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Background: MDS‐RS patients are characterized by chronic anemia and a low risk of Acute Myeloid Leukemia (AML) progression and they generally become Red Blood Cell (RBC) transfusion dependent (TD). Study design and methods: We performed a retrospective "real‐life" observational study of 6 months in 100 MDS‐RS TD patients, recruited in 12 French centers, to describe transfusion characteristics, and evaluate the frequency and causes of hospitalizations, health costs, and morbidity, associated with transfusion dependency, in a French population of RBC transfusion‐dependent MDS‐RS patients. Results: 79% of the patients had high transfusion burden (HTB) and 21% low transfusion burden (LTB). HTB patients had a longer disease duration (6 vs. 3.7 years, p = 0.0078), more frequent iron chelation (82% vs. 50%, p = 0.0052) and higher serum ferritin (p = 0.03). During the 6‐month study period, 22% of the patients required inpatient hospitalization, 36% of them for symptomatic anemia requiring emergency RBC transfusion. The 6‐month median transfusion costs, including the cost of the day care facility, transportation to and from the hospital, iron chelation, and lab tests, was 16,188€/patient. Discussion: MDS‐RS represents the archetypal type of chronically transfused lower‐risk MDS. Most of those patients have a high transfusion burden and thus frequently need visits to the hospital's day care facility, and frequent hospitalizations, with an overall high median treatment cost. Those costs should be compared with costs of new treatments potentially able to avoid RBC transfusion dependence and to reduce the complications of chronic anemia in MDS‐RS patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypoxia is found in half of the solid cancers and is a major contributor to treatment resistance and promotion of metastasis, leading to shortened patient survival. No user-friendly in vitro preclinical tool exists to study natural chronic hypoxia. The aim of this study was to design a microfluidic device allowing easy culture, maintenance, treatment, and analysis of naturally hypoxic sarcoma spheroids. We confirmed that our jumbo spheroids (>750 µm) contained hypoxic cores, as they expressed the hypoxic marker protein Carbonic Anhydrase IX (CAIX). Quantification of DNA strand breaks from radiotherapy and a hypoxia pro-drug demonstrated hypoxia-dependent treatment responses. Our novel microfluidic device is versatile and convenient for both fundamental and preclinical research, to better understand and treat hypoxic tumors. Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (>750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: p = 0.0009; SK-LMS-1: p = 0.0038), but the spheroids' hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response. [ABSTRACT FROM AUTHOR]

Le « gold standard » pour la prise en charge des médiastinites est actuellement l'utilisation de la thérapie par pression négative suivi d'un lambeau musculaire qui peut entraîner des complications à type de douleur, perte de force du membre supérieur, instabilité sternale... L'implantation d'un dispositif médical (DM) est classiquement contre-indiquée due au risque d'infection. Par ailleurs, la diffusion des antibiotiques est mauvaise au niveau du médiastin et du sternum et encore plus lorsque les artères mammaires internes ont étés prélevées, limitant l'efficacité d'antibiotiques avec des volumes de distribution faibles. Nous avons développé un DM chargé en antibiotique permettant un relargage local et ainsi une optimisation des concentrations et une protection de l'implantation. Nous avons utilisé une prothèse sternale en alumine poreuse chargée en gentamicine seule ou en association avec de la vancomycine. Le but est de remplacer mécaniquement le sternum tout en protégeant l'implantation avec l'antibiotique. Ce DM a été implanté chez 4 patients avec des destructions sternales nécessitant un remplacement. L'antibiotique n'ayant qu'un rôle prophylactique, une antibiothérapie par voie systémique était prescrite classiquement. À noter que chez le patient #4, le S. epidermidis en cause était résistant à la gentamicine (CMI : 384 μg/mL) et à la vancomycine (CMI : 8 μg/mL). Il s'agissait de 4 hommes (67,6 ans) ayant présenté une médiastinite dans les suites d'une chirurgie cardiaque. Le délai moyen entre le début de l'infection et l'implantation était de 9,5 mois. Lors de l'implantation la bactériologie était toujours positive. Les concentrations locales d'antibiotiques étaient largement supérieures à celles nécessaires (Cmax/CMI > 1500 pour la gentamicine et ASC/CMI ∼16000 pour la vancomycine) et les concentrations sanguines pendant 48 h étaient indétectables. L'administration locale des antibiotiques a permis de retrouver des paramètres pharmacologiques témoignant d'une « resensibilisation » du S. epidermidis à la gentamicine et la vancomycine grâce à l'administration locale. La cicatrisation était obtenue en moins de 10 jours. Chez les 3 patients dont la flore était sensible à l'antibiotique, il n'y a pas eu de récidive de l'infection (> 18 mois de recul). Chez un patient il y a eu un changement radical de flore entre les derniers prélèvements réalisés et l'implantation, avec un passage de totalement sensible à complètement résistant à la gentamicine. Le DM a dû être retiré après 19 mois, mais les tissus cicatriciels ont permis de ne pas remettre de matériel. L'utilisation de cette céramique chargée en antibiotique permet de reconstruire la cage thoracique et de protéger son implantation. Le relargage local permet d'obtenir des concentrations locales efficaces qui complètent le débridement, protègent le DM d'une infection bactérienne et diminue le risque de toxicité systémique. Cela permet d'optimiser les concentrations locales et de récupérer des résistances « pharmacologiques ». [ABSTRACT FROM AUTHOR]

Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100 mg/day ( n = 5) or 150 mg/day ( n = 25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III–IV extra hematological toxicities (skin ( n = 1), and diarrhea ( n = 3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML. [ABSTRACT FROM AUTHOR]

Erythropoiesis-stimulating agents (ESAs) remain the first-line treatment of anemia in lower risk myelodysplastic syndromes (MDS) without 5q deletion. A preliminary report suggested that adding all-trans retinoic acid (ATRA) to ESAs may improve their erythroid response, particularly in patients with high endogenous erythropoietin (EPO) level, and may improve other cytopenias. We conducted a prospective multicenter study of EPO-β and ATRA in anemic MDS patients with marrow blasts <10% and either previous ESA failure or relapse, endogenous EPO >500 U/l or other cytopenia(s) (absolute neutrophilic count <1.0 G/l or platelets <50 G/l). A total of 59 patients were evaluable after 12 weeks of treatment. The erythroid response rates according to IWG 2000 and 2006 criteria, respectively, were as follows: overall: 49 and 36%; patients with previous ESA failure (n=28): 43 and 32%; patients with endogenous EPO >500 U/l (n=18): 11 and 19%; patients transfused >2 red blood cells units/month (n=28) 43 and 39%. Only one neutrophil, but no platelet response, and no major side effect were observed. EPO-β–ATRA combination appears a possible therapeutic option in anemia of MDS having failed an ESA alone, but not in patients with high endogenous EPO level, and does not improve neutropenia and thrombocytopenia.Leukemia (2009) 23, 673–678; doi:10.1038/leu.2008.362; published online 8 January 2009 [ABSTRACT FROM AUTHOR]

Purpose: Chest wall resections for lung cancer treatment remain difficult to plan using standard 2-dimensional computed tomography. Although virtual reality headsets have been used in many medical contexts, they have not been used in chest wall resection planning., Description: We compared preoperative planning of a chest wall surgical resection for lung cancer treatment between senior and resident surgeons who used an immersive virtual reality device and a 2-dimensional computed tomography., Evaluation: Chest wall resection planning was more accurate when surgeons used virtual reality vs computed tomography analysis (28.6% vs 18.3%, P = .018), and this was particularly true in the resident surgeon group (27.4% vs 8.3%, P = .0025). Predictions regarding the need for chest wall substitutes were also more accurate when they were made using virtual reality vs computed tomography analysis in all groups (96% vs 68.5%, P < .0001). Other studied parameters were not affected by the use of the virtual reality tool., Conclusions: Virtual reality may offer enhanced accuracy for chest wall resection and reconstruction planning for lung cancer treatment., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: After its destruction during refractory deep sternal wound infection (DSWI), current sternum reconstructions mainly rely on muscle flaps technique, but such technique have pitfalls and limits. To tackle the limited possibilities to use device implantation because of the risk of infection, we developed a self-protected device allowing its implantation in an infected area., Methods: We used gentamicin alone or in combination with vancomycin loaded in a porous ceramic sternum to replace sternums destroyed during DSWI. The aim was to mechanically replace the sternum and to secure the implantation by killing the remaining bacteria in the wound thanks to the loaded antibiotic., Results: This device was implanted in four infected patients during DWSI with sternal dehiscence. No complication occurred during surgeries, and wound healing was obtained quickly. Local antibiotic concentrations largely exceeded the ones needed for their efficacy while no antibiotic was found in the blood. All patients are well-being. However previously unknown gentamicin resistant bacteria, present in the surgical wound at the time of positioning, required sternal implant removal for one patient after 19 months. For all patients, pulmonary function tests (PFT) improved after implantation., Conclusions: The ceramic sternum played its role consolidating the thoracic cage without stiffening. The antibiotic loaded in the sternum allowed a secure implantation, killing bacteria before the colonization of the implant even in this infected area. These four implantations are promising for patients with sternal destruction after DSWI., Competing Interests: Conflicts of Interest: F Bertin, E Denes, S El Balkhi: member of the scientific committee of I.Ceram; E Denes: Share holder of I.Ceram. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

A 68-year-old man presented with destruction of his sternum after cardiac surgery. Classical management with multiple debridements, vacuum dressings and antibiotics failed. A replacement of his sternum was performed using an antibiotic-loaded porous alumina ceramic sternum. Despite the infected wound, the ceramic sternum did not get infected due to the high antibiotic concentration obtained locally. Two years after the surgery, no relapse occurred and the pulmonary function tests improved., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)