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Previous data have demonstrated that, to handle the oxidative stress encountered with training at high intensity, skeletal muscle relies on an increase in mitochondrial biogenesis, a reduced H2O2 production, and an enhancement of antioxidant enzymes. In the present study, we evaluated the influence of voluntary running on mitochondrial O2 consumption and H2O2 production by intermyofibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM) isolated from oxidative muscles in conjunction with the determination of antioxidant capacities. When mitochondria are incubated with succinate as substrate, both maximal (state 3) and resting (state 4) O2 consumption were significantly lower in SSM than in IFM populations. Mitochondrial H2O2 release per unit of O2 consumed was 2-fold higher in SSM than in IFM. Inhibition of H2O2 formation by rotenone suggests that complex I of the electron transport chain is likely the major physiological H2O2-generating system. In Lou/C rats (an inbred strain of rats of Wistar origin), neither O2 consumption nor H2O2 release by IFM and SSM were affected by long-term, voluntary wheel training. In contrast, glutathione peroxidase and catalase activity were significantly increased despite no change in oxidative capacities with long-term, voluntary exercise. Furthermore, chronic exercise enhanced heat shock protein 72 accumulation within skeletal muscle. It is concluded that the antioxidant status of muscle can be significantly improved by prolonged wheel exercise without necessitating an increase in mitochondrial oxidative capacities. [Copyright &y& Elsevier]

Undernutrition is frequently seen in cancer and is considered as a bad prognostic factor. The mechanisms involved in this complex syndrome are not fully understood. Systemic inflammation plays an important role in the occurrence and/or development of cancer-associated undernutrition. Although it is essential to counteract cancer-associated undernutrition, modalities for nutritional treatment are still discussed. It has been shown that nutritional supplementation with n-3 polyunsaturated fatty acid could be beneficial in patients.

Background: Mesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD)., Methods: Based on our previous pilot study, we established a multicenter, prospective, randomized, double-blind trial evaluating the efficacy of co-infusing third-party MSC (1.5-3 × 10 6 /kg) versus placebo on the day of HSC transplantation (HCT) to prevent GVHD in recipients of HLA-mismatched unrelated donors after reduced-intensity conditioning., Results: The study planned to include 120 patients to improve 1-year overall survival (OS) from 55 to 77% but was stopped after 9 years for low recruitment (n = 38). One-year OS was 74% in the MSC group and 80% in the placebo group. In multivariate analysis, the incidence of grade II-IV acute GVHD was significantly lower in patients receiving MSC (HR 0.332, 95% CI 0.124-0.890, p = 0.0284). No difference was observed in the incidences of chronic GVHD, infection or relapse, overall or progression-free survival at 1 year or long-term, or hematopoietic and immune reconstitution., Conclusions: Despite premature study closure, the suggested beneficial effect of MSC co-transplantation for the prevention of acute GVHD in HLA-mismatched HCT warrants further investigation., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol “Co-transplantation of mesenchymal stem cells and HLA-mismatched allogeneic hematopoietic cells after nonmyeloablative conditioning: a phase II randomized double-blind study” was approved centrally by the “Comité d’Ethique Hospitalo-Facultaire Universitaire de Liège” on 6 July 2010 (file 2010/16) as well as by the ethics committees of all participating centers and the study was conducted in accordance with the Declaration of Helsinki. Before participating in the study, all patients (or their legal representatives if minors) signed an informed consent form. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

The mitochondrial Ca2+ uniporter (MCU) plays crucial role in intramitochondrial Ca2+ uptake, allowing Ca2+-dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2) to pathophysiological conditions has been poorly investigated. Here, we describe the role of MICU2 in cell proliferation and invasion using in vitro and in vivo models of human colorectal cancer (CRC). Transcriptomic analysis demonstrated an increase in MICU2 expression and the MICU2/MICU1 ratio in advanced CRC and CRC-derived metastases. We report that expression of MICU2 is necessary for mitochondrial Ca2+ uptake and quality of the mitochondrial network. Our data reveal the interplay between MICU2 and MICU1 in the metabolic flexibility between anaerobic glycolysis and OXPHOS. Overall, our study sheds light on the potential role of the MICUs in diseases associated with metabolic reprogramming., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Robert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The IA-DUET study aimed to compare azole-echinocandin combination with azole monotherapy for invasive aspergillosis. Recruitment was hindered by patient ineligibility, competing studies, and guidelines favoring combination therapy when azole resistance was unknown. The low IA-attributable mortality suggests future trials may benefit from cluster randomization or composite endpoints to enhance efficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In this SFGM-TC registry study, we report the results after stem cell transplantation (HSCT) in 305 myelofibrosis patients, in order to determine potential risk factors associated with outcomes, especially regarding previous treatment with ruxolitinib. A total of 102 patients were transplanted from an HLA-matched-sibling donor (MSD), and 143 patients received ruxolitinib. In contrast with previous studies, our results showed significantly worse outcomes for ruxolitinib patients regarding overall survival (OS) and non-relapse mortality (NRM), especially in the context of unrelated donors (URD). When exploring reasons for potential confounders regarding the ruxolitinib effect, an interaction between the type of donor and the use of ATG was found, therefore subsequent analyses were performed separately for each type of donor. Multivariable analyses did not confirm a significant negative impact of ruxolitinib in transplantation outcomes. In the setting of URD, only age and Fludarabine-Melphalan (FM) conditioning were associated with increased NRM. For MSD, only Karnoksfy <70% was associated with reduced OS. However, a propensity score analysis showed that ruxolitinib had a negative impact on OS but only in non-responding patients, consistent with previous data. To conclude, with all the precautions due to confounders and bias, ruxolitinib itself does not appear to increase mortality after HSCT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Venous access device-related bloodstream infection (VAD-BSI) with coagulase-negative staphylococci (CoNS) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT). Standard systemic antimicrobial therapy for uncomplicated VAD-BSI with methicillin-resistant CoNS consists of intravenous (IV) vancomycin (vanco). This requires hospitalization, needs new competent venous access, exposes patients to potential toxicity (mainly renal) and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Combined with VAD management (removal or antibiotic locks), oral minocycline (mino) has been evaluated as an alternative systemic therapy for the treatment of uncomplicated VAD-BSIs with CoNS at our center, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. Here, we retrospectively report our single center experience with this mino-based approach., Patients and Methods: From January 2012 to December 2020, 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients were treated with oral mino as systemic antibiotic therapy in combination with VAD management. VAD were implantable ports (n = 17), tunneled catheter (n = 1) or PIC-lines (n = 6). Staphylococci were S. epidermidis (n = 21) or S. haemolyticus (n = 3). Mino was administered with a loading dose of 200 mg followed by 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-BSIs were treated with oral mino as the sole antimicrobial agent for systemic therapy. VAD management consisted of catheter removal (for tunneled catheters and PIC-lines, n = 7) or antibiotic locks with vanco (n = 15) or gentamicin (n = 2) administered at least 3 times a week for 14 days (for ports)., Results: Overall, clearance of bacteremia (as assessed by negativity for the same CoNS of surveillance peripheral blood cultures drawn between day+ 3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis, distant foci of infection or BSI-related death was observed in any patient during the 3-month period after initiation of treatment. Regarding the 17 port-BSI cases for which VAD conservative strategy was attempted, failure of 3-month VAD preservation was documented in 7/17 cases and 3-month recurrence of VAD-BSI was observed in 3/17 cases (with 1 patient with cellulitis). Treatment with mino was well tolerated except for a mild skin rash in one patient., Conclusion: Further prospective studies are needed to evaluate efficacy and safety of this approach., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Despite modern antimicrobial treatments, bacterial and fungal infections remain major complications in neutropenic patients. Granulocyte transfusions appeared in the 1950s-60s but first clinical trials were limited by the difficulty of transfusing enough viable granulocytes. The refinement of apheresis techniques as well as donor pretreatment with corticosteroids and/or granulocyte colony-stimulating growth factor (G-CSF) have led to improved collection yield. Despite this, uncertainties remain regarding the real clinical usefulness of granulocyte transfusions. Few studies have been carried out since the G-CSF era and the quality of scientific evidence remains low, mainly because of small case series. The largest prospective randomized controlled study published so far failed to demonstrate any benefit of therapeutic granulocyte transfusions on mortality or infection control. However, the quality of this trial is limited due to its low statistical power (insufficient patient recruitment). Moreover, granulocyte transfusions are complex procedures, burdensome for the donor, expensive and associated with a significant risk of adverse effects. Therefore, the current place of granulocyte transfusion in clinical practice is guided by the experience of each center. With the increasing emergence of multi-resistant germs, it is likely that granulocyte transfusion will become interesting in the coming years. Standardization of collection and administration procedures and the final proof of their (in)effectiveness will remain the challenges for the future.

Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta-analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative-intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta-analysis. Studies that measured computed tomography-defined SM and/or AT change in adult patients during palliative-intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm 2 /m 2 , cm 2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex-specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta-analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Coastal wetlands, such as the Everglades, are increasingly being exposed to stressors that have the potential to modify their existing ecological processes because of global climate change. Their soil microbiomes include a population of organisms important for biogeochemical cycling, but continual stresses can disturb the community's composition, causing functional changes. The Everglades feature wetlands with varied salinity levels, implying that they contain microbial communities with a variety of salt tolerances and microbial functions. Therefore, tracking the effects of stresses on these populations in freshwater and brackish marshes is critical. The study addressed this by utilizing next generation sequencing (NGS) to construct a baseline soil microbial community. The carbon and sulfur cycles were studied by sequencing a microbial functional gene involved in each process, the mcrA and dsrA functional genes, respectively. Saline was introduced over two years to observe the taxonomic alterations that occurred after a long-term disturbance such as seawater intrusion. It was observed that saltwater dosing increased sulfite reduction in freshwater peat soils and decreased methylotrophy in brackish peat soils. These findings add to the understanding of microbiomes by demonstrating how changes in soil qualities impact communities both before and after a disturbance such as saltwater intrusion.

Introduction: Poor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT., Methods: We prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT. This multicenter trial was registered at www.clinicaltrials.gov (#NTC00603330)., Results: Within 90 days post-MSC infusion, 53% (95% CI, 35 - 71%) of patients improved at least one cytopenia (overall response, OR) and 37% (95% CI, 19 - 54%) achieved a complete hematological response (CR: absolute neutrophil count, ANC >0.5 x 10 9 /L, Hb > 80g/L and platelet count > 20 x 10 9 /L with transfusion independence). Corresponding response rates increased to 67% (95% CI, 50 - 84%) OR and 53% (95% CI, 35 - 71%) CR within 180 days after MSC infusion. A significant decrease in red blood cells and platelets transfusion requirement was observed after MSC (median of 30-days transfusion requirement of 0.5 and 0 from d90-120 post-MSC versus 5 and 6.5 before MSC, respectively, p ≤0.001). An increase in ANC was also noted by day +90 and +180, with 3/5 patients with severe neutropenia having recovered an ANC > 1 x 10 9 /L within the 90-120 days after MSC infusion. Overall survival at 1 year post-MSC was 70% (95% CI, 55.4 - 88.5), with all but one of the patients who achieved CR being alive. A single infusion of third-party MSC appeared to be safe, with the exception of one deep vein thrombotic event possibly related to the intervention., Discussion: In conclusion, a single i.v. infusion of BM-derived MSC from third party donor seemed to improve hematological function after alloHCT, although spontaneous amelioration cannot be excluded. Comparative studies are warranted to confirm these encouraging results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Servais, Baron, Lechanteur, Seidel, Baudoux, Briquet, Selleslag, Maertens, Poire, Schroyens, Graux, De Becker, Zachee, Ory, Herman, Kerre and Beguin.)

In this article, we discuss again the definition, the risk factor and guideline to treat the graft failure, the poor graft function and erythrobalstopenia. Graft failure is a severe but rare complication after hematopoietic cell transplantation (HCT). Despite disparity in the literature, we defined this complication and discussed the factor risks and recommendation for treatment based on new studies. Poor graft function is also a more frequent complication after HCT. New studies will soon be available to prove or not the current recommendation suggested in this article based on therapeutics medicine or cellular therapy. Erythroblastopenia, is a rarer complication post HCT. Despite anticipation for a better choice of compatibility donor/recipient, some patients still suffer from this complication., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Graft-versus-host disease (GVHD) remains a serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). While post-transplant administration of cyclophosphamide (PTCy) is increasingly used as GVHD prophylaxis, its precise mechanisms of action and its impact on graft-versus-leukemia effects have remained debated. Here, we studied the mechanisms of xenogeneic GVHD (xGVHD) prevention by PTCy in different humanized mouse models. We observed that PTCy attenuated xGVHD. Using flow cytometry and single-cell RNA-sequencing, we demonstrated that PTCy depleted proliferative CD8 + and conventional CD4 + T cells but also proliferative regulatory T cells (Treg). Further, T-cell receptor β variable region sequencing (TCRVB) analyses demonstrated that highly xenoreactive T-cell clones were depleted by PTCy. Although Treg frequencies were significantly higher in PTCy-treated than in control mice on day 21, xGVHD attenuation by PTCy was not abrogated by Treg depletion. Finally, we observed that PTCy did not abrogate graft-versus-leukemia effects., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Prognostic factors for epithelial ovarian cancers (EOCs) are in particular clinical factors such as pathology staging at diagnosis (FIGO stages), genetic mutation, or histological phenotypes. In the present study, FIGO stage, tumor residue after surgery, and body mass index were clinical predictors of recurrence-free survival (RFS). Nonetheless, a number of studies support a lipid metabolism disorder in ovarian cancer patients. The objective of this pilot study was to explore whether fatty acid composition of adipose reflecting the qualitative dietary intake and fatty acids metabolism may be associated with RFS. Forty-six women with EOCs and six with borderline ovarian tumors between March 2017 and January 2020 were included in this prospective study at Tours university teaching hospital (central France). The patients involved in the present study are part of the METERMUS trial (clinicaltrials.gov NCT03027479). Adipose tissue specimens from four abdominal locations (superficial and deep subcutaneous, visceral (pericolic), and omental) were collected during surgery or exploratory laparoscopy. A fatty acid profile of adipose tissue triglycerides was established by gas chromatography. Fatty acids composition was compared among the four locations using nonparametric Friedman’s ANOVA test for repeated measures. Median follow-up of EOC patients was 15 months and patients’ RFS was analyzed using Kaplan−Meier survival curves and log-rank test by separating patients into two groups according to median fatty acid levels. The content of long-chain saturated fatty acids (SFAs) was increased and that of long-chain polyunsaturated fatty acids (PUFAs) decreased in deep versus superficial subcutaneous adipose tissue in EOC patients. Nevertheless, the content of total SFAs was ~28%, monounsaturated fatty acids (MUFAs) ~55%, PUFAs n-6 ~11.5%, and PUFAs n-3 about 1.3%, whatever the adipose tissue. When EOC patients were separated into two groups by median fatty acid content, total PUFAs (n-6+n-3) levels, whatever the adipose tissue, were positively and independently associated with RFS. RFS was about two times longer in EOC patients with high versus low total PUFA content (median survival: 12 vs. 27 months, p = 0.01 to <0.0001 according to the tissue). Content of total PUFAs (n-6+n-3) in abdominal adipose tissue (visceral and subcutaneous) are new prognostic factors in EOC.

Background: Hemorrhagic cystitis (HC) with BK polyomavirus (BKPyV) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT) that may lead to severe discomfort for the patient and significant morbidity (urinary obstruction, increased transfusion requirements and prolonged hospitalization). So far, there is no clear consensus on how to manage this complication., Patients and Methods: Here, we report a single-center case series of 9 patients (4 children and 5 adults) treated with cidofovir endovesical (EV) instillation(s) for BKPyV-HC after alloHCT. EV Cidofovir was administered at a dose of 5 mg/kg, for 1 to 3 instillations (with a minimum delay between 2 successive doses of 5 days)., Results: Eight out of the 9 treated patients with EV Cidofovir achieved a complete resolution of HC after 1-3 instillation(s), without recurrence of symptomatic infection within the next 3 months. Only 1 adult patient did not improve after treatment and developed severe morbidity (emphysematous cystitis)., Conclusion: Although this single-center case series of EV cidofovir for BKPyV HC after alloHCT shows encouraging results, only large prospective studies will definitively establish the effectiveness of this therapy., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Chimeric antigen receptor T cells (also known as CAR-T cells) have already made their way into the therapeutic arsenal of specific hematological cancers, significantly improving the prognosis of patients. The prospect of such an innovative and effective treatment in solid tumors is very attractive. For this reason, several clinical studies have been initiated. Unfortunately, the antigenic heterogeneity and microenvironmental hostility of these solid tumors currently limit the effectiveness of CAR-T cells. New strategies are being sought to counteract these therapeutic obstacles.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients requiring intensive care unit (ICU) have high mortality rates. Methods. In the current study, we retrospectively assessed whether the Prognostic Index for Critically Ill Allogeneic Transplantation patients (PICAT) score predicted overall survival in a cohort of 111 consecutive allo-HCT recipients requiring ICU. Results. Survival rates at 30 days and 1 year after ICU admission were 57.7% and 31.5%, respectively, and were significantly associated with PICAT scores ( p = 0.036). Specifically, survival at 30-day for low, intermediate, and high PICAT scores was 64.1%, 58.1%, and 31.3%, respectively. At one-year, the figures were 37.5%, 29%, and 12.5%, respectively. In multivariate analyses, high PICAT score (HR = 2.23, p = 0.008) and relapse prior to ICU admission (HR = 2.98, p = 0.0001) predicted higher mortality. We next compared the ability of the PICAT and the Sequential Organ Failure Assessment (SOFA) scores to predict mortality in our patients using c-statistics. C statistics for the PICAT and the SOFA scores were 0.5687 and 0.6777, respectively. Conclusions. This study shows that while the PICAT score is associated with early and late mortality in allo-HCT recipients requiring ICU, it is outperformed by the SOFA score to predict their risk of mortality.

Background: Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, mainly due to skeletal muscle wasting, resulting in a decrease in patients' quality of life, response to cancer treatments, and survival. Our objective was to investigate skeletal muscle alterations in cachectic cancer patients., Methods: This is a prospective study of patients managed for pancreatic or colorectal cancer with an indication for systemic chemotherapy (METERMUCADIG - NCT02573974). One lumbar CT image was used to determine body composition. Patients were divided into three groups [8 noncachectic (NC), 18 with mild cachexia (MC), and 19 with severe cachexia (SC)] based on the severity of weight loss and muscle mass. For each patient, a pectoralis major muscle biopsy was collected at the time of implantable chamber placement. We used high-resolution oxygraphy to measure mitochondrial muscle oxygen consumption on permeabilized muscle fibres. We also performed optical and electron microscopy analyses, as well as gene and protein expression analyses., Results: Forty-five patients were included. Patients were 67% male, aged 67 years (interquartile range, 59-77). Twenty-three (51%) and 22 (49%) patients were managed for pancreatic and colorectal cancer, respectively. Our results show a positive correlation between median myofibres area and skeletal muscle index (P = 0.0007). Cancer cachexia was associated with a decrease in MAFbx protein expression (P < 0.01), a marker of proteolysis through the ubiquitin-proteasome pathway. Mitochondrial oxygen consumption related to energy wasting was significantly increased (SC vs. NC, P = 0.028) and mitochondrial area tended to increase (SC vs. MC, P = 0.056) in SC patients. On the contrary, mitochondria content and networks remain unaltered in cachectic cancer patients. Finally, our results show no dysfunction in lipid storage and endoplasmic reticulum homeostasis., Conclusions: This clinical protocol brings unique data that provide new insight to mechanisms underlying muscle wasting in cancer cachexia. We report for the first time an increase in mitochondrial energy wasting in the skeletal muscle of severe cachectic cancer patients. Additional clinical studies are essential to further the exploring and understanding of these alterations., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

As in younger patients, allogeneic stem cell transplantation (alloHSCT) offers the best chance for durable remission in older patients (≥60 years) with acute myeloid leukemia (AML). However, defining the best treatment strategy (and in particular, whether or not to proceed to alloHSCT) for elderly patients with AML remains a difficult decision for the hematologist, since potential toxicity of conditioning regimens, risks of graft-versus-host disease, impaired immune reconstitution and the need for prolonged immunosuppression may be of major concern in these vulnerable patients with complex needs. Hopefully, significant progress has been made over the past decade in alloHSCT for elderly patients and current evidence suggests that chronological age per se (between 60 and 75) is not a reliable predictor of outcome after alloHSCT. Here, we review the current state of alloHSCT in elderly patients with AML and also discuss the different approaches currently being investigated to improve both accessibility to as well as success of alloHSCT in these patients., (© The Author(s) 2022. Published by Oxford University Press.)