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Key PointsCoexisting psychiatric comorbidities are associated with greater increased health care utilization and cost of care in patients with MM. Clinical complications of MM are seen more frequently in patients with coexisting psychiatric conditions.

AbstractBackgroundBlepharospasm (BSP) is a type of focal dystonia characterized by involuntary orbicularis oculi spasms that are usually bilateral, synchronous, and symmetrical. Despite strong evidence for genetic contributions to BSP, progress in the field has been constrained by small cohorts, incomplete penetrance, and late age of onset. Although several genetic etiologies for dystonia have been identified through whole‐exome sequencing (WES), none of these are characteristically associated with BSP as a singular or predominant manifestation.MethodsWe performed WES on 31 subjects from 21 independent pedigrees with BSP. The strongest candidate sequence variants derived from in silico analyses were confirmed with bidirectional Sanger sequencing and subjected to cosegregation analysis.ResultsCosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. Deleterious variants in HS1BP3 (NM_022460.3: c.94C>A, p.Gly32Cys) and GNA14 (NM_004297.3: c.989_990del, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio‐cervical dystonia first manifest as BSP. Deleterious variants in DNAH17, TRPV4, CAPN11, VPS13C, UNC13B, SPTBN4, MYOD1, and MRPL15 were found in two or more independent pedigrees. To our knowledge, none of these genes have previously been associated with isolated BSP, although other CACNA1A mutations have been associated with both positive and negative motor disorders including ataxia, episodic ataxia, hemiplegic migraine, and dystonia.ConclusionsOur WES datasets provide a platform for future studies of BSP genetics which will demand careful consideration of incomplete penetrance, pleiotropy, population stratification, and oligogenic inheritance patterns.

Background: Although cubital tunnel release is a commonly performed orthopaedic procedure, the overall incidence of and independent risk factors for infection largely remain undefined in the current literature. Purpose: To establish the rate of postoperative infection after isolated cubital tunnel release and define relevant patient-related risk factors. Study Design: Case-control study; Level 3. Methods: All Medicare-insured patients undergoing ulnar nerve decompression at the cubital tunnel from 2010 through 2012 were identified. A multivariate binomial logistic regression analysis was utilized to evaluate the impact of patient-related risk factors for postoperative infection. Results: A total of 330 (2.17%) postoperative infections were identified in 15,188 cases. The majority (87%) were managed nonoperatively, while 13% required surgical debridement. The most significant risk factors for infection included hemodialysis use (odds ratio [OR], 2.47), chronic anemia (OR, 2.24), age <65 years (OR, 2.08), tobacco use (OR, 1.65), morbid obesity (OR, 1.53), inflammatory arthritis (OR, 1.43), depression (OR, 1.36), hyperlipidemia (OR, 1.33), male sex (OR, 1.32), and chronic lung disease (OR, 1.29). Conclusion: The present study was adequately powered to determine numerous patient-related risk factors for infection following cubital tunnel release.

Abstract A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend &lt; 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.

Importance The clinical and financial implications of the timing of dental rehabilitation after a fibula free tissue transfer (FFTT) for osteoradionecrosis (ORN) and osteonecrosis (ON) of the mandible have yet to be established. Objective To compare the outcomes of primary implantation vs secondary implantation after FFTT for ORN and ON of the mandible. Design, Setting, and Participants A retrospective review was conducted of 23 patients at a single tertiary academic referral center undergoing primary implantation or secondary implantation after FFTT for ORN and ON from January 1, 2006, to November 10, 2015. Interventions All patients underwent FFTT with primary implantation (n = 12) or secondary implantation (n = 11). Main Outcomes and Measures Outcomes of FFTT, dental implantation, implant use, diet, speech, and disease-free survival were reviewed. Fixed unit costs were estimated based on the mean cost analysis. Results Twenty-three patients (7 women and 16 men; mean [SD] age, 62.4 [8.2] years [range, 24-81 years]) met the inclusion criteria. Of these, 18 had ORN and 5 had ON. Dental implantation was performed at the time of FFTT for 12 patients and was performed secondarily for 11 patients. There were a mean of 5.2 implants per patient performed, for a total of 121 implants. There was 1 complete flap failure in the primary implantation group. Neither flap nor implant complications were affected by the timing of the implantation. Overall, the implant survival rate was 95% (55 of 58) in the primary implantation group and 98% (62 of 63) in the secondary implantation group. Time from FFTT to abutment placement (primary implantation, 19.6 weeks; secondary implantation, 61.0 weeks) was significantly shorter after primary implantation ( P < .001). There was no clinical difference in postoperative complications and implant outcomes for ORN vs ON. Improvement in speech and oral competence in the primary implantation group vs the secondary implantation group was not statistically significant, given an experiment-adjusted P = .001 set as significant (normal speech, 9 vs 3; P = .02; and normal oral competence, 9 vs 3; P = .02). Disease-free survival was 91% (20 of 22 patients) overall. Fixed unit (U) costs were 1.0 U for primary implantation and 1.24 U for secondary implantation. Conclusions and Relevance Patients undergoing primary implantation after FFTT for ORN and ON had a similar rate of complications compared with those undergoing secondary implantation. However, primary implantation allowed a faster return than secondary implantation to oral nutrition and prosthesis use. The fixed unit cost was reduced for those undergoing primary implantation. Although dental implantation was safe and effective in both groups, the decreased time to use and the decreased overall cost should prompt surgeons to consider primary implantation after FFTT for ORN and ON. Level of Evidence 3 .

Of all procedures in interventional radiology, percutaneous transhepatic biliary drainage (PTBD) is amongst the most technically challenging. Successful placement requires a high level of assorted skills. While this procedure can be life-saving, it can also lead to significant iatrogenic harm, often manifesting as bleeding. Readers of this article will come to understand the pathophysiology and anatomy underlying post-PTBD bleeding, its incidence, its varied clinical manifestations and its initial management. Additionally, a structured approach to its treatment emphasizing endovascular and percutaneous methods is given.

Objectives To present early safety and feasibility data from a multicentre prospective study (WATER II) of aquablation in the treatment of symptomatic men with large‐volume benign prostatic hyperplasia ( BPH ). Methods Between September and December 2017, 101 men with moderate‐to‐severe BPH symptoms and prostate volume of 80–150 mL underwent aquablation in a prospective multicentre international clinical trial. Baseline demographics and standardized postoperative management variables were carefully recorded in a central independently monitored database. Surgeons answered analogue scale questionnaires on intra‐operative technical factors and postoperative management. Adverse events up to 1 month were adjudicated by an independent clinical events committee. Results The mean (range) prostate volume was 107 (80–150) mL. The mean (range) operating time was 37 (15–97) min and aquablation resection time was 8 (3–15) min. Adequate adenoma resection was achieved with a single pass in 34 patients and with additional passes in 67 patients (mean 1.8 treatment passes), all in a single operating session. Haemostasis was achieved using either a Foley balloon catheter placed in the bladder under traction ( n = 98, mean duration 18 h) or direct tamponade using a balloon inflated in the prostate fossa ( n = 3, mean duration 15 h). No patient required electrocautery for haemostasis at the time of the primary procedure. The mean length of stay after the procedure was 1.6 days (range same day to 6 days). The Clavien–Dindo grade ≥2 event rate observed at 1 month was 29.7%. Bleeding complications were recorded in 10 patients (9.9%) during the index procedure hospitalization prior to discharge, and included six (5.9%) peri‐operative transfusions. Conclusions Aquablation is feasible and safe in treating men with men with large prostates (80–150 mL). The 6‐month efficacy data are being accrued and will be presented in future publications (ClinicalTrials.gov number, NCT 03123250).

Purpose Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but existing risk prediction models do not provide accurate individualized estimates of risk in this subset of high-risk women. Here, we used the Mayo benign breast disease cohort to develop and validate a model of BC risk prediction that is specifically for women with AH, which we have designated as AH-BC. Patients and Methods Retrospective cohorts of women age 18 to 85 years with pathologically confirmed benign AH from Rochester, MN, and Nashville, TN, were used for model development and external validation, respectively. Clinical risk factors and histologic features of the tissue biopsy were selected using L1-penalized Cox proportional hazards regression. Identified features were included in a Fine and Gray regression model to estimate BC risk, with death as a competing risk. Model discrimination and calibration were assessed in the model-building set and an external validation set. Results The model-building set consisted of 699 women with AH, 142 of whom developed BC (median follow-up, 8.1 years), and the external validation set consisted of 461 women with 114 later BC events (median follow-up, 11.4 years). The final AH-BC model included three covariates: age at biopsy, age at biopsy squared, and number of foci of AH. At 10 years, the AH-BC model demonstrated good discrimination (0.63 [95% CI, 0.57 to 0.70]) and calibration (0.87 [95% CI, 0.66 to 1.24]). In the external validation set, the model showed acceptable discrimination (0.59 [95% CI, 0.51 to 0.67]) and calibration (0.91 [95% CI, 0.65 to 1.42]). Conclusion We have created a new model with which to refine BC risk prediction for women with AH. The AH-BC model demonstrates good discrimination and calibration, and it validates in an external data set.

A lung ultrasound surface wave elastography (LUSWE) technique is developed for assessing interstitial lung disease (ILD). In LUSWE, a 0.1 second harmonic vibration is generated on the chest wall of a subject using a handheld vibrator. An ultrasound probe is aligned with the vibration indenter in the same intercostal region to measure the generated surface wave speed of the lung. A human subject is examined in a sitting position. The lung is tested at the total lung volume. The upper anterior lungs are tested through the second intercostal space in the mid-clavicular line. The lower lateral lungs are tested in the mid-axillary line and the lower posterior lungs are tested in the mid-scapular line. In a prospective clinical study, we measure both lungs through the six intercostal regions for patients and healthy controls. The surface wave speed is measured at 100 Hz, 150 Hz, and 200 Hz. Significant differences of wave speed between patients and controls were found in all lung regions at all frequencies. We also found positive correlation between LUSWE and CT analyses. LUSWE is a safe and noninvasive technique for generating and measuring surface wave propagation on the lung. LUSWE may be useful for assessing ILD.