Hospital Universitario de Toledo

BACKGROUND: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. METHODS: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. RESULTS: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. INTERPRETATION: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Health professionals predict that the number of people who will suffer and die from oncological diseases will continue to increase. It is vitally important to provide comprehensive care to these patients and prescribe physical exercise programs as adjuvant therapy. The objective of this systematic review was to determine the impact of physical exercise on advanced-stage cancer patients. A literature search was performed in eight different databases. This search focused on randomized controlled trials (RCTs) published during the last 10 years. To assess the methodological quality of the sample of 15 RCTs finally obtained, the PEDro scale was used. Aerobic and strength training methods were used. The combination of both aerobic and strength training methods was the most frequently reported. Likewise, different physical and psychological variables were recorded, from which improvements were seen in fatigue, independence, quality of life and sleep, among others. The participation in physical exercise programs by advanced-stage cancer patients has a positive impact on health. Providing these programs serves as adjuvant therapy, facilitating the comprehensive care of patients. Similarly, aerobic, strength or mixed training programs increase the muscle mass of patients and therefore reduce hypotonia, the main side effect during the advanced-stages of cancer.

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

Prostate cancer is the most commonly diagnosed cancer among men around the world. Radiotherapy is a standard of care treatment option for men with localized prostate cancer. Over the years, radiation delivery modalities have contributed to increased precision of treatment, employing radiobiological insights to shorten the overall treatment time, improving the control of the disease without increasing toxicities. Stereotactic body radiation therapy (SBRT) represents an extreme form of hypofractionated radiotherapy in which treatment is usually delivered in 1-5 fractions. This review assesses the main efficacy and toxicity data of SBRT in non-metastatic prostate cancer and discusses the potential to implement this scheme in routine clinical practice.

AIM: To determine the prevalence and risk factors for dating violence and the correlations between dating violence and violence in social networks, anxiety and depression among nursing students. DESIGN: A cross-sectional and correlational study. METHODS: This study was conducted with nursing degree students at Spanish university during May 2021. A total of 248 nursing students completed an online survey. The online survey included sociodemographic variables, the Conflict in Adolescent Dating Relationships Inventory, the Social Network Violence Scale and the Hospital Anxiety and Depression Scale. Chi-squared test, Pearson's correlation and logistic regression were used. RESULTS: Of the participants, 13.3% were men and 86.7% were women. A total of 53.2% had experienced and/or perpetrated dating violence. About violence in social networks, 22.2% of the participants had perpetrated it, and 20.2% had been victims of it. Strong correlations were found between experiencing and perpetrating dating violence. Significant associated factors were cohabitation with a partner, alcohol consumption, socioeconomic status and history of dating violence. CONCLUSIONS: Dating violence is a serious problem given its high prevalence among the surveyed nursing students, who, as future health professionals, must know how to recognize and react to possible cases of abuse. IMPACT: The study results add to international literature that men and women university nursing students are equally susceptible to intimate partner violence and report similar prevalence of dating violence. Also, dating violence is correlated with increased levels of anxiety and depression. It seems to be necessary to implement training programmes that help minimize the problem and identify possible cases.

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15-0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16-5.83); P =0.02) and albumin ≤3.5 (17 (6.3-47); P <0.01). CONCLUSIONS: SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD). CD is a health problem in Western countries such as the US and European nations and is an idiopathic disease; however, certain cases of CD have been associated with intestinal dysbiosis. A systematic review with a meta-analysis was carried out to determine the efficacy of a diet rich in fiber with or without cointervention to improve remission rates for CD. The literature in the PubMed, Scopus, Web of Science, and ClinicalTrials databases was reviewed. The quality of the studies was evaluated using the Johanna Briggs Institute (JBI) scale. This review was conducted in accordance with the structure outlined in the PRISMA statement. In addition, a meta-analysis was performed with a 95% confidence interval (CI) and a random effects model. Eleven studies were included, totaling 2389 patients with CD. Applying a diet rich in fiber with or without the administration of routine therapies improved CD remission rates. Data regarding CD activity, remission time, and adverse effects derived from fiber consumption were analyzed. Consumption of fiber in the diet could improve remission rates for CD patients who receive or do not receive other treatment to maintain remission.

Introduction/Aim: Persistent post-surgical pain (PPSP) is a common complication after breast cancer surgery; but reported prevalence rates range from 10% to 69%. We conducted a systematic review to address this uncertainty. Methods: We searched MEDLINE, EMBASE, CINAHL and PsycINFO from inception to October 2018, to identify observational studies that reported the prevalence and intensity of PPSP after breast cancer surgery. We performed random effects meta-analysis with Freeman-Tukey transformation for overall, moderate and severe PPSP prevalence, and pooled pain intensity after converting all pain scales to the 10cm VAS. Results: We included 188 observational studies with 300,025 patients. The overall prevalence of any PPSP was 34.5% (95%CI 30.1% to 39.2%). The pooled prevalence of moderate and severe pain was 14.9% (95%CI 11.5% to 18.7%) and 4% (95%CI 2.7% to 5.5%) respectively. The average pain intensity on a 10cm VAS was 2.7 (95%CI 2.2 to 3.1). We are completing analyses to inform PPSP prevalence and intensity at <1 year, 1–2 years, 2–3 years and >3 years, and prevalence of neuropathic pain. We will also perform subgroup analyses for risk of bias, any pain vs. specific pain, axillary lymph nodes dissection and radiotherapy, and meta-regression for the association between PPSP and length of follow-up and proportion of loss to follow-up. Discussion/Conclusions: PPSP after breast surgery is common and affects approximately 1 in 3 women undergoing this procedure. Of those who develop persistent pain, 43% will report at least moderate pain and 12% will experience severe pain although the average pain is mild.

•tSMS is a portable, inhibitory, non-invasive brain stimulation technique.•Repeated sessions of home-based tSMS of the motor cortex are feasible and safe.•tSMS may provide subjective benefit for the treatment of levodopa-induced dyskinesias. Levodopa-induced dyskinesias are a common complication in patients with Parkinson's disease (PD) treated chronically with levodopa. Even though dyskinesias may be more tolerable than parkinsonism, they can be highly debilitating for some patients. The difficulty to achieve satisfactory pharmacological treatment of dyskinesias often motivates the escalation toward more advanced invasive treatments. However, even with invasive treatments dyskinesias may remain problematic.A promising approach is offered by non-invasive brain stimulation (NIBS). Several small, randomized studies (sample sizes ≤17 patients) suggest that presumably reducing the excitability of motor cortical areas with repetitive transcranial magnetic stimulation (rTMS) may be effective for reducing levodopa-induced dyskinesias [[1]Wu Y. Cao X. Zeng W. Zhai H. Zhang X. Yang X. et al.Transcranial magnetic stimulation alleviates levodopa-induced dyskinesia in Parkinson's disease and the related mechanisms: a mini-review.Front Neurol. 2021; 12https://doi.org/10.3389/fneur.2021.758345Crossref Scopus (1) Google Scholar]. However, rTMS is not portable, which limits its application to a center-based therapeutic model and possibly hindered the path toward larger, longer and more definitive clinical trials.We recently introduced transcranial static magnetic field stimulation (tSMS), which can reduce cortical excitability in both healthy subjects [[2]Oliviero A. Mordillo-Mateos L. Arias P. Panyavin I. Foffani G. Aguilar J. Transcranial static magnetic field stimulation of the human motor cortex.J Physiol. 2011; 589: 4949-4958https://doi.org/10.1113/jphysiol.2011.211953Crossref PubMed Scopus (99) Google Scholar,[3]Dileone M. Mordillo-Mateos L. Oliviero A. Foffani G. Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability.Brain Stimul. 2018; 11: 676-688https://doi.org/10.1016/j.brs.2018.02.005Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar] and PD patients OFF medication [[4]Dileone M. Carrasco-López M.C. Segundo-Rodriguez J.C. Mordillo-Mateos L. López-Ariztegui N. Alonso-Frech F. et al.Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease.Sci Rep. 2017; 7: 4329https://doi.org/10.1038/s41598-017-04254-yCrossref PubMed Scopus (14) Google Scholar]. Differently from rTMS, tSMS is portable, which makes it attractive for shifting the NIBS paradigm from a center-based to a home-based therapeutic model. We thus aimed to investigate the potential of tSMS as a novel non-invasive home-based treatment to manage levodopa-induced dyskinesias.1. MethodsWe conducted a randomized, sham-controlled, double-blind, parallel trial to test the ability of repeated sessions of tSMS to safely reduce levodopa-induced dyskinesias in PD (ClinicalTrials.gov: NCT02657681). Patients received 30-min sessions [[3]Dileone M. Mordillo-Mateos L. Oliviero A. Foffani G. Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability.Brain Stimul. 2018; 11: 676-688https://doi.org/10.1016/j.brs.2018.02.005Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar] of either real or sham tSMS, one session per day, for 9 days over two weeks (Fig. 1A). Patients were allowed to receive the treatment in the hospital or self-deliver it at home. All but one preferred home treatment. The data were analyzed with Bayesian statistics (i.e. Bayes factor, BF). For detailed methods, see Online Supplementary Materials.2. ResultsA total of 50 patients were randomized, 25 were assigned to real tSMS, 25 to sham tSMS (Suppl. Table 1). Of them, 42 (21 real, 21 sham) were analyzed for the primary outcome (Fig. 1B). The objective part of the Unified Dyskinesia Rating Scale (UDysRS, primary outcome) displayed moderate evidence of improvement after treatment compared to baseline (p = 0.008, BFincl = 5.4), but there was also moderate evidence of absence of difference in the improvement between real and sham treatment (Fig. 1C and D; Suppl. Table 2). Changes in motor scores, as assessed by the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III scale, secondary outcome), were inconclusive (Suppl. Table 2). Conversely, the Patient's Global Rating of Change (P-GRC, secondary outcome) revealed moderate evidence of subjective improvement with real compared to sham treatment (p = 0.017, BF+0 = 6.6; Fig. 1E).No serious adverse events were reported. Anxiety occurred in two patients (one real, one sham), but was unlikely to be directly caused by the treatment. Transient mild dizziness and headache were reported by one patient, presumably attributed either to the static magnetic field or to the weight of the helmet. The latter was likely the cause of a mild periorbital hematoma transiently observed in one particularly fragile female patient.For detailed results, see Online Supplementary Materials.3. Discussion3.1 Objective evaluation of levodopa-induced dyskinesiasWe found non-significant difference in objective improvement (moderate evidence of absence) between patients who received real compared to patients who received sham treatment. One limitation and two experimental choices might have limited our ability to detect differences in objective improvement between groups. First, overall the patients that participated in the study displayed relatively mild dyskinesias. Our difficulty in recruiting patients with severe dyskinesias is in line with the epidemiologically decreasing prevalence and severity of levodopa-induced dyskinesias, at least in some countries [[5]Chaudhuri K.R. Jenner P. Antonini A. Should there be less emphasis on levodopa-induced dyskinesia in Parkinson's disease?.Mov Disord. 2019; 34: 816-819https://doi.org/10.1002/mds.27691Crossref PubMed Scopus (33) Google Scholar]. Second, we assessed dyskinesias after administration of 100% of the morning dose of levodopa, in order maintain real-life conditions and a stable pharmacological schedule. A higher levodopa dose might have decreased the variability of the assessment, at least in some patients. Third, since this was the first study with repeated sessions of tSMS, we conservatively delivered a relatively low number of sessions. With NIBS, it is not uncommon to observe an initial parallel improvement in patients receiving real or sham stimulation, with differences between groups becoming appreciable only after higher number of sessions and longer follow-ups [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google Scholar]. Future studies should thus test longer home-based treatments, which are feasible with tSMS [[7]Di Lazzaro V. Musumeci G. Boscarino M. De Liso A. Motolese F. Di Pino G. et al.Transcranial static magnetic field stimulation can modify disease progression in amyotrophic lateral sclerosis.Brain Stimul. 2021; https://doi.org/10.1016/j.brs.2020.11.003Abstract Full Text Full Text PDF Scopus (4) Google Scholar].3.2 Objective evaluation of motor featuresA priori, we did not strongly expect tSMS to improve PD motor features, since excitatory rather than inhibitory NIBS protocols typically provide motor improvement when applied to the motor cortex. Yet, tSMS mechanisms unrelated to cortical excitability could have ameliorated motor features, and we wanted to ensure that possible improvements in dyskinesias did not come at the expense of motor impairment. This did not seem to be the case. An attractive alternative target would be the supplementary motor area (SMA), which can be reached with tSMS [[8]Pineda-Pardo J.A. Obeso I. Guida P. Dileone M. Strange B.A. Obeso J.A. et al.Static magnetic field stimulation of the supplementary motor area modulates resting-state activity and motor behavior.Commun 2019; PubMed Scopus (14) Google Scholar] and stimulation with inhibitory NIBS protocols may improve both dyskinesias [[1]Wu Y. Cao X. Zeng W. Zhai H. Zhang X. Yang X. et al.Transcranial magnetic stimulation alleviates levodopa-induced dyskinesia in Parkinson's disease and the related mechanisms: a mini-review.Front Neurol. 2021; 12https://doi.org/10.3389/fneur.2021.758345Crossref Scopus (1) Google Scholar] and motor [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google found subjective improvement (moderate in patients who received real compared to patients who received sham also by the ability of patients to to some treatment they received Online Supplementary Even though we in some this unlikely to have the evidence of subjective the primary motor cortex is in brain for the of A. M. M. et of for PubMed Scopus (4) Google Scholar]. The observed between subjective and objective improvement thus that tSMS might have not the dyskinesias per but rather the subjective of patients dyskinesias of This is and the of tSMS A. Carrasco-López M.C. M. V. et study of transcranial static magnetic field stimulation of the human Stimul. Full Text Full Text PDF PubMed Scopus Google Scholar] to repeated sessions. The of the brain to static magnetic is also by of of the static magnetic or even are at least one order of than the field in tSMS at cortical suggest that repeated sessions of home-based tSMS of the motor cortex are and provide objective benefit (moderate evidence of absence) but subjective benefit (moderate for the treatment of levodopa-induced dyskinesias in evidence of objective studies should investigate longer tSMS treatments. Levodopa-induced dyskinesias are a common complication in patients with Parkinson's disease (PD) treated chronically with levodopa. Even though dyskinesias may be more tolerable than parkinsonism, they can be highly debilitating for some patients. The difficulty to achieve satisfactory pharmacological treatment of dyskinesias often motivates the escalation toward more advanced invasive treatments. However, even with invasive treatments dyskinesias may remain A promising approach is offered by non-invasive brain stimulation (NIBS). Several small, randomized studies (sample sizes ≤17 patients) suggest that presumably reducing the excitability of motor cortical areas with repetitive transcranial magnetic stimulation (rTMS) may be effective for reducing levodopa-induced dyskinesias [[1]Wu Y. Cao X. Zeng W. Zhai H. Zhang X. Yang X. et al.Transcranial magnetic stimulation alleviates levodopa-induced dyskinesia in Parkinson's disease and the related mechanisms: a mini-review.Front Neurol. 2021; 12https://doi.org/10.3389/fneur.2021.758345Crossref Scopus (1) Google Scholar]. However, rTMS is not portable, which limits its application to a center-based therapeutic model and possibly hindered the path toward larger, longer and more definitive clinical We recently introduced transcranial static magnetic field stimulation (tSMS), which can reduce cortical excitability in both healthy subjects [[2]Oliviero A. Mordillo-Mateos L. Arias P. Panyavin I. Foffani G. Aguilar J. Transcranial static magnetic field stimulation of the human motor cortex.J Physiol. 2011; 589: 4949-4958https://doi.org/10.1113/jphysiol.2011.211953Crossref PubMed Scopus (99) Google Scholar,[3]Dileone M. Mordillo-Mateos L. Oliviero A. Foffani G. Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability.Brain Stimul. 2018; 11: 676-688https://doi.org/10.1016/j.brs.2018.02.005Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar] and PD patients OFF medication [[4]Dileone M. Carrasco-López M.C. Segundo-Rodriguez J.C. Mordillo-Mateos L. López-Ariztegui N. Alonso-Frech F. et al.Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease.Sci Rep. 2017; 7: 4329https://doi.org/10.1038/s41598-017-04254-yCrossref PubMed Scopus (14) Google Scholar]. Differently from rTMS, tSMS is portable, which makes it attractive for shifting the NIBS paradigm from a center-based to a home-based therapeutic model. We thus aimed to investigate the potential of tSMS as a novel non-invasive home-based treatment to manage levodopa-induced dyskinesias. MethodsWe conducted a randomized, sham-controlled, double-blind, parallel trial to test the ability of repeated sessions of tSMS to safely reduce levodopa-induced dyskinesias in PD (ClinicalTrials.gov: NCT02657681). Patients received 30-min sessions [[3]Dileone M. Mordillo-Mateos L. Oliviero A. Foffani G. Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability.Brain Stimul. 2018; 11: 676-688https://doi.org/10.1016/j.brs.2018.02.005Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar] of either real or sham tSMS, one session per day, for 9 days over two weeks (Fig. 1A). Patients were allowed to receive the treatment in the hospital or self-deliver it at home. All but one preferred home treatment. The data were analyzed with Bayesian statistics (i.e. Bayes factor, BF). For detailed methods, see Online Supplementary We conducted a randomized, sham-controlled, double-blind, parallel trial to test the ability of repeated sessions of tSMS to safely reduce levodopa-induced dyskinesias in PD (ClinicalTrials.gov: NCT02657681). Patients received 30-min sessions [[3]Dileone M. Mordillo-Mateos L. Oliviero A. Foffani G. Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability.Brain Stimul. 2018; 11: 676-688https://doi.org/10.1016/j.brs.2018.02.005Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar] of either real or sham tSMS, one session per day, for 9 days over two weeks (Fig. 1A). Patients were allowed to receive the treatment in the hospital or self-deliver it at home. All but one preferred home treatment. The data were analyzed with Bayesian statistics (i.e. Bayes factor, BF). For detailed methods, see Online Supplementary ResultsA total of 50 patients were randomized, 25 were assigned to real tSMS, 25 to sham tSMS (Suppl. Table 1). Of them, 42 (21 real, 21 sham) were analyzed for the primary outcome (Fig. 1B). The objective part of the Unified Dyskinesia Rating Scale (UDysRS, primary outcome) displayed moderate evidence of improvement after treatment compared to baseline (p = 0.008, BFincl = 5.4), but there was also moderate evidence of absence of difference in the improvement between real and sham treatment (Fig. 1C and D; Suppl. Table 2). Changes in motor scores, as assessed by the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III scale, secondary outcome), were inconclusive (Suppl. Table 2). Conversely, the Patient's Global Rating of Change (P-GRC, secondary outcome) revealed moderate evidence of subjective improvement with real compared to sham treatment (p = 0.017, BF+0 = 6.6; Fig. 1E).No serious adverse events were reported. Anxiety occurred in two patients (one real, one sham), but was unlikely to be directly caused by the treatment. Transient mild dizziness and headache were reported by one patient, presumably attributed either to the static magnetic field or to the weight of the helmet. The latter was likely the cause of a mild periorbital hematoma transiently observed in one particularly fragile female patient.For detailed results, see Online Supplementary A total of 50 patients were randomized, 25 were assigned to real tSMS, 25 to sham tSMS (Suppl. Table 1). Of them, 42 (21 real, 21 sham) were analyzed for the primary outcome (Fig. 1B). The objective part of the Unified Dyskinesia Rating Scale (UDysRS, primary outcome) displayed moderate evidence of improvement after treatment compared to baseline (p = 0.008, BFincl = 5.4), but there was also moderate evidence of absence of difference in the improvement between real and sham treatment (Fig. 1C and D; Suppl. Table 2). Changes in motor scores, as assessed by the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III scale, secondary outcome), were inconclusive (Suppl. Table 2). Conversely, the Patient's Global Rating of Change (P-GRC, secondary outcome) revealed moderate evidence of subjective improvement with real compared to sham treatment (p = 0.017, BF+0 = 6.6; Fig. serious adverse events were reported. Anxiety occurred in two patients (one real, one sham), but was unlikely to be directly caused by the treatment. Transient mild dizziness and headache were reported by one patient, presumably attributed either to the static magnetic field or to the weight of the helmet. The latter was likely the cause of a mild periorbital hematoma transiently observed in one particularly fragile female For detailed results, see Online Supplementary Discussion3.1 Objective evaluation of levodopa-induced dyskinesiasWe found non-significant difference in objective improvement (moderate evidence of absence) between patients who received real compared to patients who received sham treatment. One limitation and two experimental choices might have limited our ability to detect differences in objective improvement between groups. First, overall the patients that participated in the study displayed relatively mild dyskinesias. Our difficulty in recruiting patients with severe dyskinesias is in line with the epidemiologically decreasing prevalence and severity of levodopa-induced dyskinesias, at least in some countries [[5]Chaudhuri K.R. Jenner P. Antonini A. Should there be less emphasis on levodopa-induced dyskinesia in Parkinson's disease?.Mov Disord. 2019; 34: 816-819https://doi.org/10.1002/mds.27691Crossref PubMed Scopus (33) Google Scholar]. Second, we assessed dyskinesias after administration of 100% of the morning dose of levodopa, in order maintain real-life conditions and a stable pharmacological schedule. A higher levodopa dose might have decreased the variability of the assessment, at least in some patients. Third, since this was the first study with repeated sessions of tSMS, we conservatively delivered a relatively low number of sessions. With NIBS, it is not uncommon to observe an initial parallel improvement in patients receiving real or sham stimulation, with differences between groups becoming appreciable only after higher number of sessions and longer follow-ups [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google Scholar]. Future studies should thus test longer home-based treatments, which are feasible with tSMS [[7]Di Lazzaro V. Musumeci G. Boscarino M. De Liso A. Motolese F. Di Pino G. et al.Transcranial static magnetic field stimulation can modify disease progression in amyotrophic lateral sclerosis.Brain Stimul. 2021; https://doi.org/10.1016/j.brs.2020.11.003Abstract Full Text Full Text PDF Scopus (4) Google Scholar].3.2 Objective evaluation of motor featuresA priori, we did not strongly expect tSMS to improve PD motor features, since excitatory rather than inhibitory NIBS protocols typically provide motor improvement when applied to the motor cortex. Yet, tSMS mechanisms unrelated to cortical excitability could have ameliorated motor features, and we wanted to ensure that possible improvements in dyskinesias did not come at the expense of motor impairment. This did not seem to be the case. An attractive alternative target would be the supplementary motor area (SMA), which can be reached with tSMS [[8]Pineda-Pardo J.A. Obeso I. Guida P. Dileone M. Strange B.A. Obeso J.A. et al.Static magnetic field stimulation of the supplementary motor area modulates resting-state activity and motor behavior.Commun 2019; PubMed Scopus (14) Google Scholar] and stimulation with inhibitory NIBS protocols may improve both dyskinesias [[1]Wu Y. Cao X. Zeng W. Zhai H. Zhang X. Yang X. et al.Transcranial magnetic stimulation alleviates levodopa-induced dyskinesia in Parkinson's disease and the related mechanisms: a mini-review.Front Neurol. 2021; 12https://doi.org/10.3389/fneur.2021.758345Crossref Scopus (1) Google Scholar] and motor [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google found subjective improvement (moderate in patients who received real compared to patients who received sham also by the ability of patients to to some treatment they received Online Supplementary Even though we in some this unlikely to have the evidence of subjective the primary motor cortex is in brain for the of A. M. M. et of for PubMed Scopus (4) Google Scholar]. The observed between subjective and objective improvement thus that tSMS might have not the dyskinesias per but rather the subjective of patients dyskinesias of This is and the of tSMS A. Carrasco-López M.C. M. V. et study of transcranial static magnetic field stimulation of the human Stimul. Full Text Full Text PDF PubMed Scopus Google Scholar] to repeated sessions. The of the brain to static magnetic is also by of of the static magnetic or even are at least one order of than the field in tSMS at cortical Objective evaluation of levodopa-induced dyskinesiasWe found non-significant difference in objective improvement (moderate evidence of absence) between patients who received real compared to patients who received sham treatment. One limitation and two experimental choices might have limited our ability to detect differences in objective improvement between groups. First, overall the patients that participated in the study displayed relatively mild dyskinesias. Our difficulty in recruiting patients with severe dyskinesias is in line with the epidemiologically decreasing prevalence and severity of levodopa-induced dyskinesias, at least in some countries [[5]Chaudhuri K.R. Jenner P. Antonini A. Should there be less emphasis on levodopa-induced dyskinesia in Parkinson's disease?.Mov Disord. 2019; 34: 816-819https://doi.org/10.1002/mds.27691Crossref PubMed Scopus (33) Google Scholar]. Second, we assessed dyskinesias after administration of 100% of the morning dose of levodopa, in order maintain real-life conditions and a stable pharmacological schedule. A higher levodopa dose might have decreased the variability of the assessment, at least in some patients. Third, since this was the first study with repeated sessions of tSMS, we conservatively delivered a relatively low number of sessions. With NIBS, it is not uncommon to observe an initial parallel improvement in patients receiving real or sham stimulation, with differences between groups becoming appreciable only after higher number of sessions and longer follow-ups [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google Scholar]. Future studies should thus test longer home-based treatments, which are feasible with tSMS [[7]Di Lazzaro V. Musumeci G. Boscarino M. De Liso A. Motolese F. Di Pino G. et al.Transcranial static magnetic field stimulation can modify disease progression in amyotrophic lateral sclerosis.Brain Stimul. 2021; https://doi.org/10.1016/j.brs.2020.11.003Abstract Full Text Full Text PDF Scopus (4) Google Scholar]. We found non-significant difference in objective improvement (moderate evidence of absence) between patients who received real compared to patients who received sham treatment. One limitation and two experimental choices might have limited our ability to detect differences in objective improvement between groups. First, overall the patients that participated in the study displayed relatively mild dyskinesias. Our difficulty in recruiting patients with severe dyskinesias is in line with the epidemiologically decreasing prevalence and severity of levodopa-induced dyskinesias, at least in some countries [[5]Chaudhuri K.R. Jenner P. Antonini A. Should there be less emphasis on levodopa-induced dyskinesia in Parkinson's disease?.Mov Disord. 2019; 34: 816-819https://doi.org/10.1002/mds.27691Crossref PubMed Scopus (33) Google Scholar]. Second, we assessed dyskinesias after administration of 100% of the morning dose of levodopa, in order maintain real-life conditions and a stable pharmacological schedule. A higher levodopa dose might have decreased the variability of the assessment, at least in some patients. Third, since this was the first study with repeated sessions of tSMS, we conservatively delivered a relatively low number of sessions. With NIBS, it is not uncommon to observe an initial parallel improvement in patients receiving real or sham stimulation, with differences between groups becoming appreciable only after higher number of sessions and longer follow-ups [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google Scholar]. Future studies should thus test longer home-based treatments, which are feasible with tSMS [[7]Di Lazzaro V. Musumeci G. Boscarino M. De Liso A. Motolese F. Di Pino G. et al.Transcranial static magnetic field stimulation can modify disease progression in amyotrophic lateral sclerosis.Brain Stimul. 2021; https://doi.org/10.1016/j.brs.2020.11.003Abstract Full Text Full Text PDF Scopus (4) Google Scholar]. Objective evaluation of motor featuresA priori, we did not strongly expect tSMS to improve PD motor features, since excitatory rather than inhibitory NIBS protocols typically provide motor improvement when applied to the motor cortex. Yet, tSMS mechanisms unrelated to cortical excitability could have ameliorated motor features, and we wanted to ensure that possible improvements in dyskinesias did not come at the expense of motor impairment. This did not seem to be the case. An attractive alternative target would be the supplementary motor area (SMA), which can be reached with tSMS [[8]Pineda-Pardo J.A. Obeso I. Guida P. Dileone M. Strange B.A. Obeso J.A. et al.Static magnetic field stimulation of the supplementary motor area modulates resting-state activity and motor behavior.Commun 2019; PubMed Scopus (14) Google Scholar] and stimulation with inhibitory NIBS protocols may improve both dyskinesias [[1]Wu Y. Cao X. Zeng W. Zhai H. Zhang X. Yang X. et al.Transcranial magnetic stimulation alleviates levodopa-induced dyskinesia in Parkinson's disease and the related mechanisms: a mini-review.Front Neurol. 2021; 12https://doi.org/10.3389/fneur.2021.758345Crossref Scopus (1) Google Scholar] and motor [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google Scholar]. A priori, we did not strongly expect tSMS to improve PD motor features, since excitatory rather than inhibitory NIBS protocols typically provide motor improvement when applied to the motor cortex. Yet, tSMS mechanisms unrelated to cortical excitability could have ameliorated motor features, and we wanted to ensure that possible improvements in dyskinesias did not come at the expense of motor impairment. This did not seem to be the case. An attractive alternative target would be the supplementary motor area (SMA), which can be reached with tSMS [[8]Pineda-Pardo J.A. Obeso I. Guida P. Dileone M. Strange B.A. Obeso J.A. et al.Static magnetic field stimulation of the supplementary motor area modulates resting-state activity and motor behavior.Commun 2019; PubMed Scopus (14) Google Scholar] and stimulation with inhibitory NIBS protocols may improve both dyskinesias [[1]Wu Y. Cao X. Zeng W. Zhai H. Zhang X. Yang X. et al.Transcranial magnetic stimulation alleviates levodopa-induced dyskinesia in Parkinson's disease and the related mechanisms: a mini-review.Front Neurol. 2021; 12https://doi.org/10.3389/fneur.2021.758345Crossref Scopus (1) Google Scholar] and motor [[6]Shirota Y. Ohtsu H. Hamada M. Enomoto H. Ugawa Y. Supplementary motor area stimulation for Parkinson disease.Neurology. 2013; 80: 1400-1405https://doi.org/10.1212/WNL.0b013e31828c2f66Crossref PubMed Scopus (107) Google Scholar]. found subjective improvement (moderate in patients who received real compared to patients who received sham also by the ability of patients to to some treatment they received Online Supplementary Even though we in some this unlikely to have the evidence of subjective the primary motor cortex is in brain for the of A. M. M. et of for PubMed Scopus (4) Google Scholar]. The observed between subjective and objective improvement thus that tSMS might have not the dyskinesias per but rather the subjective of patients dyskinesias of This is and We found subjective improvement (moderate in patients who received real compared to patients who received sham also by the ability of patients to to some treatment they received Online Supplementary Even though we in some this unlikely to have the evidence of subjective the primary motor cortex is in brain for the of A. M. M. et of for PubMed Scopus (4) Google Scholar]. The observed between subjective and objective improvement thus that tSMS might have not the dyskinesias per but rather the subjective of patients dyskinesias of This is and the of tSMS A. Carrasco-López M.C. M. V. et study of transcranial static magnetic field stimulation of the human Stimul. Full Text Full Text PDF PubMed Scopus Google Scholar] to repeated sessions. The of the brain to static magnetic is also by of of the static magnetic or even are at least one order of than the field in tSMS at cortical Our the of tSMS A. Carrasco-López M.C. M. V. et study of transcranial static magnetic field stimulation of the human Stimul. Full Text Full Text PDF PubMed Scopus Google Scholar] to repeated sessions. The of the brain to static magnetic is also by of of the static magnetic or even are at least one order of than the field in tSMS at cortical suggest that repeated sessions of home-based tSMS of the motor cortex are and provide objective benefit (moderate evidence of absence) but subjective benefit (moderate for the treatment of levodopa-induced dyskinesias in evidence of objective studies should investigate longer tSMS treatments. The suggest that repeated sessions of home-based tSMS of the motor cortex are and provide objective benefit (moderate evidence of absence) but subjective benefit (moderate for the treatment of levodopa-induced dyskinesias in evidence of objective studies should investigate longer tSMS treatments.

BACKGROUND: Latent trigger point (LTrP) can cause motor dysfunction and disturb normal patterns of motor recruitment. OBJECTIVE: To analyze the effects of DN in the upper trapezius (UT) LTrP on pain and the mechanical and contractile properties of the muscle. DESIGN: A randomized, double-blinded, parallel-group-trial. METHODS: Fifty healthy volunteers with LTrPs in the UT were randomly divided into a DN-group (n = 26) and a Sham-DN-group (n = 24) and received one session of DN or placebo treatment. Mechanical and contractile properties of the muscle and pressure pain perception (PPP) were evaluated before treatment and in a 30min, 24 h and 72 h follow-up after treatment. RESULTS: In the mechanical properties, the DN-group showed lower values than the Sham-DN-group for dynamic stiffness at 72 h (p = 0.04). The DN-group showed lower values for dynamic stiffness at 72 h from baseline (278.74 ± 38.40 to 261.54 ± 33.64 N/m; p = 0.01) and for tone at 72 h from 30min (16.62 ± 1.27 to 15.88 ± 1.31 Hz; p = 0.01). In the contractile properties, the DN-group showed higher values for maximal radial displacement (Dm) of the muscle belly at 72 h from baseline (5.38 ± 1.67 to 6.13 ± 1.70 mm; p = 0.04), higher values for contraction time at 30min (28.53 ± 8.80 s; p = 0.03) and lower ones at 72 h (24.74 ± 4.36 s; p = 0.04) from baseline (26.97 ± 6.63 s). The DN-group showed a decrease of PPP from baseline to 72 h after treatment (5.16 ± 1.33 to 4.02 ± 0.97 mm; p < 0.01). CONCLUSION: The application of DN in healthy volunteers over LTrPs in the UT decreased dynamic stiffness, tone and contraction time and increased Dm at 72 h after treatment. Additionally, the PPP showed a decrease at 72 h after needling. CLINICALTRIALS.GOV: NCT04466813.

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.

Abstract Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6C hi -cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6C hi -cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6C hi -cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Background: Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods: This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Results: Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions: The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.

Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL.

BACKGROUND AND PURPOSE: Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients. METHODS: A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected. RESULTS: Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG. CONCLUSIONS: LECIG was safe and effective in advanced PD patients.

CONTEXT: Few data exist about the clinical course of acromegaly, surgical and medical outcomes in patients with GH- and prolactin cosecreting pituitary adenomas (GH&PRL-PAs). Nevertheless, some series described a more aggressive clinic-radiological behavior than in growth hormone-secreting pituitary adenomas (GH-PAs). OBJECTIVE: This work aims to evaluate differences in clinical presentation and in surgical outcomes between GH-PAs and GH&PRL-PAs. METHODS: A multicenter retrospective study was conducted of 604 patients with acromegaly who underwent pituitary surgery. Patients were classified into 2 groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal (ULN) and IHC for GH and PRL was positive or PRL levels were greater than 100 ng/dL and PRL IHC was not available (n = 130) and b) GH-PA patients who did not meet the previously mentioned criteria (n = 474). RESULTS: GH&PRL-PAs represented 21.5% (n = 130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P < .001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs 77.4%; P = .001) and tended to be more invasive (33.6% vs 24.7%; P = .057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (odds ratio 2.8; 95% CI, 1.83-4.38). Insulin-like growth factor ULN levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [interquartile range (IQR) 1.73-3.29] vs 2.7 [IQR 1.91-3.67]; P = .023). There were no differences in the immediate (41.1% vs 43.3%; P = .659) or long-term postsurgical acromegaly biochemical cure rate (53.5% vs 53.1%; P = .936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs 2.4%; P = .011) in GH&PRL-PA patients. CONCLUSION: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger, and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Meniere’s disease is characterised by episodic vertigo,&#13;\nfluctuating hearing loss, aural pressure and tinnitus.&#13;\nVestibular testing is not even a recommendation in the&#13;\nAAO-HNS guidelines, one of the most used classifications to&#13;\ndiagnose Meniere’s disease.&#13;\nVestibular migraine is a term used to describe a vertigo&#13;\nsyndrome in patients with a history of migraines with or&#13;\nwithout aura1 that may affect up to 1% of the general&#13;\npopulation.2&#13;\nIn the first year after onset of symptoms, differentiation of&#13;\nVestibular migraine from Meniere’s disease is a challenge&#13;\nbecause of the overlap in clinical features.3 Some authors&#13;\nhave suggested that Meniere’s disease may coexist with&#13;\nmigraines.4–6&#13;\nThe aim of this study is to evaluate the difficulties in the&#13;\ndiagnosis based on clinical features of a population of&#13;\nrecurrent vestibulopathy congruent with Meniere’s disease&#13;\nand Vestibular migraine within a period of 2 years.&#13;\nAs vestibular testing is not even a recommendation in the&#13;\nAAO-HNS guidelines,7 and the role of vestibular tests for the&#13;\ndiagnosis of Vestibular migraine is not well established,8 we&#13;\nwant to analyse the value of vestibular testing in those&#13;\npatients.

Context: Some reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. Objective: This study aimed at identifying predictors of response to SRL in elderly patients. Design: Multicentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. Results: One-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 ± 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean ± SD) were 2.7 ± 1.4 and 11.0 ± 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 ± 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis ≤6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4-91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01-0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71-0.94). Conclusions: , were associated with a greater chance of response to SRL.