Complejo Hospitalario de Toledo

Level of Education (LoE) is widely used as an indicator of cognitive reserve and is associated with risk of dementia. The aim of the present study was to know the influence of the LoE on cognitive function (CF) in patients with Parkinson´s disease (PD). Controls and PD patients from the Spanish cohort COPPADIS with a disease duration from symptoms onset ≤ 5years, who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated at 2 (V2), 4 (V4) and 5 (V5) years of follow-up were included. Regarding LoE, patients were classified as with primary, secondary and university education. CF was assessed using the Parkinson´s Disease Cognitive Rating Scale (PD-CRS). General linear model (GLM) repeated measure was used to test for changes in the CF. A p value ≤ 0.005 was considered significant. Three hundred and ninety-nine PD patients (61.9 ± 8.9years old; 58.4% males) and 207 controls (61 ± 8.3years old; 49.8% males) were included. From V0 to V5, significant differences were observed in PD patients in global and fronto-subcortical (p < 0.0001 in all visits) between LoE groups but not in posterior-cortical (p > 0.05 in all visits) CF. LoE was associated with the change from V0 to V5 in the PD-CRS total score and fronto-subcortical sub-score (p < 0.0001) in PD patients but not in controls. After adjustment for many covariates, primary education was not a predictor of PD dementia (PD-CRS < 65) at V5 (OR = 3.31; p = 0.194). Cognitive function in Parkinson's disease is influenced by the level of education.

PURPOSEQuizartinib, an oral, selective, second-generation, type-II FMS-like tyrosine kinase 3 (FLT3) inhibitor with high binding affinity to internal tandem duplication (ITD) and wild-type (WT) FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3-ITD–negative AML. The phase III QuANTUM-First trial showed that quizartinib significantly prolonged survival versus placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3-ITD–positive AML. We investigated the safety and efficacy of quizartinib in patients with ND FLT3-ITD–negative AML.METHODSThe phase II, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients age 18-70 years with ND FLT3-ITD–negative (mutant-to-WT allelic ratio <0.03) AML. Patients were randomly assigned 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg once daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary end point was event-free survival (EFS). Secondary end points included overall survival (OS) and safety.RESULTSOverall, 273 patients were randomly assigned to quizartinib (n = 180) or placebo (n = 93). At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively (P = .046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P = .012); 3-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis.CONCLUSIONThe addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3-ITD–negative AML.

Perioperative use of mineralocorticoid receptor antagonists (MRA) in patients with unilateral primary aldosteronism (PA) awaiting surgery is not well standardized. The aim of this study was to compare the risk of postoperative complications and surgical outcomes between PA patients treated with MRA prior to adrenalectomy and those not pretreated. Adrenalectomized patients for unilateral PA from the SPAIN-ALDO registry, with clinical, hormonal, and treatment information before and after adrenalectomy, were analyzed. A total of 355 surgically treated patients were included; 76.9% (n = 273) received presurgical treatment with MRA (spironolactone [64.5%], eplerenone [35.5%]). Adrenalectomy was guided by lateralization at adrenal venous sampling in 33.5% of the overall cohort, and by imaging in all the other cases. Patients pretreated with MRA had longer duration of hypertension, higher prevalence of hypokalemia, and greater aldosterone concentrations than those not pretreated (n = 82). No differences in the rate of postsurgical hyperkalemia, hypoaldosteronism, renal function impairment, blood pressure changes, and biochemical outcomes were detected between groups in the immediate (≤30 days) and short-term (≤90 days) follow-up evaluations after surgery. At long-term follow-up (≥6 months), patients pretreated with MRA exhibited better postsurgical biochemical outcomes (81.7% had complete biochemical response vs 57.1% of non-pretreated patients; P = .004). In the multivariable analysis, the use of MRA prior to adrenalectomy was independently associated with a successful postsurgical biochemical response. Preoperative MRA therapy can be safely introduced to control blood pressure and potassium levels in patients with PA awaiting surgery, without increasing the risk of postoperative hyperkalemia, hypoaldosteronism, renal impairment, or hypotension.

The outcomes of transsphenoidal surgery (TSS) for pituitary adenoma (PA) depend on many factors, including the availability of an expert team and the volume of surgeries performed. Data on the outcomes of TSS for PA are scarce in our country. TESSPAIN evaluates TSS outcomes in Spanish centers to assess the influence of surgical volume and specialized neurosurgical teams on success and complication rates. A retrospective, nationwide, study of Spanish centers performing TSS between January 2018 and December 2022. Centers were classified as high volume (HV) [n=11, defined as centers with recognized expertise in Spain or those performing more than 25 TSS/year] or non-HV. Data collection included surgical success rates, complications, and pituitary adenoma resectability (R-PA). Additional analyses evaluated the impact of dedicated neurosurgical teams (DNT) within HV centers. A total of 2815 TSS from 29 Spanish centers were included (1421 NSPA, 436 GH-secreting, 323 Cushing's disease, 127 PRL-secreting and 25 TSH-secreting PA). The overall success rate was 50.5%, 76.8% for R-PA. HV centers had a higher overall success rate (53.1 vs. 47.7%; p=0.03). Better TSS outcomes for NSPA accounted for this difference. The overall TSS complication rate was 22.1%, which was higher for NSPA than for SPA (25.0 vs. 17.7%). The overall complication rate of TSS for PA was significantly higher in non-HV centers than in HV centers (24 vs 20.4.0; p <0.01). Centers with a DNT showed a trend to higher success rate in R-PA, while having a lower overall incidence of complications in TSS for PA than HV centers without a DNT (18.5 vs. 23.0; p=0.058), mainly reducing the rate of permanent ADH deficiency in all TSS for PA (2.7 vs. 8.4%; p<0.001). Higher surgical volume and DNT are associated with improved TSS outcomes for PA in Spain. Our results support the recommendation of concentration of pituitary surgery in a reduced number of centers of expertise in our country in order to improve the success rate and reduce complications, mainly postoperative ADH deficiency.

Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) patients, that received fix duration treatment (18 cycles of VMP/lenalidomide-dexamethasone) within the PETHEMA/GEM2010MAS65 trial and who achieved CR or VGPR. Immunoglobulin levels were measured at diagnosis, at the end of treatment (after cycle 18th) and during subsequent follow up whereas MRD was analyzed only at the end of the treatment (after cycle 18th). We found that patients who had IP at diagnosis and recovered it during or after treatment had longer progression free survival (PFS) [p < 0.001; HR 0.32 (0.19-0.52)] and longer overall survival (OS) [p = 0.007; HR 0.40 (0.20-0.80)] compared to those who failed to recover it. When we analyzed IP recovery in MRD negative patients, we found that those cases with IP recovery had longer PFS [p = 0.007; HR 0.31 (0.13-0.76)] and longer OS [p = 0.012; HR 0.21 (0.06-0.80)] as compared to MRD negative patients but without IP recovery. In conclusion, IP recovery confers better prognosis in NDTI-MM patients with fixed duration treatment who achieve CR or VGPR and the prognostic value of MRD can be complemented when combined with IP recovery.

Heart failure (HF) is the second most common initial presentation of cardiovascular disease in people with type 2 diabetes mellitus (T2DM). T2DM carries an increased risk of HF in women. The aim of this study is to analyze the clinical characteristics and the treatment received by women with HF and T2DM in Spain. The DIABET-IC study included 1517 patients with T2DM in 2018-2019 in Spain, in 30 centers, which included the first 20 patients with T2DM seen in cardiology and endocrinology clinics. They underwent clinical evaluation, echocardiography, and analysis, with a 3-year follow-up. Baseline data are presented in this study. 1517 patients were included (501 women; aged 67.28 ± 10.06 years). Women were older (68.81 ± 9.90 vs. 66.53 ± 10.06 years; p < 0.001) and had a lower frequency of a history of coronary disease. There was a history of HF in 554 patients, which was more frequent in women (38.04% vs. 32.86%; p < 0.001), and preserved ejection fraction being more frequent in them (16.12% vs. 9.00%; p < 0.001). There were 240 patients with reduced ejection fraction. Women less frequently received treatment with angiotensin converting enzyme inhibitors (26.20% vs. 36.79%), neprilysin inhibitors (6.00% vs. 13.51%), mineralocorticoid receptor antagonists (17.40% vs. 23.08%), beta-blockers (52.40% vs. 61.44%), and ivabradine (3.60% vs. 7.10%) (p < 0.001 for all), and 58% received guideline-directed medical therapy. A selected cohort with HF and T2DM attending cardiology and endocrinology clinics did not receive optimal treatment, and this finding was more pronounced in women.

To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease). This retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals. Recurrent disease was defined by the development of local recurrence and/or metastatic disease after initial complete surgical resection. A total of 303 patients with PPGLs that underwent 311 resections were included (288 pheochromocytomas and 15 sympathetic PGLs). After a median follow-up of 4.8 years (range 1-19), 24 patients (7.9%) had recurrent disease (3 local recurrence, 17 metastatic disease and 4 local recurrence followed by metastatic disease). The median time from the diagnosis of the PPGL to the recurrence was of 11.2 months (range 0.5-174) and recurrent disease cases distributed uniformly during the follow-up period. The presence of a pathogenic variant in SDHB gene (hazard ratio [HR] 13.3, 95% CI 4.20-41.92), higher urinary normetanephrine levels (HR 1.02 per each increase in standard deviation, 95% CI 1.01-1.03) and a larger tumor size (HR 1.01 per each increase in mm, 95% CI 1.00-1.02) were independently associated with disease recurrence. The recurrence of PPGLs occurred more frequently in patients with SDHB mutations, with larger tumors and with higher urinary normetanephrine levels. Since PPGL recurrence may occur at any time after the initial PPGL diagnosis is performed, we recommend performing a strict follow-up in all patients with PPGLs, especially in those patients with a higher risk of recurrent disease.

Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8). Two hundred and twenty-four PD patients (63±9.6 years old; 61.2% males) and their caregivers (58.5±12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4-5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p<.0001) and CSI (p<.0001), and a lower score on the PQ-10 (p=.001), but no significant differences were observed in the BDI-II (p=.310) and EUROHIS-QOL8 (p=.133). Moderate correlations were observed between the MNCD total score and the ZCBI (r=.496; p<.0001), CSI (r=.433; p<.0001), and BDI-II (r=.306; p<.0001) in caregivers. Staging PD according to the MNCD classification is correlated with caregivers' strain and burden.