Explore the vast range of titles available.

Studies comparing rabbit antithymocyte globulin (rATG) and horse ATG (hATG) in patients with aplastic anemia (AA) have shown conflicting results. These studies included fewer than 60 subjects in the rATG arm with relatively short follow-up. A total of 169 patients treated with rATG and 62 treated with hATG were included in this retrospective analysis, across 33 centers. Patients were treated with rATG or hATG plus cyclosporine A. Over half were classified, as having severe AA (SAA) or very severe AA (VSAA), and the mean follow-up was 45 months. There was no significant difference detected in cumulative response to treatment or survival between the rATG and hATG groups. The response to treatment was 63 % in the rATG group versus 66 % in the hATG group at 3 months. By 12 months, this pattern had reversed, and 84 % of rATG patients had responded to treatment versus 76 % in the hATG group (n.s.). Early mortality due to infection tended to be higher with rATG compared to hATG (n.s). rATG and hATG would seem to be therapeutically equivalent in SAA and VSAA. However, patients treated with rATG may take longer to respond than those treated with hATG and may also require more active prevention of early infections.

Background Myelodysplastic syndromes (MDS) encompass a heterogeneous group of haematological neoplasms characterized by ineffective haematopoiesis and a variable risk of transformation to acute myeloid leukaemia (AML). Elevated serum ferritin (SF), a marker of iron overload (IO), has been linked to poorer outcomes in MDS. However, the impact of pre‐treatment SF levels on azacytidine (AZA) response and survival outcomes remains unclear. Methods This retrospective cohort study included patients with World Health Organization‐defined MDS or AML with 20%–30% bone marrow blasts treated with AZA at the Virgen de la Victoria University Hospital (Málaga, Spain) from 2007 onwards. Patients were stratified into three groups based on pre‐treatment SF levels: < 500 ng/mL, 500–1000 ng/mL and > 1000 ng/mL. Logistic regression and Kaplan–Meier methods were used to analyse overall response (OR) and overall survival (OS). Results Among 240 patients, 190 with available SF data were analysed. Patients with SF > 1000 ng/mL showed significantly lower OR (24.2%) and shorter OS (median: 10.1 months) compared to those with SF < 500 ng/mL (OR: 71.4%, OS: 18.2 months) and 500–1000 ng/mL (OR: 82.6%, OS: 20.5 months) (p < 0.0001 for OR, p = 0.001 for OS). Multivariate analysis confirmed elevated SF as an independent predictor of poorer outcomes. Conclusions Elevated pre‐treatment SF levels are strongly associated with reduced response and survival in patients with MDS or AML treated with AZA. Early IO management, such as iron chelation, may improve treatment outcomes. Elevated serum ferritin levels before treatment with azacytidine are associated with lower response rates and shorter survival in patients with myelodysplastic syndromes. This study supports the early identification of transfusion‐related iron overload to improve treatment planning.

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12–86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0–25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.

The aim of this study was to assess the incidence of cytomegalovirus (CMV) infection and disease in patients with hematologic malignancies treated with alemtuzumab. The outcome of CMV infection in hematologic patients treated with alemtuzumab in 19 hospitals throughout Spain was assessed retrospectively. Data were collected from the medical records of patients over a period of 6 months following initiation of alemtuzumab therapy. We studied 102 patients (89 with B-cell chronic lymphocytic leukemia and 13 with other lymphoproliferative diseases, with a median age of 63 years [range 29-81 years]). Alemtuzumab was administered for a mean of 11.2 (standard deviation: 13.8) weeks, with a median total dose of 423 mg (range: 59-1440 mg). Alemtuzumab as a single agent was administered in 92.2% of patients and was associated with chemotherapy in 7.8% of cases. Prophylactic antivirals included famcyclovir (47%), acyclovir (34%), valacyclovir (14%) and valgancyclovir (5%). CMV viremia testing was performed a mean of 6.3 times (range: 1-19). The incidence of CMV infection was 38.9% (46% in patients treated with steroids and 75% in patients receiving ≥1000 mg of alemtuzumab). Treatment of CMV infection included gancyclovir or valgancyclovir in 94% of cases. Viremia became negative after a median of 20 days (95% CI: 13.4-26.6). CMV disease occurred in five patients. The incidence of CMV infection in alemtuzumab-treated patients was 38.9%. The incidence increased in patients treated concomitantly with steroids and in those treated with high doses of alemtuzumab, although only eight patients received 1000 mg or more, systematic monitoring of CMV viremia and early treatment of infection resulted in a favorable outcome of CMV reactivation.

Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms. The diversity and unpredictability of EGFR tyrosine kinase inhibitor resistance mechanisms presents a challenge for developing new treatments to overcome EGFR tyrosine kinase inhibitor resistance. Here, we show that Akt activation is a convergent feature of acquired EGFR tyrosine kinase inhibitor resistance, across a spectrum of diverse, established upstream resistance mechanisms. Combined treatment with an EGFR tyrosine kinase inhibitor and Akt inhibitor causes apoptosis and synergistic growth inhibition in multiple EGFR tyrosine kinase inhibitor-resistant non-small-cell lung cancer models. Moreover, phospho-Akt levels are increased in most clinical specimens obtained from EGFR-mutant non-small-cell lung cancer patients with acquired EGFR tyrosine kinase inhibitor resistance. Our findings provide a rationale for clinical trials testing Akt and EGFR inhibitor co-treatment in patients with elevated phospho-Akt levels to therapeutically combat the heterogeneity of EGFR tyrosine kinase inhibitor resistance mechanisms. EGFR-mutant non-small cell lung cancer are often resistant to EGFR tyrosine kinase inhibitor treatment. In this study, the authors show that resistant tumors display high Akt activation and that a combined treatment with AKT inhibitors causes synergistic tumour growth inhibition in vitro and in vivo.

Inflammation plays a pivotal role in the pathophysiology of ST-elevation myocardial infarction (STEMI). This involves neutrophil activation and the local release of pro-inflammatory mediators. The formation of neutrophil extracellular traps (NETs) in coronary thrombosis has been linked to poor short-term prognosis following STEMI, but the usefulness of specific circulating NET components as prognostic markers is unclear. We aimed to evaluate the NET-specific marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and other classical inflammatory markers to predict adverse events after STEMI. This is a single-center retrospective cohort study of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) from 2015 to 2019. We analyzed the association between serum H3Cit-DNA levels, double-stranded DNA, and classical inflammatory markers -such us interleukin (IL) 6 and 1β, TNF-α, and C-reactive protein (CRP)- on admission and the occurrence of major cardiovascular events (MACE), including death, reinfarction, urgent revascularization, or heart failure, after STEMI. A total of 487 patients were studied, of which 380 were men [78%]; mean [SD] age of patients was 63 [13] years, and median [95%CI] follow-up was 5.4 [5.2-5.5] years. Median [IQR] H3Cit level was 179.30 [105.30-281.47] ng/ml. No relevant association was found between H3Cit-DNA levels and 30-day mortality (OR, 1.03 [95%CI, 0.71-1.50], p = 0.861) or MACE (0.98 [0.72-1.32], p = 0.879), Killip class (0.95 [0.74-1.21], p = 0.664), or left ventricular ejection fraction (ref.cat. > 50%; < 35%, RRR 1.01 [95%CI, 0.74-1.38], p = 0.952; 35-50%, 1.26 [1.07-1.48], p = 0.005]. Adding CRP and IL-6 levels as covariates to a model based on classical risk factors significantly improved the prediction of MACE at 30 days after STEMI (IDI 0.13; NRI 0.32, p < 0.05). Circulating levels of the NET marker H3Cit-DNA at the time of primary PCI were not predictive of cardiovascular events following STEMI. In contrast, the classical inflammatory markers CRP and interleukin-6 significantly enhanced the discriminative capacity of a clinical 30-day risk prediction model. These findings suggest that measuring circulating NET-specific markers may have limited utility in assessing the inflammatory state during the early stages of STEMI.

Wheat flour cannot be tolerated by those who suffer allergies to gluten. Human pathologies associated with grain proteins have increased worldwide in recent years, and the only effective treatment available is a lifelong gluten-free diet, which is complicated to follow and detrimental to gut health. This manuscript describes the development of wheat bread potentially suitable for celiac patients and other gluten-intolerant individuals. We have made bread using wheat flour with very low content of the specific gluten proteins (near gliadin-free) that are the causal agents for pathologies such as celiac disease. Loaves were compared with normal wheat breads and rice bread. Organoleptic, nutritional, and immunotoxic properties were studied. The reduced-gliadin breads showed baking and sensory properties, and overall acceptance, similar to those of normal flour, but with up to 97% lower gliadin content. Moreover, the low-gliadin flour has improved nutritional properties since its lysine content is significantly higher than that of normal flour. Conservative estimates indicate that celiac patients could safely consume 67 grams of bread per day that is made with low-gliadin flour. However, additional studies, such as feeding trials with gluten-intolerant patients, are still needed in order to determine whether or not the product can be consumed by the general celiac population, as well as the actual tolerated amount that can be safely ingested. The results presented here offer a major opportunity to improve the quality of life for millions of sufferers of gluten intolerance throughout the world.

Nowadays, challenges in gluten free breads (GFB) are focused on improving the nutritional and health benefits. Acorn flour is an underexploited sustainable ingredient, naturally gluten free, with many nutritional and technological advantages. The aim of this study was to explore the interaction of acorn flour supplementation (up to 35%) to rice flour and sourdough process to obtain rice based GFB. Different levels of rice flour replacement with acorn flour (0%, 23% and 35%), and sourdough (20%) were tested in a basic GFB recipe, and technological, nutritional, and functional GFB characteristics evaluated. The combination of acorn flour and sourdough was responsible for acidifying dough and bread. Breads containing 35:65 acorn flour: rice flour led to harder breads with lower crumb luminosity and with reddish and brownish tones, besides improved structural features when adding sourdough. That combination of sourdough and acorn flour reduced the rate and the extent of starch hydrolysis, as well as increase the minerals content, total phenolic compounds and antioxidant activity. Therefore, the combination of acorn flour and sourdough process allows obtaining rice based GFB with better nutritional pattern.

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. Conclusions: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.