Day: 12/16/2022

A ‘Shocking’ Development in CPR?

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New research found that a fad in how defibrillation is done may actually save lives

A photo of a woman performing CPR on a man outdoors.

When a patient goes into cardiac arrest — that is, their heart stops beating — there are a few things medical workers can do:

  1. Chest compressions. The idea is to manually squeeze the heart, pushing blood out. It’s not only better than nothing, compression-only CPR saves a lot of lives. (Learn CPR! Anyone can do it.)
  2. Shock the heart with electricity. The idea is literally to jolt the heart’s electrical system, in hopes that disorganized activity will cease and organized conduction will resume, a kind of hard reboot. (Learn CPR! Anyone can do it.)
  3. Decompress the heart or lungs by removing fluid or air. (Medical professionals only.)
  4. Give medications that either encourage the heart to beat (which doesn’t work as well as you might have seen on TV) or that treat a life-threatening problem (e.g., giving calcium to a patient with deadly high potassium levels). (Medical professionals only.)
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The thing that matters most, especially outside of hospitals, is early and continuous chest compressions (always) and early defibrillation (electrical shock) when indicated. (Learn hands-only CPRopens in a new tab or window!)

There’s lots of fancy stuff that emergency teams also do, but really, the simple stuff is what matters most. Recently, though, a studyopens in a new tab or window published in the New England Journal of Medicine found that a change in how medical professionals do CPR could maybe — just maybe — save lives.

The idea is simple: if a patient has a certain cardiac rhythm called ventricular fibrillation, defibrillation is needed. But oftentimes, even early CPR and defibrillation (electrical shocks) don’t work. Over time, experts began to wonder: could some failures be related to a problem with how the shocks are being delivered? Two ideas were proposed. First, what if they changed the vector (i.e., the direction) of the shock, by changing where the pads are placed on patients. Instead of on the front and sides, researchers tried front and back placement, hoping that the electricity might reach more of the heart. Second, what if they tried that and the original way. In other words: give two shocks in a row; one with the old set-up and one with the new set-up. Four pads on a patient, instead of just two.

Did it work? Yes. At least, we think. This study looked at patients who had cardiac arrest outside of medical settings — as in, going about their lives and then suddenly collapsing. Patients whose hearts failed to restart after emergency workers administered three attempts using the standard approach were randomized either to receive more of the same, the revised pad placement, or the revised pad placement and the extra set of pads (i.e., two shocks going in different directions through the body). The details of this trial (a cluster randomized crossover design) are pretty impressive. (Anyone interested in those details can check out FOAMcast, the webpage and podcastopens in a new tab or window for healthcare professionals that I co-host with my good friend and colleague Lauren Westafer, DO, MPH, MS.)

Long story short, patients who received both changes in how shocks were given — i.e., the third approach, known as “dual sequence external defibrillation with vector change” — had more than twice the rate of a meaningful survival (i.e., with good neurologic outcomes), or around 1 in 3, compared to around 1 in 7.5 among those who only received the standard approach. (The revised vector-only group did a little better than the standard group, but the neurological outcomes were not improved.)

I pause to mention that for out-of-hospital cardiac arrest, the odds of survival are generally far, far lower than even 1 in 7.5. But these patients had “shockable rhythms.” While ventricular fibrillation is not a heart rhythm that can sustain life, it is a rhythm that responds to electricity (whereas flatlining, for example, does not). Patients with shockable rhythms have a much better chance of survival than those with other cardiac rhythms that shocks can’t help.

So why the, “Yes. At least, we think,” rather than just a gigantic “Yes!”? Well, there were some issues with the study. Sometimes, patients received the wrong thing (i.e., they were supposed to get one method, but got the other). Also, the trial was stopped early because of COVID. It’s possible that “regression to the mean” would have occurred and that the real effect size is much smaller. Studies are generally designed to have enough participants to make statistical noise unlikely, but when studies end before reaching the number of patients that they thought would be needed, sometimes the results look better or worse than they might otherwise eventually be found to actually be.

Lastly, the “both” approach means putting on an extra set of pads. In this study, the emergency workers did that extremely well, apparently minimizing interruptions in chest compressions (long pauses without chest compressions drastically reduce a patient’s chance of surviving). But many of us worry that “in real life” placing those extra pads might take longer (leading to lengthy and therefore deadly pauses in chest compressions) once the best efforts that occur when teams know they’re being studied (called the “Hawthorne effect”) wears off.

Still, many of us have been doing “dual sequence external defibrillation with vector change” for some of our patients for a few yearsopens in a new tab or window. Based on this, I’ll probably try to do it more often.

Coexistence of multiple myeloma with inflammatory myopathy: an incidental finding of increased generalised proximal muscles metabolic activity in a patient of the known case of multiple myeloma

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Coexistence of multiple myeloma with inammatorymyopathy: an incidental nding of increased generalised  proximal muscles metabolic activity in a patient of theknown case of multiple myeloma

Background

Inammatory myopathy is a spectrum of systemic conditions that presents as progressivemuscle weakness caused by inammation in muscles.In certain conditions it could be presented as extramuscular involvement such as parane-oplastic conditions.As a plasma cell neoplasm, multiple myeloma is often presented with multiple bone painbut association with myalgia is often rare in consideration of the same.As reported in the case report by Valeria Guglielmi at el in 2017and 2020, that borte-zomib induced muscle toxicities in patients that received VRD regimen chemotherapy (VRD(Velcade (bortezomib) + Revlimid (lenalidomide) + dexamethasone)) manifested as proximalmuscle weakness in (07 out of 24 patients) in spite of being muscular markers were normal.They also concluded the mechanism of muscle injury associated with bortezomib remains tobe elucidated. In patients a metabolic myopathy consisting of lipid accumulation within mus-cle bers was documented. The presence of mitochondrial abnormalities at ultrastructurallevel suggests that lipid deposits in muscle can be secondary to mitochondrial dysfunction;

 In the absence of abnormalities in the organic acid and acylcarnitine proles as well as in thefree and total carnitine levels rules out other causes of lipid storage myopathy.Theyfurtherillustratedthedirecteectofbortezomibonprimaryhumanmyoblasts. Theirstudydemonstratedthathumanmusclecellsexhibitedadose-andtime-dependentdecreaseincell viability only in response to relative high concentrations of bortezomib (10 and 20 nM).Bortezomibusedat5nM,whichistherangeofplasmaconcentrationfollowingadministrationof 1.3 mg/m2 in patients.As it is also known that at high concentration bortezomib can alter the catabolic processof autophagy in primary human myoblasts.

The case

A 51 years old lady, known case of multiple myeloma. presented to the department of nuclearmedicine, JIPMER on 15.10.2020 with history of multiple joints and bone pain for the past8 months as of (27.02.2020). Initially evaluated elsewhere at a local hospital where She wasevaluated with an X-ray skull on (18/2/20) that showed lytic lesions. Plasma electrophoresis(20/02/20) M-Band (7.5 g%). Albumin to globulin ratio was 0.54. On course of treatmentIFE done on 23/02/2020 suggestive of IgG kappa monoclonal gammopathy. Bence Jonesproteinuria is present in urine. Bone marrow biopsy (26/02/20) multiple myeloma. Then thepatient was referred to the department of medical oncology, JIPMER Puducherry; where shewas started on Chemotherapy with VRD (Velcade (bortezomib) + Revlimid (lenalidomide) +dexamethasone)6cyclescompleted(lastdoseon01/10/2020). Bonemarrowbiopsy(6/10/20)morphologically in remission.In October 2020, for one week she complained of progressive myalgia of bilateral upperand lower limbs. On request to assess the treatment response work up, F18 FDG PET CT wasdone on 15.10.2020.

F-18 FDG PET/CT on 15.10.2020:

The patient was instructed to have a minimum of 6 hours fasting before thescan procedure. On arrival of the patient, clinical history was noted fol-lowed by the oral consent taken while describing the procedure. Procedure:F18 FDG was administered intravenously followed by the acquisition of thewhole-body PET/NCCT images vertex of skull to toe after 70 minutes.Measured activity: 5.4 mCi at 09:56 AM; Administered time: 09:58 AM;Post injection: 0.08 mCi. Fasting blood glucose was 122 mg/dl.

 Scan interpretation and nding:

1. semiquantitative evaluation: on visual interpretation of maximum intensity projection(MIP) images, a region of interest has been drawn over the liver and mediastinal bloodpool then after the region of interest was drawn in the group of muscles showing themaximum semi-quantitative uptake value (SUVmax); lastly, the ratio of former withlater one is compared.Table: The proposed semiquantitative scoreIn fused images Generalised diuse muscle uptake of F-18 FDG was noted in exor com-partment muscles of the bilateral lower limbs which was markedly increased n comparison toliver/mediastinal blood pool background.1. On visual interpretation, there were features suggestive of generalised proximal musclemyopathy.

 

 Dubey, G.K. (2021). Coexistence of multiple myeloma with inammatory myopathy: an incidentalnding of increased generalised proximal muscles metabolic activity in a patient of the known case of multiplemyeloma.

Conclusion

There are very few case reports available showing the same kind of drug-induced myopathyin patients receiving VRD regimen caused the depletion of myoblasts causing inammation.

 

Skipping Antiplatelets Altogether Not Such a Bad Idea for Select TAVR Patients

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Promising results of letting some patients get away with no antithrombotic therapy

A computer rendering of platelets forming a clot.

Following transcatheter aortic valve replacement (TAVR), the optimal antithrombotic regimen for some people may be no antithrombotics at all, according to provocative registry data from Japan.

Compared with the single antiplatelet (SAPT) or dual antiplatelet (DAPT) approaches for TAVR patients without any other indications for antiplatelet or anticoagulation therapy, the non-antithrombotic strategy was not associated with an increased risk of adverse events counting cardiovascular death, stroke, myocardial infarction, and life-threatening or major bleeding at 3 years post-TAVR (log-rank P=0.972):
  • Non-antithrombotic strategy: 14.0%SAPT: 14.7%DAPT: 16.2%

Additionally, bleeding rates stayed similarly low, below 10%, for people assigned no antiplatelets or SAPT, whereas it crossed 10% for the DAPT cohort (log-rank P=0.018). The latter group trended toward more major or life-threatening bleeds in particular without reaching significance (4.1% for no antiplatelet group vs 6.5% for SAPT vs 8.4% for DAPT, log-rank P=0.07).

As for valve performance, mean pressure gradients and indexed effective orifice areas were similar across the three medication regimens, Kentaro Hayashida, MD, of Keio University School of Medicine in Tokyo, and colleagues reported in JACC: Cardiovascular Interventionsopens in a new tab or window.

These findings from the OCEAN-TAVI registry suggest that the 8.2% of TAVR patients who were prescribed no antiplatelets at discharge — their high bleeding risk cited frequently as the reason for the non-antithrombotic strategy — really did not need antithrombotics to reduce ischemic events and to prevent leaflet or valve thrombosis.

Contrary to the current guidelines recommending lifelong SAPT after TAVR, our findings indicate that even lifelong low-dose aspirin and short-term DAPT may not be necessary after TAVR,” Hayashida and colleagues said. Current preference for SAPT after TAVR is based on trials like POPular TAVIopens in a new tab or window, in which SAPT was associated with a lower bleeding incidence without an increased risk of ischemic events compared with DAPT.

Yet the necessity of any antiplatelets at all was questioned by Hayashida and colleagues, who noted that the assumption had been drawn from the field of coronary stenting without direct evidence from the older, more bleeding-prone TAVR population.

“The study opens up a novel and interesting perspective, which warrants further confirmation in a European or North American population,” according to an accompanying editorialopens in a new tab or window by a French group led by Vincent Auffret, MD, PhD, of Université de Rennes in France.

The editorialists warned of a narrow path ahead for the non-antithrombotic approach, as many patients will still require these medications for prior or new-onset atrial fibrillation and concomitant coronary or peripheral artery disease.

CEAN-TAVI is a nationwide observational TAVR registry that covers 15 hospitals in Japan. The present analysis included people who underwent elective TAVR for symptomatic severe aortic stenosis from October 2013 to May 2020 and excluded those who received anticoagulation or had procedural complications.

Participants were divided into groups receiving non-antithrombotic therapy (n=293), SAPT (n=1,354), or DAPT (n=1,928) at discharge. Prescriptions of SAPT after TAVR increased during the study period, in contrast with falling DAPT and stable non-antithrombotic therapy.

Overall, the study cohort had a median age in the mid-80s, and approximately one in three were men. Over 57% received a Sapien 3 TAVR valve. The non-antithrombotic therapy group tended to be younger and to have relatively few comorbidities despite high bleeding risk.

The median follow-up period was 841 days. Proportions of patients staying on their antithrombotic regimen from discharge to 1 year were 51.9% of the no-antiplatelets group, 69.4% of the SAPT group, and 40.4% of the DAPT group.

eaflet thrombosis was detected in 8.5% of the non-antithrombotic group. This compares favorably with prior reportsopens in a new tab or window of aortic valve replacement patients receiving antithrombotic therapy, though study authors acknowledged that this may be an underestimate as comprehensive imaging was not routinely performed in OCEAN-TAVI. Moreover, comparative data on leaflet thrombosis after SAPT or DAPT were not collected by Hayashida’s group.

Auffret and colleagues emphasized that systematic evaluation of subclinical leaflet thrombosisopens in a new tab or window is necessary for future work on the non-antithrombotic strategy.

Hayashida’s group also highlighted the “puzzling finding” of numerically lower all-cause mortality in DAPT patients at 3 years. As cause of death was not included in the analysis, the possibility remains that inherent selection bias was at play in the retrospective, observational report, as patients without severe comorbidities were likely to be on DAPT.

Source:Medscape

Omecamtiv Mecarbil Not Ready for Prime Time, FDA Advisors Say

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Rocky regulatory road lies ahead for the cardiac myosin activator

FDA ADCOMM omecamtiv mecarbil over a computer rendering of a heart attack.

Omecamtiv mecarbil received a thumbs-down from FDA advisors who complained of its inadequate evidence base during a Cardiovascular and Renal Drugs Advisory Committee meeting on Tuesday.

Members voted 8-3 (with no abstentions), stating that the benefits of omecamtiv mecarbil do not outweigh its risks for the treatment of heart failure with reduced ejection fraction (HFrEF), based on data coming largely from a single phase III trial.

Omecamtiv mecarbil is a first-in-class cardiac myosin activator that boosts cardiac contractility by increasing the number of myosin heads binding to an actin filament to initiate a power stroke at the start of systole.

The drug’s proposed indication of preventing cardiovascular death and heart failure events in HFrEF was “too broad of a claim for the data that we saw,” said Michael Blaha, MD, MPH, a cardiologist at Johns Hopkins University in Baltimore, who provided one of the no votes.

Nevertheless, members acknowledged that omecamtiv mecarbil could fill an unmet need for people with advanced heart failure who are often intolerant to existing therapies on the market. “I said yes on the basis of need,” said C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles.

The phase III trial in question, GALACTIC-HFopens in a new tab or window, was the basis of omecamtiv mecarbil’s marketing application and had shown that the cardiac contractility drug reduced the combined rate of cardiovascular death and hospitalization or other urgent treatment for heart failure to 37.0% compared with 39.1% with placebo over a median 21.8 months (HR 0.92, 95% CI 0.86-0.99).

Although technically a success, the trial’s modest main result did not reach a level of significance to the FDA’s likingopens in a new tab or window, and there were no benefits on any of the secondary efficacy endpoints, such as cardiovascular death or quality of life.

“I would have been encouraged if there was a quality-of-life benefit … There wasn’t any evidence, despite the 8,000-patient study here, of a quality-of-life benefit and that makes this less attractive,” commented Steven Nissen, MD, a cardiologist at Case Western Reserve University in Cleveland, who voted no on the drug.

Only in a subgroup analysis did a signal emerge that showed that HFrEF patients with the lowest ejection fractions perhaps had a larger treatment effect from omecamtiv mecarbil. FDA advisors did suggest more stringent labeling — limiting use to people with ejection fractions of 25% and below, for instance — if omecamtiv mecarbil were to be approved.

Advisory committee members also recommended including a contraindication for people with atrial fibrillation (Afib) or atrial flutter in omecamtiv mecarbil’s label if it were to be approved, as this subgroup had excess cardiovascular deaths taking the drug in GALACTIC-HF.

Due to safety concerns related to high exposure to omecamtiv mecarbil, its manufacturer, Cytokinetics, has proposed that oral dosing should be guided by plasma concentrations of the drug, albeit as measured by a central laboratory assay that has not won FDA approval or clearance. The advisory committee members agreed that pharmacokinetic-based dosing — similar to what was used in the phase III trial — would be essential for the safe and effective use of the drug.

Cardiologist Christopher O’Connor, MD, of Duke University in Durham, North Carolina, and Inova Heart and Vascular Institute in Falls Church, Virginia, said that omecamtiv mecarbil presents a path, even if it is a narrow one, to proceeding safely to provide benefit to a selected population of high-risk HFrEF patients. He was one of the three committee members who voted yes on the drug.

Nissen highlighted the need for the single trial to be replicated, recommending a future study in a focused population with no Afib and low enough ejection fraction to see clinical benefits.

The FDA is not required to follow the advice of the advisory committee, but it often does.

Source:Medscape

Billion-dollar NASA satellite launches to track Earth’s water

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SWOT satellite will bounce radar off water bodies to give scientists a new window into climate change and the global water cycle.

Aerial drone view of a river created by the melting glacier Mýrdalsjökull, Iceland

A river created by a melting glacier in Iceland: SWOT will track the world’s water bodies in unprecedented detail.

From swirling ocean eddies that help shape the global climate to millions of lakes and rivers, scientists are about to get an unprecedented view of Earth’s water.

The US$1.2-billion Surface Water and Ocean Topography satellite (SWOT), which launched at 6.46 a.m. Eastern time on 16 December from the Vandenberg Space Force Base in California, promises to transform research into the global water cycle and provide climate scientists with a fresh lens on a warming world.

A joint mission led by NASA and the French National Centre for Space Studies, SWOT will bounce radar off the surface of Earth’s water bodies — including many that are too small to be tracked from space by current methods. The satellite will enable scientists to measure and track the elevation, extent and movement of water across the planet in ground-breaking detail.

“It’s a game changer,” says Rosemary Morrow, an oceanographer at the Laboratory of Space, Geophysical and Oceanographic Studies in Toulouse, France and one of the science leads for the mission. “It will be like putting on a pair of glasses when you are short-sighted: things are sort of vague, and then suddenly everything comes into clarity.”

Lakes and rivers

There are currently publicly available data for just 10,000–20,000 of the roughly 6 million lakes and reservoirs larger than one hectare on the planet today, says Tamlin Pavelsky, a hydrologist at the University of North Carolina at Chapel Hill and another of SWOT’s science leads. SWOT will measure nearly all 6 million every 10 or 11 days. “We’ve never had measurements like this before,” says Pavelsky. “We don’t even have a baseline.”

In 2021, a team led by Sarah Cooley, a geographer at the University of Oregon in Eugene, pieced together existing satellite measurements of surface area and water elevation for some 227,000 lakes1, but Cooley says those are available only every 90 days. “The data that will be provided by SWOT is orders of magnitude beyond what we were able to do,” says Cooley.

SWOT has already helped to generate advances in river hydrology. In anticipation of the satellite’s launch, researchers developed new ways to convert measurements of water height, extent and elevation change into flow estimates2. Applying those techniques to existing satellite data, scientists estimated that rivers carried up to 17% more fresh water into the Arctic Ocean between 1984 and 2018 than previously thought3; SWOT is expected to refine this estimate while enabling similar work across the globe.

“If SWOT does what we think it’s going to do, it’s going to change the face of hydrology,” says Colin Gleason, a geographer at the University of Massachusetts Amherst and an author of both studies.

Ocean eddies

Similar advances are expected at sea, where SWOT is expected to provide high-resolution measurements that will allow scientists to track currents, swirling eddies and the ebb and flow of tides. These will bolster understanding of water circulation and improve high-resolution models that can track the transfer of heat and carbon dioxide from the warming atmosphere into the depths of the ocean.

SWOT will give scientists their first 3D view of eddies, for example, and will be able to detect perturbations around 10 kilometres wide — one-tenth the scale of the best measurements that are currently available, says Morrow. Even these small features are crucial to understanding and predicting the climate, she says.

An international consortium involving the United States, France, Australia and others is planning field expeditions at 18 ocean sites around the world next year. These will help to calibrate the SWOT data against on-site measurements under a variety of ocean conditions.

“We’re really really excited, but the proof is in the pudding,” Morrow says. “We’re waiting to see what information comes out.”

Souce:Nature

‘Avatar The Way of Water’ movie review: Visually gorgeous, James Cameron’s film repeats original’s mistakes.

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https://www.wionews.com/entertainment/hollywood/news-avatar-the-way-of-water-movie-review-visually-gorgeous-james-camerons-film-repeats-originals-mistakes-543654?utm_medium=Social&utm_source=Facebook&utm_campaign=FB-M