Leonard Appleman

Shocking disparities in utilization of essential cancer meds across the US. Or maybe not so shocking anymore . By the way, if you want great care, start in Massachusetts @DanaFarber

@cgramaglia2 @DavidSWilson12 @SpencerGuard Me, too. Squad Leader and Arab Israeli wars. Too bad they are out of print.

@DavidSWilson12 @SpencerGuard I remember this game on the shelves of the Compleat Strategist on 33rd Street when I was a high school student in the late 1980’s.

Imagine a self proclaimed “military expert” telling his followers that in all of the U.S. National Security Council, Joint Staff, CENTCOM, U.S. Naval Forces Central Command (NAVCENT), and JTF staff, they did not plan for scenarios in the Strait of Hormuz. Then imagine people still following him for “analysis.” Crazy world of overnight “X-perts”

The final analysis (9 year follow up) of checkmate 214 (IPI/Nivo vs sunitinib - 1st line RCC) @Annals_Oncology. Durable remissions with 31% 9 yr OS. Long-term benefit for IMDC good risk despite lower initial response rates (HR 0.80). OS HR for int/poor at 0.68. It remains a standard of care, and the best 1st line option for some (including good risk). @DrChoueiri @OncoAlert

In 1980, DeBakey operated on the Shah of Iran. He declares success. Soon, the patient is dead. Reoperation is psychologically brutal: how bias delay truth & what might save us from the same trap. leezhaomd.org/post/the-secon… #MedTwitter #Surgery #MedEd

In cisplatin-ineligible patients with muscle-invasive bladder cancer, enfortumab vedotin–pembrolizumab plus surgery led to better event-free survival (74.7%, vs. 39.4%) and overall survival (79.7%, vs. 63.1%) than surgery alone at 2 years. Full phase 3 KEYNOTE-905/EV-303 trial results: nej.md/4czl8sG Editorial: Enfortumab Vedotin plus Pembrolizumab as Perioperative Therapy nej.md/4twnv5T

Happy to share our newly published study on the tumor immune microenvironment in clear cell renal cell carcinoma. nature.com/articles/s4159…

@CTAhey4 @LauraPowellEsq probably waiting line for a $40 beer or the restroom

@LauraPowellEsq Bad Bunny’s show was pretty outstanding. I don’t really care about those in the stadium as that is a minority of people. Solve for the 99%.

I rewatched Prince’s iconic Super Bowl halftime show from 2007, and one difference that jumped out at me—other than the massive disparity in talent —was that Prince was performing for a live audience rather than for the cameras. Bad Bunny’s performance might as well have been prerecorded. The audience in the stands had a subpar experience. The magic that comes from a live show was missing.

@alexadoingstuff Club no longer filled with ballers with pockets full grown

“Ladies leave your man at home” not in this economy

Going out for one night without your bf will have you realizing how much things cost

Very interesting. We can get a bit sidetracked by CRS and possible ICANs risk with bispecific antibodies. And yes, important to manage properly. But infection is what we must always be on the look out for with these agents.

Excited to share our publication in CGUC - Tx sequencing post ICI in urothelial CA - preferred interval of >6mo & many ❓remain @arkhaki @PriyankaChabla1 @PGrivasMDPhD @oncologydoc @shilpaonc @ERPlimackMD @peterodonnell @DrRosenbergMSK @koshkin85 clinical-genitourinary-cancer.com/article/S1558-…

Congrats @DrIacovelli + all Italian🇮🇹 team in executing a near impossible trial and paving the way —@NatureMedicine #TACITO @Unicatt @gianluca1aniro

@Heer_khan3 Get well soon!

More @ASCO #GU26 highlights: B15/EV304 Perioperative EVP vs neoadjuvant Cisplatin-based chemo in muscle-invasive bladder cancer: We know study met EFS/OS/pCR —results to be delivered by @MattGalsky @TischCancer

So, your doctor ordered a test or treatment and your insurance company denied it. That is a typical cost saving method. OK, here is what you do: 1. Call the insurance company and tell them you want to speak with the "HIPAA Compliance/Privacy Officer" (By federal law, they have to have one) 2. Then ask them for the NAMES as well as CREDENTIALS of every person accessing your record to make that decision of denial. By law you have a right to that information. 3. They will almost always reverse the decision very shortly rather than admit that the committee is made of low paid HS graduates, looking at "criteria words." making the medical decision to deny your care. Even in the rare case it is made by medical personnel, it is unlikely that it is made by a board certified doctor in that specialty and they DO NOT WANT YOU TO KNOW THIS!! 4. Any refusal should be reported to the US Office of Civil Rights (OCR.gov) as a HIPAA violation. Be safe out there 🫵🏻✨ Know your rights 👊🏼 #ThrowbackThursday

@alfranken Thank you. Pretty sure my friends and I saw you and Tom Davis at a NYC Bobby and the Midnights show in the 80s.

Fare thee Well to Bobby Weir who brought joy and inspiration to millions for six decades. I was honored to be his friend and will miss him dearly.

This paper is wild. After 3 rounds of directed evolution, they converted a DNA polymerase into an enzyme that can do: - RNA synthesis - Reverse transcription - Synthesis of "unnatural" nucleotides - Synthesis of DNA-RNA chimeras One of the best papers I’ve read recently. For context: In nature, it is DNA polymerase that takes a DNA sequence as a template and then copies it. These enzymes are crucial in replicating the genome for cell division, and they are EXTREMELY specific for DNA over RNA. This is key because RNA nucleotides are present in the cell at concentrations ~100x higher than DNA nucleotides, so the enzyme has evolved clever strategies to select one over the other. RNA polymerases, for comparison, are the enzymes that take a DNA sequence as template and then convert it into RNA. They are involved in gene expression, for example. To convert a DNA polymerase into an RNA polymerase (and all the other functions I mentioned earlier), the authors did a fairly straightforward directed evolution experiment. First, they took four DNA polymerase enzymes belonging to various archaea. These DNA polymerases don’t check for DNA vs. RNA as stringently as other types of cells, so they’re a good starting point to evolve RNA polymerases. The authors inserted some targeted mutations into these enzymes, based on known mutations in the literature. For example, they swapped the amino acid at position 409 for a smaller amino acid, thus removing a “gate” that keeps RNA building blocks from entering the enzyme. Next, they took the four genes encoding these DNA polymerases and cut them up into 12 segments each. They randomly stitched these 12 segments together — from the four different genes — to build millions of unique variants. Each shuffled gene was inserted into an E. coli cell. Then, they grew up these cells (each carrying a unique polymerase) and put them into microfluidic droplets. A device isolates each droplet, lyses the cell open, and releases the polymerase. The droplet also contains RNA building blocks and a DNA template, encoding a fluorescent reporter. If the polymerase begins synthesizing RNA, it will produce a detectable signal. They screened about 100 million droplets in 10 hours of work, searching for those with a signal. For each well that yields a fluorescent signal, the researchers isolated the DNA and sequenced it to figure out which polymerase it was. They repeated this 3x times, finally isolating a really excellent RNA polymerase variant which they called "C28." C28 has 39 mutations compared to the wildtype enzymes. It incorporates about 3.3 nucleotides of RNA per second, with 99.8% fidelity. The crazy thing is that this enzyme can also copy DNA or RNA templates back into DNA (reverse transcription), or use chimeric DNA-RNA molecules as a template and amplify them. It is just a super versatile polymerase that can act on DNA, RNA, or modified nucleotides, to build just about anything.

ICI-Induced Diabetes: Rare but Severe Analysis of ~14,000 patients in NCI trials shows 0.5% incidence, higher with combination immunotherapy, lower with chemotherapy. Most cases require hospitalization, some ICU. @OncoAlert @JAMAOnc #Immunotherapy jamanetwork.com/journals/jamao…

@neerajaiims @ASCO @OncoAlert @urotoday @OncBrothers @montypal @DrChoueiri @DrRanaMcKay @DrYukselUrun @thenasheffect @batraatulonc @Dr_AmerZeidan @NazliDizman @SuyogCancer @DrNikitaMehra @nataliagandur @shilpaonc @AmandaNizamMD congratulations!!

Truly humbled by the support of colleagues across the American Society of Clinical Oncology (@ASCO) global community. Thank you for the trust and encouragement—I’m deeply grateful and excited to serve. @OncoAlert @urotoday @OncBrothers @montypal @DrChoueiri @DrRanaMcKay

💣 Important Shift in Cytopenia Grading: CTCAE v6.0 Update If you are a PI running #Hematology or #Oncology trials, note these key changes in the new CTCAE v6.0 vs v5.0: 📉 General Trend: "Downgrading" of severity. Many counts that were previously Grade 3/4 are now lower grades. 🧪 Neutrophils: Grade 1 Gone: ANC 1000–1500 is now Grade 1 (was G2). The old Grade 1 (1500–LLN) is no longer graded. Stricter G4: threshold drops from <500 to <100/mm³. 🩸 Platelets (Thrombocytopenia): Wider G3: Now covers 10k–50k (previously 25k–50k). Stricter G4: threshold drops from <25k to <10k/mm³. v6.0 also adds "transfusion indicated" to Grade 3 and "urgent intervention indicated" to Grade 4 criteria. Overall, IMO these new thresholds align better with clinical practice. #ClinicalTrials #MedEd #OncTwitter #DrugSafety

@ThatEricAlper I saw him open for the Clash at Pier 42 in NYC the night before the Clash opened for the Who at Shea. the punk crowd was not kind to him.

On this day in 1980, “Christmas Rappin’” by Kurtis Blow became the first rap song released on a major label. It sold around 400,000 copies and paved the way for “The Breaks,” hip-hop’s first Gold single.