BLOCKADE Classic [hack]l

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Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.


Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components-β2-microglobulin, MHC class I, and MHC class II-by immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. Results Patients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a > 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.


Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 wee

BLOCKADE Classic [hack]l

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In this World Shared Practice Forum Podcast, Dr. Martin Kneyber discusses the implementation of the PALICC-2 guidelines in bedside monitoring and management of pediatric acute respiratory distress syndrome (PARDS). He shares insights on how the concepts of positive end-expiratory pressure (PEEP), driving pressure, patient self-inflicted lung injury (P-SILI), and the use of non-invasive ventilation are translated to the bedside management of PARDS.

LEARNING OBJECTIVES
- Explain the concept of driving pressure and its significance in the management of pediatric acute lung injury
- Identify the potential benefits and drawbacks of neuromuscular blockade in pediatric acute lung injury patients
- Describe the concept of non-invasive ventilation in the management of acute respiratory failure in pediatric patients, including its potential benefits, limitations, and challenges in implementation

AUTHORS
Martin Kneyber MD, PhD, FCCM
Chief of the Division of Paediatric Critical Care Medicine
Beatrix Children’s Hospital
University Medical Center Groningen, Groningen, the Netherlands

Jeffrey Burns MD, MPH
Chief and Shapiro Chair, Division of Critical Care Medicine; Executive Chair, International Health Services
Senior Associate in Critical Care Medicine; Department of Anesthesiology, Critical Care and Pain Medicine
Boston Children's Hospital
Professor of Anesthesia
Harvard Medical School

DATES
Initial Publication Date: February 26, 2024.

ARTICLES REFERENCED
00:58 https://pubmed.ncbi.nlm.nih.gov/36661420/
Emeriaud G, López-Fernández YM, Iyer NP, et al. Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2). Pediatr Crit Care Med. 2023;24(2):143-168.
 
01:46 https://pubmed.ncbi.nlm.nih.gov/29373802/
Khemani RG, Parvathaneni K, Yehya N, Bhalla AK, Thomas NJ, Newth CJL. Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality. Am J Respir Crit Care Med. 2018;198(1):77-89.

02:53 https://pubmed.ncbi.nlm.nih.gov/30361119/
Khemani RG, Smith L, Lopez-Fernandez YM, et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study [published correction appears in Lancet Respir Med. 2018 Nov 13;:] [published correction appears in Lancet Respir Med. 2019 Mar;7(3):e12]. Lancet Respir Med. 2019;7(2):115-128.

07:45 https://pubmed.ncbi.nlm.nih.gov/25693014/
Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755.
 
07:49 https://pubmed.ncbi.nlm.nih.gov/36661438/
Yehya N, Smith L, Thomas NJ, et al. Definition, Incidence, and Epidemiology of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2023;24(12 Suppl 2):S87-S98.

18:09 https://pubmed.ncbi.nlm.nih.gov/20843245/
Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-1116.

18:27 https://pubmed.ncbi.nlm.nih.gov/27779896/
Huang DT, Angus DC, Moss M, et al. Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome. Ann Am Thorac Soc. 2017;14(1):124-133.

19:26 https://pubmed.ncbi.nlm.nih.gov/27748627/
Doorduin J, Nollet JL, Roesthuis LH, et al. Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes. Am J Respir Crit Care Med. 2017;195(8):1033-1042.

Kneyber MCJ, O’Hara JE, Burns JP. Bedside Implementation of the PALICC-2 Guidelines. 2/2024. OPENPediatrics. Online Podcast. https://soundcloud.com/openpediatrics/bedside-implementation-of-the-palicc-2-guidelines-by-m-kneyber-openpediatrics.

Bedside Implementation of the PALICC-2 Guidelines by M. Kneyber | OPENPediatrics

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Blockade

When I got word that people were once again organizing to sail in the direction of Gaza from ports around the world, I wrote a song about it, last month.  I recorded it a few days ago and now my musical collaborator, Chet Gardiner, has spent quite a chunk of time making it all much more interesting from his studio in Hawai'i, and here it is.

The Freedom Flotilla Coalition is currently mobilizing all over the world in 13 national campaigns in Norway, Sweden, the UK, France, Spain, Italy, Turkey, Canada, US,  Australia, New Zealand, South Africa and Malaysia.  Check the website for links to each of the national campaigns where you can donate for the 2024 flotilla.

As completely horrific as things are on the ground in Gaza -- with untold numbers of people living in misery and dying of famine and disease, right now -- the opening of the port south of Gaza City may be a moment of great possibility, in terms of boats actually reaching Gaza, rather than being turned away violently by Israeli forces, which has of course been the usual state of affairs for decades at this point.

If this campaign is going to be successful, more people need to know about it.  That's where a song like this one can potentially be helpful, but only if people do things with it -- make high-quality videos using the audio, chop it up for TikToks as you see fit, play it on the radio, etc., this is a collective effort.

Taking To The Waves

Audio zum Block "Schreibblockade" von Simply Tihyowe

Schreibblockade

The Berlin Airlift began on June 26, 1948, only two days after the Soviet Union's blockade of West Berlin. 

Written by Ian Gammon. Narration by Dr. Nicholas B. Breyfogle. A textual version is available at https://origins.osu.edu/read/berlin-airlift. Production by Laura Seeger and Dr. Nicholas B. Breyfogle. 

Additional resources:
To Save a City: The Berlin Airlift, 1948-1949 (https://www.tamupress.com/book/9781603440905/to-save-a-city/)

Berlin on the Brink: The Blockade, the Airlift, and the Early Cold War
(https://www.kentuckypress.com/9780813136134/berlin-on-the-brink/)

"The Incomplete Blockade: Soviet Zone Supply of West Berlin, 1948–49" (https://www.jstor.org/stable/24913337)

"The Role of Britain in the Berlin Airlift" (https://www.jstor.org/stable/24428813)

"The Berlin Blockade Revisited" (https://www.jstor.org/stable/40105349)

This is a production of Origins: Current Events in Historical Perspective at the Goldberg Center in the Department of History at The Ohio State University and the Department of History at Miami University. Be sure to subscribe to our channel to receive updates about our videos and podcasts. For more information about Origins: Current Events in Historical Perspective, please visit origins.osu.edu.

The Berlin Airlift

Following his December plea "Restore UNRWA Funding. Stop Famine in Gaza" (United Nations Relief and Works Agency for Palestine Refugees in the Near East), Legislative Director for Middle East Policy at the Friends Committee on National Legistlation, Hassan El-Tayyab visited the Gaza area for a month, and reports back on the effects of starvation from total blockade of food, water, fuel, shelter, and medical assistance that would normally be coordinated by this U. N. aid group. With over 3000 aid trucks waiting to cross into Gaza with aid, El-Tayyab urges people to contact their congressional representatives to put pressure on Israel to let the aid continue and stop the killing.

buzz-4-30-25-Hassan-El-Tayyab

This week Tamsin Phillipa Paige and Douglas Guilfoyle discuss the IDF's interdiction of the Madleen aid vessel bound for Gaza, the law of blockade in naval warfare, and its contested relationship with the crime of starvation.

Sidebar: we discuss hypotheticals in cases of state responsibility for interdicting vessels at sea and the possibility of ITLOS hearing cases under UNCLOS - we should have noted in this particular case Israel is not a party to UNCLOS.

Recommendations:

Douglas Guilfoyle, The Mavi Marmara Incident and Blockade in Armed Conflict, https://academic.oup.com/bybil/article/81/1/171/329512

Phillip Drew, The Law of Maritime Blockade: Past, Present, and Future, https://global.oup.com/academic/product/the-law-of-maritime-blockade-9780198808435

Music: Sam Barsh, Oils of Au Lait

43. Emergency cast: Israel's blockade of Gaza

The ideological enforcer of MAGA-fascism in American higher education (just met with craven capitulation by Columbia and Brown University) is the Trump regime's Joint Task Force to Combat Anti-Semitism. Purporting to act on behalf of Jewish students, the Trump regime simultaneously attacks policies to promote campus diversity. This replicates the historical function of anti-Semitism—setting up Jews to take the hit for for the oppressive policies of (overwhelmingly) non-Jewish rulers. The perverse fascist pseudo-anti-fascism of the Trump regime has now become anti-Semitic pseudo-anti-anti-Semitism. This cynical feigned opposition to anti-Semitism is especially dangerous when actual anti-Semitism is very much in evidence—not least by the Trump regime itself, over and over! Yet the ever-more egregious manifestations of Jew-hatred are increasingly weaponized by the political right—and ignored or even normalized by the ostensible "left." In Episode 289 of the CounterVortex podcast, Bill Weinberg takes some encouragement from the growing ranks of Jewish voices breaking with the pro-Israel consensus to protest the Gaza genocide—while being clear in drawing the line against anti-Semitism.

Listen on SoundCloud or via Patreon.

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Production by Chris Rywalt

We ask listeners to donate just $1 per weekly podcast via Patreon -- or $2 for our new special offer! We now have 65 subscribers. If you appreciate our work, please become Number 66!

MAGA-fascism and anti-Semitic pseudo-anti-anti-Semitism II

Die humanitäre Situation in Gaza ist derzeit katastrophal. Fast alle Menschen leiden unter akutem Hunger, obwohl nur wenige Kilometer entfernt tausende Hilfstransporter bereitstehen, um Hilfe zu leisten. Doch der Zugang wird blockiert.

Ralf Südhof, Direktor des Center for Humanitarian Action, erläutert im Interview die dramatische Lage vor Ort und erklärt die Herausforderungen, mit denen Hilfsorganisationen konfrontiert sind. Er gibt Einblicke in die Arbeit von Organisationen wie Amnesty International, Human Rights Watch und dem Internationalen Roten Kreuz, die sich für die Einhaltung des humanitären Völkerrechts einsetzen.

Interview mit Ralf Südhof, Direktor des Center for Humanitarian Action

Aus Print mach mehr - iz3w on Air! So die Devise der iz3w-Zeitschriften-Redaktion. Mit dem südnordfunk startete das iz3w im Juni 2014 eine monatliche Magazinsendung auf Radio Dreyeckland. Mit ausgewählten Inhalten und Debatten der nord-südpolitischen Zeitschrift iz3w aus Freiburg.
Jeden ersten Dienstag im Monat um 16 Uhr auf 102,3 mhz. Und als Podcast. 
Siehe auch www.iz3w.org

A podcast of informal conversation about topical issues in international law, life in academia and whatever else is on our mind. Hosted by Douglas Guilfoyle and featuring Juliette McIntyre, Tamsin Paige, Imogen Saunders, Nitna Tzouvala. 

Music: Sam Barsh, Oils of Au Lait

Singer/songwriter, writer, podcaster (on Spotify, Substack & Patreon), libertarian socialist, dad, lover of life.

Listener-sponsored, volunteer-powered, noncommercial community radio broadcasting to south-central Wisconsin at 89.9 FM and online at wortfm.org via our studios in Madison. 

We provide an outlet for communication, education, free expression, entertainment, training and access for the purpose of sharing music, information, news, and cultural experiences, and strive to give people underrepresented elsewhere in traditional media a voice. 

NOTE: Most of the content posted at this time are news stories or talk shows. 

MUSICIANS:  We NEVER look on our SoundCloud for music submissions, so it's not a very efficient way to contact us. Please go to www.wortfm.org and click on Music --> Music Submissions for our submission info and guidelines. Thanks and we look forward to hearing your music!

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