We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict ...in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61-70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71-80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p = 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.
IntroductionBackground: leptin and adiponectin are associated with cardiovascular disease in chronic kidney disease (CKD) patients and could be useful prognostic factors. Objectives. to explore the ...usefulness of the leptin/adiponectin ratio (LAR) to predict the presence or worsening of dyslipidemia during 1 year of follow-up in children receiving kidney replacement therapy (KRT). Material and methods: a prospective cohort study was performed. Pediatric KRT patients aged between 8 and 17 years who were undergoing hemodialysis or peritoneal dialysis were included. At enrollment, the lipid profile, adiponectin and leptin levels, and somatometric measurements, including body fat percentage, were determined. At the one-year follow-up, the lipid profile was reassessed. Results: of the 70 patients included, the median age was 13 years, and there was no sex predominance (52.8 % males). At the end of follow-up, the patients were divided into three groups: those without dyslipidemia (WOD), those who developed or experienced worsening of their dyslipidemia (DWD) and those with persistent dyslipidemia (PD). A LAR > 0.85 (OR, 16.7) and body fat percentage (OR, 1.46) were associated with an increased risk of PD and DWD at 12 months, independently of urea level, BMI Z-score, benzafibrate treatment, CKD progression time, and replacement treatment. Conclusions: a LAR > 0.85 and fat body percentage at the beginning of follow-up were strongly associated with the presence, persistence or worsening of dyslipidemia at the 12-month follow-up in children with KRT.
Introduction and objectives: Nonagenarians are a fast-growing age group among cardiovascular patients, especially with aortic stenosis, but data about their prognosis after transcatheter aortic valve ...implantation (TAVI) is scarce. The objective of our study is to analyze the baseline characteristics of nonagenarians treated with TAVI and determine whether age "65; 90 years is associated with a worse prognosis compared to non-nonagenarian patients.
Methods: We included all patients "65;75 years enrolled in the multicenter prospective Spanish TAVI registry between 2009 and 2018. Patients < 75 years were excluded.
Results: A total of 8073 elderly patients ("65; 75 years) from 46 Spanish centers were enrolled in the Spanish TAVI registry; 7686 were between "65; 75 and < 90 years old (95.2%), and 387 were nonagenarian patients (4.79%). A gradual increase of nonagenarians was observed. The transfemoral access was used in 91.6% of the cases, predominantly among the nonagenarian patients (91.4% frente a 95.1%, P = .01). Nonagenarians were more likely to die during their hospital stay (4.3% frente a 7.0% among nonagenarians, P = .01). However, no difference was seen in the all-cause mortality rates reported at the 1-year follow-up (8.8% frente a 11.3%, P = .07). In the multivariate analysis, age "65; 90 years was not independently associated with a higher adjusted all-cause mortality rate (HR, 1.37, 95%CI, 0.91- 1.97, P = .14). The baseline creatinine levels, and the in-hospital bleeding complications were all associated with a worse long-term prognosis in nonagenarians treated with TAVI.
Conclusions: Nonagenarians are a very high-risk and growing population with severe AS in whom TAVI may be a safe and effective team is mandatory to achieve maximum efficiency in this population where baseline kidney function and bleeding complications may determine the long-term prognosis after TAVI.
Introducción y objetivos: Los nonagenarios son un grupo de edad en rápido crecimiento entre los pacientes cardiovasculares, en especial con estenosis aórtica, pero los datos sobre su pronóstico después de la implantación transcatéter de válvula aórtica (TAVI) son escasos. El objetivo de este estudio es analizar las características basales de los nonagenarios tratados con TAVI y determinar si la edad "65; 90 años está relacionada con un peor pronóstico en comparación con los pacientes no nonagenarios.
Métodos: Se incluyó a todos los pacientes "65; 75 años inscritos en el registro prospectivo multicéntrico español de TAVI entre 2009 y 2018. Se excluyó a aquellos < 75 años.
Resultados: Se inscribieron en el registro español de TAVI 8.073 pacientes "65; 75 años de 46 centros de España; 7.686 de > 75 a 90 años (95,2%) y 387 nonagenarios (4,79%). Se observó un aumento progresivo de los nonagenarios. El acceso transfemoral se utilizó en el 91,6% de los casos, predominantemente en los nonagenarios (91,4 frente a 95,1%; p = 0,01). Los nonagenarios tenían más probabilidades de morir durante la hospitalización (4,3 frente a 7,0%; p = 0,01). Sin embargo, no hubo diferencia en la tasa de mortalidad por cualquier causa al año de seguimiento (8,8 frente a 11,3%; p = 0,07). En el análisis multivariable, la edad "65; 90 años no se asoció de forma independiente con un aumento de la mortalidad por cualquier causa ajustada (HR = 1,37; IC95%, 0,91-1,97; p = 0,14). La creatinina basal y las complicaciones hemorrágicas intrahospitalarias se asociaron a un peor pronóstico a largo plazo en pacientes nonagenarios tratados con TAVI.
Conclusiones: Los nonagenarios son una población creciente y de muy alto riesgo, con estenosis aórtica grave, para quienes la TAVI podría representar una estrategia segura y efectiva. Una cuidadosa selección de los pacientes por un equipo multidisciplinario la máxima eficiencia en esta población, en la que la función renal basal y las complicaciones hemorrágicas pueden determinar el pronóstico a largo plazo tras la TAVI.
Introduction: asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor that potently inhibits aberrant kinase activity of the BCR-ABL1 oncoprotein via ...allosteric binding. asciminib has shown high efficacy profile in heavily pretreated Chronic Myeloid Leukemia (CML) patients with an adequate safety profile in phase I and III clinical trials. However, data from the use of asciminib in real life setting are still scarce.
Methods: We gathered real-life retrospective data from 49 patients with BCR-ABL1 positive CML treated with asciminib (mean dose: 40 mg twice daily) between October 2018 and July 2021 at 33 institutions. The indication of asciminib was made according to the criterion of the attending physician and the drug was granted by Novartis under a controlled access program. Molecular biology tests were performed according to ELN guidelines and BCR-ABL/ABL ratios were expressed as % IS in all centers. Treatment responses were calculated with the patients at risk at each specific time points. For the event free survival (EFS), the events were treatment discontinuation due to any reason, progression or death. Data collection followed the local regulations for observational studies.
Results: Median time on asciminib was 11,69 months for the entire cohort. Patients' characteristics are displayed on Table 1. Most patients were heavily pretreated with at least 3 prior TKI lines in 45 patients (91,83%), 18 of them receiving prior Ponatinib. Switch to asciminib occurred due to intolerance in 32 patients and due to resistance in the remaining 17. Fifteen patients (30,61%) harbored mutations in BCR-ABL1 (3 with a T315 mutation). Regarding efficacy (Table 2), probability of reaching or maintaining previous responses were 94%, 45% and 21% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Considering probabilities of improving previous response, rates were 40%, 42% and 33% for the same parameters. Probabilities to obtain CCyR and MMR in resistant and intolerant patients were 29% (4/14) vs 55% (6/11) and 27% (4/15) vs 52% (11/21), respectively. Amid the patients previously treated with Ponatinib, probabilities of reaching or maintaining previous response were 53% (9/17) and 35% (6/17) for CCyR and MMR respectively, and 30% (3/10), 23% (3/13) displayed improvement of response. Regarding responses in patients with mutations, 39% (5/13) achieved or maintained CCyR and 31% (4/13) MMR; whereas 20% (2/10) and 18% (2/11) improved such responses. Of the three patients with T315I mutation, one discontinued due to progression to advanced stages, and the rest maintained the previous response. With a median follow-up of 11,69 months, the estimated EFS was 80% (figure 1).
In terms of safety (Table 3), the most frequent extra-hematological adverse events (AE) were: fatigue (16,2%), joint pain (13,5%) and nausea (8,1%), most of them grade 1-2. Grade 3-4 AE were observed in 10% of patient (fatigue (2), cholestasis enzyme elevation (1), hypertension (1), pancreatitis (1) and pericardial effusion (1)). Thrombocytopenia was shown as the most frequent AE (16,3%), with 6% of patients suffering from grade 3-4. Dose reduction was required in 15 patients (30,6%). After a median follow up of 51 weeks, 73,5% of the patients remained on treatment. Only fourteen patients discontinued treatment due to progression or loss of efficacy, whereas 6% of patients discontinuing treatment due to intolerance.
Conclusions: The results presented are in line with the data obtained in clinical trials, positioning asciminib as a potential safe and efficacious treatment for CML patients with failure to several TKI lines.
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Sanchez-Guijo: Novartis: Consultancy, Honoraria, Research Funding; Celgene/Bristol-Myers-Squibb,: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.
Background: Relapsed/refractory (R/R)acute leukemia withalterations in KMT2A (also called MLL1; 9-15% of adult AML, 10% of ALL) or NPM1 (30% of adult AML) are often associated with poor outcomes. ...Pre-clinical studies demonstrated the relevance of the menin-KMT2A protein-protein interaction in sustaining leukemic cells with KMT2A and NPM1 alterations (Kuhn 2016). JNJ-75276617 is a potent and selective inhibitor of the interaction between the scaffolding protein menin and the methyltransferase KMT2A with preclinical activity in KMT2A-rearranged or NPM1-mutated leukemic cell lines and primary leukemia patient samples in vitro and in vivo (Kwon 2022). We report initial data investigating JNJ-75276617 in adult participants (pts) with R/R acute leukemia harboring KMT2A alterations (rearrangements, amplifications, or partial tandem duplications) or NPM1 mutations. Methods: 75276617ALE1001 (NCT04811560) is an ongoing Phase 1, multicenter, open-label, dose-finding study. Pts in dose escalation receive JNJ-75276617 orally on a 28-day cycle. As of 8 April 2023, multiple dose levels ≥15 mg have been explored on either a daily or twice daily (BID) dosing schedule. AEs were graded by CTCAE v5.0. Responses were investigator-assessed per ELN2017. Preliminary safety, efficacy and PD data are reported herein, with a focused review of the efficacy in higher dose levels with ≥3 pts dosed. Results: Fifty-eight pts received JNJ-75276617. The median age was 63 (range: 19-83) years; 56 pts (97%) had R/R AML and 2 (3%) had R/R ALL. The median number of prior lines of treatment was 2 (range: 1-7), including 10 (17%) pts with a prior allogeneic stem cell transplant. A KMT2A or NPM1 alteration was present in 33 (57%) and 25 (43%) pts, respectively. Thirty (52%) pts experienced ≥1 treatment-related AE (TRAE); most commonly differentiation syndrome (DS) (8 14%). Grade ≥3 TRAEs were observed in 17 (29%) pts; those reported in ≥2 pts were neutropenia (6 10%), anemia and thrombocytopenia (4 7% each), DS (3 5%), and ALT and AST increase (2 3% each). Dose limiting toxicities (DLTs) were observed in 5 (9%) pts, with DS (2 3%) as the only DLT reported in ≥2 pts. In 26 (63%) of the 41 pts with disease evaluation data, there was a reduction in bone marrow (BM) disease burden ( Figure 1). Of these, a ≥50% decrease in BM blasts was observed in 16 (39%) pts. In the highest dose level with ≥3 pts (90 mg BID; n=8), the ORR (≥PR) was 50% (n=4), with all responders ongoing ( Figure 2). These responders (2 NPM1-, 2 KMT2A-altered) achieved CR (1 pt), CRh (1 pt), and CRi (2 pts). In a review of higher dose levels with ≥3 pts (≥45 mg BID; n=20), the ORR was 40% (n=8), with 7 responders ongoing ( Figure 2). These responders (5 NPM1-, 3 KMT2A-altered) achieved CR (3 pts), CRh (1 pt), CRi (3 pts), and PR (1 pt); median (range) time to first response (≥PR) 1.81 mos (1.0-3.3; n=8); time to CR, CRh, or CRi 1.77 mos (1.0-3.3; n=7); and time to CR 2.79 mos (1.8-2.9; n=3). Across all cohorts there were 12 responders, including 1 MRD negative CR. One responder discontinued treatment for allogeneic transplant; however, 8 responders continue on treatment, including 2 pts in cycle 9. Preliminary PD data from unfractionated BM and/or PBMCs in paired samples among responders (n=12) show biologic activity as indicated by reduction in expression (mean fold change from baseline calculated as on-tx-baseline/baseline range) of menin-KMT2A target genes ( MEIS1 -0.42 -1.0-9.0; HOXA9 -0.03 -1.0-21.7; FLT3 18.6 -1.0-425) and induction of genes associated with differentiation ( ITGAM 55.0 -0.93-1467; MNDA 5.9 -1.0-83.5). Compared to baseline, the percentage of KMT2A-altered cells or NPM1 variant allele frequency (VAF) was reduced in responders, with a decrease in KMT2A-altered cells by break-apart FISH probe from 59.2% at baseline to 8.1% post-treatment and in NPM1 VAF using a myeloid gene NGS panel from 13.1% at baseline to 2.8% post-treatment. Conclusions: Dose escalation in 75276617ALE1001 is ongoing with the RP2D(s) yet to be determined. Pts in dose expansion will receive JNJ-75276617 at the identified RP2D(s). Preliminary results of this FIH Phase 1 study demonstrate that JNJ-75276617 monotherapy has an acceptable safety profile, encouraging antileukemic activity, and emerging biologic activity consistent with the proposed mechanism of action in pts with R/R acute leukemia harboring KMT2A or NPM1 alterations.
Aim
There is scant evidence regarding surgical outcomes of patients with colon cancer in Latin America. The aim of this work was to compare perioperative (30 day) outcomes of patients undergoing ...surgery for right colon cancer in Latin America based on centre volume.
Method
This is a multi‐institutional retrospective cohort study. Individuals operated on for right colon cancer with curative intent in an urgent or elective setting between 2016 and 2021 were eligible for inclusion in the study. Patients were divided into two groups according to whether they were operated on in low‐volume or high‐volume centres (defined as more than 30 cases/year).
Results
A total of 2676 patients from 46 hospitals in 11 countries of Latin America were included, with 389 (14.5%) in the low‐volume group. The median age was 67.37 years. The high‐volume group presented higher rates of laparoscopic procedures (56.8 vs. 35.7%, p < 0.001, OR 2.36), with lower conversion rates, fewer intraoperative complications and a shorter operating time. The high‐volume group had a shorter length of hospital stay. The overall complication rate for the whole group was 15.9%, with a lower incidence of these events in the high‐volume group (13.7 vs. 28.7%, p < 0.001, OR 0.40). Overall, anastomotic leakage, reoperation and mortality rates were 5.6%, 9.2% and 6.1%, respectively, with differences favouring high‐volume centres. On multivariate analysis, low‐volume group, history of cardiac disease, emergency surgery, operation performed by a general surgeon, open approach and intraoperative complications were independent predictors of major postoperative complications.
Conclusion
This is the first study in Latin America to show better postoperative outcomes at a regional scale when surgery for right colon cancer is performed in high‐volume centres. Further studies are needed to validate these data and to identify which of the factors can explain the present results.
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