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DOWN May Release New Music in 2024, Says Guitarist KIRK … – Metal Injection

Crowbar guitarist Kirk Windstein has hinted that Down may release new music in 2024. In a new interview with Scott PenfoldofLoaded Radio earlier in October, Windstein said that he and his bandmates are planning to get together soon to start writing and recording.

Down is a supergroup that besides Windstein features Philip Anselmo of Pantera, Pepper Keenan of Corrosion of Conformity, plus Jimmy Bower and Pat Bruders of Eyehategod. The band has released four albums to date, the most recent being Down IV Part Two in 2014.

"I talked toPhila pretty good bit, and we're all gonna go out to his house and his property later this month He kind of does like a little Halloween thing or whatever. So we're gonna do that." Windstein offered.

"Phil's attitude is kind of just like, 'Look, fellas, I'm doing what I'm doing withPantera. I love it. We're killing it.' And boy, are they. We had the pleasure of playing withPanterain Poland in early June. It was unbelievable. I mean, I laughed, I cried. My emotion was something else, because I was very tight withDimebag. It's real what they're doing is real. But whatPhilsaid, 'Hey, man, in the big picture of things, dude, I really don't have a band. I'm doing aPanterareunion thing.' And of course they're gonna do it as long as they can. I mean, I don't blame them. Who would? You do what you've gotta do. And they're killing it and doing it heartfelt for the right reasons, and I love it."

"But like he said, 'Look, you are the guys.' And I talked toPepperabout two or three days ago. I think he's got a few shows in early November withC.O.C.and he's off for a while.Crowbar's next gig is in Ireland in late February, so we're off for a good bit. And when you have five guys well, Phil, of course, will be kind of out of the picture for now but me, Pepper, Jimmy and Pat in a room together, when you've got all these guys writing riffs off of each other And that's the way I like to write I like to write spontaneously off the cuff. I don't like to [go], 'Okay, this is my new song. Boom. Here y'all go,' or whatever. I like to write off the cuff, on the spot. I feel what the other guys are giving me vibe-wise and whatnot. And that, to me, is a winning formula. It really is."

Windstein also said that he hopes the band can release an EP of six new songs in 2024. However, he admitted that it's too early to say for sure if that will happen.

"We talked about doing like a cover-song EP. But we threw around like a hundred songs and we can't pick and choose any of them. So, to me, it's easier to just go, 'Hey, guys, let's get in the fucking room and just write some shit.' Come out with six songs and do an EP. So I hope that that's what happens."

"To be honest, I don't know," he added. "And this is not from Phil or Rex or anything. They can do the Pantera thing forever. Like as far as festivals in South America, Europe and whatnot, they can they can always go do a weekend or two in the summer here and there between Zakk and Charlie's schedules whatever they're up to with their respective bands. So I hope that they do. I hope they do it forever."

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DOWN May Release New Music in 2024, Says Guitarist KIRK ... - Metal Injection

SHARON OSBOURNE Blames Greedy Managers For The End Of … – Metal Injection

If you were into rock and metal inthe late '90s and early 2000s, you went to Ozzfest and you've got an insane story about it. The fest ran as a touring entity between 1996 and 2010, and then as a one-off thing between 2013 and 2018 (sometimes in conjunction with Knotfest). Ozzfest was notable not only featuring the biggest names in the rock and metal worlds during its touring days, but also for breaking smaller bands to much wider audiences.

So what the hell happened to one of the most beloved touring festivals? Money. According to Sharon Osbourne in the newest episode of The Osbournes Podcast, Ozzfest's demise had everything to do with finances.

"Yeah, it was a very weird beast because all the bands were our mates, but the managers were greedy and for some reason they thought that we were making billions on it and we weren't. We made a profit. But it was not like we couldn't retire on it. And managers and agents wanted more and more and more, and it just wasn't cost effective anymore. We stopped, because it just wasn't cost effective."

Osbourne continued: "Years and years ago, one of the bands it was the second Ozzfest we did, or the third wouldn't go on stage until I agreed to give them 10,000 more dollars. And they were holding everything up, and I said, 'Of course, of course I'll give it you.'" Sharon's son Jack Osbourne asked who demanded the money, to which Sharon replied "Glenn Danzig." Jack was clearly not pleased and responded: "Why are you gonna protect that twat?"

Sharon clarified: "[I] didn't give them the money They went on and played, and I went, 'Fuck you. You signed a contract, your agent agreed it, and you're just gouging.'"

For the record, there was also a digital Ozzfest in 2022 and it sucked.

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SHARON OSBOURNE Blames Greedy Managers For The End Of ... - Metal Injection

IN FLAMES Frontman ANDERS FRIDN On Watching A Live Show … – Metal Injection

In a recent interview with Jaimunji of Australia's Metal Roos, In Flames frontman Anders Fridn was posed with a question that has been plaguing live music events for quite some time now: the proliferation of smartphones and their role in our concert experiences. The issue of concertgoers incessantly using cell phones to capture moments instead of immersing themselves in the music is a topic of debate that continues to divide fans and artists alike.

Fridn expressed his own stance, asserting, "For me personally, being on stage, I'm not bothered anymore. It's up to you. Sorry to say, but if you're that stupid to go to a live show and then you watch your little screen instead of experience what's going on, I feel that's a missed opportunity." While his words may come across as blunt, they convey a sentiment that many live music enthusiasts can understand.

"But who am I to judge? You do whatever you want. It's your money, it's your experience, and I can't change that. But I wish people put the phones in their pockets. 'Cause when they look back at this, it will be a shitty sound on your phone or you watch something on YouTube or you upload it whatever you do. And then you were in that room and you could have had that experience, which is way greater than watch your little screen. But people can do whatever they want." he added.

Fridn concluded, "I will never lock up their phones and say anything. Once in a while, I say stuff on stage where I go, 'Put that phone in your pocket and go into the circle pit.' But I don't mean that in a bad way. It's just a recommendation. It is what it is, and you can't change people. It's the way we live now."

In an era where live performances are shared instantly across social media platforms and stored as digital keepsakes, the allure of experiencing a concert in the present moment often gets buried beneath a barrage of screens.

The live music experience is a unique and fleeting moment in time. Remember that the next time you have your phone in the air filming a video you'll probably never watch again. The mosh-pit is a hell of a lot funner!

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IN FLAMES Frontman ANDERS FRIDN On Watching A Live Show ... - Metal Injection

LARS ULRICH Reveals How METALLICA Kept On During The … – Metal Injection

In a recent interview with the official Metallica fanzine So What!, drummer Lars Ulrich reflected about the turbulent journey the band undertook while navigating the challenges of crafting new music and supporting their lead singer, James Hetfield, during and after his rehab stint.

Batting back a question about whether he considered that the band might be over in the wake of Hetfield's situation, Ulrich noted: "That falls into the 'what-if' questions, and Im never a big proponent of the 'what-if' question. 'What if this happened instead of that?' Well, it didnt. We moved forward with the situation that were in."

The drummer went on to say that the band knew they needed to give Hetfield the space he needed to recover, and that they were willing to suspend everything else in the meantime. He also said that the pandemic, which hit shortly after Hetfield's return to rehab, gave the band even more time to focus on their inner dynamics and figure out how they wanted to move forward.

"What James went through at the tail end of 19 into 20 was something where it really felt like I and the rest of the guys in the band had to give him the space that he needed, had to really take a step back, and just suspend everything that was on the table. We needed to do that for our friend and for our bandmate and partner. Then, slowly, the pieces started coming back together in the spring of 20, and then everything got side-swiped by the horrific [events] of Covid and the lockdown. So, as we were giving the inner-band dynamics the time that they needed, we realized that there was no need to rush anything. And at the same time, like I said before, [we were] trying to figure out: how does Metallica make a difference, how can music make a difference, what can we do?"

For Ulrich, the key to making sure Metallica emerged from that period intact and in a good place to kickstart their next chapter was to simply keep the band moving, however slowly or methodically.

"I still cant get away from the analogy Ive said a million times: youre trying to keep the train on the tracks," he explained. "You dont want to necessarily 100% force its direction, but you want to ensure the train doesnt derail. And when I think back on 2020, thats kind of the overview. Obviously, there were a couple of things. There was the drive-in theater concert, and every time that we got back together, every time we would do Zoom calls or whatever, we would start understanding what headspace everybody was in and what everybody was capable of and willing to do. Also, where all the boundaries were as you were trying to move it forward." Ulrich explained.

"But nothing radically different than other times that wed been challenged in the past, so theres a part of me that sort of just you roll your sleeves up" Ulrich added. "You want to get back and get engaged. You accept the parameters that are put on it, and you try to make progress within those. Three years later, we have this incredible record. Its hard to believe that a part of what lives in this record the energy, the lyrics, the themes, production, all of it isnotsomehow correlated to the challenges that were thrown our way."

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MIKE MANGINI On DREAM THEATER Reuniting With MIKE … – Metal Injection

Dream Theater reunited with founding drummer Mike Portnoy in late October, meaning longtime drummer Mike Mangini was out of the band. Portnoy parted ways with Dream Theater in 2010 and was replaced by Mangini between from then until this year. Mangini's time in Dream Theater also yielded the band's only GRAMMY, which they won for Best Metal Performance in 2022 for the song "The Alien".

In an interview with The Mistress Carrie Podcast, Mangini spoke a little about Dream Theater's choice to have Portnoy rejoin, saying that he simply understood the decision.

"The situation made sense to me when I heard it in that I don't know, I guess I just skipped out and thought, 'Oh, that's an original band member going back to a band. Oh, I get that. Okay, I get it.'" said Mangini. "And that's it. I mean, that is literally it."

He continued: "A decision was made that I understood. That's all it is. 'Cause when I heard the decision, I understood it. I tried to explain that I understood the parameters of that being a music thing. Anyway, it's as simple as that. And I'm telling you, I was, like, 'Okay, 'I get that.' I was with the band for 13 years. It was an unbelievable experience."

Mangini has since announced his new solo album Invisible Signs due out November 11. Upon Portnoy's rejoining, Mangini offered similar sentiments on his departure: "I understand Dream Theater's decision to get Mike Portnoy back at this time. As was said from Day 1, my place was not to fill all the roles that Mike held in the band. I was to play the drums in order to help the band carry on. My main role of keeping our live show working tightly on a nightly basis was an intense and rewarding experience.

"Thankfully, I got to experience playing music with these iconic musicians, as well as some fun times laced with humor. I also really enjoyed spending lots of time with the crew. And then there's the GRAMMY win, which was amazingly satisfying. To the fans: thank you so much for being amazing to me. I cherish the pictures I have of you all losing your minds and having fun. Finally, I really love the band, crew and management and wish them and the entire organization all the best."

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CHIMAIRA Announces First Festival Appearance In 14 Years – Metal Injection

Chimaira has announced their first festival appearance in 14 years for the upcoming Inkcarceration Music & Tattoo Festival. The festival will take place between July 19 and 21, 2024 at the Ohio State Reformatory in Mansfield, OH. Chimaira has only promised that there's more news coming this week, so stay tuned! Here's hoping there's a full-on reunion in the works.

"We are pleased to announce our first US Festival appearance in 14 years," wrote Chimaira of the appearance. "Join us this July at the Mansfield Reformatory for Inkcarceration Festival 2024!" They added: "More announcements to come this week."

Chimaira's lineup for the shows is vocalist Mark Hunter, guitarists Rob Arnold and Matt DeVries, bassist Jim LaMarca, keyboardist Chris Spicuzza, and drummer Austin D'Amond. Tickets are available here.

As for Chimaira, they split up in 2014 and have thus far played three reunion shows (outside the planned 2024 one) one in 2017 and two in May of this year to celebrate the 20th anniversary of The Impossibility Of Reason. Chimaira has not reunited in any long-term capacity just yet, though new music seems like a very slim possibility? In an interview with The Ex-Man With Doc Coyle, Arnold said the situation was complex.

"I won't say that new Chimaira material, while we're not talking about it, is completely off the table. But there's a very good chance we may never have it, but there may be. We all know in Chimaira that people want more music but like you guys I'm sure, we're not a band that's going to throw something together just because. There's going to be so much planning and stewing to make that happen.

"We've actually tried maybe you heard we were kind of geared up after that last show as you know, things were great. As you know, God Forbid is probably fired up right now, but then the pandemic hit and it just wiped everything out. It just stopped completely. Now for these shows it's re-getting everything going again."

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CHIMAIRA Announces First Festival Appearance In 14 Years - Metal Injection

The Year of the Periwinkle Rio Renato Pulido Constantino – BusinessMirror

Every weekend, amateur botanists and semi-professional gardeners gather in eager droves at the Quezon City Memorial Circle Plant Center.

Sheltered from the heat and smoke of Metro Manila, a sea of green in the concrete jungle, the place is a plantitas paradise. Orchids, lilies, and hoyas, monsteras and aloe vera, forests of dahlias, begonias, and geraniums. If theres any place to look for the Madagascar periwinkle, scientific name Catharanthus roseus, known locally as tsitsirika, its here.

Borne out of Africa by European ships sometime in the 16th century, the periwinkle is a healers plant. Ayurvedic sages squeeze the flowers juice out to relieve wasp stings. Chinese herbalists brew the glossy green leaves into a decoction for malaria. Search for the plant on Facebook; look it up on Lazada. Many claim the plant can treat acne, eczema, diabetes, cancer, and more.

Not all these therapeutic claims are supported by the facts. Most lack sufficient clinical testing and evidence. Still, theres reason why the plant is known to apothecaries and pharmacists alike. Of all the illnesses reputedly healed by the periwinkle, there is one disease for which it can irrefutably provide a cure. Can you guess which one? Hint: it starts with the letter C.

Ever since it spurred the development of new chemotherapeutic drugs during the mid-20th century, the Madagascar periwinkle has helped save hundreds of thousands of lives. Last year, to my unending surprise, it helped save mine.

I was diagnosed with a rare form of Non-Hodgkins lymphoma, a cancer of the immune system, last December 9, 2021, at the age of 23. I was in my last year of a B.S. Biology program, and had just won first prize in a research competition about Philippine biodiversity. When I was rushed to the hospital late one night for excruciating chest pain, my first thought was COVID-19. Instead, the doctors found a tumor the size of two clenched fists wrapped around my heart, with smaller tumors splattered across my lungs, liver, and spleen.

I remember only a few searing images from the days surrounding my diagnosis. My mother and I in the ER, about to be referred to the oncology department; an ominous PET-CT machine, thrumming as it scanned my body for cancer; a revolving door of doctors asking repeated questions about my symptoms. Had I noticed anything odd in the weeks leading up to admission? No, just some vague shortness of breath, which I thought was asthma.

For the next four months, I was told, I would need to shuttle back and forth between home and hospital for treatment. One week spent in-patient to receive chemotherapy, two weeks at home to recover, and then again, rinse and repeat, until the entire ordeal was done. Because chemotherapy weakens the immune system, I was banned from eating sushi and salads for fear of Salmonella. I would need to remain in isolation the entire time to avoid COVID-19. No one outside my immediate family, not even my grandparents, would be allowed to visit.

My father and I marked the holidays by getting rid of our hair. I shaved his head, he shaved mine. By the time chemo began just a few days before Christmas, I was already falling into an abyss so deep and black it swallowed everything, leaving only a blank terror in the mind.

To appreciate the power of the Madagascar periwinkle, we first have to understand life at the scale of the cell. Every human cell contains organelles, tiny structures roughly analogous to the larger organs of our bodies. The cellular version of the skeleton is called the cytoskeleton. It has three types of bones: microfilaments, intermediate filaments, and last but not least, microtubules, which span the entire volume of the cell like a network of microscopic pipes. During cell division, microtubules are responsible for directing newly duplicated chromosomes to their respective daughter cells. Without microtubules, the cells entire internal organization collapses, its ability to reproduce itself snuffed.

Our cells normally run like tightly controlled machines. They divide only when they need to, stay docile when they dont, following the instructions contained by their genes to the letter. However, when these instructions are effaced by mutation, which can be caused by anything from radiation to cigarette smoke or just plain old bad luck, the cell goes haywire. It rampages, a berserk robot on a malfunctioning assembly line, only this time the robot can make more and more of itself until the entire factory is overrun. The mutated cells spread to the lungs, liver, and spleen. Left unchecked they will invade gut and kidney, brain and bone. This is cancer.

The team of Canadian scientists who stumbled upon the Madagacar periwinkle werent actually looking for new anti-cancer drugs. A Jamaican colleague had sent them a few periwinkle leaves, explaining that the plant was used locally to brew a tea for diabetics. He wanted them to check if the leaves had any actual anti-diabetic effect.

The Canadians began their tests by injecting diabetic mice with crude periwinkle extract. The mice died. Why? Apparently, rather than controlling blood sugar, some compound present in the extract disintegrated microtubules, especially those found in rapidly dividing cells. One consequence of this was the destruction of the mices rapidly dividing, blood-forming bone marrow, leading to a catastrophic drop in white blood cell counts and a dysfunctional immune system. Taken orally as part of a tea, the compound had no significant effects. However, at higher concentrations, and injected directly into the bloodstream, the result was deadly.

The mice died of blistering infection.

Some cancers, however, like lymphoma, are caused by the abnormal proliferation of mutated white blood cells. By interfering with microtubule formation, the periwinkle extract could also short-circuit cancerous cell division. The rampaging robot stops, falls apart.

Realizing the significance of their discovery, the Canadians worked to refine their crude extract. By 1962, they could reliably isolate the first of a class of microtubule disrupting, cancer- killing drugs now called the Vinca alkaloids, after the Madagascar periwinkles old scientific name, Vinca roseus. Vincristine, one such alkaloid, became part of the first multi-drug regimen to produce a durable cure in cancer patients.

Unfortunately, vincristine can be a double-edged sword. Chemotherapy disrupts cell division in healthy tissues as well. Hair, the acid-worn lining of the stomach, blood-forming bone marrow, all require constant cell division to regenerate themselves and function properly. Hence the familiar side-effects of cancer treatment: hair loss, debilitating nausea, crippling fatigue.

My chemotherapy regimen consisted of five drugs: vincristine, as well as rituximab, etoposide, cyclophosphamide, and doxorubicin. In an IV bag the latter three form an evil- looking, reddish orange liquid, a potion straight from hell.

By the third day of every week-long hospital stay I would be wholly confined to the bed. Think of the worst flu possible. Imagine running a ten-mile marathon and being mauled by sledgehammers immediately after. Its unexplainable. Your muscles crumble, your gut falls apart. Locked in the chilly confines of a cramped hospital room, assisted by my mother whenever I needed to go to the toilet, I would spend entire afternoons trying not to vomit.

Overwhelmed by the sudden awareness of my own mortality, I became obsessed with my disease. I read each and every WebMD article, prowled Facebook patient groups at 3 a.m., skimmed the latest obscure reports on the latest arcane drug trials. I memorized survival rates: about 90% of patients with my kind of cancer are cured with first-line treatment. The remaining 10% tend to be unresponsive to further therapy people of dismal prognoses, as one research paper called it.

The fact that about 90% of patients are cured, that I could be cured at all, should have been reassuring. Except it wasnt, not really. Think of it like a game of Russian roulette. Five out of six chambers promise salvation and are empty. The last contains a bullet. Put the barrel against the side of your head and consider: when its life or death, are there ever any safe bets?

Not that I had a choice. Back home, exhausted, I watched the ashen light pouring past my window. Stranded in my own personal limbo, barred from any meaningful contact with anyone beyond immediate family, life took on a spare, ascetic quality. Time shrank. The past became a fading blur, the future disintegrated. My room became my monastery. There was only treatment and what was necessary to get past it.

Sometime that summer, a pair of olive-backed sunbirds made a nest above my parents balcony. Tiny, joyfully-colored birds with bright yellow chests and long thin beaks for probing nectar, sunbird males can be differentiated from females by their iridescent blue throats. The pair in question had been scouting my parents balcony for some time. They came by every morning, whistling their high-pitched, outsized song weet weet! while hopping from branch to branch. Evidently something about the place made them happy, and we were relieved to have them too.

The one point of hope during those impossible days was my oncologist, a fierce, grey- haired tiger of a woman who made tumors tremble at her approach. At the beginning of my treatment, she explained the plan clearly and succinctly. If A happens, then B. If C happens, then D. Would I be ok? What were my chances? I dont like talking about chances, she said. Dont worry, well take care of you.

I completed chemotherapy early April. I wasnt expecting much. A while before I had done a mid-therapy PET/CT scan to assess how treatment was going, and the results werent encouraging. The main mass choking my heart had shriveled away, and so had the smaller tumors in my lungs, but the ones peppering my spleen and liver were unchanged. No growth, but no decrease either, which suggested a dire possibility. As with antibiotics, the best bet with chemotherapy is to eradicate the disease entirely by the first attack. Should any cancer cell survive the initial wave of medication, they will, by force of evolution, pass down their chemo- resistant genes to their offspring, who will continue to explosively multiply.

Undeterred, my oncologist scheduled another PET/CT scan. The morning after the scan I went immediately to the hospitals online portal to download the results. I read it from top to bottom: complete remission. No detectable cancer. No active tumor anywhere in the body. I was clean. Clean, clean, clean.

My mother wept with joy. So did my aunts, my grandmother, and probably my grandfather as well, at least after the video call was over. My father became teary eyed too. But not me. I felt empty. My emotions were less happiness than exhausted relief. The marathon, for now, was over. Time to crawl back into bed for a long nap. Everything else could come after.

Once I had awoken weeks later, it was finally time to put the pieces back together. And of the many thoughts and desires that crystallized out of the chaos, there was one that burned with immediate urgency: Field. Work.

As Ive mentioned before, Im a training biologist, specifically a budding field biologist, a would-be sage of tropical biodiversity. I dont know why. Ive been a city boy all my life. Maybe it was all the National Geographic Channel programs as a child. Or maybe its because I live in one of the most biodiverse countries on Earth, a place so dense with life that in terms of species per square kilometer it rivals the Amazon Rainforest. In any case, there is something about the non-human world, the secrets of birds, the intelligence of bees, the constant flow of energy from mortal coil to fertile soil, which calls me.

Except, of course, that I was a student during a global pandemic, and face to face classes were still suspended, including fieldwork classes. I got desperate. Nobody wants to be a field biologist with only theoretical knowledge of the field. More than anything I wanted to avoid dying not even a full apprentice of my chosen trade.

An opportunity arose in July. With the recent dip in COVID cases and loosening of quarantine restrictions, my college was organizing a week-long field ecology class in a forest near Subic Bay. One of the professors sent a message. Would I like to come?

I was at the college by 5:00AM on departure day, bags full of shiny new gear: wet boots, sleeping bag, Swiss knife, journal, pencil, headlamp. We left about an hour late under a pale drenched sky and had breakfast at a Pancake House by the highway. By the time our vans arrived at the trail to the campsite, a grove of mahogany trees by a rushing river, the ground had long turned to squelching mud.

An important lesson: always bring your own tent. I had the brilliant idea of saving money by borrowing an extra from the professors, only to discover that extra tents are extra because theyre old and leaky and nobody wants them.

We caught, measured, tagged, and released a number of beautiful birds, including an ashy ground thrush and an indigo-banded kingfisher. Our guide poked open a small hole in a rod of bamboo, revealing a wriggling colony of tiny, snub-nosed bats, insectivorous members of the genus Tylonycteris, smaller than your palm and crabby at having their home broken into (the bamboo was glued and tied back into place later). We ran after frogs and toads, snakes and lizards, chased after insects with glass jars in hand. An absurdly wishful part of me wanted to see a cloud rat, an adorably furry rodent found only on Philippine mountaintops, but alas, it was not to be. Our rodent traps failed, the coconut and peanut butter bait eaten by ants. We spent an entire day counting and identifying trees, arguably the most exhausting part of the entire class. After all, how many trees do you think are there in a forest?

A wasp stung my palm as I blundered through the underbrush. It swelled for the entire day. Mosquitoes and other ungodly bugs feasted on my legs. Blisters, scratches, welts. None of it mattered. The rain stopped. Patches of blue sky shone through the canopy. I was here, alive, surrounded by tropical heat, slipping through pools of verdant sunlight.

I mentioned receiving five drugs for chemotherapy. Two of them were created solely in the lab: rituximab, a monoclonal antibody, and cyclophosphamide, manufactured from the same class of chemicals used to make mustard gas (which, I was surprised to learn, has no actual relation with the mustard plant, except for the name and similar odor). The remaining three can be traced back to wild plants and bacteria. Vincristine comes from the Madagascar periwinkle. Etoposide comes from the wild mandrake, a poisonous plant common to North America, once used by First Nation communities to heal warts. Doxorubicin was isolated from a mutated strain of Italian soil-inhabiting bacteria.

This shouldnt come as a surprise. Many modern drugs and technologies come from the most innocuous of natural sources. PCR tests for COVID-19 depend upon an enzyme from Thermus aquaticus, a heat-resistant species of bacteria first discovered from a geyser in Yellowstone National Park. Ziconotide, a potent painkiller about a thousand times more powerful than morphine, is derived from the poison of Conus magus, a cone snail native to the Philippines. Artemisinin, used to treat malaria, is extracted from Artemisia annua, the sweet wormwood, an herb commonly used in Chinese traditional medicine. According to writer-oncologist Siddhartha Mukherjee, between 1954 and 1964, the National Cancer Institute of the United States would test 17,200 plant derivatives looking for new cancer drugs, using up close to one million mice for experiments in the process.

Screening the natural world for new products is big business. So it was with the Madagascar periwinkle. The Canadian researchers who worked on the plant were supported by the Eli Lilly company, perhaps better known for releasing the first commercially available insulin in the early 20th century. Eli Lilly gave the Canadians access to expensive chemicals and bigger, better equipment. In return, the researchers helped generate a lucrative, life-saving product. By the early 2000s, Vinca alkaloid sales would net Eli Lilly around 100 million dollars in annual profit.

Yet rampant extraction has a price. The United Nations Food and Agriculture Association warns that around 10 million hectares of forest are destroyed each year. Conservationists estimate that Madagascar has lost close to half its forest cover since the 1950s. The Philippines has lost its forests at a similar if not greater rate. What happens when all forests have been logged down? When all springs have been polluted with filth? What new miracle cures then?

Near the end of our field ecology class, we went to a nearby shore to practice aquatic sampling. We waded into the sea, nets and other scientific instruments in hand to study fish. By mid-morning, we had set the nets aside and spent the rest of the day swimming. Why? There were barely any fish. There was barely anything to do science with. Our professor had been bringing students to that spot for just over half a decade, and in that span of time he witnessed the bay go from somewhat intact coast to a barren, garbage strewn wasteland. The fish had been consumed, replaced by industrial waste. We are literally, he said, in a combination of indignation, disbelief, and sorrow, emptying the sea.

On the ride home from Subic, I watched the silver countryside rush gleaming by. Interconnection is a fundamental theme of ecology. Its a tangled science, sensitive to obscure yet essential linkages. Sunlight is captured by leaves, which are plucked by herbivores, who are hunted by carnivores, who themselves eventually die of hunger or old age, to be decomposed by fungi back into the earth. Ultimately, even the most urban of us need good soil, clean air, and clear water to survive.

With that as my starting point, I wanted to know: How many beings do I owe my life to? Its a question of gratitude. By all rights I should be dead, and yet I wasnt. I was saved. By who? And how many? How far back do the vital connections go?

The 1958 paper publicly announcing the discovery of a new class of chemotherapeutic drugs from the Madagascar periwinkle has three listed authors: James Cutts, research fellow of Canadas National Cancer Institute, Charles Beer, distinguished chemist and British Empire Cancer Exchange Fellow, and Robert Noble, team lead and member of the Canadian Medical Hall of Fame.

At the end of the paper, briefly mentioned in the acknowledgements, is Halina Czajkowski Robinson, Polish immigrant and survivor of Auschwitz, who joined the team as a lab technologist in 1951. She was the first to notice the stark drop in white blood cell counts caused by periwinkle injections in mice. Recognizing the significance of her observations, she was quick to inform her supervisor. He had another hospital double-check her results. Without Robinsons keen work, nobody might have noticed anything amiss about the poor mice.

Where did the lab get their samples from? The initial material came from Dr. C. D. Johnston of Black River, Jamaica, who sent the first periwinkle leaves to Canada.

He learned about the plant from a chatty local, who brewed a tea for diabetics from the leaves of an alien plant. The doctors wife, Mrs. Julia Johnston, organized a troop of boy scouts to scour local forests for the leaves, before drying and preparing them for delivery on her own veranda.

The list of names goes on and on. How did that chatty local first learn of the periwinkle? Remember, the plant isnt native to Jamaica. Perhaps they heard about it from Indian and Chinese immigrants to the country (mostly indentured laborers under the British empire), or overheard a passing merchant extolling its qualities on the docks (19th-century British salesmen marketed the plant as a cure-all for diabetes). So many chance conversations, so many small meetings had to happen for the periwinkle to reach me. Each of us exists embedded in a web of relationships, the trail of connections extending far back in space and time.

Some parts of the story I do know for certain. Who saved my life? First and foremost, my medical team. My general of an oncologist. The residents and fellows who work with her. My surgeons, pathologists, and anesthesiologists. My cardiologist. My nurses, who always checked in on me when I was in the hospital, and who never failed to fix the beeping IV drip when it woke me up at night.

Family and friends. Cutts, Beer, and Noble. Czajkowski and Dr. Johnston. The mice.

In case of emergency, wrote the poet Sandra Cisneros, Contact nearest/cloud. Begin by/calling Milky way. Summon the Madagascar periwinkle. Call the wild mandrake. Invoke bacteria. Greet the sunbirds. Stretch and exercise the human capacity for empathy, because isnt a little stretching good every once in a while? Think of all the mice sacrificed for the sake of modern medicine. How many legions of murine souls watch us from rodent heaven, observing our silly antics with beady, inscrutable eyes? I imagine them peering at me through a break in the clouds: all this, just to save a life.

The weeks after fieldwork were filled with joyful excess. I went bar-hopping with friends. I ate everything I was banned from eating during chemotherapy. In August, we flew with my grandparents to Turkey, eager to experience Turkish hospitality and the winding, weaving, melting-pot chaos of their bazaars. We arrived in Istanbul one sunny afternoon, our plane flying over the waters of the Golden Horn, an estuary so named for its molten glow at sunset.

I vividly remember our second day at the ancient capital, once the home of Byzantine then Ottoman emperors. We were at a crowded square near the core of the city, surrounded by graceful mosques, fresh from the cardamom aroma of a spice market. Silver trees stood shining in the sunlight. The call to prayer rolled singsong over red-tiled hills. Our train card was empty and nobody knew how to refill it using the ticket machine.

We tried inserting the card into various slots. Nothing worked. We pressed random buttons, hoping for the best. The machine responded with angry gibberish. It flashed a series of terse instructions on the screen. The instructions were in Turkish.

Our hotel was an hours walk away. As families often do in such dire situations, we quarreled. Youre doing it wrong. Lets ask somebody for help. Again? None of us can speak the language! What if we just walk instead? Im hungry, lets eat.

Our furious chatter drew the attention a slender young man wearing a neon safety vest. Hello, he said, gingerly approaching us. Can I help you?

We stood for a moment like a herd of deer caught in the headlights. Oh! Oh, yes. We dont how to refill our train card.

Here, let me show you. He asked for the card and placed it on the screen. You press this, then this. You put your money in this slot.

We fumbled for cash in our pockets. No need, he said, fishing out a 50 lira bill from his wallet. Ill refill it for you.

We asked the young man about himself. Where did he come from? Syria, he said. He had come to Istanbul several years ago with his parents to escape the war.

Refugees. Right now he was working with the local tourist office to help lost visitors like us.

My father, effusive with gratitude, replied in Arabic. Hataa naltaqi mujadadan, inshallah. Till we meet again, God willing.

The young mans large brown eyes lit up in pleasant surprise. Mashallah! La mushkilata! Shkran! Yaetani! Wonderful! No problem! Thank you! Take care!

And we were on our way.

How breathtaking, the kindness of strangers. It reminded me of home. Like a wellspring, so many people stepped forward to help me during my time of need: aunts and uncles, godparents, old classmates, fellow cancer survivors, former teachers. To be loved is a permanent gift, carried across years and continents, a shelter to take refuge in during dark and difficult times.

After Istanbul we made short visits to the cities of Izmir and Bursa, saw the Roman Agora, lingered in the airy interior of the Grand Mosque, stayed for a while in dusty, golden Cappadocia. The warm memory of our Syrian friend would remain, together with all the other memories made during that trip, as our plane returned to Manila during a downpour, grey skies churning in the wake of a passing typhoon, in time for me to catch the lump that would appear on my neck later that September.

It has been difficult to describe, even to myself, the terror of the past year, the pain and grueling nature of chemotherapy, and the strain of living every day with death perched silently on your shoulder. It has been difficult to communicate the profound awareness of ones own mortality, the irrevocable loss of youthful invulnerability, and the feeling of having received, in what should have been the prime of your life, a glimpse of your frailty at 80. I am in ordinary times an avid journal keeper. I try my best to jot down an entry every day. But from the time I realized my cancer was back in September up to the beginning of a stem cell transplant in December, I wrote down nothing. Blank. Dead silence on every page.

I felt like a man on the execution block. I felt like someone scheduled to die. My namesake, Macario Sakay, was betrayed by a comrade while fighting against the Americans early in the 20th century. With the noose around his neck, he somehow found the grace and resolve necessary to bid farewell to his beloved country and hope for a brighter future. With death on my mind as well, I looked back at him with renewed awe. How did he ever muster the courage? From where are such reserves of willpower drawn?

My oncologist referred me to a new specialist, a hematologist, who explained that the next step would be a stem cell transplant. I would be given chemotherapy so intense and in such high doses that my bone marrow would be entirely seared away, leaving me, for a time, without an immune system, just like the mice experimented on during the early days of Vinca alkaloid research. To let me survive the procedure, they would extract stem cells from my blood before beginning treatment, putting the cells back into my body only once chemo was over, where they would then grow and replace my destroyed bone marrow. It would be hard, he promised, but Id get past it.

A litany of possible short- and long-term side-effects: Hair loss. Crippling nausea. Fatigue. Breakdown of the mucous membranes lining my digestive tract. Mouth sores. Loss of appetite. Vulnerability to infection for at least a year, while my new marrow develops. A small risk of heart failure. A small risk of developing a second cancer in the future, particularly leukemia.

Just half a year ago I thought I was cured, and now here I was again, seemingly back to square one. I could hear the angels of doubt swirling above my head. Why? How could this have happened?

Well, an angel answers. Around 400 million years ago a fish walks out of the sea. That walking fish gives birth to more walking fish, whose descendants become amphibians, reptiles, birds, mammals. From the mammals come the apes, and from the apes, humans. Some humans, the Austronesians, sail out of what is now Taiwan toward the Philippines. Those who stay in the archipelago intermingle with native communities, trade with China, embrace Islam, are colonized by the Spaniards, become Filipino, rebel, stage a revolution, eject the Spaniards, are invaded by the Americans, fail, resist again. Other Austronesians move on, some sailing all the way across the Indian Ocean, to a large island near the African coast, where they encounter a dainty-looking shrub with pretty flowers, a hardy inhabitant of sandy soil. Its the Madagascar periwinkle. You are born, a Filipino of the 21st century. We have come full circle.

Before handing me off to her hematologist colleague, my oncologist gave me her rosary. Keep faith, she said. Youll get through this. My oncologist has always been a bit taken aback by her patients stubborn agnosticism, one of the rare heretics in a majority Catholic country. She has always tried her best to understand all the strange talismans I bring with me to the hospital: wooden crosses, Buddhist prayer beads, a lucky sock, a favorite pen, the notebook my sister gave me for my birthday.

What lies beyond death? Perhaps birdsong, suggests Dr. Joey A. Tabula. Placing his stethoscope against the heaving chest of a man dying from COVID-19, he hears, to his surprise, crickets/the chirp of nesting sparrows/rustling of bamboo/burble of stream/the silence of an earthen jar filled with spring water. Whatever your approach to mystery, any gift sincerely given forms by itself a kind of miracle.

My hematologist was right the stem cell transplant was the hardest of all my cancer treatments. I was in the hospital for a month, reeling from body pains, nausea, and fatigue. All my food had to be sterilized beforehand to prevent infection. My white blood cell counts dipped close to zero. At one point I went down with a fever so harsh I became delirious, imagining myself writing poetry in some strange desert, the individual lines ringing so clear and true that the air sang as I spelled out the words in the sand.

And yet, after all that, here I am. I surfaced from delirium with a lingering sense of transformation. My stem cells engrafted to my bone marrow on December 7, 2022, a successful transplantation, almost a year to the day after my initial diagnosis. A few weeks later, the good news came through. I am cancer-free once again.

Theres a certain kind of vertigo that haunts patients who emerge intact from treatment. After spending so much time with your minds eye locked on the certainty of your own ending, the sudden influx of possibilities can be overwhelming. Will my cancer come back? What if I catch COVID-19? Are they still looking for research assistants in the lab? What happens now? Its like seeing the sky for the first time. Its like falling into space. The agony of hope is that no one can ever really predict the future.

Either way, I have lived a good life. An odd thing to say, but its true. I have seen my share of the globe. I have given my tiny contribution to science, however humble. I have had the pleasure of reading, of touching through countless pages radiant minds both living and long- dead, and of entering the boundless realms of story many times beyond measure. I have had the privilege and luck of affording quality medical care. And I have been blessed with the warm company of family and friends; the gift, in this winter of discontent, of witnessing love tried and tested and found true. The lens through which you view the world has been fractured and remade, infused with a different color, and now when you peer through the glass everything appears just an inch or so off-center.

Back at the Quezon City Memorial Circle Plant Center, I pay the shopkeeper for my potted periwinkle. I try to study the way her leaves branch off the main stem, the number of petals on each flower, how the yellow core of stamens and ovaries at the center of each pink bloom shines golden under the sun. Up above, white clouds float idly by. How nice it would be, to pass away under the infinite blue sky. There I will rise like smoke and become air. Ash to ash, dust to dust. Breath to shining breath. What was once I will melt away, the carbon, nitrogen, and oxygen of my body spinning away to join the atmosphere.

But first, home. My new companion needs a spot in the garden. Shes a pretty plant, tougher than she looks, with laughing flowers and long grasping branches. I cradle her close to my chest. So this is why people get into gardening. Theres something reassuring about carrying such a burden, the responsibility of it, the weight. It grounds you, steadies you, to hold a piece of life blooming in your hand.

Rio Constantino is a writer, biologist, and research associate. One of his essays was featured in the Bay Area anthology Humanity by Paloma Press (2018). Rios recent pieces are in https://lunariver.substack.com.

The Year of the Periwinkle won first prize in the Essay Category at the Carlos Palanca Memorial Awards for Literature (2023). This story was first published in the BusinessMirror.

Image credits: Zz3701 | Dreamstime.com

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The Year of the Periwinkle Rio Renato Pulido Constantino - BusinessMirror

The salvage role of allogeneic hematopoietic stem-cell … – Nature.com

Baseline characteristics

A total of 52 adult patients with R/R DLBCL were identified and enrolled. The median age at diagnosis was 45years (range, 1763), with marginal male predominance (n=30, 57.7%). 36 patients (69.2%) were identified as having an advanced-stage disease (Ann Arbor stage IIIIV), whereas 15 (28.8%) suffered from B symptoms. Thirteen patients (25.0%) had BM involvement of DLBCL at the time of diagnosis, and 8 of 13 (61.5%) had complex karyotypes. All enrolled patients were classified as low (n=15, 28.8%), low-intermediate (n=13, 25.0%), high-intermediate (n=14, 26.9%), and high (n=10, 19.2%) risks based on international prognostic index (IPI) risk classification. Four patients had a double-hit mutation (7.7%), and according to Hans criteria, 32 and 13 patients were categorized as ABC type (61.5%) and GCB type (25.0%), respectively. The baseline characteristics at the time of diagnosis are summarized in Table 1.

Notably, most enrolled patients had previously undergone intensive treatments, and the median number of chemotherapy lines before allo-HSCT was 4 (range, 26). Sixteen patients (30.8%) had previously undergone auto-HSCT, and the median time from diagnosis and auto-HSCT to allo-HSCT was 27.1months (range, 6.2117.7months) and 18.5months (range, 6.544.8months), respectively. The disease status at the time of transplantation was CR (n=14, 26.9%), PR (n=16, 30.8%), and active disease (n=22, 42.3%). Donor types included matched sibling (n=18, 34.6%), haploidentical (n=18, 34.6%), matched unrelated (n=11, 21.2%), and unrelated donors with one allele mismatch (n=5, 9.6%). The conditioning regimen comprised MAC (n=2, 3.9%) and RIC (n=50, 96.1%). Half of the enrolled patients were ABO-type matched (n=26, 50.0%), 27 (51.9%) were in donor-to-recipient sex mismatch, and 44 (84.6%) were both donor and recipient cytomegalovirus (CMV) IgG seropositive. Table 2 presents the demographic information of the patients who underwent allo-HSCT.

Over a median follow-up period of 38.3months (range, 1.9112.0), the estimated 5-year OS and EFS were 38.4% (95% CI, 24.751.8) and 30.6% (95% CI, 18.843.3), respectively. The estimated 5-year CIR, NRM, and GRFS were 36.7% (95% CI, 23.649.8), 32.7% (95% CI, 20.345.6), and 15.1% (95% CI, 6.926.2), respectively. Figure1 shows the 1-year (100days outcomes in CIR and NRM) and 5-year survival outcomes. Compared to the active-disease group, the remission-achieved group showed a significantly superior rate of CR in the first 3months after allo-HSCT (76.7% vs. 36.4%, p=0.003) and at the last follow-up (50.0% vs. 13.6%, p=0.006) (Fig.2). Moreover, except for NRM (26.7% vs. 40.9%, p=0.217), the clinical outcomes of OS (54.1% vs. 15.6%, p=0.001), EFS (46.4% vs. 9.1%, p<0.001), and GRFS (22.9% vs. 4.6%, p=0.002) were significantly superior in the remission-achieved group with lower CIR (26.9% vs. 50.0%, p=0.047). In detail (Fig.3), among patients in the remission-achieved group before allo-HSCT (n=30), 23 achieved CR, one achieved PR, four experienced disease relapse after allo-HSCT and died due to disease progression, and three died after engraftment (two from bacterial septic shock and one from veno-occlusive disease [VOD]) without relapse. In contrast, among patients in the active-disease group before allo-HSCT (n=22), eight achieved CR. However, only two remained in CR, four experienced disease relapse, and two died due to septic shock during disease remission. All eight of the remaining patients who achieved PR eventually relapsed, and six died after engraftment either due to allo-HSCT-related complications (one with grade IV hemorrhagic cystitis combined with renal failure, one with VOD, and two with grade IV acute hepatic GVHD complicated with liver failure) or infection (two with CMV pneumonia).

Survival outcomes of patients with relapsed/refractory diffuse large B-cell lymphoma after undergoing allogeneic hematopoietic stem-cell transplantation. The estimated 1- and 5-year (A) OS is 45.0% (95% CI, 30.758.3) and 38.4% (95% CI, 24.751.8). The estimated 1- and 5-year (B) EFS is 32.7% (95% CI, 20.545.4%) and 30.6% (95% CI, 18.843.3). The CIR and NRM at day 100 after allo-HSCT is (C) 15.4% (95% CI, 7.126.5) and (D) 17.3% (95% CI, 8.528.8). Furthermore, the estimated 5-year CIR and NRM are 36.7% (95% CI, 23.649.8) and 32.7% (95% CI, 20.345.6), respectively. The estimated 1- and 5-year (E) GRFS is 17.3% (95% CI, 8.528.6) and 15.1% (95% CI, 7.026.2). CI, confidence interval; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease-free, relapse-free survival; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

Response rate and clinical course of patients with diffuse relapsed/refractory large B-cell lymphoma after undergoing allogenic hematopoietic stem-cell transplantation. (A) Remission-achieved group: Among 30 patients in the remission-achieved group, the overall response rate (23 CR and 1 PR) was 80.0% (n=24) at 3months after allo-HSCT. At the last follow-up, 15 patients remained CR (including 1 PR patient who achieved CR after donor leukocyte infusion), but three died after engraftment without relapse, and six experienced DLBCL relapse. (B) Active-disease group: Among 22 active-disease group patients, the overall response rate (8 CR and 8 PR) was 72.7% (n=16) at 3months after allo-HSCT. However, at the last follow-up, only two patients remained CR, two died after engraftment without relapse, and 12 (4 CR and 6 PR) experienced DLBCL relapse. CMV, cytomegalovirus; CR, complete remission; GVHD, graft-versus-host disease; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; PD, progression of disease; PR, partial remission.

Comparison of survival outcomes between the remission-achieved and active-disease groups in patients with diffuse large B-cell lymphoma who underwent allogeneic hematopoietic stem-cell transplantation. The clinical outcomes of (A) OS (54.1% vs. 15.6%, p=0.001), (B) EFS (46.4% vs. 9.1%, p<0.001), and (E) GRFS (22.9% vs. 4.6%, p=0.002) were significantly superior in the remission-achieved group with (C) lower CIR (26.9% vs. 50.0%, p=0.047), except for (D) NRM (26.7% vs. 40.9%, p=0.217). CI, confidence interval; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease-free, relapse-free survival; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

The overall cumulative incidence of grade 3 to 4 acute GVHD and moderate-to-severe chronic GVHD that required steroid pulse therapy was 17.3% (95% CI, 8.528.8%) and 29.1% (95% CI, 17.242.0%), respectively. The active-disease group had a significantly higher incidence of grade 34 acute GVHD than the remission-achieved group before allo-HSCT (6.7% vs. 31.8%, p=0.023). However, no significant differences in moderate-to-severe chronic GVHD incidence (37.1% vs. 18.2%, p=0.172) were observed between the two groups. The allo-HSCT-related complication incidence, response rate, and survival outcomes in the remission-achieved and active-disease groups before allo-HSCT are presented in Table 3.

The results of the univariate analysis for OS, EFS, CIR, NRM, and GFRS are presented in Supplementary Tables 1 and 2. In the multivariate analysis, a shorter interval from diagnosis to allo-HSCT (median of<27.1months), which reflects relatively rapid disease progression, showed significantly poor OS (hazard ratio [HR], 3.92; 95% CI, 1.838.43; p<0.001) and EFS (HR, 2.65; 95% CI, 1.285.46; p=0.008). Complex karyotypes in BM involving DLBCL were also associated with poor OS (HR, 1.42; 95% CI, 1.061.90; p=0.018) and NRM (HR, 1.41; 95% CI, 1.021.94; p=0.040). Active disease before allo-HSCT was associated with significantly lower EFS (HR. 2.50; 95% CI, 1.215.17; p=0.014), GFRS (HR, 2.54; 95% CI, 1.374.72; p=0.003), and higher CIR (HR, 3.03; 95% CI, 1.148.02; p=0.026). The MAC regimen for allo-HSCT was associated with significantly higher CIR (HR, 11.3; 95% CI, 3.3338.1; p<0.001), and patients with previous autologous stem-cell transplantation (ASCT) had significantly better GRFS (HR, 0.50; 95% CI, 0.260.98; p=0.043). The results of the multivariate analysis are presented in Fig.4.

Multivariable analysis of survival outcomes related to allogeneic hematopoietic stem-cell transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma. (A) The multivariable analysis for each survival outcome shows that a shorter interval of the median of<27.1months from diagnosis to allo-HSCT (HR, 3.92; 95% CI, 1.838.43; p<0.001) and complex karyotype presenting bone marrow (HR, 1.42; 95% CI, 1.061.90; p=0.018) are significantly related to poor OS. In the case of EFS, a shorter interval compared to the median of<27.1months from diagnosis to allo-HSCT (HR, 2.65; 95% CI, 1.285.46; p=0.008) and active disease before allo-HSCT (HR, 2.50; 95% CI, 1.215.17; p=0.014) are significantly related to poor EFS. Previous ASCT are significantly related to better GRFS (HR, 0.50; 95% CI, 0.260.98; p=0.043), but active disease before allo-HSCT are significantly related to poor GRFS (HR, 2.54; 95% CI, 1.374.72; p=0.003). (B) Active disease before allo-HSCT (HR, 3.03; 95% CI, 1.148.02; p=0.026) is also significantly related to higher CIR with MAC conditioning (HR, 11.3; 95% CI, 3.3338.1; p<0.01). Complex karyotype presenting bone marrow is also related to higher NRM (HR, 1.41; 95% CI, 1.021.94; p=0.040). CI, confidence interval; ASCT, autologous stem-cell transplantation; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease free, relapse-free survival; HR, hazard ratio; HSCT, hematopoietic stem-cell transplantation; MAC, myeloablative conditioning; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

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The salvage role of allogeneic hematopoietic stem-cell ... - Nature.com

Mesenchymal Stem Cell Therapy Shows Cognitive and Biomarker … – Neurology Live

A new interim analysis of an open label trial presented at the 2023 MSMilan, the 9th Joint ECTRIMS-ACTRIMS meeting, held October 1113, in Milan, Italy, revealed significant beneficial effects on cognition and on objective biomarkers of neuroinflammation and neurodegeneration, among patients with progressive multiple sclerosis (MS) treated with repeated intrathecal (IT) injections of autologous mesenchymal stem cells (MSC).1

In 15 tested patients treated by at least 2 injections of MSC, 9 such patients improved between 5% and 18% in 25 feet walking. In addition, the average standard score of 4 cognitive tests taken by patients improved from 0.11 at baseline to 0.33 following 3 MSC injections over a year. Among 22 patients who received at least 1 MSC treatment, 13 of them showed improvement in the Symbol Digit Modalities Test (SDMT) scores, one of the cognitive tests. Notably, 6 of 17 treated patients improved by more than 4 degrees in SDMT in 3 consecutive tests over a year.

In this analysis, lead author, Petrou Panayiota, MD, senior neurologist, Unit of Neuroimmunology and Multiple Sclerosis Center and The Agnes-Ginges Center for Neurogenetics at Hadassah University Hospital in Jerusalem, Israel, and colleagues primarily evaluated the effect of repeated MSC transplantations on cognition in patients with progressive MS. Additionally, the researchers investigated objective serum biomarkers of neuroinflammation and neurodegeneration, specifically neurofilaments light chain (NfL) and glial fibrillary acidic protein (GFAP) with the therapy.

The open-label extension enrolled 48 patients with either secondary progressive MS or primary progressive MS who participated in the previous double-blind trial (NCT02166021) with MSC injections. The researchers used 4 cognitive tests including the SDMT, California Verbal Learning Test, Brief Visuospatial Memory Test, and Controlled Oral Word Association Test to assess patients at baseline before treatment, and at 4-5 time points following the first MSC-injection. At the same time, researchers also tested for serum NfL and GFAP levels using Quanterix technology (SIMOA).

READ MORE: Satralizumab Continues to Show Long-Term Efficacy in AQP4-IgG-Seropositive NMOSD

Among available data, 17 patients were treated with at least 2 intrathecal injections of MSC between 3 and 6 months apart, and 12 patients received 3 MSC injections. For treated patients, NfL levels reduced from a mean of 15.7 pmol/ml at baseline to 12.8 pmol/ml during the post-treatment year while GFAP levels also reduced from 191.4 pmol/ml at baseline to 155.4 pmol/ml.

In the previous double-blind randomized study conducted by Petrou and colleagues, IT injection of autologous bone marrow derived MSC showed robust clinical and radiological effects in patients with active and progressive MS.2 Enrolled patients had evidence of either clinical worsening or activity during the previous year between 2015 and 2018 andwere randomized into 3 groups: IT or intravenous (IV) autologous MSCs (1 106/kg) or sham injections.

After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into 2 subgroups and treated with either MSC-IT or MSC-IV. After 14 months of the study, instigators did not observe any serious treatment-related safety adverse events. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = .0003 and P = .0008).

During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, had no evidence of disease activity compared with 9.7% in the sham-treated group (P <.0001 and P <.0048, respectively). In addition, the MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Overall, treatment with MSCs was well-tolerated and induced short-term beneficial effects, especially in the patients with active disease. Notably, the IT administration was more efficacious than the intravenous in several parameters of the disease.

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Mesenchymal Stem Cell Therapy Shows Cognitive and Biomarker ... - Neurology Live

Berkshire Humane Society Pet of the Week: Meet Tilly – Live 95.9

Every Wednesday at 8:30we're joined by John Perreault, Executive Director of theBerkshire Humane Societyto discuss all the happenings at their Barker Road facility, plus talk about their Pet of the Week.

This week's Pet of the Week is a beautiful brindle-coated girl named Tilly. Tilly is an approximately 2-year-old American Pit Bull terrier mix who arrived at Berkshire Humane Society as an unclaimed stray.

An energetic girl, who is equally sweet,Tilly issure to keep you on an exercise regimen and will provide you with endless entertainment. She has been doing wonderfully keeping her kennel clean, so Berkshire Humanestaff believe she was mostly housetrained in her previous living situation.

Tilly can be a little weary and become stressed with excessive handling, mostly with the veterinarian, so an adopter who is willing to watch and understand her body language and signals would be ideal for Tilly. She loves to hang out with her people and receive pets and love, but she also likes her own personal time.

Tilly does not prefer the company of other female dogs or rambunctious male dogs, but she could possibly live with a calm and mellow male dog. She can be a bit reactive to other dogs while outside, but the kennel staff have been working with her on this and she has been making great progress! Tilly could potentially live with kids aged 10 years or older, but not small animals please as she does have a high prey drive.

If you are interested in more information on Tilly, please reach out to the Berkshire Humane kennel staff at (413)-447-7878 ext. 126 to learn more!

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

Gallery Credit: Rachel Cavanaugh

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Berkshire Humane Society Pet of the Week: Meet Tilly - Live 95.9

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