Citations

ABSTRACTIntroductionPneumothorax is a potentially serious complication of electromyography (EMG). Data on the frequency of pneumothorax after EMG are lacking. The purpose of this study was to determine the frequency, timing, and risk factors for iatrogenic pneumothorax after EMG. Methods: Cases of pneumothorax after EMG were reviewed for clinical, electrophysiological, and radiological data. Results: Of 64,490 EMG studies, 7 patients had an association between the EMG and pneumothorax. All patients were symptomatic and presented within 24 hours of EMG. Sampling of serratus anterior and diaphragm was causative in 1 patient each. In 5 patients, multiple high‐risk muscles were sampled. The highest frequency of pneumothorax was observed with examination of serratus anterior (0.445%) and diaphragm (0.149%). Conclusions: The frequency of symptomatic iatrogenic pneumothorax after EMG appears to be low, and examinations of serratus anterior and diaphragm carry the highest risk. Electromyographers should be aware of the risk of pneumothorax and should counsel patients accordingly. Muscle Nerve 53: 518–521, 2016

BACKGROUND: Poliomyelitis is a viral infectious disease caused by 1 of the 3 strains of poliovirus. The World Health Organization launched an eradication campaign in 1988. Although the number of cases of poliomyelitis has drastically declined, eradication has not yet been achieved, and there are a substantial number of survivors of the disease. Survivors of poliomyelitis present a unique set of challenges to the anesthesiologist. The scientific literature regarding the anesthetic management of survivors of poliomyelitis, however, is limited and primarily experiential in nature. Using a retrospective, matched cohort study, we sought to more precisely characterize the anesthetic implications of poliomyelitis and to determine what risks, if any, may be present for patients with a history of the disease. METHODS: Using the Mayo Clinic Life Sciences System Data Discovery and Query Builder, study subjects were identified as those with a history of paralytic poliomyelitis who had undergone major surgery at Mayo Clinic Rochester between 2005 and 2009. For each case, 2 sex- and age-matched controls that underwent the same surgical procedure during the study period were randomly selected from a pool of possible controls. Medical records were manually interrogated with respect to demographic variables, comorbid conditions, operative and anesthetic course, and postoperative course. RESULTS: We analyzed 100 cases with 2:1 matched controls and found that the peri- and postoperative courses were very similar for both groups of patients. Pain scores, postanesthesia care unit admission, length of postanesthesia care unit stay, intensive care unit admission, length of intensive care unit stay, and initial extubation location were not significantly different between the 2 groups. Looking at pulmonary complications in our primary outcome, there was no significant difference between the 2 groups (17% vs 14% for polio versus control, respectively; conditional logistic regression odds ratio = 1.5; 95% confidence interval, 0.7–3.3; P = 0.33). In addition, no difference was noted in those requiring a code or rapid response team intervention (4% vs 3% for polio versus control; P = 0.46) and the 30-day mortality rate was also not significantly different, with 2% of polio patients dying compared with 3% of controls ( P = 0.79). The analysis of the primary outcome was repeated for the subset of patients with a history of poliomyelitis who had persistent neurologic deficits preoperatively ( n = 36) and their matched controls ( n = 72). In this subset analysis, there were 4 (11%) polio patients and 8 (11%) control patients who experienced pulmonary complications (conditional logistic regression odds ratio = 1.00; 95% confidence interval, 0.27–3.72; P = 1.00). The percentage of patients experiencing specific pulmonary complications of interest was similar between groups (postoperative mechanical ventilation: 6% vs 8% for polio and control patients, respectively; prolonged mechanical ventilation: 0% vs 1%; reintubation: 8% vs 4%; pulmonary infection: 6% vs 6%; and aspiration: 0% vs 1%). CONCLUSIONS: This study suggests that patients with a history of poliomyelitis do not seem to have an increased risk of pulmonary complications in the perioperative period. However, an odds ratio as great as 3.3-fold may be present.

Abstract Background: Traditional adjuvant therapy for oropharyngeal squamous cell carcinoma (OPSCC) consists of 60-66 Gy of radiation therapy (XRT) given in 2 Gy daily fractions along with high dose cisplatin if the patient has high risk factors. Despite the excellent cure rates for HPV+ OPSCC, one in three patients treated with conventional treatment will develop grade >3 long-term sequelae from therapy. There is intense interest in de-intensifying adjuvant therapy for this patient population in order to maximize quality of life while maintaining excellent historical rates of disease control. Methods: MC1273 is a phase II non-randomized trial open at Mayo Clinic Rochester testing a novel course of aggressive therapy de-escalation following surgery for HPV+ OPSCC. The primary endpoint is local/regional control at 2 years while secondary endpoints include toxicity and quality of life (QOL). The eligibility criteria include all patients with p16-positive OPSCC with less than a ten pack-year smoking history who have had a complete surgical resection. Exclusion criteria include positive surgical margins, prior history of malignancy, and history of connective tissue disorders. Patients are divided into two prospective cohorts depending upon risk factors found at surgery. Patients with intermediate risk disease (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) are enrolled in MC1273A while patients with extracapsular extension (ECE) are enrolled in MC1273B. Patients on MC1273A receive 30 Gy of radiation delivered in 1.5 Gy twice-daily fractions over the course of two weeks along with weekly docetaxel (15 mg/m2) given on day 1 and day 8. Patients on MC1273B receive a similar treatment regimen but also have the nodal level with positive ECE concurrently boosted to 36 Gy in 1.8 Gy twice-daily fractions. In addition to standard of care follow-up, patients receive a swallowing assessment with speech therapy immediately before XRT, one month post-XRT, and one year post-XRT. Patients also have QOL assessment consisting of the XeQOLS, Eq-5D, FACT H&N (Vers 4) and Dermatology Life Quality Index assessed at pre-XRT and 3, 12, and 24 months post-XRT. Results: Each cohort of MC1273 is powered to detect a 10% local/regional failure rate with 85% confidence. Each cohort will accrue 35 evaluable patients and 5 additional patients to account for ineligibilities and violations (40 patients total per cohort.) MC1273A began accrual in September 2013. The first five patients were monitored for grade ≥4 acute toxicities before proceeding to open accrual. MC1273B began accrual in May 2014 and has also proceeded to open accrual. Accrual will also begin in Mayo Clinic Scottsdale in the first quarter of 2015. Conclusions: MC1273 is meeting its accrual targets and should finish accrual by 2016. We anticipate that preliminary results for toxicity will be available by 2017 and local/regional data will be available by 2018. Citation Format: Daniel J. Ma, Katharine A. Price, Eric J. Moore, Joaquin J. Garcia, Scott H. Okuno, Daniel L. Price, Jeff A. Sloan, Nathan R. Foster, Robert L. Foote. MC1273: Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiation in HPV associated oropharynx cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT227. doi:10.1158/1538-7445.AM2015-CT227

Abstract Background: Protein kinase Cβ (PKCβ) is critical for B-cell signaling and survival and overexpression of PKCβ in DLBCL is associated with inferior survival. ENZA, an oral serine/threonine kinase inhibitor, targets PKCβ. Here we report immunohistochemical (IHC) and fluorescence in-situ hybridization (FISH) correlative analyses. Methods: PRELUDE (NCT00332202) was a phase III, double-blind maintenance study of 758 pts with DLBCL who were randomized 2:1 to ENZA 500 mg daily (1125-mg loading dose) (n = 504) or PBO (n = 254), respectively, following CR to induction therapy with R-CHOP. The primary endpoint was disease-free survival (DFS). Overall survival (OS) and assessment of biomarkers specific to ENZA and DLBCL were secondary endpoints. Pre-treatment formalin-fixed, paraffin-embedded samples were assessed via IHC staining in a blinded manner (Eric Hsi) for cell of origin (COO) using Hans’ algorithm. In addition, IHC was performed for c-MYC, BCL2, BCL6, FOXP1, and MUM1 (10% increments/% tumor cells stained), markers relevant to ENZA, including PKCβ2. FISH was performed to identify translocations involving c-MYC, BCL2, and BCL6. Cox regression was used to determine statistical associations between efficacy outcomes and dichotomized markers, adjusting for treatment and additional baseline covariates. All tests of association were conducted at a 2-sided α = 0.05. Results: There was no difference in 4-year DFS (70% vs 71%) or OS (81% vs 82%) between ENZA and PBO arms, respectively. A total of 243 (32%) pts had ≥1 evaluable sample available for IHC and FISH. There was no difference in outcome for pts based on COO (GCB vs non-GCB). Independent of treatment, significant associations were observed for BCL2 (pre-specified cutpoint 20%) and MUM1 (cutpoint 30%) with OS, and FOXP1 (cutpoint 80%) by IHC with DFS (HR [95% CI]: 2.19 [1.01-4.73]), p = 0.031; 1.97 [1.04-3.71], p = 0.032; 1.74 [1.04-2.90], p = 0.032, respectively). Associations were not significant for other IHC markers, including c-MYC and BCL6. Low PKCβ2 (<50% expression) had numerically better (but not significant) DFS/OS vs high PKCβ2. Dual translocation lymphoma by FISH was identified in two pts (1.2%) each for c-MYC/BCL2 and c-MYC/BCL6, and one pt (0.6%) had a triple hit involving c-MYC/BCL2/BCL6. Conclusions: No difference in outcomes between treatment arms was observed for the trial. Independent of treatment, COO was not prognostic of outcomes. Pts with low PKCβ2 expression had numerically better DFS/OS compared with high PKCβ2 expression. Significant treatment-independent associations were observed for BCL2 and MUM1 with OS and for FOXP1 with DFS (low IHC expression corresponded to better outcomes). The small number of double hit and triple hit lymphomas seen in the study may reflect the enrollment of CR patients with more favorable biology. Citation Format: Eric D. Hsi, Kerry J. Savage, Sonali M. Smith, Fritz Offner, Scott P. Myrand, Thomas M. Habermann, Donald E. Thornton, Boris K. Lin, Tuan S. Nguyen, Oday Hamid, Michael Crump. Correlative results from PRELUDE, a phase III study of enzastaurin (ENZA) vs placebo (PBO) in patients (pts) with high-risk diffuse large B-cell lymphoma (DLBCL) following a response to R-CHOP therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5303. doi:10.1158/1538-7445.AM2015-5303

Abstract Genome-wide association studies (GWAS) of multiple myeloma (MM) in Northern Europeans have identified seven novel risk loci (2p23.3, 3p22.1, 3q26.2, 6p21.33, 7p15.3, 17p11.2, 22q13.1). We performed a multiethnic meta-analysis of these regions in 1,274 MM patients and 1,486 controls of European ancestry (EA) and 1,049 MM patients and 7,080 controls of African ancestry (AA), leveraging the differential linkage-disequilibrium of these populations in order to better localize the putative functional variants. We observed directionally consistent effects for all seven index SNPs in both populations, with four significantly associated (p<0.05) with risk in EAs (3p22.1, 7p15.3, 17p11.2, 22q13.1), and two significantly associated with risk in AAs (7p15.3 and 22q13.1). In a fixed effects meta-analysis of six regions (excluding the HLA region on chromosome 6), variation in five of the regions (2p33.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) had statistically significant associations with risk (Table 1). In one region, the index variant had the strongest association [rs4487645 at 7p15.3, (OR = 1.30, p = 8.7×10−8)]. Five of the six most significantly associated variants identified in the multiethnic analyses overlapped with biologically relevant features indicating regulatory activity based on CD20+ (B lymphocyte) cells, showing evidence of potential function; those included a missense variant in (17p11.2, rs34562254, Pro251Leu) in TNFRSF13B, which encodes a lymphocyte-specific protein in the tumor necrosis factor receptor family that interacts with the NF-kb pathway. Our study shows that these regions are important in MM risk across ethnicities and further supports the use of multiple ethnic groups in genetic studies to enhance identification of risk variants. Table 1.Most significant associations for each region in the multiethnic meta-analysis.Individuals of European AncestryIndividuals of African AncestryMulitethnic Metar2 with IndexcCHRSNPRAaFreqbORP-valueFreqbORP-valueORP-valueP-het2rs732075G0.591.222.0×10−30.621.122.0×10−21.162.6×10−40.280.09/0.283rs73069394A0.191.243.0×10−30.621.181.5×10−21.201.3×10−50.550.77/0.963rs12637184G0.761.136.0×10−20.921.192.7×10−11.151.0×10−20.640.94/1.007rs4487645C0.671.237.0×10−40.891.485.5×10−51.308.7×10−80.07-d17rs34562254A0.121.452.4×10−50.131.212.2×10−31.312.5×10−60.120.33/0.9022rs139400T0.491.224.0×10−40.531.172.1×10−31.191.2×10−60.630.63/0.96aRisk allelebFrequency of the risk allele in European and African ancestry studiescr2 metrics based on 1000 Genomes Project AFR/EUR populationsdIndex SNP Citation Format: Kristin A. Rand, Chi Song, Eric Dean, Daniel Serie, Karen Curtin, Dennis Hazelett, Amie E. Hwang, Xin Sheng, Alex Stram, David J. Van Den Berg, Carol Ann Huff, Leon Bernal-Mizrachi, Michael H. Tomasson, Sikander Ailawadhi, Anneclaire De Roos, Seema Singhal, Karen Pawlish, Edward Peters, Catherine Bock, David V. Conti, Graham Colditz, Todd Zimmerman, Scott Huntsman, John Graff, African Ancestry Prostate Cancer GWAS Consortium,African Ancestry Breast Cancer GWAS Consortium, Stephen J. Chanock, Michael Lieber, Jayesh Mehta, Eric A. Klein, Nalini Janakiraman, Richard K. Severson, Angela R. Brooks-Wilson, Vincent Rajkumar, Elizabeth E. Brown, Laurence Kolonel, Susan Slager, Brian E. Henderson, Graham G. Giles, John J. Spinelli, Brian Chiu, Kenneth C. Anderson, Jeffrey Zonder, Robert Z. Orlowski, Sagar Lonial, Nicola Camp, Celine Vachon, Elad Ziv, Dan O. Stram, Christopher A. Haiman, Wendy Cozen. Multiple myeloma susceptibility loci examined in African and European ancestry populations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4629. doi:10.1158/1538-7445.AM2015-4629

Objective Cardiac changes of hypertensive pregnancy include left ventricular hypertrophy (LVH) and diastolic dysfunction. These are thought to regress postpartum. We hypothesised that women with a history of hypertensive pregnancy would have altered LV geometry and function when compared with women with only normotensive pregnancies. Methods In this cohort study, we analysed echocardiograms of 2637 women who participated in the Family Blood Pressure Program. We compared LV mass and function in women with hypertensive pregnancies with those with normotensive pregnancies. Results Women were evaluated at a mean age of 56 years: 427 (16%) had at least one hypertensive pregnancy; 2210 (84%) had normotensive pregnancies. Compared with women with normotensive pregnancies, women with hypertensive pregnancy had a greater risk of LVH (OR: 1.42; 95% CI 1.01 to 1.99, p=0.05), after adjusting for age, race, research network of the Family Blood Pressure Program, education, parity, BMI, hypertension and diabetes. When duration of hypertension was taken into account, this relationship was no longer significant (OR: 1.19; CI 0.08 to 1.78, p=0.38). Women with hypertensive pregnancies also had greater left atrial size and lower mitral E/A ratio after adjusting for demographic variables. The prevalence of systolic dysfunction was similar between the groups. Conclusions A history of hypertensive pregnancy is associated with LVH after adjusting for risk factors; this might be explained by longer duration of hypertension. This finding supports current guidelines recommending surveillance of women following a hypertensive pregnancy, and sets the stage for longitudinal echocardiographic studies to further elucidate progression of LV geometry and function after pregnancy. Clinical trial registrations GENOA- NCT00005269; HyperGEN- NCT00005267; Sapphire- NCT00005270; GenNet- NCT00005268.

We conducted a review of 144 consecutive patients who underwent proximal row carpectomy from 1967 to 2010 for the diagnosis of wrist arthritis. At a mean follow-up of 13.4 years, patients experienced good pain relief with preservation (but not improvement) of wrist motion. A total of 17 patients (12%) required revision surgery at an average of 44.6 months. Improved pain, function, and survival outcomes were seen in those who underwent proximal row carpectomy after the age of 40, had a preoperative diagnosis of Kienbock’s disease, who underwent a concomitant neurectomy procedure, patients who were non-labourers, and patients who underwent surgery after 1990. Although 45% of patients developed moderate to severe radiocapitate arthrosis postoperatively, these findings did not correlate with clinical outcomes or risk of revision surgery. Patients with type II lunate and type II and III capitate shapes had higher rates of postoperative radiocapitate arthrosis. Level of Evidence: III, Prognostic