Citations

Abstract Breast implants are typically placed for cosmetic or reconstructive purposes, and are recognized to have a substantial impact on aesthetics and quality of life. In addition, the presence of a breast implant on the chest wall has a potential benefit of force diffusion or force absorption in traumatic injury. This article reports a series of three patients with preexisting breast implants who suffered penetrating chest trauma. In each case, the presence of a breast implant was potentially lifesaving. We describe the cases in detail, provide a conceptual discussion, and discuss directions for future research. Level of Evidence: 5

Background: The Acoustic Neuroma Association (ANA) is a national, nonprofit organization, focused on the education and support of patients with vestibular schwannoma (VS). The aim of the present study is to characterize the profile of ANA survey respondents and compare them with non-ANA patients evaluated at a single tertiary academic referral center to investigate the potential influence of selection bias. Methods: A prospectively maintained VS quality-of-life (QOL) database, comprised of patients evaluated at the authors’ center and members of the ANA, was queried. Demographic variables, patient-reported symptoms and tumor characteristics, as well as patient-reported outcome scores were captured. Health-related QOL was evaluated using the disease-specific Penn Acoustic Neuroma QOL (PANQOL) questionnaire. Multivariable regression models were fitted for PANQOL domain and total scores as well as satisfaction with treatment adjusting for baseline demographics, symptoms, and PANQOL scores. Results: A total of 1,060 patients (802 [76%] ANA respondents) were analyzed. Overall, ANA patients were slightly younger (mean age: 59 vs 60 yr, p = 0.145), more likely to be women (72 vs 55%, p < 0.001), and had a larger tumor size (overall p < 0.001). Furthermore, a significantly higher proportion of ANA patients were more likely to undergo microsurgery (57 vs 21%) or radiation (21 vs 8%) and less likely to be managed with observation (16 vs 65%, overall p < 0.001). A significantly higher proportion of ANA patients reported hearing loss (95 vs 88%, p < 0.001), tinnitus (80 vs 73%, p = 0.034), dizziness (78 vs 64%, p < 0.001), headache (56 vs 45% p = 0.003), and facial paralysis (37 vs 12%, p < 0.001). On multivariable analysis, ANA respondents exhibited significantly lower PANQOL scores for hearing (OR: 0.47, 95% CI: 0.35–0.64, p < 0.001), balance (OR: 0.51, 95% CI: 0.38–0.70, p < 0.001), pain (OR: 0.63, 95% CI: 0.46–0.86, p = 0.004), facial function (OR: 0.58, 95% CI: 0.42–0.80, p = 0.001), energy (OR: 0.44, 95% CI: 0.32–0.59, p < 0.001), anxiety (OR: 0.54, 95% CI: 0.40–0.74, p < 0.001), general (OR: 0.72, 95% CI: 0.53–0.98, p = 0.03), and total QOL (OR: 0.40, 95% CI: 0.30–0.55, p < 0.001). No statistically significant difference was seen with regard to treatment satisfaction. To determine the true clinical relevance of these differences, the two groups were compared using the minimal clinically important difference (MCID) for each domain. MCID is defined as the smallest difference in score in the domain of interest that patients perceive as important, either beneficial or harmful. The domains for hearing, balance, energy, anxiety, and total QOL reached their respective MCID thresholds, indicating that the ANA cohort has QOL scores that are clinically, perceptually worse for these domains compared to the non-ANA group. Conclusion: These data help delineate some of the inherent limitations and biases associated with survey studies incorporating data from national patient support organizations. The population profile of ANA survey respondents likely differs significantly from the greater population of patients with VS that may be encountered at a tertiary referral center.

AbstractThe detection of recurrent genetic abnormalities in B‐lymphoblastic leukemia (B‐ALL) is critical for risk stratification and therapy‐related decisions. Near‐haploidy (24‐30 chromosomes), a subgroup of hypodiploidy (<46 chromosomes), and BCR/ABL1 gene fusions are both recurrent genetic abnormalities in B‐ALL and are considered adverse prognostic findings, although outcomes in BCR/ABL1‐positive patients have improved with tyrosine kinase inhibitor therapy. While near‐haploid clones are primarily observed in children and rarely harbor structural abnormalities, BCR/ABL1‐positive B‐ALL is primarily observed in adults. Importantly, recurrent genetic abnormalities are considered mutually exclusive and rarely exist within the same neoplastic clone. We report only the second case to our knowledge of a near‐haploid clone that harbors a BCR/ABL1 fusion in an adult with newly diagnosed B‐ALL. Conventional chromosome studies revealed a near‐haploid clone (27 chromosomes) along with a der(22)t(9;22)(q34.1;q11.2) in 17 of 20 metaphases analyzed. Our B‐ALL fluorescence in situ hybridization (FISH) panel confirmed the BCR/ABL1 fusion and monosomies consistent with chromosome studies in approximately 95% of interphase nuclei. Moreover, no evidence of a “doubled” near‐haploid clone was observed by chromosome or FISH studies. This highly unusual case illustrates that while rare, recurrent genetic abnormalities in B‐ALL can exist within the same neoplastic clone.

AbstractWhole exome sequencing (WES) has become a fundamental component of genetic evaluation and diagnosing rare genetic diseases. This test is now offered to patients from a wide variety of cultural backgrounds and in various clinical and research settings. This commentary is a reflection of one group of clinical genetic counselors’ experiences in facilitating WES for patients who come from outside the United States for genetic evaluation and pursue WES. This patient population in our clinic primarily consists of individuals from the Middle East and presents recurrent logistical and counseling challenges. We aim to describe our international patient population, illuminate the challenges we have faced and illustrate how we have addressed these challenges.

DDX3X (Xp11.4) encodes a DEAD‐box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in DDX3X have been shown to cause X‐linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated with DDX3X variants are heterogeneous and include brain and behavioral abnormalities, microcephaly, hypotonia, and movement disorders and/or spasticity. The majority of DDX3X variants described are de novo mutations in females with ID. In contrast, most male DDX3X variants are inherited from an unaffected mother, with one documented exception being a recently identified de novo splice site variant. It has been suggested, therefore, that DDX3X exerts its effects through haploinsufficiency in females, and that affected males carry hypomorphic alleles that retain partial function. Given the lack of male de novo DDX3X variants, loss‐of‐function variants in this gene are suspected to be male lethal. Through whole‐exome sequencing, we identified three unrelated males with hemizygous missense DDX3X variants and ID. All three variants were confirmed by Sanger sequencing, with two established as de novo. In silico analyses were supportive of pathogenicity. We report the male phenotypes and compare them to phenotypes observed in previously reported male and female patients. In conclusion, we propose that de novo DDX3X variants are not necessarily male lethal and should be considered as a cause of syndromic ID in both males and females.

ObjectivesConflicting research exists surrounding the utility of aspirin to prevent tumor growth in the medical management of vestibular schwannoma (VS). Recent studies demonstrated no association between aspirin and VS growth using linear tumor measurements. Given the heightened sensitivity of volumetric analyses to monitor tumor growth, the current study was conceived with the chief objective of assessing the association between aspirin or other nonsteroidal anti‐inflammatory drug (NSAID) use and VS growth using volumetric analyses.Study DesignRetrospective review.SettingTertiary referral center.Subjects and MethodsA total of 361 patients totaling 1601 volumetrically analyzed magnetic resonance imaging studies who underwent initial observation since January 1, 2003.ResultsIn total, 123 (35%) patients took 81 mg aspirin daily, 23 (7%) took 325 mg aspirin daily, and 41 (11%) reported other NSAID use. Among those taking aspirin, 112 (72%) exhibited volumetric tumor growth during observation compared to 33 (80%) among other NSAID users and 137 (67%) among nonaspirin users. Patients taking aspirin or other NSAIDs were significantly older at time of diagnosis (median, 66 vs 56 years; P <. 001). Neither aspirin use (hazard ratio [HR], 0.96; P =. 73) nor other NSAID use (HR, 1.39; P =. 081) was significantly associated with a reduced risk of volumetric tumor growth. These results were similar following age adjustment (P =. 81 and. 087, respectively). When separating aspirin users by 81‐mg or 325‐mg dosing, neither group exhibited a reduced risk of growth (P =. 95 and. 73, respectively).ConclusionDespite promising initial results, the preponderance of existing literature suggests that aspirin and other NSAID use does not prevent tumor growth in VS.

AbstractPurposeThe aim of this review was to compare the clinical outcomes of anterior cruciate ligament reconstruction (ACLR) with either meniscal repair or meniscectomy for concomitant meniscal injury. The primary hypothesis was that short‐term clinical outcomes (≤ 2‐year follow‐up) for ACLR concomitant with either meniscal repair or resection would be similar. The secondary hypothesis was that ACLR with meniscal repair would result in better longer term outcomes compared with meniscal resection.MethodsThe authors searched two online databases (EMBASE and MEDLINE) from inception until March 2018 for the literature on ACLR and concurrent meniscal surgery. Two reviewers systematically screened studies in duplicate, independently, and based on a priori criteria. Quality assessment was also performed in duplicate. The Knee injury and Osteoarthritis Outcome Score (KOOS) sub‐scale scores at 2 years post‐operatively were combined in a meta‐analysis of proportions using a random‐effects model.ResultsOf 2566 initial studies, 25 studies satisfied full‐text inclusion criteria. Mean follow‐up was 2.09 years, with a total sample of 37,087 subjects including controls. The meta‐analysis demonstrated equivocal results at 2 years, except for KOOS symptom scores which favoured meniscal resection over repair. Mean KT‐1000 side‐to‐side difference (SSD) scores were 1.51 ± 0.60 mm for meniscal repair, 1.96 ± 0.36 mm for meniscal resection, and 1.58 ± 0.20 for control patients (isolated ACLR). Medial meniscal repair showed decreased anterior knee joint laxity compared to medial meniscal resection (P < 0.001). Patients with meniscal repair had higher rates of re‐operation (13.3% vs 0.8% for meniscal resection, P < 0.001).ConclusionPatients with ACLR combined with meniscal resection demonstrate better symptoms at 2‐year follow‐up compared to patients with ACLR combined with meniscal repair. ACLR combined with meniscal repair results in decreased anterior knee joint laxity with evidence of improved patient‐reported outcomes in the long term, but also higher re‐operation rates.Level of evidenceIII.