Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial.

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.

Synthesis of homogeneous spherical selenium nanoparticles through a chemical method for cancer therapy applications.

Oxidative stress is associated with pathologies affecting various organs or metabolic pathways. Thus, targeting oxidative stress might represent a valid therapeutic option. Selenium nanoparticles (SeNPs) are reported to exert antioxidant effects by many mechanisms. Our purpose was to assess in vitro on normal (MRC-5) and cancer (PANC-1) cell lines the potential of SeNPs for inducing cytotoxicity and redox modulation. They were synthesized through a chemogenic method and characterized through advanced microscopy techniques. SeNPs were spherical, with 100 nm average diameters and low dimension variability. Cancer and normal cells were exposed for 24 h to different concentrations of SeNPs ranging from 1 to 25 µg/mL. According to the LDH and MTT assay results, SeNPs treatment caused a more pronounced decrease in cancer cell viability compared to normal cells, suggesting a possible therapeutic benefit on tumors, thus supporting the hypothesis of therapeutic use of SeNPs with the benefit of cell type selectivity. Neither an elevation nor an inhibition of intracellular ROS production was detected in MRC-5 cells exposed to concentrations between 1 and 25 µg/mL SeNPs. The results of this study suggest that SeNPs could represent potential candidate for treatment of cancer, especially pancreatic adenocarcinoma.

Modernising physician resource planning: a national interactive web platform for Canadian medical trainees.

BACKGROUND: Healthcare systems rely heavily upon human resources to ensure high-quality access to care for the general population. With significant health worker shortages predicted worldwide in the coming decades, maximizing the current workforce by means of a physician resource planning (PRP) strategy that ensures the right number, mix, and distribution of physicians to meet population needs is warranted. In Canada, there is an insufficient number of primary care providers, and disproportionately low numbers of specialist physicians in rural compared to urban regions. Currently, Canadian medical students are not effectively included in PRP strategy and lack the required information for career orientation to help rebalance the population's workforce needs. This paper present the Health Human Resource (HHR) Platform, a comprehensive web tool that includes relevant workforce data to empower medical students in choosing a discipline based on both personal interests and social accountability. RESULTS: Physician workforce data, comments from Canadian residency program directors, and career planning resources were collected by the Canadian Federation of Medical Student's (CFMS) HHR Task Force. This information was consolidated to create a national interactive platform that uses a map, comparison table, and trend graphs to illustrate over 500,000 unique data points from 37 datasets, including specific information and resources spanning 62 medical specialties from 2015 onwards. There was a 24.6% response rate for program director comments. During the first 4 months of the HHR Platform launch, there were 2434 different users, of which 985 were returning, with an average of 20.0 users per day spending on average 3 min on the platform. CONCLUSIONS: The HHR Platform constitutes a national approach to PRP informing medical students on the mix and distribution of physicians needed to meet the future healthcare demands of the Canadian population.

Alterations of heart rate variability and turbulence in female patients with hyperthyroidism of various severities.

OBJECTIVE: The objective of the this study is to document the existence of statistically significant differences between parameters of heart rate variability (HRV) and heart rate turbulence (HRT), determined in women with overt hyperthyroidism (hT), compared to controls and to highlight their correlations with the level of thyroid hormones and the incidence of arrhythmias. METHODS: We studied the HRV in time and frequency domain, and the HRT in a group of 113 women with overt hT, without other cardiovascular risk factors or comorbidities, admitted to the endocrinology clinic of our hospital, between 2012 and 2016. Depending on the severity and duration of hT and levels of thyroid hormones, the patients were assigned to three groups: mild and moderate forms, severe hT with thyrotoxicosis and persistent cases with a relapse of hT. We performed 24 h Holter monitoring in all patients. RESULTS: HRV parameters in time domain (TD) were significantly depressed in patients comparing to controls. All patients had abnormal, positive values of turbulence onset (TO) with significant statistically differences (P < 0.0001) comparing to controls. Although positive, the values of turbulence slope (TS) decreased according to the severity of hT. CONCLUSION: Patients with hT had depressed values of HRV parameters in TD, correlated with the severity of the thyroid disease and with the incidence of arrhythmias. All patients presented pathological values of TO. TS values were positive, but lower compared to controls.

Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients.

Sensorimotor representations of movements are created in the sensorimotor network through repeated practice to support successful and effortless performance. Writer's cramp (WC) is a disorder acquired through extensive practice of finger movements, and it is likely associated with the abnormal acquisition of sensorimotor representations. We investigated (i) the activation and connectivity changes in the brain network supporting the acquisition of sensorimotor representations of finger sequences in patients with WC and (ii) the link between these changes and consolidation of motor performance 24 h after the initial practice. Twenty-two patients with WC and 22 age-matched healthy volunteers practiced a complex sequence with the right (pathological) hand during functional MRI recording. Speed and accuracy were measured immediately before and after practice (day 1) and 24 h after practice (day 2). The two groups reached equivalent motor performance on day 1 and day 2. During motor practice, patients with WC had (i) reduced hippocampal activation and hippocampal-striatal functional connectivity; and (ii) overactivation of premotor-striatal areas, whose connectivity correlated with motor performance after consolidation. These results suggest that patients with WC use alternative networks to reach equiperformance in the acquisition of new motor memories.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

Effect of electric field on laser induced damage threshold of multilayer dielectric gratings.

This paper studies gratings engraved in multilayer dielectric stacks for ultra high intensity laser compressors application. We design various grating profiles with high reflected efficiencies for 1780 l/mm multilayer dielectric gratings (MLD). Each grating is defined to exhibit a different electric field maximum value in the pillars of the grating. A damage testing facility operating at 1.053 mum, 500 fs pulse duration is used to damage test the parts manufactured from these designs. It is evidenced that for fixed incident angle and materials the damage of the grating is directly related to the electric field intensity maximum in the material, which depends on the groove profile. Laser induced damage thresholds of 5 J/ cm(2) are experimentally reached with very high and uniform efficiencies.

[Ophthalmologic involvement of intracranial tumors--report of a case]. / Implicatii oftalmologice ale proceselor intracraniene înlocuitoare de spatiu--referire la un caz.

Bilateral papillary edema is considered to be the expression of a tumoral process that reduces the intracranial space resulting in elevation of the intracranial cerebrospinal fluid pressure. The authors present the case of a 21-year-old man consulting for mild visual loss of the left eye. The ophthalmologic examination showed bilateral papilledema and visual field defects in the left eye (enlargement of the blind spot), with no clinic or imagistic signs of increased intracranial pressure. Intracranial pathologic processes that bear like a tumor, reducing the intracranial space are not always associated with papilledema, but papilledema is always associated with intracranial tumor. Increased intracranial pressure is frequently associated with intracranial tumoral processes, but in this case was not showed increasing of intracranial pressure.

[Trabeculectomy and nonpenetrating surgery in glaucoma]. / Trabeculectomia si chirurgia nonperforanta în glaucom.

The purpose of the study is to compare the efficiency of classical trabeculectomy and with the punch and nonpenetrating deep-sclerectomy in patients with primary open angle glaucoma. The studied groups comprise patients with uncontrolled intra-ocular pressure with medical therapy and/or laser. The results of the study emphasize the following conclusions: the decrease of intra-ocular pressure is comparable in classical trabeculectomy and with punch the decrease of intra-ocular pressure is comparable in classical trabeculectomy and nonpenetrating surgery. we consider the non penetrating surgery an interesting alternative to the classical trabeculectomy, with better control of intra-ocular pressure the complications of non penetrating surgery are reduced.

[Non surgical alternatives in the treatment of the primitive open angle glaucoma]. / Alternative nechirurgicale in tratamentul glaucomului primitiv cu unghi deschis.

Lowering of the intraocular pressure--the main risk factor in glaucoma neuropathy--is the major goal in the treatment for primary open angle glaucoma. The goal of the study is to compare the results of topical administration of the next therapeutical agents: b-blockers, prostaglandin analogs, topical carbonic anhydrase inhibitors and selectives adrenergic a-2 agonists. The studied groups emphasize the efficiency of the first line monotherapy and of the combined therapy, maintaining the quality of life, preserving the visual function, the minimal side effects and the compliance of the patients.

[Postcontusion glaucoma]. / Glaucomul postcontuziv.

Secondary posttraumatic glaucoma. Blunt ocular trauma may cause transient or permanent high IOP, occurring immediately or in time after the injury. This study presents some clinical and therapeutical considerations about 16 cases which developed secondary glaucoma. The elevation of IOP was associated with hyphema, iridodialysis, zonular tears (with lens luxation or subluxations), alterations of the iridocorneal angle.

The effect of bone compaction on early fixation of porous-coated implants.

The effect of a bone compaction technique versus conventional drilling on the early fixation of porous-coated implants was examined in a canine model. Compaction dilation resulted in a significant increase in implant fixation stiffness (P < .01) and ultimate fixation strength (P < .01) at 0 and 3 weeks. Fixation stiffness remained significantly increased at 6 weeks (P < .01); however, the ultimate fixation strength was not statistically significant between the 2 techniques (P > .05). There was no significant difference in either fixation value at 9 weeks (P > .05). Histological examination of the bone-implant interface demonstrated an increase in the density of cancellous bone immediately adjacent to the implants placed in the compaction dilated holes. The results of this study suggest that the compaction method of host bone preparation may optimize the initial stability of the implant interface of porous-coated prostheses.

[Nocturnal bruxism. Contributions to the detection and assessment of involvement in the craniomandibular pain dysfunction syndrome]. / Bruxismul nocturn. Contributii la depistarea si aprecierea afectiunii in cadrul sindromului disfunctional dureros cranio-mandibular (S.D.D.C.M.).

The authors review the most updated information concerning the etiopathogenesis of nocturnal bruxism, stressing the co. destructive role of psychosomatic factors and of traumatogenic ones, of the type of premature dental contacts, and of occluding interferences, with evident direct implications in the buccal cavity and at a distance, giving rise to hypnic masticatory automatism, with painful hypercontraction of the masticatory muscles, and stress exerted on the temporomandibular articulations. On the basis of original studies of the interdisciplinary type (prosthetic gnathology and neurophysiology), with the aid of polygraphic investigations during sleep carried out in subjects with nocturnal bruxism it was possible to demonstrate that this oral parafunction may determine sleep disturbances at a central level which makes necessary a complex stomatologic and neuropsychiatric medical therapy.