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Background: The semantic variant of primary progressive aphasia (svPPA) is characterized by a progressive loss of semantic knowledge impairing the ability to name and to recognize the meaning of words.Objective: We aimed to evaluate the immediate and short-term effect of errorless learning speech therapy on the naming and recognition of commonly used words in patients with svPPA.Methods: Eight participants diagnosed with svPPA received 16 sessions of intensive errorless learning speech therapy. Naming and word comprehension tasks were evaluated at baseline, immediately postintervention, and at follow-up after 1, 3, and 6 months. These evaluations were performed using two item sets (a trained list and an untrained list).Results: In the naming tasks, patients showed a significant improvement in trained items immediately after the intervention, but that improvement decayed progressively when therapy ended. No improvements were found either in trained comprehension or in untrained tasks.Conclusion: Errorless learning therapy could improve naming ability in patients with svPPA. This effect may be due to the relative preservation of episodic memory, but the benefit is not maintained over time, presumably because there is no consolidation. [ABSTRACT FROM AUTHOR]

Objective: To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies.Methods: We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with <0.05% memory B cells in peripheral blood lymphocytes.Results: In 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow-up was 19 (range = 9-38) and 38 (13-79) months. Under RTX, 10 relapses occurred in 6 of 16 (37.5%) patients with MOG antibodies, and 13 occurred in 7 of 29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6-5.8) and 7 (0.8-13) months, respectively (p < 0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p < 0.001).Interpretation: In AQP4 antibody-associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody-associated disorder, the efficacy of RTX is not constant, because one-third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B-cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms. These findings should be used to improve treatment strategies for MOG antibody-associated disorder. ANN NEUROL 2020;87:256-266. [ABSTRACT FROM AUTHOR]

The objective of this cross-sectional study was to evaluate the frequency, impact, and management of sexual dysfunction associated with commonly prescribed antidepressants available in psychiatry outpatient clinics in Spain. We recruited 2163 adult patients who had undergone treatment with antidepressants for at least 8 weeks and had a history of normal sexual functioning before the prescription of the antidepressant, except for mildly impaired libido. We used the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) for evaluating the frequency and tolerance of sexual dysfunction and whether this side effect was spontaneously reported. Overall, 79% patients showed sexual dysfunction, as indicated by a total score ≥ 3 on the PRSexDQ-SALSEX; 64% showed moderate-severe sexual dysfunction, with no differences between men and women on these outcomes. In the multivariate logistic regression analysis, treatment with a serotonergic antidepressant and having a severe clinical state of psychiatric illness were the factors associated with the highest likelihood of presenting with sexual dysfunction. Sexual dysfunction was spontaneously reported by 838 (41%) of the 2066 evaluable patients for this outcome. Among patients with sexual dysfunction, this condition was poorly tolerated by 22% of the patients, with these frequencies being significantly higher in men than in women. The most frequently used strategies employed by the psychiatrists in our study for dealing with sexual dysfunction were switching to another antidepressant (34%) and waiting for spontaneous resolution (33%). In conclusion, our results indicate that despite being a well-known, long-standing side effect of antidepressants, sexual dysfunction continues to be extremely common in patients receiving antidepressants, especially serotonergic ones, potentially jeopardizing treatment success in a substantial proportion of patients. There are important sex differences in the reporting and tolerance of sexual dysfunction that require further investigation. [ABSTRACT FROM AUTHOR]

Background: Preclinical results showing therapeutic effect and low toxicity of metronomic chemotherapy with cyclophosphamide (Cy) + celecoxib (Cel) for mammary tumors encouraged its translation to the clinic for treating advanced breast cancer patients (ABCP).Patients and Methods: A single-arm, mono-institutional, non-randomized, phase II, two-step clinical trial (approved by Bioethics Committee and Argentine Regulatory Authority) was designed. Patients received Cy (50 mg po.d) + Cel (200 mg p.o.bid). Patient eligibility criteria included: ABCP who progressed to anthracyclines, taxanes and capecitabine, ≤4 chemotherapy schemes, with good performance status. Several pro- and anti-angiogenic molecules and cells were determined as biomarkers. Informed consent was signed by all patients. Primary endpoint was clinical benefit (CB).Results: Twenty patients were enrolled. Main clinical outcomes were prolonged disease stabilization and partial remission in 10/20 and 1/20 patients, respectively. CB was 55 %, and time to progression (TTP) was 21.1 weeks. Median TTP in patients who achieved CB was 35.6 weeks, and mean overall survival was 44.20 weeks. There were no grade 3/4 toxicities associated with treatment. Circulating endothelial cells (CECs) increased at the time of progression in patients who showed CB (P = 0.014). Baseline CECs and circulating endothelial progenitor cells showed marginal associations with TTP. Serum VEGF decreased (P = 0.050), sVEGFR-2 increased (P = 0.005) and VEGF/sVEGFR-2 ratio decreased during treatment (P = 0.041); baseline VEGF and VEGF/sVEGFR-2 were associated with TTP (P = 0.035 and P = 0.030, respectively), while sVEGFR-2 did not.Conclusions: Treatment was effective, showing low toxicity profile and excellent tolerability. The combination had anti-angiogenic effect. Increased levels of CEC could be useful for detecting progression. Baseline VEGF and VEGF/sVEGFR-2 values could be useful as early predictors of response.Trial Registration: ANMAT#4596/09. [ABSTRACT FROM AUTHOR]

Background: Multiple factors can account for surgical complexity during laparoscopic partial nephrectomy (LPN); severe adhesion of perirenal fat (PRF) is a crucial one. Consequent renal decapsulation can deem renorrhaphy a very challenging task. We propose a novel technique (synthetic renal capsule tailoring [SYRCT]) to facilitate renorrhaphy in decapsulated kidneys and suggest early decapsulation as a safe option in cases with severe PRF.Materials and Methods: We retrospectively analyzed perioperative results of this novel technique performed in cases with severe PRF. All cases were classified as high grade in the Mayo Adhesive Probability (MAP) score.Results: A total of six cases were performed with the SYRCT technique. All patients were male with a mean age of 70 years (62-76 years) and mean body mass index of 30 kg/m2 (23.66-33.86). Of the six cases, five were T1a and 1 T1b. Mean tumor size was 2.83 cm (range 1.2-6 cm). Mean operative time was 121 minutes (range 74-150 minutes); mean warm ischemia time was 17.2 minutes (range 13-25 minutes). Mean operative bleeding was 128 mL (range 50-250 mL). Mean hospital stay was 2.3 days. There were no surgical complications greater or equal to Clavien II.Conclusion: Performing complete renal decapsulation with subcapsular dissection and SYRCT in cases with high MAP score and severe PRF is safe and reproducible. Using this novel technique, we were able to obtain perioperative results comparable to the ones we found in LPN with normal PRF. [ABSTRACT FROM AUTHOR]

Background: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.Methods: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437.Results: Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients.Conclusions: A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients. [ABSTRACT FROM AUTHOR]

Background: Residual depressive symptoms are associated with a poor prognosis for relapse or recurrence and are recognized as impeding factors of functionality. Recovery to the pre-depression level of functioning should be the goal of treatment.Aim: To evaluate outcomes in depressed outpatients treated with escitalopram regarding response, recovery, residual symptoms, functionality and ability to work over 48 weeks.Method: 3278 outpatients were evaluated at weeks 8, 24 and 48. A simple questionnaire was used to rate severity of illness, impairment of functionality, treatment response, tolerability, presence and severity of residual symptoms, whether remission with residual symptoms or recovery was achieved, and to what degree the patient was able to work.Results: Data over the full 48-week period were available for 75.8% of patients, for whom treatment response was rated as "very good" or "good" in 81%. However, only 42% of the completing patients achieved recovery without residual symptoms, while 41% were rated as remitters with residual symptoms. Lack of energy/motivation was the most common reported residual symptom and was present in 23.5% of patients at study end. Concentration difficulties were present in 15.8% and impaired sleep in 13.9% of patients. Complete inability to work decreased from 36% at baseline to 9% at week 48, while full-time working capacity increased from 37% to 62%.Limitations: Non-controlled observational real life study using simple ratings rather than established rating scales.Conclusion: <50% of patients completing a one-year antidepressant treatment regimen were rated as being symptomatically fully recovered, and ≈50% still reported functional deficits. [ABSTRACT FROM AUTHOR]

We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. [ABSTRACT FROM AUTHOR]

Metronomic chemotherapy refers to the chronic, equally spaced, delivery of low doses of chemotherapeutic drugs, without extended interruptions. Previously, we developed two combined metronomic schemes for the treatment of murine mammary tumors. The aim of this study was to compare their effects on tumor and metastasis growth, survival, and toxicity. Metronomic chemotherapy with Cyclophosphamide + Celecoxib (Cy + Cel) showed higher antimetastatic power than Cyclophosphamide + Doxorubicin (Cy + Dox), while being similar in other aspects. That difference, plus the advantage that represents its oral administration, suggests that the Cy + Cel combination is more suitable than Cy + Dox for metronomic chemotherapy of mammary tumors and could be proposed to the translation to the clinic. [ABSTRACT FROM AUTHOR]

Objective: Female sex has been associated with differences in diagnostic and management of acute coronary syndrome (ACS). Our aim was to analyze sex differences in ACS with interventional management in a tertiary care hospital.Methods: Patients with ACS admitted to a Spanish tertiary care referral center were included prospectively and consecutively. All patients included in the study underwent a coronary angiography.Results: From the total cohort of 1214 patients, 290 (24%) were women. Women were older (71 ± 12.8 vs 64 ± 13.4 years, p < 0.001) and showed lower ischemic risk and higher hemorrhagic risk scores (GRACE 159 ± 45 vs 171 ± 42, p = 0.005; CRUSADE 41 ± 19 vs 28 ± 17, p < 0.001). There were no significant differences in time to coronary angiography and revascularization rates between sex groups. A lower proportion of women received high-potency antiplatelet agents (29% vs 41.3%, p = 0.004). In-hospital evolution and one-year mortality were similar between groups.Conclusions: In our population, there were no gender differences in management and prognosis of ACS. Differences in risk profile among groups could have an influence on antiplatelet therapy. [ABSTRACT FROM AUTHOR]