Early spermatogenesis changes in traumatic complete spinal cord-injured adult patients.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on the spermatogenesis of patients studied in the early subacute stage and ensuing months. SETTING: National hospital for SCI patients. METHODS: A prospective follow-up study was conducted on 28 male patients with complete SCI who were evaluated in the early subacute phase (~1 month), and 3 and 6 months after the injury. At each time point, fine needle aspiration biopsy samples were taken from the testes for cytological assessment, and serum levels of relevant hormones were measured. At the end of the study period, ejaculation was attempted for standard semen analyses. RESULTS: Cytological patterns indicative of defective spermatogenesis were found in 61%, 52% and 20% of the patients at 1, 3 and 6 months after SCI, respectively, suggesting an improvement over time. Serum hormone analyses showed a steady elevation of estradiol levels above the reference range, and increasing levels of testosterone, inhibin B and prolactin throughout the study period. Prolactin levels were above the reference range at all time points. Only 2 out of the 10 patients who were able to ejaculate at 6 months post injury showed normal sperm parameters. CONCLUSION: A majority of the patients showed impaired spermatogenesis soon after the injury, which in most cases recovered over time. That was accompanied by parallel increases in serum levels of inhibin B, testosterone and prolactin, possibly driving or reflecting the spermatogenesis recovery. Further studies are needed to elucidate the biological mechanisms underlying these changes.

Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study.

BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.

Dermatologic emergencies in a tertiary hospital: A descriptive study. / Estudio descriptivo de urgencias dermatológicas en un hospital terciario.

BACKGROUND AND OBJECTIVE: Dermatology in-house call is uncommon in the Spanish national health system. The objective of the present study was to define the groups of dermatologic diseases and conditions most frequently seen in the emergency department and to evaluate the need for dermatology in-house call in the training of medical residents. MATERIAL AND METHODS: We performed a descriptive study of all patients who attended the emergency department with a skin complaint during a 1-year period (June 2013 to May 2014) and were assessed by 9 dermatology residents. The study variables were date/day, sex, age, diagnosis, special surgical procedures, additional laboratory tests, and need for hospitalization and/or follow-up. We also evaluated patients attending their first scheduled visit to the dermatologist between January and June 2014 in order to compare the most frequent conditions in both groups. RESULTS: A total of 3084 patients attended the emergency room with a skin complaint (5.6% of all visits to the emergency department), and 152 different diagnoses were made. The most frequent groups of diseases were infectious diseases (23%) and eczema (15.1%). The specific conditions seen were acute urticaria (7.6%), contact dermatitis (6.1%), and drug-induced reactions (4.6%). By contrast, the most frequent conditions seen in the 1288 patients who attended a scheduled dermatology appointment were seborrheic keratosis (11.9%), melanocytic nevus (11.5%), and actinic keratosis (8%). A follow-up visit was required in 42% of patients seen in the emergency department. Fourth-year residents generated the lowest number of follow-up visits. CONCLUSIONS: We found that infectious diseases and eczema accounted for almost 40% of all emergency dermatology visits. Our results seem to indicate that the system of in-house call for dermatology residents is very useful for the hospital system and an essential component of the dermatology resident's training program.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

Clinical, molecular, and immune correlates of the Immunotherapy Response Score in patients with advanced urothelial carcinoma under atezolizumab monotherapy: analysis of the phase II IMvigor210 trial.

BACKGROUND: In the advanced urothelial carcinoma (aUC) scenario there are no consistent immune checkpoint blockade predictive biomarkers. Recently a novel pan-tumor molecular tissue-based biomarker, the Immunotherapy Response Score (IRS), has been proposed. We conducted a retrospective study to validate the prognostic/predictive utility of the IRS in patients with aUC under atezolizumab monotherapy and to characterize its underlying molecular/immune features in the context of the IMvigor210 phase II trial. PATIENTS AND METHODS: This is a post hoc pooled analysis of 261 patients with available clinical, molecular, and immune tumor data treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial. Efficacy endpoints were overall survival (OS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using chi-square or Fisher's exact tests. All P values were two-sided, and those <0.05 were considered statistically significant. RESULTS: High IRS was significantly associated with a better OS in univariable [hazard ratio (HR) = 0.49, P < 0.001] and multivariable (HR = 0.60, P = 0.018) analyses. DCR and ORR were significantly higher among high IRS patients (DCR for high IRS versus low IRS patients: 57% versus 32%, P < 0.001; ORR: 42% versus 10%, P < 0.001). High IRS patients presented a higher probability of DC and response in univariable [DC: odds ratio (OR) = 2.72, P < 0.001; response: OR = 3.92, P < 0.001] and multivariable (DC: OR = 2.72, P < 0.001; response: OR = 3.92, P < 0.001) analyses. CONCLUSIONS: This study validates IRS as a strong independent prognostic and predictive biomarker for OS and DC/response in patients with aUC treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues.

Electronic health records and patient registries in medical oncology departments in Spain.

PURPOSE: We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain. METHODS: This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM. RESULTS: We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department. CONCLUSION: Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes. CLINICAL TRIAL REGISTRATION: Not applicable.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Prefrontal hemodynamic changes produced by anodal direct current stimulation.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been investigated for the treatment of many neurological or neuropsychiatric disorders. Its main effect is to modulate the cortical excitability depending on the polarity of the current applied. However, understanding the mechanisms by which these modulations are induced and persist is still an open question. A possible marker indicating a change in cortical activity is the subsequent variation in regional blood flow and metabolism. These variations can be effectively monitored using functional near-infrared spectroscopy (fNIRS), which offers a noninvasive and portable measure of regional blood oxygenation state in cortical tissue. We studied healthy volunteers at rest and evaluated the changes in cortical oxygenation related to tDCS using fNIRS. Subjects were tested after active stimulation (12 subjects) and sham stimulation (10 subjects). Electrodes were applied at two prefrontal locations; stimulation lasted 10 min and fNIRS data were then collected for 20 min. The anodal stimulation induced a significant increase in oxyhemoglobin (HbO(2)) concentration compared to sham stimulation. Additionally, the effect of active 10-min tDCS was localized in time and lasted up to 8-10 min after the end of the stimulation. The cathodal stimulation manifested instead a negligible effect. The changes induced by tDCS on HbO(2), as captured by fNIRS, agreed with the results of previous studies. Taken together, these results help clarify the mechanisms underlying the regional alterations induced by tDCS and validate the use of fNIRS as a possible noninvasive method to monitor the neuromodulation effect of tDCS.

[Therapeutic behavior to follow in the following clinical case: treatment of type 2 diabetes]. / Conducta terapéutica en la diabetes tipo 2. Cuanto más breve, mejor.

A 62-year old woman with obesity, high blood pressure and type 2 diabetes mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850 mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always regains what she has lost. Furthermore, she monitors her glucose levels in fasting every two weeks and generally has between 120 and 160 mg/dL. Her high blood pressure is being treated with enalapril/HCTZ and she also takes aspirin 100mg/day and simvastatin 20 mg/day. It is seen in her family background that one brother died suddenly at 50 years of age. Her physical examination shows a BMI of 32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is normal. What treatment do you think would be the more appropriate? 1 - Add glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

Brain metastases from prostate adenocarcinoma.

Brain metastases of prostate adenocarcinoma are rare. We report a case of brain metastases from prostate adenocarcinoma 15 months after the diagnosis of the primary tumour. The patient had headache and one solitary metastasis upon magnetic resonance imaging (MRI). The biopsy performed showed metastatic prostate adenocarcinoma. He was treated with surgery and cranial irradiation.

Bcl-2 expression in a diabetic embryopathy model in presence of polyamines.

The frequency of congenital malformations is 3-5 times higher in mothers with pregestational diabetes mellitus than in general population. Apparently, this problem is due to change in the expression of apoptotic and antiapoptotic genes induced by the oxidative stress derived from the diabetes/hyperglycemia. One of these genes is Bcl-2, which is associated with the control and inhibition of apoptosis. The purpose of the present work was to study the effect of polyamine addition over expression of Bcl-2 gene in a model of diabetic embryopathy. For this, gestational day 10.5 (GD10.5) rat embryos were incubated at 37°C for 24 h in control medium, medium with high glucose, or medium with high glucose and supplemented with spermidine or spermine. Post-cultured embryos were harvested and observed to obtain morphological scores; some of them were subjected to molecular biology studies: DNA isolation plus conventional PCR or RNA isolation plus RT-PCR; other embryos were fixed with paraformaldehyde and used for immunohistochemical detection of Bcl-2 protein. Although Bcl-2 mRNA was similarly expressed in all rat embryo treatments, Bcl-2 protein was found only in control-incubated embryos. In conclusion, it seems that the inhibition of Bcl-2 gene expression induced by glucose was not reversed by polyamines.

PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PURPOSE: Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. METHODS: PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. RESULTS: This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. CONCLUSION: The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Retention of inorganic arsenic by coryneform mutant strains.

The natural resistance mechanisms of corynebacteria to respond to the environments containing high levels of arsenic were successfully adopted to develop inexpensive and selective extractants for submicrogram amounts of arsenic. Kinetic and equilibrium characteristics were evaluated, and a preliminary exploration of the capability of these strains to be used for arsenic speciation was also made in this work. Three kinetics models were used to fit the experimental data. It was found that the pseudo-first-order kinetics model was not quite adequate to describe the retention process, while the intraparticle diffusion and the pseudo-second-order kinetics models provide the best fits. The equilibrium isotherm showed that the retention of arsenic was consistent with the Langmuir equation and that the Freundlich and Dubinin-Radushkevich models provided poorer fits to the experimental data. The maximum effective retention capacity for arsenic was about 15.4 ng As/mg biomass. The amount of arsenic retained was directly measured in the biomass by forward planning a slurry electrothermal atomic absorption spectrometric procedure.

[Utility of FDG-PET for early evaluation of efficiency of imatinib mesylate (Glivec) in the treatment of gastrointestinal stromal tumors]. / Utilidad de la FDG-PET en la evaluación precoz de la eficacia de imatinib (Glivec) en el tratamiento de tumores del estroma gastrointestinal.

The management of gastrointestinal stromal tumors, usually defined as c-KIT-positive mesenchymal neoplasias, has evolved very rapidly in the last five years. Imatinib mesylate (Glivec(R)) is the standard treatment in unresectable or metastatic gastrointestinal stromal tumors. Imatinib should be given until development of intolerance or progressive disease. It is not uncommon for gastrointestinal stromal tumors to become larger during the early post-treatment phase and conventional response to treatment criteria in solid tumors have a limited value for evaluation the efficiency of imatinib in this period. FDG-PET has proven to be highly sensitive in detecting early response tumor. A 53-year old woman was diagnosed of relapsed gastrointestinal stromal tumor 18 months after adyuvant imatinib mesylate finished. Imatinib was started and 72 hours later the tumor showed a decrease of fluorodeoxyglucose F18 uptake on positron emission tomography scan.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study / Factores predictivos de la mortalidad a las seis semanas en pacientes críticos con SARS-CoV-2: estudio multicéntrico prospectivo

Objective: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. Design: Prospective descriptive multicenter cohort study. Setting: 26 Intensive care units (ICU) from Andalusian region in Spain. Patients or participants: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. Interventions: None. Variables: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. Results: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. Conclusion: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor (AU)

Objetivo: Identificar los factores de riesgo asociados con la mortalidad a las seis semanas. Diseño: Estudio prospectivo multicéntrico. Ámbito: Se incluyeron a 26 pacientes de la Unidad de Cuidados Intensivos (UCI) de Andalucía. Pacientes o participantes: Pacientes ingresados en UCI por neumonía grave por SARS-CoV-2 del 8 de marzo al 30 de mayo de 2020. Intervenciones: Ninguna. Variables de interés principales: Características demográficas, clínicas y escalas de gravedad. Se analizaron tratamientos de soporte, fármacos y la mortalidad. Resultados: Se incluyeron 495 pacientes, 73 fueron excluidos por incompletos y 422 pacientes se incorporaron en el análisis final. La mediana de edad fue de 63 años, 305 (72,3%) eran hombres. La mortalidad en la UCI fue: 144/422 34%; mortalidad a los 14 días: 81/422 (19,2%); mortalidad a los 28 días: 121/422 (28,7%); mortalidad a las seis semanas 152/422 36,5%. Los factores asociados con la mortalidad a los 42 días fueron la edad, APACHE II, SOFA > 6 y LDH al ingreso > 470 U/L, uso de vasopresores, necesidad de técnicas de reemplazo de la función renal, porcentaje de linfocitos a las 72 horas del ingreso en UCI < 6,5%, y trombocitopenia, mientras que el uso de lopinavir/ritonavir fue identificado como un factor protector. Conclusiones: La edad, gravedad y fracaso orgánico junto con la necesidad de terapias de soporte fueron identificadas como factores predictores de mortalidad a las seis semanas. La administración de corticoesteroides a dosis altas no mostró beneficios en la mortalidad, al igual que el tratamiento con tocilizumab, lopinavir/ritonavir se identificaron como un factor protector (AU)

Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease.

Transcranial static magnetic field stimulation (tSMS) is a recent low-cost non-invasive brain stimulation technique that decreases cortical excitability in healthy subjects. The objective of the present study was to test the ability of tSMS to modulate cortical excitability in patients with Parkinson's disease. We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the more affected motor cortex of patients with Parkinson's disease. Cortical excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). tSMS significantly decreased MEP amplitudes in patients OFF medication (after overnight withdrawal of dopaminergic drugs), but not ON medication (after an acute dose of levodopa). The between-patients variability of tSMS-induced changes was significantly greater ON medication. The variability ON medication could be partly explained by disease progression, i.e. the more advanced the patient, the more likely it was to observe a switch from inhibitory tSMS plasticity OFF medication to paradoxical facilitatory plasticity ON medication. These results suggest that tSMS induces dopamine-dependent changes of cortical excitability in patients with Parkinson's disease.