fluorouracil + salicylic acid (Actikerall / LAS41005 / ADP18998)

Challenges of Conducting a Feasibility Pilot Randomized Controlled Trial During COVID-19 Restrictions: Rivaroxaban Versus Acetyl Salicylic Acid in Patients with Multiple Myeloma on Lenalidomide-Based Therapy (RithMM).

Strelau Matthew M, Gal Gregoire Le GL, McCurdy Arleigh A, Shivakumar Sudeep S et al.

Venous thromboembolism is a serious medical complication with an increased risk in patients with multiple myeloma undergoing combination treatment regimens. Acetylsalicylic acid is routinely used as a method of thromboprophylaxis in multiple myeloma patients treated with lenalidomide, and rivaroxaban has been assessed in small-scale studies in multiple myeloma patients treated with immunomodulatory drugs; yet, no study has compared the two methods. In this pilot, we asked if a full-scale trial would be feasible to assess the benefits of rivaroxaban over acetylsalicylic acid as a thromboprophylactic approach. This pilot recruited patients with multiple myeloma on lenalidomide-based therapy and randomized them to either low-dose acetylsalicylic acid or rivaroxaban, then monitored bleeding and thrombotic events throughout lenalidomide-dexamethasone treatment. A total of 55 patients were recruited across three Canadian centres, with two venous thromboembolic events and two bleeding events, all in the acetylsalicylic acid arm. We conducted a post hoc analysis of active recruitment time as a definition of recruitment feasibility, as we did not achieve our pre-defined feasibility goals. Despite the challenges in enrollment, possibly due to social restrictions during the COVID-19 pandemic, we maintain that a full-scale trial is feasible and offers insight into thromboprophylactic management in this population.

Pantoea ananatis-triggered systemic resistance requires root sensing through the LORE receptor kinase in Arabidopsis.

Duchateau Simon S, Crouzet Jérôme J, Cordelier Sylvain S, Touchard Matthieu M et al.

Systemic immunity induced by beneficial bacteria enhances plant resilience to subsequent pathogen attacks. However, the mechanisms by which plants perceive these bacteria and translate this perception into a systemic response remain poorly understood. The Brassicaceae LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) receptor kinase is the direct sensor of bacterial medium-chain-length 3-hydroxy fatty acids (mc-3-OH-FAs) and 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs), both of which activate local Brassicaceae immunity. Here, we show that the HAA-producing bacterium Pantoea ananatis BRT175 can colonize Arabidopsis thaliana roots independently of the production of HAAs, but these compounds induce a lore-dependent local immune response in roots. P. ananatis triggers induced systemic resistance (ISR) against the necrotrophic fungus Botrytis cinerea, but not against the hemibiotrophic bacterium Pseudomonas syringae pv. tomato DC3000. This ISR can be mimicked by HAAs or 3-hydroxy-decanoic acid (3-OH-C10), the strongest agonist of LORE. Both bacterium- and 3-hydroxylated fatty acid MAMP-induced ISR against B. cinerea rely on LORE-mediated sensing, involve salicylic acid, jasmonic acid/ethylene signaling pathways, and activate similar defense gene expression profiles in infected leaves. Our results demonstrate that lipidic microbe-associated molecular patterns (MAMPs) produced by beneficial microorganisms are necessary and sufficient to trigger rhizobacteria-mediated ISR and could differentially activate systemic resistance against biotrophic and necrotrophic pathogens.

Carbon Dioxide Laser Debulking With Immediate Intralesional 5-Fluorouracil and Triamcinolone for Recurrent Auricular Keloids.

Rebollo Caballero Blanca B, Ruiz Martínez Javier J, Gómez-Olit Pérez Manuel M, Romera Pallarés Juan C JC

Beyond the Threatened Limb: Acute Limb Ischemia as a Diagnostic Attractor.

Smith Antoine A, Zahir Soheil S

Acute limb ischemia is a time-sensitive vascular emergency, but in older patients with active cancer and multimorbidity, the threatened limb can become a diagnostic attractor: a correct specialized diagnosis that narrows attention before whole-patient physiology is integrated. We report an 81-year-old man with metastatic cecal adenocarcinoma receiving folinic acid, fluorouracil, and oxaliplatin (FOLFOX) who presented on day one with three days of progressive left lower limb claudication, coldness, discoloration, absent pulses, preserved motor and sensory function, and no rest pain. The presentation was clinically compatible with Rutherford I-IIa acute limb ischemia; bedside Doppler signals were not documented, precluding a definitive retrospective distinction between these categories. Concurrent findings included new atrial fibrillation, basal crackles, peripheral edema, markedly elevated N-terminal pro-B-type natriuretic peptide and troponin, bilateral pleural effusions, and radiological concern for low cardiac output. Computed tomography angiography (CTA) showed severe distal superficial femoral artery stenosis, long popliteal occlusion, slow distal flow, and limited runoff, favoring an acute-on-chronic ischemic process. On day two, a 6 mm x 60 mm covered stent was placed across the distal superficial femoral artery lesion. The treated lesion had a satisfactory technical result, but distal runoff remained severely compromised. Therapeutic anticoagulation initiated on day one was not maintained; discharge treatment on day three included prophylactic-dose enoxaparin and aspirin, with no rationale for the change documented in the available record. He returned on day five with recurrent coldness and toe necrosis despite normal lactate. No repeat vascular imaging was available to define the mechanism. Care became palliative on day 13, and he died on day 58. This case illustrates that a correct vascular diagnosis should not terminate integrative emergency reasoning. We propose that a vascular-plus-physiology cross-check may help preserve attention to systemic physiology and goals of care, but it is an educational framework rather than a validated clinical algorithm.