Citations

ABSTRACTIntroduction: Neuromuscular ultrasound (NMUS), an emerging diagnostic subspecialty field, has become an important extension of the electrodiagnostic examination. However, there are no formal guidelines on how to appropriately report NMUS results. Methods: The AANEM convened an expert panel to develop recommendations for reporting NMUS findings. Results: Providers should describe the reason for referral, the nerves or muscles studied, and normal values as well as numerical values for the results of imaging. Muscle imaging reports should also include a description of how gray‐scale values were calculated. NMUS‐guided needle placement reports should include a description of the length and gauge of needle, the type of probe used, and an indication of how well the patient tolerated the procedure. All reports should clearly state whether the findings were normal or abnormal and include a definitive diagnosis. Conclusions: NMUS reports should provide comprehensive information along with a succinct conclusion, mirroring guidelines for electrodiagnostic reports. Muscle Nerve, 2013

Abstract Some studies show that childbearing at older age is associated with lower risk of endometrial cancer, but whether the association is independent of number of children or other factors still requires clarification. We pooled individual-level data from epidemiologic studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Data on age at last birth and/or last pregnancy were available from 14 studies: 11 case-control studies and 3 cohort studies; the latter were analyzed using a nested case-control design. A total of 9,613 endometrial cancer cases and 17,112 controls were included in the analysis. The majority of women were White (82%) and older than 55 years (69%). We estimated the effects of age at last birth using data from 12 studies and age at last pregnancy using data from 10 studies on the risk of endometrial cancer by calculating odds ratios (OR) and 95% confidence intervals (95% CI) using logistic regression models. Potential confounders included in the analysis were race, body mass index, parity, age at menarche, age at first birth, oral contraceptive use, postmenopausal hormone use, smoking status, and report of diabetes. After adjusting for potential confounders, a reduction in endometrial cancer risk was observed in women with increasing age at last birth (P trend <0.0001) and age at last pregnancy (P trend <0.0001). The OR per five-year increase in age at last birth and age at last pregnancy was 0.90 (95%CI: 0.86, 0.94) and 0.91 (95% CI: 0.87, 0.95), respectively. Women who had their last child at an age >40 years were at a 34% decreased risk compared with women who had their last child at an age <25 years (95% CI: 0.52, 0.82). Compared to women with age at last pregnancy <25 years, those with age at last pregnancy >40 years had a 30% decreased risk of endometrial cancer (95%CI: 0.57, 0.86). Inverse associations were observed for Whites and Asians in race-specific analysis and also in analysis restricted to women with at least 2 births. In this large pooled analysis, we show that late age at last birth or last pregnancy is a strong and independent protective factor for endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1900. doi:10.1158/1538-7445.AM2011-1900

Abstract We performed a multi-stage genome-wide association study (GWAS) for drug response in ovarian cancer. We selected 313 chemotherapy treated patients from the Australian Ovarian Cancer Study (AOCS). Patients were treated with paclitaxel/carboplatin and the trait of interest was Progression Free Survival (PFS). We maximized power for a fixed genotyping budget by genotyping individuals from the tails of the distribution: 94 with good survival and 94 with poor survival, taking into account extent of residual disease following surgery. Patients were genotyped on Illumina HumanOmni1-Quad arrays (1140419 loci).Two further cohorts with measures of PFS and whole genome data available; 134 ovarian patients from the Mayo clinic (genotyped on Illumina HumanHap 610 arrays, 620901 loci) and 68 patients from The Cancer Genome Atlas ovarian cancer set (genotyped on Illumina Human1M arrays, 1199187 loci) were meta-analyzed with the AOCS set (stage 1). We have imputed all the stage 1 samples with reference of the 1000 Genome data to allow more direct comparison of SNPs not common to all of the arrays used (up to 6 million SNPs with good imputation quality). Based on the chemotherapy treatment received by each patient, we assigned the patients into primary and secondary analysis, with primary analysis using a more strictly defined treatment subgroup. We followed up the stage 1 findings by genotyping 26 SNPs in more than 3,000 samples collected from 8 study sites of Ovarian Cancer Association Consortium (OCAC). These 26 SNPs were mainly genotyped SNPs, chosen from 23 distinct regions showing the strongest association with chemotherapy response from either primary or secondary analysis. 2 SNPs showed nominal significance in the replication sample (chr 12: rs1861932, chr 22: rs708444). We are currently genotyping more regions to seek replication of the initial findings. In summary, we sought to identify genes that underlie individual differences in chemoresistance. In the future, typing variations in these genes will be important for personalizing drug regimes for patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4679. doi:10.1158/1538-7445.AM2011-4679

Studies were performed in dogs to determine if inhibition of neuronal reuptake of norepinephrine was the cause of the enhanced response to sympathetic nerve impulses seen in the cutaneous veins when the temperature of the blood perfusing them was decreased. Changes in driving pressure of the saphenous vein perfused with blood at constant flow were used to measure venomotor responses. The increases in venoconstrictor response to norepinephrine infusion caused by cooling the perfusate were similar in both hindlegs, one subjected to acute and the other to chronic sympathectomy. Blocking the reentry of norepinephrine into the sympathetic nerve endings by treating the vein with cocaine did not affect the augmentation by local cooling of the constrictor response to norepinephrine or electric stimulation of the lumbar sympathetic chain. The venoconstrictor responses to norepinephrine, epinephrine, 5-hydroxytryptamine, and molar potassium chloride were all augmented by local cooling. The results suggest that the sensitizing effect of cold on the smooth muscle of the veins cannot be explained by inhibition of norepinephrine re-uptake by the nerve terminals.

The cutaneous veins of the dog constrict and dilate with local cooling and warming, respectively. This response, which is dependent on the integrity of the adrenergic nerves, might be explained by an altered response of the smooth muscle to a given frequency of sympathetic nerve impulses or by local temperature receptors that initiate alterations in sympathetic nerve activity. In the lateral saphenous vein perfused at 42°, 27°, and 17°C, the constriction caused by stimulation of lumbar sympathetic nerves was 40%, 160%, and 200%, respectively, of that at 37°C; the constriction caused by norepinephrine at the same temperatures was 70%, 187%, and 318% of that at 37°C. Division of the dorsal spinal roots from L-1 to S-1 made no difference to the veno-constrictor response to local cooling. It is concluded that an alteration in the sensitivity of the smooth muscle to arriving sympathetic nerve impulses accounts for the venous responses to local temperature changes seen in the intact dog.

To study the separate actions of peripheral and central temperature-sensitive systems on the cutaneous veins of the dog, a cross-circulation preparation was made in which hindleg and central temperatures could be varied independently. The lateral saphenous vein of a vascularly isolated hindleg was cross-perfused at constant flow; the difference between perfusion and femoral vein pressures was a measure of venomotor activity. With central temperature constant, local cooling of one leg from 47° to 17°C caused the lateral saphenous vein to constrict; sensitivity to cooling was maximal between 42° and 27°C. With leg temperature constant, central cooling caused the lateral saphenous vein to constrict; over the range of 40° to 33°C, the constriction was linearly related to the decrease in temperature. Central heating reduced the response to local cooling, whereas central cooling had the opposite effect. Thus a decrease in central temperature from 38° to 34°C increased the venoconstrictor response to local cooling from 42° to 22°C by a factor of ten or more.

The lateral saphenous vein of the dog was perfused with homologous blood at constant, flow. Changes in perfusion pressure were used to measure active changes in venous tone. Cooling of the perfusate caused the vein to constrict and warming to relax. Most of the change occurred over the temperature range of 27° to 42°C. The powerful venoconstrictor response to cooling depended on intact sympathetic nerves, since it was reduced by lumbar sympathectomy and largely abolished by alpha-receptor or ganglionic blockade. The response was confined to the vein being cooled. By comparison, cooling the body core when the temperature of the blood in the vein was 37°C caused a generalized constriction of the superficial limb veins. These responses were impaired by anesthetic agents (for example, pentobarbital), by generalized hypoxia, and by arterial hypotension. The data indicate a role for the cutaneous veins in temperature regulation. In the cold, the venous return is directed preferentially to the venae comitantes for heat preservation through countercurrent exchange with the arteries, and in warmth to the superficial veins for heat dissipation.

Abstract Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms) ≥ very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).