Drug metabolism and clearance system in tumor cells of patients with multiple myeloma

Resistance to chemotherapy is a major limitation of cancer treatments with several molecular mechanisms involved, in particular altered local drug metabolism and detoxification process. The role of drug metabolism and clearance system has not been satisfactorily investigated in Multiple Myeloma (MM), a malignant plasma cell cancer for which a majority of patients escapes treatment. The expression of 350 genes encoding for uptake carriers, xenobiotic receptors, phase I and II Drug Metabolizing Enzymes (DMEs) and efflux transporters was interrogated in MM cells (MMCs) of newly-diagnosed patients in relation to their event free survival. MMCs of patients with a favourable outcome have an increased expression of genes coding for xenobiotic receptors (RXRα, LXR, CAR and FXR) and accordingly of their gene targets, influx transporters and phase I/II DMEs. On the contrary, MMCs of patients with unfavourable outcome displayed a global down regulation of genes coding for xenobiotic receptors and the downstream detoxification genes but had a high expression of genes coding for ARNT and Nrf2 pathways and ABC transporters. Altogether, these data suggests ARNT and Nrf2 pathways could be involved in MM primary resistance and that targeting RXRα, PXR, LXR and FXR through agonists could open new perspectives to alleviate or reverse MM drug resistance.     

Sagittal alignment and kinematics at instrumented and adjacent levels after total disc replacement in the cervical spine

Background

The purpose of the study was to report radiological outcomes after total disc replacement (TDR) in the cervical spine through a 24 months follow-up (FU) prospective study with a special focus on sagittal alignment and kinematics at instrumented and adjacent levels.

Materials and methods

Thirty-two patients, who sustained one-level TDR with a ball-and-socket arthroplasty (Discocerv^™ implant, Scient’x/Alphatec Spine, USA) were consecutively included in the study. Clinical (visual analogical scale and neck disability index) and radiological parameters were measured preoperatively and postoperatively at 3/6 months, 1-year and 2-year FU. Sagittal alignment, ranges of motion (ROM) and center of rotations (CORs) were analyzed using specific motion analysis software (Spineview^™, Paris, France). Patients CORs were compared with those of a control group of 39 normal and asymptomatic subjects.

Results

Both local and C3–C7 lordosis significantly increased postoperatively (+8° and +13° at 2 years, respectively). At instrumented level ROM in flexion–extension (FE) was measured to 10.2° preoperatively versus 7.5° at 1 year and 6.1° at 2 years. There were no differences in ROM at adjacent levels between pre and postoperative assessments. When compared with control group and preoperative measurements, we noted postoperative cranial shift of the COR at instrumented level for patients group. In contrast, there was no difference in CORs location at adjacent levels.

Conclusion

Through this prospective study, we observed that cervical lordosis consistently increased after TDR. In addition, although ball-and-socket arthroplasty did not fully restore native segmental kinematics with significant reduction of motion in FE and consistent cranial shift of the COR, no significant changes in terms of ROM and CORs were observed at adjacent levels.     

Determinants for the use of ambulation AIDS in a geriatric rehabilitation care unit: a retrospective study

ObjectivesThis study aimed at assessing the profile of ambulation aid users among patients admitted for geriatric rehabilitation care.DesignRetrospective chart review.SettingGeriatric Rehabilitation Department of the Hôpital Albert Chenevier, Créteil, France.ParticipantsThe sample comprised 206 records of patients aged 65 or older with no previous use of assistive device before admission and length of stay longer than 7 days.MeasurementsAmbulation levels were classified as independent ambulators (IA, reference category), ambulation aid users (AA), or nonambulatory patients (NA). we explored age, gender, purpose of initial admission, comorbidities, and past medical history as factors potentially associated with ambulation levels, using multinomial logistic regression.ResultsThe study population (mean age 84 years [6.1 standard deviation], 68.5 % women) comprised 110 IA (53.4% of the overall population), 72 AA (34.9%), and 24 NA (11.6%). Factors independently associated with AA use were the following: older age (odds ratio = 1.17; [95% confidence interval 1.09–1.25]), previous history of lower limb surgery (2.15; [1.0–4.73]), and admission for hip surgery (8.14; [2.60–25.53]). Factors independently associated with NA were the following: older age (1.12 [1.02–1.23]) and low Mini-Mental State Exam score (0.77 [0.70–0.85]). A borderline association was observed for visual impairment (3.36 [0.93–12.95]). Cardiac disease, respiratory disease, falls, and dementia were not associated with ambulation aid use.ConclusionsHistory of lower-limb surgery, particularly recent hip surgery, and old age are the primary predictive factors of ambulation aid use in a geriatric rehabilitation hospital.     

African League Against Rheumatism (AFLAR) preliminary recommendations on the management of rheumatic diseases during the COVID-19 pandemic

Objectives

To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic.

Method

A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1–3, 4–6 and 7–9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a ‘low’ level of agreement.

Results

A total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting.

Conclusions

The preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges.

Comparison of prostate volume, shape, and contouring variability determined from preimplant magnetic resonance and transrectal ultrasound images

PurposeTo compare preimplant prostate contours and contouring variability between magnetic resonance (MR) and transrectal ultrasound images.Methods and MaterialsTwenty-three patients were imaged using ultrasound (US) and MR before permanent brachytherapy treatment. Images were anonymized, randomized, and duplicated, and the prostate was independently delineated by five radiation oncologists. Contours were compared in terms of volume, dimensions, posterior rectal indentation, and observer variability. The Jaccard index quantified spatial overlap between contours from duplicated images.ResultsThe mean US/MR volume ratio was 0.99 ± 0.08 (p = 0.5). The width, height, and length ratios for the prostate were 0.98 ± 0.06 (p = 0.09), 0.99 ± 0.08 (p = 0.4), and 1.05 ± 0.14 (p = 0.1). Rectal indentation was larger on US by 0.18 mL (p = 0.01) and correlated with prostate volume (p < 0.01). MR and US interobserver variability in volume were similar at 3.5 ± 1.7 and 3.3 ± 1.9 mL (p = 0.6). Intraobserver variability was smaller on US at 1.4 ± 1.1 mL compared with MR at 2.4 ± 2.2 mL (p = 0.01). Local intraobserver variability was lower on US at the midgland slice (p < 0.01) but lower on MR at the base (p < 0.01) and apex (p < 0.01) slices.ConclusionsUS is comparable to MR for preimplant prostate delineation, with no significant difference in volume and dimensions. Rectal indentation because of the transrectal ultrasound probe was measurable, although the effects were small. Intraobserver variability was lower on US for the prostate volume but was lower on MR locally at the base and apex. However, the difference was not observed for the interobserver variability, which was similar between MR and US.     

The impact of variation in access to care on the management of Hirschsprung disease

IntroductionVariation in access to care has a significant impact on the disease management process and outcomes. Variable access to care might have similar effects on the management of Hirschsprung disease (HD). However, such variation has not been highlighted.Materials and MethodsAll patients referred to 3 academic centers (ACs) with HD were reviewed. Patient presentations, referral patterns, timing, and type of surgical intervention were compared between patients born in AC and those born in non-AC. Babies born with major congenital anomalies (MCAs) or total colonic HD were excluded.ResultsBetween 1998 and 2011, 129 patients were identified. After excluding 30 patients, 99 were split into 20 inborn patients (AC) and 79 outborn patients. Outborn patients more often presented with constipation (95% vs 65%, P = .001), whereas inborn patients presented with feeding intolerance or vomiting (75% vs 39%, P = .004). Outborn patients were diagnosed and had their pull-through (PT) at an older median age (in days) of 186 (1-2621) vs 4.5 (1-451) (P = .001) and 345 (11-2757) vs 92 (3-928) (P = .001), respectively. Moreover, inborn patients were more likely to undergo primary PT (75% vs 46%, P = .02) and avoid bowel diversion (95% vs 66%, P = .02).ConclusionVariation in access to care can have a significant impact on the quality of care delivery in HD. Limited access to AC is associated with staged PT in addition to delay in the diagnosis and management.