Hospital Universitario De Cabueñes

CONTEXT: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. OBJECTIVE: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. EVIDENCE ACQUISITION: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. EVIDENCE SYNTHESIS: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. CONCLUSIONS: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. PATIENT SUMMARY: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

INTRODUCTION: Sepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain. METHODS: We conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death. RESULTS: A total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, DeltaSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days. CONCLUSIONS: We found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.

The pool of microbes inhabiting our body is known as "microbiota" and their collective genomes as "microbiome". The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life. Alterations of the intestinal microbiota can occur by changes in composition (dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases. The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. Nonetheless, alterations in composition and function of the microbiota have been associated with several gastrointestinal diseases (inflammatory bowel disease, colorectal cancer, or irritable bowel syndrome), as well as extra-intestinal pathologies, such as those affecting the liver, or the respiratory tract (e.g., allergy, bronchial asthma, and cystic fibrosis), among others. Species of Bifidobacterium genus are the normal inhabitants of a healthy human gut and alterations in number and composition of their populations is one of the most frequent features present in these diseases. The use of probiotics, including bifidobacteria strains, in preventive medicine to maintain a healthy intestinal function is well documented. Probiotics are also proposed as therapeutic agents for gastrointestinal disorders and other pathologies. The World Gastroenterology Organization recently published potential clinical applications for several probiotic formulations, in which species of lactobacilli are predominant. This review is focused on probiotic preparations containing Bifidobacterium strains, alone or in combination with other bacteria, which have been tested in human clinical studies. In spite of extensive literature on and research into this topic, the degree of scientific evidence of the effectiveness of probiotics is still insufficient in most cases. More effort need to be made to design and conduct accurate human studies demonstrating the efficacy of probiotics in the prevention, alleviation, or treatment of different pathologies.

The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19–attributable mortality was calculated using propensity score–matched historic control data and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%–21.4%) in 3285 patients receiving dialysis and 19.9% (17.5%–22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44.3% (35.7%–53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02–1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity. The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19–attributable mortality was calculated using propensity score–matched historic control data and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%–21.4%) in 3285 patients receiving dialysis and 19.9% (17.5%–22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44.3% (35.7%–53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02–1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity. Editor’s NoteThis is one of several articles we think you will find of interest that are part of our special issue of Kidney International addressing the challenges of dialysis and transplantation during the COVID-19 pandemic. Please also find additional material in our commentaries and letters to the editor sections. We hope these insights will help you in the daily care of your own patients. This is one of several articles we think you will find of interest that are part of our special issue of Kidney International addressing the challenges of dialysis and transplantation during the COVID-19 pandemic. Please also find additional material in our commentaries and letters to the editor sections. We hope these insights will help you in the daily care of your own patients. Since the initial outbreak in Wuhan, China, in December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly across the world, prompting a global pandemic. The disease—caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus—causes pneumonia, but also affects other organs. According to the European Centre for Disease Prevention and Control, the number of reported COVID-19 cases in the European Union (EU) is 2783 (range 281–6648) per million general population (pmp), representing 0.28% (range 0.03%–0.66%) of the EU population, with variation in numbers depending on governmental control measures, definition of cases, and testing capacity.1European Centre for Disease Prevention and ControlCOVID-19 situation update for the EU/EEA and the UK.https://www.ecdc.europa.eu/en/cases-2019-ncov-eueeaDate accessed: June 9, 2020Google Scholar Mortality due to the SARS-CoV-2 virus is high compared with most other viral infections. Although a case fatality rate of 2.3% was reported from China,2Wu Z. McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention.JAMA. 2020; 323: 1239-1242Crossref PubMed Scopus (12778) Google Scholar the average rate is 11.7% (range 0.6%–18.9%) in the EU general population.1European Centre for Disease Prevention and ControlCOVID-19 situation update for the EU/EEA and the UK.https://www.ecdc.europa.eu/en/cases-2019-ncov-eueeaDate accessed: June 9, 2020Google Scholar Among hospitalized patients in United Kingdom suffering from severe COVID-19, the case fatality rate reaches 26%.3Docherty A.B. Harrison E.M. Green C.A. et al.Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol.medRxiv. 2020; 04: 20076042Google Scholar Patients treated with kidney replacement therapy (KRT; either dialysis or kidney transplantation) represent a vulnerable population. Under normal circumstances, age-standardized cardiovascular and noncardiovascular mortality rates in dialysis patients are already 8.8 and 8.1 times higher than in the general population, respectively,4de Jager D.J. Grootendorst D.C. Jager K.J. et al.Cardiovascular and noncardiovascular mortality among patients starting dialysis.JAMA. 2009; 302: 1782-1789Crossref PubMed Scopus (593) Google Scholar and compared with their age- and sex-matched counterparts in the general population, kidney transplant recipients experience a 30%–50% reduced life expectancy.5ERA-EDTA RegistryERA-EDTA Registry Annual Report 2017. 2019.https://www.era-edta.org/en/registry/publications/annual-reports/#2017Google Scholar It may be expected that COVID-19 causes substantial mortality in both dialysis and kidney transplant populations due to their underlying chronic kidney disease and a high prevalence of comorbid conditions such as diabetes mellitus and cardiovascular disease. In transplant recipients, the potential effect of their long-term use of immunosuppression is a matter of debate. Some argue they may be at greater risk of severe infection because of their impaired immune system,6Coates P.T. Wong G. Drueke T. et al.Early experience with COVID-19 in kidney transplantation.Kidney Int. 2020; 97: 1074-1075Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar whereas others speculate that immunosuppressive therapy may be protective as it might address the COVID-19–induced cytokine storm.7Tay M.Z. Poh C.M. Rénia L. et al.The trinity of COVID-19: immunity, inflammation and intervention.Nat Rev Immunol. 2020; 20: 363-374Crossref PubMed Scopus (2942) Google Scholar Although no deaths were reported among 5 COVID-19 cases on hemodialysis in a single Chinese center,8Wang R. Liao C. He H. et al.COVID-19 in hemodialysis patients: a report of 5 cases.Am J Kidney Dis. 2020; 76: 141-143Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar several case series from Italy (n = 41, n = 94),9Scarpioni R. Manini A. Valsania T. et al.Covid-19 and its impact on nephropathic patients: the experience at Ospedale “Guglielmo da Saliceto” in Piacenza.G Ital Nefrol. 2020; 37: 4Google Scholar,10Alberici F. Delbarba E. Manenti C. et al.A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection.Kidney Int. 2020; 98: 20-26Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar Spain (n = 36),11Goicoechea M. Sánchez Cámara L.A. Macías N. et al.COVID-19: clinical course and outcomes of 36 maintenance hemodialysis patients from a single center in Spain.Kidney Int. 2020; 98: 27-34Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar and the United States (n = 59)12Valeri A.M. Robbins-Juarez S.Y. Stevens J.S. et al.Presentation and outcomes of patients with ESKD and COVID-19.J Am Soc Nephrol. 2020; 31: 1409-1415Crossref PubMed Scopus (258) Google Scholar with varying follow-up suggest a high mortality in the dialysis population with rates ranging from 29% to 41%. Preliminary reports in transplant recipients seem to suggest a somewhat lower mortality, with estimates ranging from 13% (n = 15) in the United States to 25% in Italy (n = 20).13Mohan S. Early description of coronavirus 2019 disease in kidney transplant recipients in New York.J Am Soc Nephrol. 2020; 31: 1150-1156Crossref PubMed Scopus (191) Google Scholar, 14Banerjee D. Popoola J. Shah S. et al.COVID-19 infection in kidney transplant recipients.Kidney Int. 2020; 97: 1076-1082Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar, 15Alberici F. Delbarba E. Manenti C. et al.A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia.Kidney Int. 2020; 97: 1083-1088Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar The largest study to date is from Spain, reporting on a group of 868 KRT patients (67% dialysis patients and 33% transplant patients) with a mortality rate of 23%.16Sánchez-Álvarez J.E. Fontán M.P. Martín C.J. et al.Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN).Nefrologia. 2020; 40: 272-278PubMed Google Scholar Risk estimates from studies with small sample sizes are known to suffer from inaccuracy due to random variation. In addition, because some of the above-mentioned samples were derived from in-hospital populations, the estimates reflect risk in a selected group of more severely ill patients and may not be generalizable to the broader KRT patient population. Moreover, most of these studies, including the largest one, used the case fatality rate as a measure of mortality, which is often calculated while the individual outcome (recovery or death) is known only for a proportion of infected patients.17Natale F. Ghio D. Tarchi D. Goujon A. Conte A. COVID-19 cases and case fatality rate by age.https://ec.europa.eu/knowledge4policy/publication/covid-19-cases-case-fatality-rate-age_enDate accessed: June 9, 2020Google Scholar To date, large population-based studies on mortality in the KRT population with complete follow-up information are lacking. Therefore, the first aim of the present study was to investigate the COVID-19 attributable mortality 28 days after diagnosis in European dialysis and kidney transplant recipients with the use of historic cohorts of prevalent dialysis and transplant patients without COVID-19. The second aim was to compare mortality between dialysis and transplant patients with COVID-19. Finally, we aimed to determine the role of patient characteristics, KRT treatment-related factors, and country as risk factors for death in both groups. From February 1, 2020, to April 30, 2020, a total of 4298 KRT patients were diagnosed with COVID-19, of which 3285 (76.4%) were on dialysis—3160 on hemodialysis and 125 on peritoneal dialysis—and 1013 (23.6%) were living with a functioning transplant (Table 1). The majority of dialysis patients diagnosed with COVID-19 originated from France (49.6%) and Spain (29.7%). In dialysis patients, the median age at COVID-19 diagnosis was 71.7 years (interquartile range [IQR] 60.6–80.5), ranging from 63.2 years in Romania to 74.0 years in Spain. Two-thirds were ≥65 years of age, almost two-thirds were male, almost half suffered from either diabetes mellitus (25.5%) or hypertension/renovascular disease (RVD) (21.2%) as primary renal disease (PRD), and 96.2% were on hemodialysis. Sufficient numbers of transplant patients with COVID-19 were available from France (50.5%) and Spain (49.5%). Transplant recipients were younger than those on dialysis (P < 0.001), with a median age of 60.9 years (IQR 51.1–69.4) and 37.3% being ≥65 years. Similarly to dialysis patients, 65.4% were male (P = 0.23), however, the share of patients with diabetes mellitus (12.8%) and hypertension/RVD (10.6%) as PRD was lower.Table 1Characteristics of KRT patients diagnosed with COVID-19, by treatment modality and countryDialysisTransplantAllHDPDAustriaFrench-speaking part of BelgiumaData on patients younger than 20 years were not included.FranceRomaniaSpainSwitzerlandThe NetherlandsAllFranceSpainNo. of patients32853160125441401631270976871371013512501Age at diagnosis, yr, median (IQR)71.7 (60.6–80.5)71.8 (60.8–80.6)70.2 (59.4–78.5)71.8 (62.8–81.3)71.2 (57.9–78.5)72 (60.8–81.2)63.2 (52.7–70.2)74 (63–81.2)73.7 (59.6–81.9)73.4 (61–81.5)60.9 (51.1–69.4)59.6 (49.9–67.9)62.5 (52.3–70.9) 0–199 (0.3)8 (0.3)1 (0.8)0 (0)NA3 (0.2)1 (0.4)5 (0.5)0 (0)0 (0)8 (0.8)4 (0.8)4 (0.8) 20–44225 (6.8)215 (6.8)10 (8.0)2 (4.5)11 (7.9)127 (7.8)26 (9.6)46 (4.7)7 (8.0)6 (4.4)128 (12.6)80 (15.6)48 (9.6) 45–64854 (26.0)817 (25.9)37 (29.6)10 (22.7)41 (29.3)401 (24.6)123 (45.6)222 (22.7)22 (25.3)35 (25.5)499 (49.3)263 (51.4)236 (47.1) 65–74857 (26.1)823 (26.0)34 (27.2)15 (34.1)34 (24.3)429 (26.3)82 (30.4)245 (25.1)16 (18.4)36 (26.3)260 (25.7)115 (22.5)145 (28.9) ≥751340 (40.8)1297 (41.0)43 (34.4)17 (38.6)54 (38.6)671 (41.1)38 (14.1)458 (46.9)42 (48.3)60 (43.8)118 (11.6)50 (9.8)68 (13.6)Sex Male2077 (63.2)1993 (63.1)84 renal disease modality of KRT median of starting treatment of starting treatment coronavirus disease kidney replacement not peritoneal are as n or median are country was only it had dialysis or transplant patients with on patients younger than 20 years were not of starting treatment in a COVID-19, coronavirus disease kidney replacement not peritoneal disease. are as n or median are country was only it had dialysis or transplant patients with COVID-19. 1, 2020, COVID-19 cases of all prevalent patients on dialysis range and of those living with a functioning range with dialysis and transplant patients without COVID-19, those with COVID-19 were years The proportion of male patients was with more among dialysis patients, and more among transplant recipients In both dialysis and transplant patients with COVID-19 were more patients with diabetes mellitus as PRD and days after COVID-19 diagnosis, of hemodialysis patients and of 125 patients on peritoneal dialysis had that in the dialysis group as a had 28 days after diagnosis, with of deaths on the of In transplant recipients, of 1013 had after 28 28-day of death of was to that in the dialysis with of deaths on the of 28 the to that most of the deaths due to COVID-19 had this with the expected mortality in the matched control group of dialysis patients without COVID-19, the COVID-19 attributable mortality was 20.0% and mortality risk was (95% confidence interval times higher in dialysis patients diagnosed with COVID-19 In transplant recipients diagnosed with COVID-19, the attributable mortality was 19.9% the expected mortality in the matched control mortality is lower in transplant patients compared with dialysis patients, their mortality risk was (95% times higher compared with their matched control patients 1). that the mortality risk in transplant recipients with COVID-19 was higher compared with the selected group of dialysis patients that be matched In dialysis patients, the of mortality by age substantial differences across age with 28-day mortality in patients ≥75 years of age as high as (Table The risk of death in was in patients with hypertension/RVD as PRD had the of death by diabetes mellitus and The 28-day of death was in those treated with peritoneal dialysis and in hemodialysis patients. were substantial differences in mortality across the 7 it was in the and in Romania identified higher age and male as risk factors for 28-day mortality in COVID-19 dialysis patients (Table for all available dialysis patients in Romania and France had a lower mortality risk than those in The of death by age and PRD is in and the COVID-19–attributable mortality is in of death in and risk factors in dialysis patients with of death 28 days (95% (95% for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT was for age, and the for treatment modality was for age, of KRT and and the for country was for age, and of KRT for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT was for age, and the for treatment modality was for age, of KRT and and the for country was for age, and of KRT at COVID-19 diagnosis, renal disease of KRT Spain this was of dialysis modality The confidence COVID-19, coronavirus disease kidney replacement peritoneal The for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT was for age, and the for treatment modality was for age, of KRT and and the for country was for age, and of KRT Spain this was of dialysis in a of death among dialysis patients and transplant patients with coronavirus disease 2019 by confidence confidence COVID-19, coronavirus disease kidney replacement peritoneal disease. In kidney transplant recipients, the of mortality by age group a high 44.3% of death in those ≥75 years of age, which for almost half of the patients (Table The of death was in and in and in patients suffering from diabetes mellitus as PRD by hypertension/RVD and in those with The of death was higher in Spain than in France In only higher age was identified as a risk for 28-day mortality (Table The of death by age and PRD is in and the COVID-19–attributable mortality is in of death in and risk factors in transplant patients with of death 28 days (95% (95% for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT and of transplant was for age, and and the for country was for age, and of KRT transplantation in for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT and of transplant was for age, and and the for country was for age, and of KRT transplantation in at COVID-19 diagnosis, renal disease of KRT of transplantation confidence COVID-19, coronavirus disease kidney replacement peritoneal The for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT and of transplant was for age, and and the for country was for age, and of KRT transplantation in in a confidence COVID-19, coronavirus disease kidney replacement peritoneal disease. In this we present complete population-based data on more than KRT patients by COVID-19 collected and renal in We report the of death at 28 days after diagnosis and risk factors in dialysis patients from 7 European countries and in transplant recipients from 2 European In both the dialysis and the transplant of patients had by 28 days after matched that transplant recipients had a higher risk of death compared with their dialysis in dialysis patients higher age, male and country as risk factors, whereas in transplant recipients only higher age was with an increased risk of The data suggest that the of diagnosed COVID-19 in the KRT population was as of the prevalent dialysis population and of those living on a functioning were by COVID-19, this disease to had a greater impact on the KRT population compared to the general Centre for Disease Prevention and ControlCOVID-19 situation update for the EU/EEA and the UK.https://www.ecdc.europa.eu/en/cases-2019-ncov-eueeaDate accessed: June 9, 2020Google Scholar which may be due to their older age, or the of more our COVID-19 patients were from population-based they may not represent all KRT patients with COVID-19. The majority of are or and not not of a general or a patients may not and may testing in dialysis more during the of the this is the case for hemodialysis patients their dialysis center a times a The of patients with COVID-19 were lower in patients on peritoneal dialysis and in transplant We speculate that in these testing may to the and more severe cases, and our data for these populations represent a group of patients. This is by the high number of transplant recipients on the of diagnosis This may our that transplant patients are at higher risk of death than dialysis patients of propensity the other being may more of a while the infection than an the cytokine P.T. Wong G. Drueke T. et al.Early experience with COVID-19 in kidney transplantation.Kidney Int. 2020; 97: 1074-1075Abstract Full Text Full Text PDF PubMed Scopus (44) Google M.Z. Poh C.M. Rénia L. et al.The trinity of COVID-19: immunity, inflammation and intervention.Nat Rev Immunol. 2020; 20: 363-374Crossref PubMed Scopus (2942) Google Scholar Although the risk of COVID-19 was in KRT patients, 28-day mortality in COVID-19 patients the mortality that may be expected for KRT patients of propensity on the historic control on the 28-day of death due to COVID-19 by age in the general population is lacking. data on the rate in the general population to in and to for those years of G. G. S. rate and characteristics of patients in to COVID-19 in 2020; 323: Google Scholar data from Spain higher and COVID-19, no COVID-19 a accessed: June 9, 2020Google Scholar This may suggest that mortality from COVID-19 in the dialysis population age 71.7 is times higher and in transplant patients age 60.9 times compared with patients with COVID-19 of in dialysis and transplant patients will an important role in this substantial mortality, but our data did not on this We however, in that in both the dialysis and the transplant almost of patients COVID-19 at to 28 days after diagnosis, the that a substantial number of may not admitted to the care to their high risk of In both dialysis and transplant patients with COVID-19, higher age the most important risk for mortality in our The that male was a risk in dialysis patients with COVID-19 is of It in the general population and also the increased cardiovascular mortality in compared with on dialysis without Jager D.J. M. et al.Cardiovascular and noncardiovascular mortality among and starting J Am Soc Nephrol. PubMed Scopus Google Scholar studies disease to be a risk in dialysis F. Delbarba E. Manenti C. et al.A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection.Kidney Int. 2020; 98: 20-26Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar We did not to but PRD be as a for In our the estimates of the additional risk by diabetes mellitus and hypertension/RVD did suggest a in an additional effect of PRD on of age not be as a of In dialysis patients with COVID-19, we that the of death across Although it is we not to from that because of the variation may be to in the of COVID-19 cases a of varying testing differences in the of and the to for and This study reports data from renal that aim to complete data with the in and this it to reporting on patient populations with COVID-19, renal the of impaired testing from of cases, of the of care of or not reporting to the KRT treatment will to an of This is to be small for hemodialysis patients, but it may be more important for peritoneal dialysis patients and transplant recipients, more severe cases were The of this by varying testing may across countries and using data as a we had no to additional information on patient and treatment characteristics that be important to the outcome of COVID-19 patients on Finally, this study the number of COVID-19 patients on KRT to date, it may suffer from of in an to The COVID-19 pandemic has had a substantial effect on mortality in all of KRT patients by the in KRT patients and in transplant It is that in the hemodialysis may as important of It is of that in the and control in and be to to the of their patients and the to their as as in this and studies on of COVID-19 in KRT patients are

BACKGROUND: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. PATIENTS AND METHODS: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. RESULTS: Three Crohn's disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. CONCLUSIONS: Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.

Better knowledge of the risk factors associated with the appearance of hepatocellular carcinoma (HCC) could improve the efficacy of surveillance programs. A total of 463 patients aged 40 to 65 years with liver cirrhosis in Child-Pugh class A or B were included in a program of early diagnosis. The predictive value of different risk factors was evaluated using the Kaplan-Meier method and Cox regression model. Thirty-eight patients developed HCC. In the multivariate analysis, 4 variables showed an independent predictive value for the development of HCC: age 55 years or older, antibody to hepatitis C virus (anti-HCV) positivity, prothrombin activity 75% or less, and platelet count less than 75 x 10(3)/mm(3). According to the contribution of each of these factors to the final model, a score ranging between 0 and 4.71 points was constructed to allow the division of patients into 2 different risk groups. The low-risk group included those with a score of 2.33 points or less (n = 270; 4 with HCC; cumulative incidence of HCC at 4 years, 2.3%), and the high-risk group included those with a score greater than 2.33 (n = 193; 34 with HCC; cumulative incidence of HCC at 4 years, 30.1%) (P =.0001). In conclusion, a simple score made up of 4 clinical and biological variables allowed us to distinguish 2 groups of cirrhotic patients at high and low risk for the development of HCC. We believe this score can be useful in establishing a subset of cirrhotic patients in whom a surveillance program for early detection of HCC could be unjustified.

Microbial colonization of the infant gut is essential for the development of the intestine and the immune system. The profile of intestinal microbiota in the full-term, vaginally delivered, breast-fed infant is considered as ideally healthy. However, in preterm infants this process is challenging, mainly because of organ immaturity, antibiotics use, and hospital stay. To assist in a proper microbiota development in these infants, a detailed knowledge of the colonization process, and the differences from that of full-term breast-fed infants, is needed. We assessed the establishment of the gut microbiota and its metabolic activity in preterm neonates (n = 21) during the first 3 months of life and compared it with that of vaginally delivered, exclusively breast-fed full-term infants (n = 20) using qualitative and quantitative culture-independent methods. Differences in the gut microbiota composition between both groups were observed. Preterm infants showed higher levels of facultative anaerobic microorganisms and reduced levels of strict anaerobes such as Bifidobacterium, Bacteroides, and Atopobium. Short-chain fatty acids concentrations were lower in preterm infants during the first days of life. Alterations occur in the process of microbiota establishment in preterm infants, indicating the need for intervention strategies to counteract them.

BACKGROUND: Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. METHODS: We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. RESULTS: Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3-30.2%] in kidney transplant and 25.0% (95% CI 20.2-30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59-1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07-0.56, P < 0.01). CONCLUSIONS: The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

BACKGROUND: To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. METHODS: Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. RESULTS: Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. CONCLUSIONS: As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.

OBJECTIVES: The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy. METHODS: Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn. RESULTS: A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO. CONCLUSION: The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10-6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9). We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

BACKGROUND: There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus (HCV). AIM: To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD. METHODS: Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome. RESULTS: 162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg. CONCLUSION: Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.

Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials.

OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

Carotid blowout syndrome (CBS) refers to rupture of the carotid artery and is an uncommon complication of head and neck cancer that can be rapidly fatal without prompt diagnosis and intervention. CBS develops when a damaged arterial wall cannot sustain its integrity against the patient's blood pressure, mainly in patients who have undergone surgical procedures and radiotherapy due to cancer of the head and neck, or have been reirradiated for a recurrent or second primary tumor in the neck. Among patients irradiated prior to surgery, CBS is usually a result of wound breakdown, pharyngocutaneous fistula and infection. This complication has often been fatal in the past, but at the present time, early diagnosis and modern technology applied to its management have decreased morbidity and mortality rates. In addition to analysis of the causes and consequences of CBS, the purpose of this paper is to critically review methods for early diagnosis of this complication and establish individualized treatment based on endovascular procedures for each patient.