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The article discusses the study on the clinical impact of heart iron overload. It states the cardiac iron overload in 18-2 percent of regularly transfused patients with myelodysplastic syndrome (MDS). It cites the inverse correlation between the number of PRBC units transfused with cardiac T2 value. It also mentions that iron overload is an aggravating factor in pathology of cardiac failure.

The article presents information on a study which showed that the outcome of high risk myelodysplastic syndrome (MDS) after azacitidine (AZA) failure. The study the outcome of 74 patients with secondary acute myeloid leukaemia (AML) after AZA treatment failure, collected from two Johns Hopkins University trials and the French AZA compassionate programme.

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The article offers information on the wishes for the new year 2024 from the editorial committee of the journal Cahiers Santé/Médecine Thérapeutique (Cs/Mt) to its readers, emphasizing health, happiness, and success. Topics include the importance of reader participation in contributing original articles, literature reviews, case studies, and other relevant contributions to the journal.

Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resected stage III B/C melanoma. We report a similar case of acral vasculitis occurring with a combination of anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) prescribed for the management of a metastatic urothelial bladder cancer. In contrast to Padda A. et al., we observed a significant improvement with oral corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory and autoimmune diseases (SIADs) occur in 10–20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow. [ABSTRACT FROM AUTHOR]

Impaired platelet production is a mechanism of immune thrombocytopenia (ITP). Morphological abnormalities of megakaryocytes (MKs) are sometimes observed in this disease. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for thrombopoietin-receptor agonists (TPO-RAs). This was the aim of this study. The source of population was the French CARMEN registry with prospective follow-up of adult patients with incident ITP. We included patients with primary ITP, treated by TPO-RA and with a bone marrow smear before initiating TPO-RA. MK abnormalities were categorized by the presence of dysplasia and by the stage of maturation. Among 451 patients screened, 38 were included in the analysis. There was no difference in the median percentage of dysplastic MKs between responders to TPO-RA (4.0%, 95% confidence interval – CI: 2.3–6.4) and non-responders (4.5%, 95% CI: 0.7–7.1). There was a slightly higher proportion of granular MKs (4.5%, 95% CI: 3–6) and basophilic MKs (30.1%, 95% CI: 21.9–39.1) in non-responders compared to responders (granular: 2.0%, 95% CI: 0–4.1; basophilic: 21.3%, 95% CI: 11.4–40.7). In conclusion, MK abnormalities were not associated with response achievement in ITP patients treated with TPO-RA in this series of 38 patients. [ABSTRACT FROM AUTHOR]

In order to improve the outcome observed with azacitidine (AZA) in higher‐risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA‐PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher‐risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA‐LEN And AZA‐IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy‐related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA. [ABSTRACT FROM AUTHOR]

Abstract: Outcome of patients with myelodysplastic syndrome after azacitidine failure is poor. In this population, we combined cytarabine (10–20mg/m2/day 14 days) with vorinostat (400mg/day) for escalating durations (7 days, 10 days and 14 days), and starting on day 1 (concomitant arm) or on day 14 (sequential arm) following a 3+3 phase I design. 40 patients were treated. Dose limiting toxicities were all seen in sequential arm. The overall response rate was 15% with 4 responses in concomitant arm (ORR=25%). We conclude that this combination is tolerable and concomitant administration might be less toxic and have better therapeutic effect (clinicaltrials.gov NCT00776503). [Copyright &y& Elsevier]

Summary: Data about the presentation and the management of primary immune thrombocytopenia (ITP) in very elderly patients (VEPs; aged ≥80 years) are lacking. The aim of the present study was to describe ITP in this subgroup. The data source was the prospective CARMEN‐France registry. Patients included between 2013 and 2018 were selected. ITP presentation and management in VEPs was compared to elderly patients (EPs; aged 65–79 years). We assessed factors associated with bleeding at ITP onset in VEPs. Of 541 patients, 184 were included: 87 in the VEP group and 97 in the EP group. The mean age was 85·7 years in the VEP group. Comorbidities were more frequent in the VEP group (67·4% vs. 47·9%). The median platelet count at ITP onset was similar but severe bleeding tended to be more frequent in VEPs (10·3% vs. 4·1%, P = 0·1) as well as mortality. Exposure to ITP drugs, response to first‐line treatment, need of second‐line treatment, evolution towards persistency, occurrence of bleeding, infection and thrombosis did not differ between groups. In VEPs, factors associated to bleeding were female sex [odds ratio (OR) 4·75, 95% confidence interval (CI) 1·31–17·32] and platelet count of <20 × 109/l (OR 10·05, 95% CI 4·83–67·39). Exposure to anticoagulants was strongly associated with severe bleeding (OR 7·61, 95% CI 1·77–32·83). [ABSTRACT FROM AUTHOR]

Objective: Hematological treatment decisions in older adults with hematological malignancies are complex. Our objective is to study the impact of a comprehensive geriatric assessment on hematological treatment decision in older patients and the factors associated with change in treatment plan. Methods: We conducted a cross‐sectional analysis of patients aged 65 years and above with hematological malignancies, hospitalized between 2008 and 2019 at the University Cancer Institute of Toulouse. They were assessed by a geriatrician/nurse team using a comprehensive geriatric assessment (CGA). A penalized logistic regression model with elastic net regularization was used to identify factors associated with change in hematological treatment plan. Results: A total of 424 patients were included. Main hematological malignancies were lymphoma (36.1 %), acute myeloid leukemia (26.9 %) and myelodysplastic syndrome (19.8%). Change in hematological treatment plan was suggested after CGA for 92 patients (21.7%). Factors associated with change in treatment plan were functional impairment according to ADL and IADL scale, mobility impairment, the presence of comorbidity defined by the Charlson score >1 and increasing age. Conclusion: A CGA has a significant impact on hematological treatment decision in older patients. Functional and mobility impairment, comorbidities and age are predictive factors of change in treatment plan. [ABSTRACT FROM AUTHOR]

Objectives: To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. Methods: Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary end-points were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. Results: Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. Conclusion: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload. [ABSTRACT FROM AUTHOR]

Summary: Treatment with azacitidine (AZA) has been suggested to be of benefit for higher‐risk myelodysplastic syndrome (HR‐MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR‐MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time‐varying variable in multivariable analysis. A Cox Regression model with time‐interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non‐CK) and International Prognostic Scoring System risk (high versus intermediate‐2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P < 0·001 at 1 year, 0·7 P = 0·019 at 2 years; 0·73 P = 0·029 at 3 years). This benefit was present in all chromosome 7 categories, but tended to be greater in patients with CK (risk reduction of 82%, 68% and 53% at 1, 3 and 6 months in CK patients; 79% at 1 month in non‐CK patients, P < 0·05 for all). AZA also significantly improved progression‐free survival (P < 0·01). This study confirms a time‐dependent benefit of AZA on outcome in patients with HR‐MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK. [ABSTRACT FROM AUTHOR]

Background Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified. Methods In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics. Results We included 29 patients (median age 67 years [interquartile range 62–76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis ( n = 6; 20%), relapsing polychondritis ( n = 8; 30%) and vasculitis ( n = 10; 34%). During a 3-year median follow-up (IQR 1.3–4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) ( p < 0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection. Conclusion This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising. [ABSTRACT FROM AUTHOR]

Non-del(5q) transfusion-dependent low/intermediate-1 myelodysplastic syndrome (MDS) patients achieve an erythroid response with lenalidomide in 25% of cases. Addition of an erythropoiesis-stimulating agent could improve response rate. The impact of recurrent somatic mutations identified in the diseased clone in response to lenalidomide and the drug's effects on clonal evolution remain unknown. We investigated recurrent mutations by next-generation sequencing in 94 non-del(5q) MDS patients randomized in the GFM-Len-Epo-08 clinical trial to lenalidomide or lenalidomide plus epoetin ß. Clonal evolution was analyzed after 4 cycles of treatment in 42 cases and reanalyzed at later time points in 18 cases. The fate of clonal architecture of single CD34+CD38- hematopoietic stem cells was also determined in 5 cases. Mutation frequency was >10%: SF3B1 (74.5%), TET2 (45.7%), DNMT3A (20.2%), and ASXL1 (19.1%). Analysis of variant allele frequencies indicated a decrease of major mutations in 15 of 20 responders compared with 10 of 22 nonresponders after 4 cycles. The decrease in the variant allele frequency of major mutations was more significant in responders than in nonresponders (P < .001). Genotyping of single CD34+CD38- cell-derived colonies showed that the decrease in the size of dominant subclones could be associated with the rise of founding clones or of hematopoietic stem cells devoid of recurrent mutations. These effects remained transient, and disease escape was associated with the re-emergence of the dominant subclones. In conclusion, we show that, although the drug initially modulates the distribution of subclones, loss of treatment efficacy coincides with the re-expansion of the dominant subclone. [ABSTRACT FROM AUTHOR]

Background: The clinical presentation of myelodysplastic syndromes is highly variable and so accurate prediction of outcomes in these patients is crucial. We aimed to assess whether self-reported fatigue severity predicts overall survival beyond gold-standard prognostic indices in patients with higher-risk myelodysplastic syndromes.Methods: We did a multicentre, prospective, observational, cohort study of patients from 37 centres in Europe, USA, and east Asia. Adults (≥18 years) with myelodysplastic syndromes were consecutively enrolled within 6 months of diagnosis with an intermediate-2-risk or high-risk score according to the International Prognostic Scoring System (IPSS). Patients were enrolled irrespective of older age, comorbidities, performance status, and progression from a lower IPSS risk score category. All patients had to complete a quality of life assessment at baseline. With use of univariate and then multivariate Cox proportional hazards regression analysis, we constructed a multivariate model of how prognostic variables, including IPSS and fatigue score from the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-core 30, predicted overall survival. The primary endpoint was overall survival by baseline self-reported fatigue scale ratings. This study was registered with ClinicalTrials.gov, number NCT00809575.Findings: Between Nov 10, 2008, and Aug 13, 2012, we enrolled 280 patients with a median age of 71 years (IQR 64-77). The median follow-up was 15 months (IQR 8-27), and the last patient was assessed Feb 16, 2015. The median overall survival from diagnosis was 17 months (95% CI 15-19). In univariate analysis, the baseline factors that were significantly associated with reduced overall survival were increasing age, transfusion dependency (defined as having received at least one red blood cell transfusion every 8 weeks over a period of 4 months), Eastern Cooperative Oncology Group (ECOG) performance status of two or more, increased white blood cell count, high-risk IPSS score, and higher self-reported fatigue severity. In multivariate analysis, baseline factors independently associated with reduced overall survival were high-risk IPSS score (hazard ratio [HR] 2·525, 95% CI 1·357-4·697; p=0·0035) and a higher score for fatigue (1·110, 1·040-1·170, for every ten points of fatigue deterioration; p=0·0007). In further multivariate models for survival, including either the WHO-based prognostic scoring system or the revised version of the IPSS classification, fatigue remained a statistically significant independent prognostic factor with a HR of 1·120 (1·050-1·180, p=0.0003) and a HR of 1·130 (1·060-1·190, p=0·0002), respectively.Interpretation: In patients with newly diagnosed higher-risk myelodysplastic syndromes, self-reported fatigue severity provides prognostic information for survival independent from gold-standard risk classifications. Our findings suggest that fatigue assessment should be included in routine diagnostic investigation for these patients and considered as a standard baseline stratification factor in future randomised controlled trials.Funding: Associazione Italiana contro le Leucemie, Linfomi e Mieloma (AIL). [ABSTRACT FROM AUTHOR]

The article discusses the use of Ribavirin for chronic hepatitis prevention among patients with hematologic malignancies. Topics include Ribavirin monotherapy for infected immunocompromised patients, diagnosis of Hepatitis E (HEV) infection, summary of the outcomes of HEV infection and hematologic malignancies, and solid organ transplant (SOT) patients showing high response rate to ribavirin treatment.

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]

Objective A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System ( IPSS)-defined Low-/ Intermediate ( Int)-1-risk myelodysplastic syndromes ( MDS) with isolated del(5q). Methods Patients received lenalidomide 10 mg/d (days 1-21; n = 47) or 5 mg/d (days 1-28; n = 43) on 28-d cycles or placebo ( n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively. Results Rates of red blood cell-transfusion independence ( RBC- TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% ( P < 0.0001), 23.1% ( P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC- TI ≥182 d vs. non-responders ( P = 0.0072). The most common grade 3-4 adverse event was myelosuppression. Conclusions These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/ Int-1-risk MDS with isolated del(5q). [ABSTRACT FROM AUTHOR]

Abstract: We treated 95 RBC transfusion dependent lower risk MDS with del 5q with Lenalidomide (10mg/day, 3 weeks/4 weeks). Median age was 70.4, median interval from diagnosis 29 months. IPSS was low in 31% and intermediate-1 in 69% patients. Del 5q was isolated, with 1 additional and >1 additional abnormality in 79%, 14%, and 6% patients, respectively. 62 (65%) patients achieved transfusion independence (TI). The only significant factor predicting TI was baseline platelet count >150G/L and platelet decrease by at least 50% during the first weeks of treatment (p =0.001). Grade III–IV neutropenia and thrombocytopenia were seen in 74% and 37.9% of the cases, respectively, and 3 deaths were attributed to cytopenias. Eight (8%) patients developed deep venous thrombosis (DVT). Platelet decrease by less than 50% predicted a higher risk of DVT. Only 6 patients (6.3%) patients progressed to AML, but median follow-up time was short (18 months). We confirm the high rate of TI with Lenalidomide in lower risk MDS with del 5q. Very close patient monitoring for cytopenias and DVT is mandatory, especially during the first weeks of treatment. [Copyright &y& Elsevier]

Abstract: Isolated 20q deletion is common in MDS and considered of good prognosis, but no large series have been reported. We compared characteristics of 62 MDS patients with isolated del 20q, 36 patients with del 20q and other cytogenetic abnormalities, and 1335 MDS patients without del20q. Significant differences between MDS with isolated del 20q and patients without del 20q were lower platelet count (mean 144 vs. 196 G/l, p =0.005), lower marrow blast count (mean 3.9% vs. 5.6%, p =0.0008), and higher reticulocyte count (mean 72.5 vs. 51.7 G/l, p =0.04). Ten (16%) patients with isolated del 20q had Hb>12g/dl and platelets <100 G/l, compared to 7.3% of patients without del 20q (p =0.025). Review of marrow slides of those 10 patients showed that could be readily identified as MDS prior to cytogenetics. Fourteen percent of patients with isolated del 20q progressed to AML compared to 11% with one and 24% with several additional abnormalities. Median survival was 54 months in patients with isolated del 20q, not reached and 12 months for del 20q with one and several additional abnormalities, respectively (p =0.035) confirming the favorable prognosis of del 20q without complex abnormalities. [Copyright &y& Elsevier]

Abstract: ESAs are increasingly used to treat anemia of lower risk MDS, even before RBC transfusion requirement. From a previously published patient cohort treated with ESAs, we selected 112 patients with de novo low or int-1 IPSS MDS with Hb<10g/dl, serum EPO<500UI/l and who had never been transfused. Erythroid response rate at 12 weeks was 63.1% (IWG 2006). In multivariate analysis, an interval between diagnosis and ESA onset<6 months, Hb level>9g/dl, and serum EPO<100UI/l predicted better response to ESA while shorter interval between diagnosis and ESA onset (p =0.01), lower serum EPO (p =0.04) and WHO diagnosis of RCMD-RS (p =0.03) were associated with longer response. Median interval from diagnosis to transfusion dependency was 80 months and 35 months, respectively, in patients with onset of ESA <6 months and ≥6 months from diagnosis (p =0.007). Those results support early onset of ESA in lower risk MDS, to better avoid the consequences of anemia. Early introduction of ESA may also delay the need for RBC transfusions, hypothetically by slowing the disease course, but prospective studies are required to further assess this point. [ABSTRACT FROM AUTHOR]

Abstract: Background: Iron chelation therapy (CT) improves survival in thalassemia major but its beneficial effects on survival in MDS patients remain uncertain. Methods: We analyzed, by multivariate analysis, survival and causes of deaths in 97 low or intermediate 1 IPSS patients regularly transfused as outpatients, chelated or not, who were included during a month period and followed for 2.5 years. Results: 44 (45%) of patients were not chelated and 53 (55%) received CT, mainly with deferoxamine, for at least 6 months (median duration of chelation 36 months, range 6–131+). During the follow-up period, 66 of the 97 patients died, including 51% and 73% of chelated and non-chelated patients, respectively. Median overall survival was 53 months and 124 months in non-chelated and in chelated patients (p <0.0003). Causes of death did not significantly differ between the two groups (p =0.51). In multivariate Cox analysis, adequate chelation was the strongest independent factor associated with better OS. Conclusion: Iron chelation therapy appears to improve survival in heavily transfused lower risk MDS, but prospective randomized studies are required to confirm our findings, and to determine more precisely the mechanisms of this potential survival benefit. [Copyright &y& Elsevier]

In the phase III AZA-001 trial, low-dose cytarabine (LDara-C), the most widely used low-dose chemotherapy in patients with higher-risk myelodysplastic syndrome (MDS) who are ineligible for intensive treatment, was found to be associated with poorer survival compared with azacitidine. This analysis further compared the efficacy and the toxicity of these two drug regimens. Before randomization, investigators preselected patients to receive a conventional care regimen, one of which was LDara-C. Of 94 patients preselected to LDara-C, 45 were randomized to azacitidine and 49 to LDara-C. Azacitidine patients had significantly more and longer haematologicalal responses and increased red blood cell transfusion independence. Azacitidine prolonged overall survival versus LDara-C in patients with poor cytogenetic risk, presence of −7/del(7q), and French-American-British subtypes refractory anaemia with excess blasts (RAEB) and RAEB in transformation. When analyzed per patient year of drug exposure, azacitidine treatment was associated with fewer grade 3–4 cytopenias and shorter hospitalisation time than LDara-C in these higher-risk MDS patients. [ABSTRACT FROM AUTHOR]

Patients ( n = 47) with low-risk myelodysplastic syndrome were treated with thalidomide [200 mg/d, increased by 200 mg/d/4 weeks up to week 16]. Responses were evaluated according to the International Working Group criteria at week 16 for 39 patients who received at least 8 weeks of treatment. Twenty-three (59%) patients showed haematological improvement (HI): four major erythroid response (HI-EM), 15 minor erythroid response, six major neutrophil response, two major platelet response. Side effects caused 22/39 to stop thalidomide before week 16. Nine of 23 responders continued thalidomide after week 16 [19% of trial patients] with sustained response in eight of nine. Six reached week 56, including the four HI-EM patients [13% of trial patients]. Nineteen of 36 red blood cell transfusion-dependent patients (53%) showed erythroid response, but only four became transfusion-independent. Among the 23 responders, the median duration of response was 260 d (range 30–650). Responses were sustained in all patients except one, and were observed between week 4 and week 8 in 85% of patients, at doses ranging from 200 to 400 mg. Only two patients responded at 600 mg/d and none at 800 mg/d. No clinical characteristics of responding versus non-responding patients were identified. The erythroid response rate was identical in all cytogenetic subgroups, including 5q31.1 deletions. Pretreatment vascular endothelial growth factor levels were lower in responders compared with non-responders ( P = 0·004). Microvessel density (MVD) increased and apoptosis decreased in four of six and in all six responders studied respectively whereas MVD and apoptosis were unchanged in three non-responders. [ABSTRACT FROM AUTHOR]

Immunological checkpoint inhibitors are now part of the oncological therapeutic arsenal in many solid cancers and malignant blood diseases, at the cost of immuno-mediated toxicities, of which dermatological disorders are among the most frequent. The most common, following treatment with anti-PD1 or anti-CTLA4, are maculopapular erythema, pruritus, vitiligo, or lichenoid lesions, but other more atypical conditions may lead to the internist being called upon. Here, we present a case series of these less common dermatological manifestations including fasciitis, dermatomyositis, scleroderma, granulomatosis and immune-induced vasculitis. Some manifestations appear similar to the primary forms or seem to correspond to paraneoplastic syndromes, but some diagnostic and therapeutic particularities are specific to ICI toxicity that the internist must be aware of., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Since the early 2000's, the appeal of certain operating room specialties has decreasedamong medical school graduate students. The recent reform of the second and third cycles of medical studies in France provides an opportunity to set up teaching programs around operating room specialties. We have organised a teaching unit which is part of the final year of medical studies. The main objectives are: (1) to examine whether a boot camp can modify students' opinions and preconceived assumptions about a surgical and/or anaesthetist career (2) to determine whether these changes in perception, have an impact on students' interest in pursuing a surgical/anaesthetic career compared with the current situation., Materials and Methods: The "working in the operating theatre" boot camp (UETB) took place after the written exams of the sixth year of medical school, before students choose their future specialty for residency. This program included practical workshops, readings and time for exchanges surgeons and anaesthetists. At the beginning and at the end of the UETB, feedback forms were collected., Results: The cohort included 59 students from the Toulouse medical school, academic year 2023-2024. After attending the UETB, there was a significant qualitative improvement in interest in a surgical and intensive care-anaesthesia career. Feedback on how the UETB influenced the choice of a future specialty was very positive, with statistically significant qualitive improvement., Additionally, the students' perception of a work-life quality as a surgeon and/or anaesthetist improved significantly., Conclusion: The outcome of this study makes a strong case for integrating additional exposure to the various surgical subspecialties into the graduate medical curriculum in France. By helping to dispel misperceptions of "a surgical/anaesthetist career" early on, opportunities such as the UETB program may enable addressing the attrition rate observed among surgical and anaesthetic residency applications., (© 2024. The Author(s).)

Rationale: On the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists., Method: The survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU-PH) and 18 hospital practitioners assistant professors (MCU-PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04)., Results: Seventy-three HUs (56.1%) responded to the survey, including 65 PU-PH, 7 MCU-PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students., Conclusion: Internal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The 2017 reform of the third cycle of medical studies (R3C) was accompanied by modifications in the formats and number of specialty diplomas. The aim of this study was to investigate the evolution of the choice of the internal medicine and clinical immunology specialty before and after 2017., Methods: We used the median ranking and its evolution, as well as incoming and outgoing remorse rights, as markers of attractiveness. Data on the number of position offered, rankings and affectation were collected from decrees published in the French "Journal Officiel" each year. A survey conducted by the "Amicale des Jeunes Internistes" investigated the reasons for the outgoing or incoming rights to remorse., Results: Before 2017, internal medicine was accessible to 52% of students on average, with a median rank of 1118 [339-2640]. From 2017 onwards, the internal medicine specialty was accessible to an average of 76.6% of students, with a median rank of 2772 [1039-5155]. The balance of incoming and outgoing remorse rights was -4.7% before 2017 and varied between -4.1 and -12.4% from 2017., Conclusion: Since 2017, the median and cut-off ranks of students choosing internal medicine specialty have increased, and balance of incoming and outgoing remorse rights was increasingly negative. A reflection on the attractiveness of the internal medicine specialty is undertaken by the National College of Internal Medicine Teachers in order to make the richness of the specialty and its different modes of practice known to future residents., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)