Citations

AbstractBackgroundRecipients of implantable cardioverter defibrillator (ICD) generator replacement with multiple medical comorbidities may be at higher risk of adverse outcomes that attenuate the benefit of ICD replacement. The aim of this investigation was to study the association between the Charlson comorbidity index (CCI) and outcomes after ICD generator replacement.MethodsAll patients undergoing first ICD generator replacement at Mayo Clinic, Rochester and Beth Israel Deaconess Medical Center, Boston between 2001 and 2011 were identified. Outcomes included: (a) all‐cause mortality, (b) appropriate ICD therapy, and (c) death prior to appropriate therapy. Multivariable Cox regression analysis was performed to assess association between CCI and outcomes.ResultsWe identified 1421 patients with mean age of 69.6 ± 12.1 years, 81% male and median (range) CCI of 3 (0‐18). During a mean follow‐up of 3.9 ± 3 years, 52% of patients died, 30.6% experienced an appropriate therapy, and 23.6% died without experiencing an appropriate therapy. In multivariable analysis, higher CCI score was associated with increased all‐cause mortality (Hazard ratio, HR 1.10 [1.06‐1.13] per 1 point increase in CCI, P < .001), death without prior appropriate therapy (HR 1.11 [1.07‐1.15], P < .0001), but not associated with appropriate therapy (HR 1.01 [0.97‐1.05], P = .53). Patients with CCI ≥5 had an annual risk of death of 12.2% compared to 8.7% annual rate of appropriate therapy.ConclusionsCCI is predictive of mortality following ICD generator replacement. The benefit of ICD replacement in patients with CCI score ≥5 should be investigated in prospective studies.

AbstractBackgroundIn microvascular free‐tissue harvest and transfer, the need for repositioning from lateral decubitus position and the inability to use a two‐team approach are major drawbacks of the subscapular system. We present our experience with the subscapular system for upper and lower extremity reconstruction using a two‐team approach without need for repositioning.MethodsWe conducted a retrospective chart review for all patients undergoing free flap transplant based on the subscapular system to the upper or lower extremity at our microsurgical facility from January 1, 2007 to December 31, 2011. Only cases not requiring intraoperative repositioning were included. Sixty‐four patients underwent the two‐team approach (37 upper extremity and 27 lower extremity transplants). Flap types included latissimus dorsi musculocutaneous, partial superior latissimus, dorsal thoracic fascia, serratus, scapular bone, and thoracodorsal artery perforator, either alone or as chimeric flaps. All patients were placed in the lateral decubitus position for the duration of the surgery.ResultsThe ipsilateral subscapular system was used in 16% of cases for lower extremity defects, where the anterior tibial vessels served as recipient vessels. The contralateral subscapular system was used in all remaining cases for upper extremity or the vast majority for lower extremity (84%) defects, where either the superficial femoral, genicular, popliteal, sural, or posterior tibial vessels served as recipient vessels. With the exception of one partial flap loss secondary to infection, all flaps survived.ConclusionsProper lateral decubitus positioning allows for a two‐team approach without compromising safety or outcomes.

Background: Considerable craniofacial features of Crouzon syndrome are attributed to the dysmorphology of the cranial base. As cephalometric studies have focused mainly on the facial deformity, rather than the cranial base, the underlying cause of deformity is not as well understood. Therefore, the authors compared the cranial base development of Crouzon syndrome to controls to trace the timing of deformity in the cranial base and face, to analyze their temporal correlation. Methods: Ninety computed tomographic scans were included (Crouzon, n = 36; controls, n = 54) and divided into five age subgroups. Craniofacial cephalometric measurements were analyzed by Materialise software. Results: The overall cranial base length in Crouzon syndrome compared with controls decreased 8 percent (p = 0.014) on average. The posterior cranial fossa shortening accounted for most of this reduction. The cranial base displaced with the distances from basion, sella, and ethmosphenoid to posterior nasal spine shortened by 21%, 18%, and 16%, respectively (all p < 0.01) during life. Although the cranial base angle on intracranial surface remains normal, the angles on facial surface narrowed were reduced. Conclusions: The cranial base deformity of Crouzon syndrome consists of the whole skull base and particularly anterior skull base shortening early, leading to a compensatory widened anterior skull base. However, when this widening did not compensate fully for the rapid enlargement of the brain, the posterior skull base displaced inferiorly and became kyphotic. The cranial base deformity develops sequentially anterior to posterior in a probable cascade of influence pattern. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Many clinical laboratories supporting solid organ transplant programs use multiple HLA genotyping technologies, depending on individual laboratory needs. Sequence‐specific primers and quantitative polymerase chain reaction (qPCR) serve the rapid turnaround necessary for deceased donor workup, while sequence‐specific oligonucleotide probe (SSOP) technology is widely employed for higher volumes. When clinical need mandates high‐resolution data, Sanger sequencing‐based typing (SBT) has been the “gold standard.” However, all those methods commonly yield ambiguous typing results that utilize valuable laboratory resources when resolution is required. In solid organ transplantation, high‐resolution typing may provide critical information for highly sensitized patients with donor‐specific anti‐HLA antibodies (DSA), particularly when DSA involve HLA alleles not discriminated by SSOP typing. Arguments against routine use of SBT include assay complexity, long turnaround times (TAT), and increased costs. Here, we compare a next generation sequencing (NGS) technology with SSOP for accuracy, effort, turnaround time, and level of resolution for genotyping of 11 HLA loci among 289 specimens from five clinical laboratories. Results were concordant except for SSOP misassignments in eight specimens and 21 novel sequences uniquely identified by NGS. With few exceptions, SSOP generated ambiguous results while NGS provided unambiguous three‐field allele assignments. For complete HLA genotyping of up to 24 samples by either SSOP or NGS, bench work was completed on day 1 and typing results were available on day 2. This study provides compelling evidence that, although not viable for STAT typing of deceased donors, a single‐pass NGS HLA typing method has direct application for solid organ transplantation.

Epithelioid hemangioendothelioma (EHE) is an uncommon low-grade malignant vascular tumor that may arise in soft tissue/bone or visceral sites such as the liver and lung. As this tumor exhibits epithelioid morphology, it frequently causes diagnostic confusion with other epithelioid vascular neoplasms as well as carcinoma. While 90% of classic EHE are driven by aWWTR1-CAMTA1fusion gene, a histologically distinctive subset of EHE has been recently shown to harbor a different fusion gene,YAP1-TFE3. This variant is likely underrecognized given its rarity and only recent description. Notably, EHE frequently involves the liver but only one case of hepaticYAP1-TFE3rearranged EHE has been reported to date. We present the second case ofYAP1-TFE3rearranged EHE affecting a 65-year-old woman and presenting as multiple liver masses, with characterization of the fusion gene at the transcriptomic and genomic levels. There are several educational points noted from this case.YAP1-TFE3rearranged EHE shows distinctly vasoformative foci, unlike classic EHE and mimicking angiosarcoma or epithelioid hemangioma. The tumors cells show a histiocytoid appearance with voluminous cytoplasm, similar to otherTFE3-rearranged tumors. Finally, in the liver, this tumor may in part mimic focal nodular hyperplasia of the liver which is an underrecognized diagnostic pitfall. This report highlights the key diagnostic and genetic features of this newly recognized variant of hepatic EHE to aid pathologists in appropriately classifying these tumors.

Background: Eyelid melanoma (EM) is a rare condition that accounts for <1% of all cutaneous melanomas. In this analysis, patients diagnosed with EM in the United States were compared to those with other melanomas in the head and neck. Methods: The National Cancer Database was used to select patients with head and neck melanoma from 2004 to 2015. Results: A total of 137,233 patients met the criteria of the study. Among them, 2694 were diagnosed with EM (2%) and 134,539 in other head and neck locations (98%). Regarding the patients with EM, the mean age was 68.56 years (standard deviation 14.04). A greater number of them were treated in Academic/Research Programs (53.6%), insured by Medicare (55.7%), tumor in situ (52.2%), stage 0 (49%), and without ulceration (75.9%). The mean time to treatment commencement was 18.96 days for EM compared to 14.4 days for other melanoma in the head and neck regions (P < 0.001). There was a greater proportion of EM in female patients (odds ratio [OR] 2.371 [2.191–2.566], P < 0.001), compared to male; age greater than 80 years (OR 1.622 [1.360–1.934], P < 0.001) compared to 0 to 49 years. Moreover, EM was an independent predictor for treatment in Academic/Research Programs (OR 1.258 [1.160–1.365], P < 0.001) and diagnosis at autopsy (OR 1.414 [1.083–1.847], P = 0.011) compared to other melanoma in the head and neck region. Conclusion: These novel findings have the potential to guide clinical decision making in head and neck melanoma management.

Background: While trauma to the upper extremity is known to cause acute compartment syndrome (ACS), nontraumatic causes of ACS of the upper extremity are rare. Nontraumatic ACS of the upper extremity can lead to adverse outcomes if not recognized early. There are limited reports of spontaneous ACS published in the literature. The aim of this comprehensive systematic review is to increase awareness among plastic surgeons and hand surgeons of this acute event and provide an algorithmic approach to management in the acute setting through an illustrative case example. Methods: A comprehensive systematic review of published literature was conducted in the Medline/PubMed database with the search terms, “compartment syndrome,” “extremity,” “spontaneous,” “nontraumatic,” and “atraumatic” without timeframe limitations. Articles were identified and included in this review based on ACS localization in the upper extremity and etiology of nontraumatic, spontaneous origin. Results: Sixteen publications and 19 total cases of nontraumatic ACS of the upper extremity from 1993 to 2016 met our search criteria. A bleeding disorder was the etiology in three cases, systemic anticoagulation in three cases, infection in six cases, and unknown in three cases. The remaining four cases included systemic sclerosis, Ehlers-Danlos syndrome, rhabdomyolysis, and McArdle disease. Conclusions: Nontraumatic causes of ACS of the upper extremity include infection, anticoagulation therapy, and bleeding disorders. Even though trauma is the most common cause of ACS, clinicians should be aware of these other potential causes of ACS in the nontraumatic setting. Appropriate medical and surgical intervention should be done to avoid potential adverse outcomes.

Background:Mutations localized in the tyrosine kinase domain activation loop of FLT3 (FLT3‐TKD), induce constitutive tyrosine phosphorylation, and activation of the receptor tyrosine kinase similarly to FLT3 internal tandem duplication (ITD) mutations. However, the prognostic role of FLT3‐TKD in AML is not well established. In the phase 3 RATIFY trial [CALGB 10603/Alliance; NCT00651261; Stone et al. N Engl J Med. 2017] midostaurin, in combination with standard chemotherapy, improved survival outcomes across all three FLT3 stratification subgroups (ITD high allelic ratio (AR) [≥ 0.7], ITD low AR [< 0.7] and TKD) vs placebo.Aims:Here, a post hoc analysis was used to establish the efficacy of midostaurin in patients (pts) in the RATIFY trial stratified by FLT3‐TKD AR and NPM1 mutational status.Methods:In RATIFY, newly diagnosed pts with AML 18–60 years (y) old were randomly assigned to receive midostaurin or placebo together with standard induction and consolidation therapy followed by twelve 28‐day cycles of maintenance therapy with midostaurin or placebo. FLT3‐TKD mutation was detected by PCR and capillary electrophoresis at nine reference laboratories. The FLT3‐TKD AR was calculated as the ratio between the areas under the curve of mutant to wild‐type allele. Pts were categorized as NPM1 mutated (mut) or NPM1 wild‐type (WT) using PCR. Efficacy outcomes included complete remission (CR), overall survival (OS), event‐free survival (EFS) and disease‐free survival (DFS). EFS and DFS analyses were performed considering CR within a 60‐day window. P values presented were not adjusted for multiplicity.Results:Of 163 FLT3‐TKD pts, 134 with available NPM1 data had consented for exploratory analysis and were included in this study. Overall, 58.9% of pts had NPM1‐mut, 47.8% were male and the median age was 49 y (range: 19.3–59.9 y). The median white blood cell (WBC) count was higher in pts with NPM1‐mut than in pts with NPM1‐WT (34.1 vs 15.5 × 109 /L). The median FLT3‐TKD AR was 0.4 (range: 0–2.7). Overall CR rate (regardless of NPM1 genotype) was 64% for midostaurin and 56% for placebo in FLT3‐TKD pts. Pts with FLT3‐TKD AR ≥ 0.4 treated with midostaurin showed a trend towards improved OS and reduced cumulative incidence of relapse (CIR) (Figure). In FLT3‐TKD AR ≥ 0.4 pts, the presence of a NPM1 mutation had a significant prognostic effect for all endpoints consistently with hazard ratios (HRs) around 0.50 or lower. Regardless of treatment OS, EFS, and DFS estimates at 3 y were 73% vs 52%, 48% vs 25%, and 74% vs 47%, respectively, for the 45 pts with FLT3‐TKD/NPM1‐mut vs the 25 pts with FLT3‐TKD/NPM1‐WT. It should be noted that the number of pts in each subgroup was small. Multivariate analyses in these FLT3‐TKD pts revealed that NPM1 genotype was an independent prognostic factor for OS and EFS (2‐sided P < 0.05), whereas study drug, age, sex, TKD AR, WBC at baseline and stem cell transplantation (SCT) (no/yes) did not reach this level of significance in the Cox model.Summary/Conclusion:This post hoc analysis of the subset of FLT3‐TKD pts in the RATIFY trial showed the high prognostic value of NPM1 mutational status. Midostaurin showed an overall benefit in the FLT3‐TKD pts for OS, EFS, CR and DFS, with the impact of treatment on outcome for NPM1‐mut pts being greatest in those with higher FLT3‐TKD allelic burden. U10CA180821, U10CA180882, U24CA196171, U10CA180861; Novartis; htt∗∗∗ps://acknowledgments.alliancefound.orgimage

OBJECTIVESurgical performance evaluation was first described with the OSATS (Objective Structured Assessment of Technical Skills) and modified for aneurysm microsurgery simulation with the OSAACS (Objective Structured Assessment of Aneurysm Clipping Skills). These methods rely on the subjective opinions of evaluators, however, and there is a lack of objective evaluation for proficiency in the microsurgical treatment of brain aneurysms. The authors present a new instrument, the Skill Assessment in Microsurgery for Brain Aneurysms (SAMBA) scale, which can be used similarly in a simulation model and in the treatment of unruptured middle cerebral artery (MCA) aneurysms to predict surgical performance; the authors also report on its validation.METHODSThe SAMBA scale was created by consensus among 5 vascular neurosurgeons from 2 different neurosurgical departments. SAMBA results were analyzed using descriptive statistics, Cronbach’s alpha indexes, and multivariate ANOVA analyses (p < 0.05).RESULTSExpert, intermediate-level, and novice surgeons scored, respectively, an average of 33.9, 27.1, and 16.4 points in the real surgery and 33.3, 27.3, and 19.4 points in the simulation. The SAMBA interrater reliability index was 0.995 for the real surgery and 0.996 for the simulated surgery; the intrarater reliability was 0.983 (Cronbach’s alpha). In both the simulation and the real surgery settings, the average scores achieved by members of each group (expert, intermediate level, and novice) were significantly different (p < 0.001). Scores among novice surgeons were more diverse (coefficient of variation = 12.4).CONCLUSIONSPredictive validation of the placenta brain aneurysm model has been previously reported, but the SAMBA scale adds an objective scoring system to verify microsurgical ability in this complex operation, stratifying proficiency by points. The SAMBA scale can be used as an interface between learning and practicing, as it can be applied in a safe and controlled environment, such as is provided by a placenta model, with similar results obtained in real surgery, predicting real surgical performance.