Dynamic Brain Imaging Response to Spinal Cord Stimulation Differential Frequencies DiFY SCS-PET clinical trial

OBJECTIVES: This study with sequential 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scanning was designed to investigate any objective measurable effect of differential frequency stimulation (40 Hz, 4000 Hz, and 10,000 Hz) on specific pain matrix areas in patients who underwent spinal cord stimulation (SCS) for intractable lumbar neuropathic pain. MATERIALS AND METHODS: In this single-center, randomized, blinded study, four brain 18F-FDG PET scans were performed for each patient-at baseline before SCS implant and after 40-Hz, 4000-Hz, and 10,000-Hz stimulation. After 40-Hz stimulation for four weeks, patients were randomized 1:1 (4000 Hz/10,000 Hz), crossing over at another four weeks. 18F-FDG PET-CT brain scans acquired on the GE-Discovery 710 PET system (GE Healthcare, Chicago, IL) with 128-slice CT (250-MBq dose) were analyzed using the PMOD software (PMOD Technologies Ltd, Zurich, Switzerland). A total of 18 pain regions, the right and left prefrontal cortex (PFC), insula, anterior cingulate cortex (ACC), hippocampus, amygdala, primary somatosensory cortices, secondary somatosensory cortices (SSCII), thalami, parabrachial, and periaqueductal gray (PAG), were analyzed. RESULTS: A total of 14 patients received 40 Hz for four weeks before crossing over to 10,000 Hz/4000 Hz. A total of 57 PET-CT scans (15 for baseline and 14 each for 40 Hz, 4000 Hz, and 10,000 Hz) were analyzed for maximum standardized uptake value (SUVmax), with a statistically significant difference in SUVmax between 40 Hz and baseline (p = 0.002) and 4000 Hz and baseline (p = 0.001) when pooled across 18 pain matrices. There was no statistical difference in SUVmax between 10,000 Hz and baseline. The pooled analysis showed a proportionately higher thalamic region reduction (59.5%) in metabolic activity than other pain matrices, PFC (52%), insula (50%), ACC (52%), SSCII (49%), and PAG (52%). CONCLUSION: This large cohort of brain PET scans (n = 57) shows statistically significant differences in brain metabolic activity at 40 Hz and 4000 Hz from baseline, with effect on both nociceptive and affect-cognitive pathways (proportionately higher reduction in the thalamus), highlighting the possible mechanism of SCS. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03716557

Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: The AVATAR Trial

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated. ------ Methods: The AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm2 with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mm Hg), and with normal left ventricular function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite end point of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries. ------ Results: Between June 2015 and September 2020, 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in the conservative treatment group. In the early surgery group, 72 patients (92.3%) underwent SAVR with operative mortality of 1.4%. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite end point than those in the conservative arm (hazard ratio, 0.46 [95% CI, 0.23-0.90]; P=0.02). There was no statistical difference in secondary end points, including all-cause mortality, first heart failure hospitalizations, major bleeding, or thromboembolic complications, but trends were consistent with the primary outcome. ----- Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms

Monitoring of coral reefs on contrasting sites (Mayotte and Iles Eparses) in the MozambiqueChannel, Indian Ocean: Application to management

International audienceBackgroundUnderstanding the functioning of coral reefs and their resilience to disturbances requires studyof sites subjected to contrasting anthropogenic pressure while undergoing similar climaticforcing. The SIREME program (Monitoring and inventory of coral reefs of Mayotte and theIles Eparses, 10e FED Indian Ocean) was conducted in the Indian Ocean to measure andelucidate the state of health of coral reefs at Mayotte, where the reefs are subject to highanthropogenic pressure, and Iles Eparses (Glorieuses Islands and Europa) where thesepressures are minimal.MethodsExpeditions in 2015 at Glorieuses, and in Mayotte and Europa in 2016 enabled monitoring ofvarious organisms: corals (and associated diseases), fish and microplankton. An inventory ofsoft corals and habitat mapping using satellite and field data were also undertaken. The degreeof connectivity between reef populations in the Mozambique Channel was assessed through 2genetic studies and current data between islands were generated using a hydrodynamic model.Finally, monitoring indicators have been proposed to managers to assess the health status ofcoral reefs and to estimate the effectiveness of management measures.ResultsConcerning the health of coral reefs in Mayotte, the levels of benthic cover and the taxonomicdistribution of corals varied widely according to locality and reef geomorphology, with thebest coral health observed on the inner and fringing reefs. The coral and fish diversities werehigh, as was the total species richness, due to the favourable geological and hydrodynamicconditions in the north of the Mozambique Channel. Nevertheless, fish biomass was clearlydeclining at all the stations over the last decade, a consequence of high fishing pressure, inparticular on the higher trophic level species. Coral bleaching monitoring in Mayotte revealedan average colony morality of 24% in 2016 but almost half of the coral colonies were notaffected.In the Iles Eparses, the coral reefs were in very good health, which was reflected either byvery high coral cover (e.g. Europa: CV 80% on average and >235 coral sp) or by thedominance of "living corals-crustose coralline algae" compared to soft algae (e.g. Glorieuses).A high prevalence of coral diseases (> 31%) was recorded at Glorieuses at some stations nearLys Island, which can be explained by the proximity of colonies of thousands of seabirds thatcan be vectors and/or reservoirs of diseases released via faecal contamination. In contrast, avery low disease prevalence was observed at Europa (2%), which confirmed the exceptionalstate of health of its coral reefs. Fish communities were characterized by high proportions ofpredators (groupers, snappers, snappers, jacks, sharks) and large adult individuals.Nevertheless, at Glorieuses, although fish biomasses remained higher relative toanthropogenically-affected sites elsewhere in the Indian Ocean, this has decreased specificallyin terms of pelagic species probably preferentially targeted by illegal fishing. Hydrologicalanalyses of water chemistry and biological indicators confirmed the ultra-oligotrophic statusof the Glorieuses, its waters being characterized by very low concentrations ofpicocyanobacteria and nitrogen and carbon nutrients. In terms of bacterial contamination,there was no evidence of faecal contamination (coliforms and streptococci) at Glorieuses,whereas some stations in Mayotte exhibited high contamination levels and poor water qualitycompared to WFD (EU Water Framework Directive) thresholds. Indices integrating theautotrophic (and not heterotrophic) trophic levels thus provided relevant information on thehealth status of the systems studied.ConclusionThe selection of priority sites for conservation (species and/or habitats) is now underdiscussion with managers and this needs to be balanced with other considerations that can betake into account such as the functional role or the particular biology of certain species ofinterest, as well as socio-economic concerns. The exceptional coral reef of Europa displayedreef communities that are close to “pristine”, suggesting that they could be reference areas forthe Southwest Indian Ocean. Long-term scientific studies of these environments is essential tomonitor changes in their condition and propose appropriate management measures in thecontext of climate change that is rapidly impacting populations and ecosystems

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| < 0.8) in the transverse momentum range 1 < pt < 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain

OBJECTIVES: The aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain. MATERIALS AND METHODS: A novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP. The scientific theory and testing presented in this article provide the preliminary justification for the potential MOAs by which PSP may operate. RESULTS: During the pilot study, aPSP (n = 31) yielded a greater decrease in both back and leg pain than did T-SCS (back: -60% vs -46%; legs: -63% vs -43%). In addition, aPSP yielded higher responder rates for both back and leg pain than did T-SCS (61% vs 48% and 78% vs 50%, respectively). DISCUSSION: The novel, multilayered approach of PSP may provide multimechanistic therapeutic relief through preferential fiber activation in the dorsal column, optimization of the neural onset response, and use of both the medial and lateral pathway through the thalamic nuclei. The results of the pilot study presented here suggest a robust responder rate, with several subjects (five subjects with back pain and three subjects with leg pain) achieving complete relief from PSP during the acute follow-up period. These clinical findings suggest PSP may provide a multimechanistic, anatomical, and clinically effective management for intractable chronic pain. Because of the limited sample size of clinical data, further testing and long-term clinical assessments are warranted to confirm these preliminary findings