Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Cyclophosphamide-bortezomib-dexamethasone compared with bortezomib-dexamethasone in transplantation-eligible patients with newly diagnosed multiple myeloma.

Introduction: Cyclophosphamide-bortezomib-dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib-dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods: In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results: Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony-stimulating factor (gcsf). Plerixafor was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions: Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide-gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship.

Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients.

Therapy for multiple myeloma (MM) has markedly changed in the past decade with the introduction of new drugs, but it is not clear whether the improvements have been sustained. We studied 1038 patients diagnosed between 2001 and 2010, grouping patients into two 5-year periods by diagnosis, 2001-2005 and 2006-2010. The median estimated follow-up for the cohort was 5.9 years with 47% alive at the last follow-up. The median overall survival (OS) for the entire cohort was 5.2 years: 4.6 years for patients in the 2001-2005 group compared with 6.1 years for the 2006-2010 cohort (P=0.002). The improvement was primarily seen among patients over 65 years, the 6-year OS improving from 31 to 56%, P<0.001. Only 10% of patients died during the first year in the latter group, compared with 16% in the earlier cohort (P<0.01), suggesting improvement in early mortality. The improved outcomes were linked closely to the use of one or more new agents in initial therapy. The current results confirm continued survival improvement in MM and highlight the impact of initial therapy with novel agents. Most importantly, we demonstrate that the improved survival is benefitting older patients and that early mortality in this disease has reduced considerably.

Long-term outcome of patients with multiple [corrected] myeloma-related advanced renal failure following auto-SCT.

Renal failure commonly complicates multiple myeloma (MM) and is associated with reduced survival. It is not clear whether auto-SCT results in improved renal function or attainment of independence from dialysis in patients with advanced renal impairment due to MM. We conducted a retrospective cohort study of all patients who underwent auto-SCT for MM complicated by advanced renal failure at our institution over a 10-year period (2000-2010). We aimed to assess the association between auto-SCT and renal outcome in patients with serum creatinine (SCr) over 3 mg/dL, attributable to MM, including those who were dialysis dependent. Thirty patients (2.8% of all auto-SCT patients) met inclusion criteria. Fourteen of 15 patients who were dialysis dependent before auto-SCT remained dialysis dependent in the long term despite hematological response (HR). Of the remaining 15 patients with SCr >3 mg/dL, an improvement in glomerular filtration rate (GFR) from 15 to 19.4 mL/min/1.73 m(2) was noted post auto-SCT (P=0.035); however, neither HR post auto-SCT or pre-existing renal function were independently associated with renal outcome. Auto-SCT was not associated with independence from dialysis in patients with renal failure due to MM at our institution. Although auto-SCT was associated with an improvement in GFR in patients with SCr >3 mg/dL, this improvement was not related to HR.

Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma (MM). Although the initial response rates and toxicity are well known, long-term outcome is not well described. We studied 286 consecutive patients with newly diagnosed MM initially treated with Len-Dex. The median (range) age at diagnosis was 63 (28-92) years, 166 (58%) patients ≤ 65 years and 175 (61%) male. The median estimated duration on Len-Dex was 5.3 months with overall response (≥ partial response) of 72%, including 26% with very good partial response or better. The median overall survival (OS) from the diagnosis was not reached (NR) and the estimated 5-year survival was 71%. The median time to first disease progression, irrespective of transplant status, was 30.2 months. Overall, 143 (50%) patients underwent stem cell transplant. The median OS was NR for patients ≤ 70 years and 5.8 years for the older patients (P=0.01). The 5-year OS estimate for patients in International Staging System stage 1, 2 and 3 were 82, 65, and 44% respectively. There were 21 new second malignancies after MM diagnosis (6.6%). The median survival exceeding 7 years reflects the efficacy of novel agents. The risk of second malignancies doesn't appear to be excessive in this population.

Compact measurement of low-PMD optical telecommunication fibers.

Accurate polarization mode dispersion (PMD) measurements on modern telecommunication fiber involve significant fiber layout and handling problems. These problems severely limit the quality and quantity of data that can be taken. A new method is proposed for measuring PMD using a large diameter collapsible spool with localized external perturbation (LEP). This method allows the necessary repeated measurements, and virtually eliminates environmental effects, which complicate measurements of low-PMD modern fibers. It is shown that the method produces nearly identical PMD results to a more laborious, conventional method.

Exposure to extremely low frequency magnetic fields among working women and homemakers.

Given concerns with potential health effects of exposure to magnetic fields, the goal of this study was to examine the magnitude and sources of occupational and residential exposure to extremely low frequency (primarily 60 Hz) magnetic fields among women. Exposure to 60 Hz magnetic fields was surveyed among cases and controls recruited for a study of breast cancer in 25 counties in North Carolina. The 273 women who participated wore an integrating personal magnetic-field exposure meter (AMEX 3-D) that measured their time-weighted average (TWA) exposure. A questionnaire was administered to determine the duration and frequency of electric appliance and machinery use. The geometric mean (GM) of the TWA exposure for employed women was 0.138 microT (range 0.022-3.636 microT) and for homemakers 0.113 microT (range 0.022-0.403 microT). Women working in manufacturing and industrial facilities had the highest exposure (GM 0.265 microT, range 0.054-3.436 microT), while nurses and health technicians (GM 0.134 microT, range 0.032-0.285 microT) and teachers and school administrators (GM 0.099 microT, range 0.035-0.673 microT) had the lowest exposures. Job titles, unless very limited in scope and/or environment, self-reported information about equipment use, potential exposure sources, time, and distance were not good predictors of magnetic-field exposure. Furthermore, the results show that occupations previously observed to have increased risk of breast cancer, such as teachers, nurses, administrative support, and housewives, did not have elevated average magnetic field exposures. Therefore, it is questionable whether exposure to power frequency magnetic fields is the cause of the increased breast cancer risk seen in these occupations.

Application of reversed-phase liquid chromatography and prepacked C18 cartridges for the analysis of oxytetracycline and related compounds.

The reversed-phase (RP) chromatographic separation of oxytetracycline (OTC) 4-epioxytetracycline (4-epiOTC), alpha-apooxytetracycline (alpha-apoOTC), and beta-apooxytetracycline (beta-apoOTC) has been accomplished on an Inertsil C8 column at ambient temperature. Using the simplex method of solvent optimization, a 0.1 M ammonium acetate buffer (pH 3.0)-acetonitrile-tetrahydrofuran (72.5:12.5:15, v/v/v) mobile phase was found to give excellent separation of the compounds. OTC, 4-epiOTC, alpha-apoOTC and beta-apoOTC were resolved in 35 min with calculated detection limits of 40, 20, 50 and 140 ng/ml, respectively. Solid-phase extraction (using RP C18 cartridges) of OTC and OTC degradation compounds from distilled water and porcine muscle was tested at four concentration levels ranging from 200 to 2000 ng/ml (g); overall mean recovery of OTC from distilled water and porcine tissue was greater than 90% and 70%, respectively.

Identification of psychrotrophic Micrococcaceae spp. isolated from fresh beef stored under carbon dioxide or vacuum.

Seventy-four Gram-positive, catalase-positive coccal strains were isolated from fresh beef stored under carbon dioxide (< 500 ppm O2) or vacuum for up to 15 weeks at 0, 2 or 4 degrees C. Isolates were identified using biochemical tests listed in several published protocols and the API Staph-Ident System. No isolates were identified as Staphylococcus aureus. Twenty-nine isolates were identified as Staphylococcus saprophyticus (five distinct groups), 24 isolates were identified as Staphylococcus gallinarum and 21 isolates were identified as Micrococcus varians. The staphylococcal isolates were coagulase-negative, non-hemolytic and novobiocin resistant. They produced acid from several carbohydrates under aerobic conditions, hydrolysed gelatin but not collagen, showed lipolytic activity and grew in 15% NaCl. The Micrococcus varians isolates also were salt-tolerant, produced acid only from glucose, fructose and galactose (two strains), and were resistant to lysozyme (1600 micrograms/ml). Lactic acid was the major end product of aerobic glucose metabolism. All S. saprophyticus and M. varians isolates tested contained cell wall fatty acids with chain length > or = C20:0.

Effect of lighting treatment on the productivity, health, behavior and sexual maturity of heavy male turkeys.

1. Turkey poults (1620) were used to compare the effects of three lighting programmes on heavy strain males reared to 188 d: constant light (24L:0D, CON); increasing light (6L:18D at 7 d gradually increasing to 20L:4D by 63 d, INC); a pattern identical to INC followed by a decrease in daylength from 84 d to 10L:14D at 112 d (DID). 2. Lighting affected growth pattern but had no effect on body weight at 118 d or overall food to gain ratio. 3. Both INC and DID lighting reduced overall mortality in comparison to CON light primarily because of a reduction in the incidence of skeletal disease and spontaneous cardiomyopathy. INC and DID lighting increased the incidence of cannibalism. 4. Turkeys given INC or DID lighting had a superior ability to walk in comparison to those birds given CON light. 5. INC and DID males stood, ate and drank more frequently, and sat less often than CON turkeys during behavioural observation. 6. There were no lighting effects on carcase composition except that INC and DID birds had heavier keel bones. The ultimate force per cm2 (stress) required to break femora was greater for turkeys given INC and DID lighting (P = 0.065). 7. Plasma testosterone concentrations at 117 d were 272.5, 115.2 and 29.5 pg/ml for turkeys given CON, INC and DID lighting, respectively (P = 0.072). Testosterone concentration was not related to growth rate.

The influence of pre-slaughter oral loading of acid or base on post-mortem changes in Longissimus Dorsi muscle of pork.

Twenty-four pigs were assigned to one of four ad libitum water treatments: control, sodium bicarbonate (12·6 g/litre), low ammonium chloride (4 g/litre) or high ammonium chloride (8 g/litre) for 5 days, to study the influence of an oral acid or base load on post-mortem changes in longissimus dorsi muscle and ultimate pork quality. Physiological changes before slaughter were monitored by measuring blood pH, pCO(2) and HCO(3)(-). The influence of dietary treatments on post-mortem changes and ultimate meat quality was determined by measuring glycolytic enzymes and intermediates, and muscle pH, color and water-holding capacity (WHC). As expected, sodium bicarbonate generated a metabolic alkalosis, whereas ammonium chloride resulted in a metabolic acidosis. Pre-slaughter acid-base status was positively correlated with muscle WHC (P < 0·05). However, no significant dietary treatment effect was observed in muscle quality traits such as color (a, b, L) and WHC. Muscle pH(45) was significantly (P < 0·05) higher in bicarbonate than control and high ammonium chloride treatments. The activity of Ca(2+)-dependent protein kinase was significantly (P < 0·05) higher at 45 min post-mortem but that of pyruvate kinase was significantly lower at 2 and 4 h post mortem in bicarbonate-treated pigs. At 45 min post mortem, the activity of fructose-1,6-diphosphatase in the control pigs was significantly higher (P < 0·05) than on other treatments. The concentration of glycogen was significantly (P < 0·05) higher in bicarbonate and high ammonium chloride pigs; bicarbonate-treated pigs also has significantly higher adenosine-5'-triphosphate (ATP) and pH values than other treatment groups (P < 0·05) at early post-mortem. It was concluded that pre-slaughter oral loading of acid or base could induce changes in muscle metabolism and post-mortem muscle pH. Further research is required to confirm that altering diet acidogenicity or alkalinogenicity may be a means of enhancing ultimate pork quality.

Detachment ofPseudomonas fluorescens from biofilms on glass surfaces in response to nutrient stress.

The effects of glucose and nitrogen depletion on the colonization of glass Petri plates byPseudomonas fluorescens were studied in batch culture. Colonization of the surfaces was initiated before colonization of the bulk phase, and biofilm formation was observed. This resulted in an apparent lag in the batch growth curve for the cell suspension. The lag phase was an artifact caused by the partitioning of cells between the bulk and solid phase of the culture and was not due to a reduction in the growth rate of unattached cells. The specific growth rate of the unattached cells (0.331 hour(-1)) was almost twice that determined for the total population (0.171 hour(-1)). Consequently the growth rate of biofilm-forming bacteria cannot be determined in batch culture unless the growth of both attached and unattached cells is monitored, and batch growth curves may contain artifacts due to the formation and dispersion of biofilms. The depletion of either glucose or nitrogen led to the active detachment of cells from the biofilm. An increase in the hydrophobicity of unattached cells was noted on depletion of carbon. This increase was the result of emigration of cells from the surface into the bulk phase.

Metabolic labeling of human thyroglobulin with [35S]sulfate: incorporation into chondroitin 6-sulfate and endoglycosidase-F-susceptible carbohydrate units.

To study the incorporation of sulfate into thyroglobulin, human thyroid tissue was incubated with [35S]sulfate. Labeled thyroglobulin was purified by ammonium sulfate precipitation, gel exclusion chromatography, and equilibrium density gradient centrifugation, the last of these specifically to remove proteoglycans. [35S]Sulfate was found in thyroglobulin with low density, indicating that sulfate was incorporated into newly synthesized molecules before their iodination. Chondroitin ABC lyase and chondroitin AC lyase released equal amounts of [35S]sulfate, demonstrating the presence of chondroitin units, and TLC showed this to be predominantly chondroitin 6-sulfate. Additional [35S]sulfate was released by endoglycosidase-F (Endo-F), but not by Endo-H. The Endo-F-sensitive sulfate-labeled complex carbohydrate units were heterogeneous, one fraction passing through a Concanavalin-A-Sepharose column without delay and another fraction showing weak affinity for the lectin. More than 90% of the incorporated [35S]sulfate was accounted for by the chondroitin ABC lyase and Endo-F-sensitive fractions. Thus, human thyroglobulin contains sulfate in at least three types of carbohydrate units, 1) chondroitin 6-sulfate units, 2) complex units with no affinity for Concanavalin-A (tri- or tetraantennary forms), and 3) complex units with weak affinity for Concanavalin-A (biantennary forms).

Evaluation of Four Media for Recovery of Heat-Stressed Streptococci.

Two strains of Streptococcus faecium and one strain of Streptococcus faecalis were subjected to heat stress in a ham broth and recovered on all purpose tween agar; deMan, Rogosa, Sharpe agar; tryptone-dextrose-yeast extract-meat extract-peptone agar; and tryptic soy agar. Survival curves for the organisms recovered on each agar were constructed and D values (death rates) were calculated. Differences in death rates were noted for each organism between different media. The greatest recovery of cells that had received sub-lethal heat treatment occurred using all purpose tween agar.

Altered DNA topoisomerase II activity in Chinese hamster cells resistant to topoisomerase II inhibitors.

Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks. We have characterized previously a line of Chinese hamster cells (DC3F/9-OHE cells) the resistance of which to the cytotoxic effect of intercalators and etoposide is associated with a reduced formation of protein-associated DNA strand breaks. In the present study, topoisomerases of these cells were compared to those of the parental sensitive cells (DC3F). NaCl extracts (0.35 M) of isolated DC3F/9-OHE nuclei did not form 4'-(9-acridinylamino)methanesulfon-m-anisidide-induced DNA-protein linking, whereas DC3F nuclear extracts did. In addition, DC3F/9-OHE nuclear extract had an unusually high level of DNA linking activity in the absence of 4'-(9-acridinylamino)methanesulfon-m-anisidide. Topoisomerases II from DC3F/9-OHE and DC3F nuclei appeared similar qualitatively. DC3F/9-OHE nuclear extract had approximately twice less topoisomerase II molecules than did DC3F nuclear extract but similar topoisomerase II activity. Topoisomerase I activities appeared also similar in sensitive and resistant cells. However, part of DC3F/9-OHE topoisomerase I copurified with a DNA linking activity which was not present in DC3F nuclei. This unusual DNA linking activity was not sensitive to the stimulatory effect of 4'-(9-acridinylamino)methanesulfon-m-anisidide.

Microbiological Stability of Pasteurized Ham Subjected to a Secondary Treatment in Retort Pouches.

A ham processing procedure consisting of pasteurizing, packaging in retort pouches, and subjecting the hams to a secondary heat treatment was evaluated as a method of increasing microbial stability. Pasteurized hams reheated at 121°C for 10 min and stored at 1±1°C or 6±1°C showed no microbial growth after 6 or 12 months of storage. The number of microorganisms in pasteurized hams not receiving the secondary heat treatment ranged from 103/g to >108/g and from 102 to >108/cm2 on the surface after 3 to 5 months of storage. Pasteurized hams that had been inoculated with Clostridium sporogenes spores before pasteurization followed by a secondary heat treatment at 121°C for 10 min showed a delay in the occurrence of swollen packages when stored at room temperature compared to hams not receiving the secondary heat treatment. However, the secondary heat treatment did not prevent spoilage of hams. Ham that has not been treated to eliminate spores should be refrigerated.

Pelvis-shoulder dysplasia.

Pelvis-shoulder dysplasia is rare skeletal dysplasia characterised by symmetrical hypoplasia of the iliac wings and scapulae. It may be associated with unstable hips in infancy, a prominent lumbar lordosis and a waddling gait. Symptoms tend to lessen with increasing age. A child with this condition who has been followed up to the age of five years is described. Her pelvic dysplasia is milder than in previous cases and has caused no disability. Minor skeletal abnormalities are also present in the lumbar spine, femora and rib cage. Radiography of other members of the family was normal.