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.

Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.

Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a bona fide target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology.

White matter-Maximien Parchappe and the integration of articulate language.

The Imperial Academy of Medicine of Paris met in the spring of 1865 to discuss the localization of speech. One of the participants was Maximien Parchappe (1800-1866), an alienist whose research interests lay in the cerebral cortex. This article addresses Maximien Parchappe's concept that the cognitive elements of language-such as the translation of thoughts into words, the will to express them, and the means to do so-reside within the cortical gray matter, and that they are integrated through white-matter fibers. In so doing, Parchappe anticipated Carl Wernicke's linking of the posterior aspects of the dominant frontal and temporal lobes in verbal expression, and Jules Dejerine's linking of the angular gyrus and Wernicke's area in the understanding of written language. Functional imaging has revived interest in language as a network of neuronal aggregates and has given new relevance to Parchappe's concept of the functional organization of language.

Updates from the 2019 American Society of Clinical Oncology and European Hematology Association annual meetings: a Canadian perspective on high-risk cytogenetics in multiple myeloma.

The 2019 annual meetings of the American Society of Clinical Oncology and the European Hematology Association took place, respectively, in Chicago, Illinois, 31 May-4 June, and in Amsterdam, Netherlands, 13-16 June. At the meetings, results from key studies on the treatment of patients with relapsed or refractory multiple myeloma with high-risk cytogenetics were presented. Our meeting report describes those studies and includes interviews with investigators and commentaries by Canadian hematologists about the potential impact on Canadian practice.

Prevalence and predictors of airflow obstruction in an HIV tertiary care clinic in Montreal, Canada: a cross-sectional study.

OBJECTIVES: The reported prevalence of chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWHIV) varies widely. Our objective was to estimate the prevalence of airflow obstruction and COPD in unselected PLWHIV and identify characteristics that increase the risk of nonreversible airflow obstruction in order to guide case finding strategies for COPD. METHODS: All adults attending the Chronic Viral Illness Service were invited to participate in the study, regardless of smoking status or history of known COPD/asthma. Individuals underwent spirometric testing both before and after use of a salbutamol bronchodilator. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.7 post-bronchodilation, whereas COPD was defined as FEV1 /FVC < 0.7 post-bronchodilation and Medical Research Council (MRC) score > 2. Multivariate logistic regression was used to evaluate risk factors associated with airflow obstruction, reported as adjusted odds ratios (aORs). RESULTS: Five hundred and three participants successfully completed spirometry testing. The median (Q1; Q3) age was 52 (44; 58) years. The median (Q1; Q3) CD4 count was 598 (438; 784) cells/µL and the median (Q1; Q3) nadir CD4 count was 224 (121; 351) cells/µL. There were 119 (24%) current smokers and 145 (29%) former smokers. Among those screened, 54 (11%) had airflow obstruction whereas three (1%) of the participants had COPD. Factors that were associated with airflow obstruction included a history of smoking [aOR 2.2; 95% confidence interval (CI) 1.1; 4.7], older age (aOR 1.6; 95% CI 1.2; 2.2), and lower CD4 count (aOR 0.8; 95% CI 0.7; 1.0). CONCLUSIONS: Airflow obstruction was relatively uncommon. Our findings suggest that PLWHIV who are ≥50 years old, smokers and those with nadir CD4 counts ≤ 200 cells/µL could be targeted to undergo spirometry to diagnose chronic airflow obstruction.

Canadian cost analysis comparing maintenance therapy with bortezomib versus lenalidomide for patients with multiple myeloma post autologous stem cell transplant.

BACKGROUND: Multiple myeloma (MM) is a cancer caused by malignant plasma cells that accumulate mostly in the bone marrow. In Canada, the most common maintenance therapy options after autologous stem cell transplant (ASCT) are bortezomib and lenalidomide. OBJECTIVE: To determine the incremental cost between bortezomib and lenalidomide maintenance therapies for patients with MM post ASCT. METHODS: Analyses were conducted to compare the annual costs of bortezomib and lenalidomide maintenance treatments for patients with MM post ASCT in Canada. The base case analysis included the acquisition costs of the drugs and administration costs. Additional analyses were conducted which considered the cost of experiencing adverse events (AEs) and the cost of treating second primary malignancies (SPMs). RESULTS: In the Canadian healthcare system, the total annual per patient cost was $33,967 for bortezomib maintenance therapy versus $131,765 for lenalidomide maintenance therapy. One-way sensitivity analyses demonstrated that both AEs and SPMs had little impact on the incremental cost, and that differences between the two maintenance therapies were mainly due to the acquisition costs of the drugs. CONCLUSIONS: Bortezomib is significantly less costly than lenalidomide, and is an economically reasonable maintenance treatment option for patients with MM post ASCT.

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation.

Despite survival improvement with novel agents and use of autologous hematopoietic stem cell transplantation (HSCT), cure of patients with multiple myeloma (MM) remains anecdotal. Initial observations suggested that chronic GvHD was accompanied by an anti-myeloma effect after myeloablative HSCT, but unfortunately this procedure was hampered by high non-relapse mortality (NRM). To maximize the anti-myeloma effect and minimize NRM, we developed a non-myeloablative (NMA) regimen associated with a high incidence of chronic GvHD and tested its efficacy on patient survival and disease eradication. From 2001 to 2010, 92 patients aged ⩽ 65 years with a compatible sibling donor received autologous HSCT followed by an outpatient NMA allogeneic HSCT using a conditioning of fludarabine and cyclophosphamide. Patient median age was 52 years and 97% presented Durie-Salmon stages II-III disease. After a median follow-up of 8.8 years, probability of 10-year progression free and overall survival were 41% and 62%, respectively. Although the cumulative incidence of extensive chronic GvHD was high (at 79%), the majority of long-term survivors were off immunosuppressive drugs by year 5 and NRM was low (at 10%). Together, our results suggest that potential MM cure can be achieved with NMA transplantation regimens that maximize graft-versus-myeloma effect and minimize NRM.

Histoplasmosis and subcutaneous nodules in a kidney transplant recipient: erythema nodosum versus fungal panniculitis.

Erythema nodosum (EN)-like lesions are a rare occurrence after solid organ transplantation. Differential diagnosis includes infective panniculitis, which can be a feature of progressive disseminated histoplasmosis (PDH), an uncommon but severe form affecting primarily immunocompromised hosts. We report on a fatal case of PDH, which presented as fungal panniculitis masquerading as EN in a renal allograft recipient 25 years after transplantation. We discuss the clinical, histopathological, and microbiological characteristics of this rare complication, with focus on its distinction from EN. This case emphasizes the central role of biopsy in transplant recipients presenting with cutaneous lesions, and the importance of clinicopathologic correlation and complementary microbiological investigations.

[Precarious parturients and readmission: pilot study at the Lariboisière-Fernand-Widal Hospital Group in Paris]. / Parturientes précaires et réhospitalisation : étude pilote au groupe hospitalier Lariboisière-Fernand-Widal de Paris.

OBJECTIVES: We wondered whether pregnant women with social handicap benefited from readmissions which could have been prevented, and if there was a selection of patients? PATIENTS AND METHOD: This is a retrospective study of 127 pregnant women with social handicap having given natural childbirth in a public health establishment. The research was based on analysis of data from DRG's (PMSI), legislation and other documents. RESULTS: Between mid March 2007 and mid June 2009, 27 of the 127 pregnant women with social handicap have benefited from 35 readmissions. There were 171.5 ± 255.1 days between readmissions. There was no second readmission on the same day for the same patient. According to the criteria of the Appropriateness Evaluation Protocol (AEPf), none of the readmissions were considered avoidable. No parturient was readmitted for non-medical reasons. Readmitted patients presented low to severe social handicaps and had 79.6 % more coded diagnosis compared to their first hospitalization. This service plays its public service role to fight against social exclusion. DISCUSSION AND CONCLUSION: This pilot study provides encouraging results but also underlines the limits of our approach. We nevertheless wished to explore whether this low resource intensive initiative could make interesting indicators emerge, which seems to be the case.

Cyst formation following radiosurgery for AVMs: report of 3 cases.

BACKGROUND: Stereotactically-focused radiosurgery (SRS) for the treatment of arteriovenous malformations (AVM) has been in widespread use for over two decades. Over this timeframe the indications for treatment, standardization of radiation dosage, and the results expected from treatment have been elaborated. Less well known are the long-term complications associated with SRS. We report three patients who had SRS for the treatment of AVM who developed a cyst at the site of treatment as a late complication. METHODS: From 201 patients treated by SRS for an AVM, three developed a cyst at the treatment site. Their clinical presentation, the characteristics of the AVMs and the treatment were reviewed, as well as similar cases gleaned from the literature. RESULTS: Three women, aged 28-43 years, had an AVM treated by: craniotomy and clipping of arterial feeders followed by SRS, by craniotomy for resection followed by SRS or by endovascular embolization and SRS. The patients did well following treatment but two of them developed a symptomatic and the other an asymptomatic cyst at the treatment site 3-19 years later. The symptomatic patients underwent marsupialization of the cyst and the other is under observation. CONCLUSION: Stereotactic radiosurgery is an established and safe treatment for patients with AVMs. Delayed cyst formation can occur many years after treatment and long term follow-up is indicated in patients whose AVM has been treated with SRS.

Ultrasonic pretreatment of sludge: a review.

Ultrasonication is an emerging and very effective mechanical pretreatment method to enhance the biodegradability of the sludge, and it would be very useful to all wastewater treatment plants in treating and disposing sewage sludge. Ultrasonication enhances the sludge digestibility by disrupting the physical, chemical and biological properties of the sludge. The degree of disintegration depends on the sonication parameters and also on sludge characteristics, therefore the evaluation of the optimum parameters varies with the type of sonicater and sludge to be treated. The full-scale installations of ultrasonication have demonstrated that there is 50% increase in the biogas generation, and in addition evaluation of energy balance showed that the average ratio of the net energy gain to electric consumed by the ultrasound device is 2.5. This review article summarizes the benefits of ultrasonication of sludge, the effect of sonication parameters, impact of sludge characteristics on sludge disintegration, and thereby the increase in biogas production in anaerobic digester. Due to uncertainty in the unit representation by many researchers and nonavailability of the data, comparison of these results is complicated. Comparison of ultrasonication with other pretreatment options is necessary to evaluate the best economical and environmental pretreatment technology for sludge treatment and disposal. The optimum parameters for the ultrasonication vary with sludge characteristics.

Surface chemistry and photophysical properties of a diacetylene-peptide derivative capped quantum dots Langmuir monolayer.

A diacetylene derivative, 10,12-pentacosadiynoic acid (PDA), was conjugated to a small peptide chain Cysteine-Cysteine-Glycine (CCG) through the solid-phase peptide synthesis. The (CdSe)ZnS core-shell quantum dots (QDs) capped with trioctylphosphine ligands were modified through a surface ligand reaction to prepare the PDA-CCG QDs conjugate. Both systems, PDA-CCG and PDA-CCG QDs, were investigated as Langmuir monolayer at the air-water interface through the surface pressure-area (pi-A) isotherms, compression-decompression cycles, stability measurements, and in situ UV-vis and fluorescence spectroscopy. Two different pi-A isotherms were observed for the systems investigated showing the importance of the peptide moiety in PDA-CCG to form a Langmuir monolayer up to a surface pressure of 50 m Nm(-1) compared with 15 m Nm(-1) for the PDA component alone. The compression-decompression cycles and stability measurements for both systems suggest the formation of a stable Langmuir monolayer over 1h time period. Although the in situ UV-vis spectroscopy of PDAA-CCG and PDA-CCG QDs does not show an absorption spectrum, we observed by in situ fluorescence spectroscopy the photoluminescence (PL) of the PDA-CCG QDs at 560 nm, with an intensity of the PL increasing linearly with the increase of the surface pressure. Irradiating the PDA-CCG QDs Langmuir monolayer at 254 nm, we observe the photopolymerization with two distinct bands at 575 (blue band) and 630 nm (red band) of the polymer.

A unique, environmentally sustainable and cost-effective programme to re-vegetate military training lands utilising composted wastewater biosolids at a large Canadian military training centre.

The Greater Moncton Sewerage Commission has developed, in concert with National Defence Canada, an environmentally sustainable and cost effective biosolids management and land reclamation programme at the Canadian Forces Base (CFB) Gagetown, New Brunswick, Canada (the second largest land based Military Training Facility in the British Commonwealth). The use of composted biosolids to revegetate military training lands is thought to be a unique application for the beneficial use of biosolids. Results and practical experience gained from this approach to successfully re-vegetate initial sections of extremely large and vast tracts of these lands are described. The paper also overviews the Commission's modern 115000 m3 x d(-1) advanced, chemically assisted primary wastewater treatment facility and associated alkaline (lime) sludge stabilisation process. Planning strategies, security aspects, special and unique challenges in operating adjacent to an active military training facility, costs, spreading techniques, monitoring, next steps and conclusions are also presented.

Hypofractionated stereotactic radiotherapy for low grade glioma at McGill University: long-term follow-up.

Small, well-defined, unresectable low-grade gliomas are attractive targets for stereotactic irradiation. Fractionated stereotactic irradiation of these targets has the theoretical benefit of increased normal tissue sparing beyond that provided by the physical characteristics of stereotactic radiosurgery. From July 1987 to November 1992, 21 patients were treated for low-grade glioma at our institution using a hypofractionated regimen of stereotactic radiotherapy. All patients had well-circumscribed, < 40 mm tumors. No patient had had prior radiotherapy. All lesions were histologically proven WHO grade I or II glial tumors. Lesions involved sensitive brain structures and were deemed unresectable. A typical dose of 42 Gy was delivered in 6 fractions over a two-week period using rigid immobilization and a linac-based dynamic stereotactic radiosurgical technique. Patients had a median age of 23 years (9-74) and were predominantly female (60%). Median tumor diameter was 20 mm. With a median follow-up for living patients of 13.3 years, the actuarial 5, 10, and 15-year overall survival rates are 76%, 71%, and 63%, respectively. Treatment was acutely well tolerated although three patients experienced late post-therapy complications. Our results and those of 241 patients treated in nine other institutional series are reviewed. Despite some examples of favorable short-term outcomes, all reported series are highly selected and thus likely biased. The data regarding the use of SRS is limited and, in our opinion, insufficient to claim a clear therapeutic advantage to SRS in the initial management of low-grade glioma. Our own results with hypofractionated stereotactic radiotherapy are similar to those expected with standard therapy.

Central corneal thickness and progression of the visual field and optic disc in glaucoma.

AIMS: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. METHODS: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. RESULTS: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. CONCLUSIONS: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.

Influence of RANTES, SDF-1 and TGF-beta levels on the value of interleukin-7 as a predictor of virological response in HIV-1-infected patients receiving double boosted protease inhibitor-based therapy.

OBJECTIVES: Interleukin-7 (IL-7), RANTES (regulated on activation, normal T cell expressed and secreted), stromal cell-derived factor-1 (SDF-1) and transforming growth factor-beta (TGF-beta) appear to share certain biological properties in vitro and all are involved in HIV-1 disease progression. Our earlier observations indicated that IL-7 levels decrease upon CD4 T-cell recovery and represent a new, independent predictor of virological response. Here, we examine associations among circulating levels of IL-7, RANTES, SDF-1 and TGF-beta in hopes of gaining insight into their contribution to the predictive value of IL-7. METHODS: Levels of IL-7, RANTES, SDF-1 and TGF-beta, and immune and viral parameters were assessed in HIV-1-infected patients. RESULTS: Cross-sectional (n=148) and longitudinal (n=36) analyses showed that levels of IL-7, but not RANTES, SDF-1 or TGF-beta, were increased in HIV-1-infected adults compared with those of healthy controls. In the cross-sectional study, levels of IL-7 were correlated with RANTES (r=0.31, P=0.002) and TGF-beta (r=0.53, P<0.001) but not with SDF-1 (r=0.12, P=0.22), and these associations were more pronounced in patients with CD4 T-cell counts >200 cells/microL. In contrast to IL-7, levels of RANTES, SDF-1 and TGF-beta were not correlated with CD4 T-cell counts. Longitudinal analysis revealed a marked decline in IL-7 levels accompanied by an increase in CD4 T-cell count following antiretroviral therapy (ART), but no changes in RANTES, SDF-1 or TGF-beta levels. Multivariate regression analysis showed no influence of baseline RANTES, SDF-1 or TGF-beta levels on the value of IL-7 as a predictor of virological response at 48 weeks. CONCLUSIONS: Collectively, these results indicate that changes in IL-7 levels did not induce changes in RANTES, SDF-1 or TGF-beta. Furthermore, they indicate that RANTES, SDF-1 or TGF-beta levels do not explain the predictor value of IL-7 in patients receiving ART.

Modulated photoacoustic spectroscopy study of an artificial tanning on human skin induced by dihydroxyacetone.

A modulated photoacoustic spectroscopy study on the effect of dihydroxyacetone, commonly used for artificial tan, is presented. The study was carried out in the presence and absence of dimethylisosorbide (a solvent for dihydroxyacetone) on fresh human skin, obtained from the breast region of recent autopsy cases (two females), at a frequency of 25 Hz, which enabled us to study the effect at a depth of 30 microm in the stratum corneum and beneath. By monitoring the photoacoustic signal intensity with time in the region of 300-400 nm, which is a specific region for melanin pigment, it is demonstrated that dihydroxyacetone in combination with dimethylisosorbide enhances the process of tanning. Dihydroxyacetone also has an effect on the amino acids and nucleic acids which is bad for the skin.