment for psoriasis but its use is limited by its toxicity. Folate supplementation can be used to reduce the adverse effects of MTX, though this may impact efficacy. The frequency of folic acid supplementation is not well characterized.
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Raftery L, Tepper JE, Goldberg RM, Blackstock AW, Aklilu M, Bernard SA, Ivanova A, Davies JM, O'Neil BH.
Am J Clin Oncol. 2013 Jun ;36(3):250-3.
PMID: 22547007
: Gemcitabine is a potent radiosensitizer. When combined with standard radiotherapy (XRT) the gemcitabine dose must be reduced to about 10% of its conventional dose. Oxaliplatin and erlotinib also have radiosensitizing properties. Oxaliplatin and gemcitabine have demonstrated synergy in vitro. We aimed to determine the maximum tolerated dose of oxaliplatin and gemcitabine with concurrent XRT, then oxaliplatin, gemcitaibine, and erlotinib with XRT in the treatment of locally advanced and low-volume metastatic pancreatic or biliary cancer.
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Blackham AU, Farrah JP, McCoy TP, Schmidt BS, Shen P.
Am J Surg. 2013 Jun ;205(6):647-54.
PMID: 23375758
This study evaluates the efficacy of negative-pressure therapy (NPT) in preventing surgical site infections (SSIs) in high-risk surgical oncology patients.
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Yang Y, Zuo W, Hu J, Esch GW, Zuo Y.
Am J Trop Med Hyg. 2013 Jun ;88(6):1209-11.
PMID: 23509123
Abstract. Hemophagocytic syndrome is a rare disease that is often fatal, despite treatment. An immunocompetent patient was presented with fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia, which conformed to a hemophagocytic syndrome diagnosis. Despite broad antibiotic treatment, the patient's clinical condition rapidly deteriorated and he died within 8 days of admission. Blood cultures and a serology test were negative; however, based on morphological characteristics, tissue cysts Toxoplasma gondii were found in the bone marrow. Based on polymerase chain reaction analysis, identity of the parasite was confirmed. Although very rare, T. gondii-associated hemophagocytic syndrome should be suspected in the case of cytopenia or multiorgan failure symptoms. To our knowledge, this is the first fatal toxoplasmosis case reported from China.
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Sun Y, Shen P, Stewart JH, Russell GB, Levine EA.
Am Surg. 2013 Jun ;79(6):644-8.
PMID: 23711278
Peritoneal carcinomatosis arising from small bowel adenocarcinoma (PCSBA) carries a dismal prognosis. Presently, limited data have been published on the outcome of PCSBA treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). This series represents the largest series published to date examining our experience with 17 patients. From 1995 to 2011, 17 patients underwent HIPEC with mitomycin for PCSBA. Patients in this study were identified from a prospectively maintained database. Twenty HIPEC procedures were performed on 17 patients with a mean age of 52.2 years. Patients have achieved a mean overall postoperative survival of 18.4 months after progression on chemotherapy with an overall postoperative one- and three-year survival of 52 and 23 per cent, respectively. The mean total length of hospital stay was 10 days. There was no treatment-related mortality. Six patients were readmitted to the hospital within 30 days of discharge (35%). Eight patients (47%) experienced postoperative complications, in which two patients had major postoperative complications in the form of intra-abdominal abscess requiring interventions (12%). HIPEC has encouraging survival results for patients with PCSBA compared with similar patients treated with conventional treatments. However, even with such advancement in management, treatment for small bowel adenocarcinoma still remains a challenge.
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Randle RW, Swett KR, Shen P, Stewart JH, Levine EA, Votanopoulos KI.
Am Surg. 2013 Jun ;79(6):620-4.
PMID: 23711273
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the treatment most likely to achieve prolonged survival for peritoneal surface disease from various primaries, yet management of peritoneal sarcomatosis is controversial as a result of the propensity of sarcomas for hematogenous spread and the paucity of effective chemotherapy. Therefore, we reviewed our experience in patients with sarcomatosis. A retrospective analysis of a prospective database of 990 procedures was performed. Eastern Cooperative Oncology Group, age, type of primary, resection status, morbidity, mortality, and outcomes were reviewed. Over 20 years, 17 cytoreductions for sarcomatosis were performed. After excluding patients with gastrointestinal stromal tumor or uterine leiomyosarcoma, 10 procedures performed in seven patients remained. Median follow-up was 84.8 months. R0/1 resection was achieved in 60 per cent. The 30-day morbidity was 50 per cent; no operative mortality rate was observed. R2 resection had no long-term survivors. The reason for death was peritoneal recurrence in 57 per cent. Median survival was 21.6 months and five-year survival was 43 per cent. Median survival for patients with peritoneal sarcomatosis treated with CRS-HIPEC is similar with the historical reported survival before introducing chemoperfusion. Although a complete cytoreduction is related to improved survival, the role of HIPEC in these patients is unknown. A multi-institutional review will help define the role of CRS-HIPEC in this population.
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Claiborne JR, Crantford JC, Swett KR, David LR.
Ann Plast Surg. 2013 Jun ;70(6):698-703.
PMID: 23673567
Plastic surgery continues to be a very competitive program to match into out of medical school. To analyze the match process, all applicants to our plastic surgery residency program in 2012 were surveyed. Our results showed that with matching into plastic surgery as the primary outcome measure, those who matched applied to more plastic surgery programs, received and accepted more interview invitations, were younger, were less likely to be foreign medical graduates, reported higher costs, had higher Step 1 and Step 2 scores, were more likely to be an Alpha Omega Alpha member, and conducted more research. In addition to looking at variables that affected the success of the match, other questions regarding the match process were posed. Most interestingly, 10% of applicants still reported violations of the match communication guidelines. Furthermore, the mean cost of interviewing for the plastic surgery match was $6073.In summary, applicants with diversified strengths had the best chance of matching. On the basis of the results of this study, applicants should attend a large number of interviews to optimize their match success. With medical student debt a growing problem, programs need to find ways to control interview costs. Residency program compliance with match communication guidelines has improved, but compliance should be universal. With these data, applicants can be better prepared for the match to optimize their success and programs can work to improve the match process.
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