Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Clinical study types and guidance for their correct post-pandemic interpretation.

Randomized clinical trials (RCTs) are key to the advancement of medicine and microbiology, but they are not the only option. Observational studies provide information on long-term efficacy and safety, are less expensive, allow the study of rare events, and obtain information more quickly than RCTs. On the other hand, they are more vulnerable to confounding factors. Prospective exploratory pilot studies share many aspects with RCTs but are not subject to supervision by external commissions or mandatory registration. Multitesting can pervert the balance of publications in favor of the desired effect. Bonferroni's reasoning shows that if 10 studies are performed with an ineffective antibiotic, the probability that at least one will show P <0.05 might be 40%. Scenarios in which there is intensive pressure to perform research, such as the recent pandemic, might result in many research teams trying to study the effect of an antimicrobial. Even if the drug has no efficacy, if 100 research teams conduct a study to assess its usefulness, it might be virtually certain that at least one will get a P value <0.05. If the other studies (with P >0.05) are not published, the scientific commu nity would consider that there is strong evidence in favor of its usefulness. In conclusion, RCTs are a very good source of clinical information, but are not the only one. The systematic registration of all research can and should be applied to all types of clinical studies.

Respiratory syncytial virus: A new era.

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain.

COVID-19: On the threshold of the fifth year. The situation in Spain.

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection.

Veno-venal extracorporeal membrane oxygenation to support whole-lung lavage in a severe case of pulmonary alveolar proteinosis.

We present the case of a 71-year-old woman with severe bilateral primary alveolar proteinosis admitted for bilateral whole lung lavage (WLL) with a double-lumen endotracheal tube. She had a cardiac arrest of respiratory origin during the procedure and recovered after one minute of advanced resuscitation. A second LLP was scheduled under respiratory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO). During this second WLL the patient was completely VV-ECMO-dependent, and the procedure was successfully completed. She was gradually weaned over the next 48 h. The patient was finally discharged after clinical improvement and home oxygen therapy was discontinued. WLL is the treatment of choice for severe cases of alveolar proteinosis. In rare cases the intervention may be poorly tolerated due to the degree of lung involvement. This case illustrates how VV-ECMO support is an option that may benefit this subgroup of at-risk patients.

Tuberculosis in Spain: An opinion paper.

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Illustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapulmonary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observation in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal implications of this disease are not a minor issue and our situation in this regard has been reviewed.

Advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in Spain. How and when is it justified to maintain it?

We address the advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in the current epidemiological situation in Spain and after the declaration of the World Health Organization on May 5, 2023 of the end of COVID-19 as public health emergency. We advocate for prudence and flexibility, respecting the individual decision to wear a mask and emphasizing the need for its use when symptoms suggestive of a respiratory infection appear, in situations of special vulnerability (such as immunosuppression), or when caring for patients with those infections. At present, given the observed low risk of severe COVID-19 and the low transmission of other respiratory infections, we believe that it is disproportionate to maintain the mandatory use of masks in a general way in health centers and nursing homes. However, this could change depending on the results of epidemiological surveillance and it would be necessary to reconsider returning to the obligation in periods with a high incidence of respiratory infections.

Sexually transmitted infections in Spain: Current status.

Sexually Transmitted Infections (STI) are a major public health problem. The problems inherent to their diagnosis, treatment and prevention have to do not only with their nature, but also with organizational issues and overlapping competencies of the different health authorities in Spain. The real situation of STI in Spain, at present, is poorly known. For this reason, the Scientific Committee on COVID and Emerging Pathogens of the Illustrious Official College of Physicians of Madrid (ICOMEM) has formulated a series of questions on this subject which were distributed, not only among the members of the Committee, but also among experts outside it. The central health authorities provide very high and increasing figures for gonococcal infection, syphilis, Chlamydia trachomatis infection and lymphogranuloma venereum (LGV). Both HIV infection and Monkeypox are two important STI caused by viruses in our environment, to which it should be added, mainly, Herpes simplex virus (HSV) and Human papillomavirus (HPV) infections. Emerging microorganisms such as Mycoplasma genitalium pose not only pathogenic challenges but also therapeutic problems, as in the case of N. gonohrroeae. The pathways that patients with suspected STI follow until they are adequately diagnosed and treated are not well known in Spain. Experts understand that this problem is fundamentally managed in public health institutions, and that Primary Care and Hospital Emergency Services, together with some institutions that deal monographically with this problem, are the recipients of most of these patients. One of the most serious difficulties of STI lies in the availability of the microbiological tests necessary for their diagnosis, particularly in this era of outsourcing of microbiology services. Added to this is the increased cost of implementing the latest generation of molecular techniques and the difficulties of transporting samples. It is clear that STI are not diseases to which the entire population is equally exposed and it is necessary to have a better knowledge of the risk groups where to focus the necessary interventions adapted to their characteristics. It should not be forgotten that STI are also a problem in the pediatric age group and that their presence can be a marker of sexual abuse with all that this implies in terms of health care and medicolegal activity. Finally, STI are infections that are associated with a high cost of care for which we have very little information. The possibility of expanding the automatic performance of laboratory tests for STI surveillance through laboratory routines is encountering ethical and legal problems that are not always easy to solve. Spain has created a ministerial area of specific attention to STI and there are plans to improve the diagnosis, treatment and prevention of these problems, but we still lack the necessary evidence on their impact. We cannot forget that these are diseases that transcend the individual and constitute a Public Health problem.

Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.

Herpes zoster infection (HZ) is an important public health problem due to its high incidence and frequent complications, especially post-herpetic neuropathy . The incidence of HZ increases with age and is more frequent in immunocompromised patients. It is estimated that at least 60,000 people develop HZ each year in Spain. The usual forms of HZ are so clinically characteristic that they do not usually require microbiological confirmation, which is reserved for cases without cutaneous manifestations or with atypical presentation. There are currently two vaccines approved by the regulatory agencies and marketed in Spain to prevent the onset of HZ and its complications. The first (Zostavax®) was marketed by the company MSD and licensed in Europe in 2006 and is a live attenuated virus vaccine that is administered in a single dose, while the second (Shingrix®) is a recombinant vaccine, marketed in 2017 and requires two doses. While the former cannot be administered to immunocompromised persons, the latter can be prescribed to any group of adults. The criteria for the indication and financing of these vaccines have not been uniform in the various autonomous communities of Spain. These and other aspects of HZ have been discussed by a group of experts from the Illustrious Official College of Physicians of Madrid (ICOMEM) whose criteria and opinions are included in this paper.

Insights for COVID-19 in 2023.

Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources.

Monkeypox in humans: a new outbreak.

Infection caused by Monkeypox Virus (MPVX) has small rodents as its natural reservoir and both monkeys and humans are occasional hosts. The causative agent is an Orthopoxvirus (MPVX) that was isolated in monkeys in 1958 and proved capable of passing to humans in 1970. It remained contained in Africa, causing isolated episodes of infection, until 2003 when an outbreak occurred in the United States following importation of animals from that continent. Since then, anecdotal cases have continued to be reported outside Africa, usually very clearly linked to travelers to those countries, but in May 2022, a broad outbreak of this disease has begun, now affecting several continents, with the emergence of human cases of MPVX (H-MPVX) infection mainly among Men that have Sex with Men (MSM). The disease has an incubation time ranging from 5 to 15 days and is characterized by the presence of pustules, fever, malaise and headache. The presence of significant regional lymphadenopathy is a differential feature with episodes of classical smallpox. Proctitis and pharyngitis, with minimal skin lesions, may be another form of presentation. Diagnosis can be confirmed by PCR testing of lesions or by demonstration of MPVX in other body fluids or tissues, although in the appropriate epidemiologic setting the clinical picture is highly suggestive of the disease. Effective drug treatment has been developed as part of programs to protect against potential bioterrorist agents and smallpox vaccinees are known to have high protection against monkeypox. New vaccines are available, but neither the drugs nor the vaccines are yet freely available on the market. The prognosis of the disease appears, at least in adults in developed countries, to be good, with very low mortality figures and much less aggressive behavior than that described in classical smallpox. Isolation measures, essential for the control of the outbreak, have been published by the health authorities.

Lessons from COVID-19 for future disasters: an opinion paper.

A "Pandemic/Disaster Law" is needed to condense and organize the current dispersed and multiple legislation. The State must exercise a single power and command appropriate to each situation, with national validity. The production of plans for the use of land and real estate as potential centers for health care, shelter or refuge is recommended. There should be specific disaster plans at least for Primary Health Care, Hospitals and Socio-sanitary Centers. The guarantee of the maintenance of communication and supply routes is essential, as well as the guarantee of the autochthonous production of basic goods. The pandemic has highlighted the need to redefine the training plans for physicians who, in their different specialties, have to undertake reforms that allow a more versatile and transversal training. National research must have plans to be able to respond quickly to questions posed by the various crises, using all the nation's resources and in particular, all the data and capabilities of the health sector. Contingency plans must consider ethical aspects, and meet the needs of patients and families with a humanized approach. In circumstances of catastrophe, conflicts increase and require a bioethical response that allows the best decisions to be made, with the utmost respect for people's values. Rapid, efficient and truthful communication systems must be contained in a special project for this sector in critic circumstances. Finally, we believe that the creation of National Coordination Centers for major disasters and Public Health can contribute to better face the crises of the future.

Dilatación de la aurícula izquierda en deportistas de alta competición y electrofisiología auricular / Left atrial enlargement in competitive athletes and atrial electrophysiology

Introducción y objetivos: Existe poca información sobre la dilatación de la aurícula izquierda (AI) y los parámetros electrocardiográficos en deportistas. Métodos: Estudio observacional multicéntrico en deportistas de competición y controles. La dilatación de la AI se definió como un volumen indexado por área de superficie corporal ≥ 34ml/m2. Se estudió su relación con parámetros electrocardiográficos auriculares. Resultados: Se incluyó en total a 356 sujetos: 308 deportistas de competición (media de edad, 36,4±11,6 años) y 48 controles (49,3±16,1 años). Los deportistas de competición tenían un mayor volumen medio indexado de la AI (29,8±8,6 frente a 25,6±8,0ml/m2; p=0,006) y una mayor prevalencia de dilatación de la AI (113 [36,7%] frente a 5 [10,4%]; p <0,001), sin diferencias relevantes en cuanto a la duración de la onda P (106,3±12,5 frente a 108,2±7,7 ms; p=0,31), la prevalencia de bloqueo interauricular (40 [13,0%] frente a 4 [8,3%]; p=0,36) ni la puntuación Morphology-Voltage-P-wave duration (1,8±0,84 frente a 1,5±0,8; p=0,71). El entrenamiento competitivo se asoció de manera independiente con la dilatación de la AI (OR=14,7; IC95%, 4,7-44,0; p < 0,001), pero no con la duración de la onda P (OR=1,02; IC95%, 0,99-1,04), el bloqueo interauricular (OR=1,4; IC95%, 0,7-3,1) o la puntuación Morphology-Voltage-P-wave duration (OR=1,4; IC95%, 0,9-2,2). Conclusiones: La dilatación de la AI es frecuente en deportistas de competición, pero no se acompaña de una modificación relevante en los parámetros electrocardiográficos (AU)

Introduction and objectives: There are scarce data on left atrial (LA) enlargement and electrophysiological features in athletes. Methods: Multicenter observational study in competitive athletes and controls. LA enlargement was defined as LA volume indexed to body surface area ≥ 34mL/m2. We analyzed its relationship with atrial electrocardiography parameters. Results: We included 356 participants, 308 athletes (mean age: 36.4±11.6 years) and 48 controls (mean age: 49.3±16.1 years). Compared with controls, athletes had a higher mean LA volume index (29.8±8.6 vs 25.6±8.0mL/m2, P=.006) and a higher prevalence of LA enlargement (113 [36.7%] vs 5 [10.4%], P <.001), but there were no relevant differences in P-wave duration (106.3±12.5ms vs 108.2±7.7ms; P=.31), the prevalence of interatrial block (40 [13.0%] vs 4 [8.3%]; P=.36), or morphology-voltage-P-wave duration score (1.8±0.84 vs 1.5±0.8; P=.71). Competitive training was independently associated with LA enlargement (OR, 14.7; 95%CI, 4.7-44.0; P <.001) but not with P-wave duration (OR, 1.02; 95%CI, 0.99-1.04), IAB (OR, 1.4; 95%CI, 0.7-3.1), or with morphology-voltage-P-wave duration score (OR, 1.4; 95%CI, 0.9-2.2). Conclusions: LA enlargement is common in adult competitive athletes but is not accompanied by a significant modification in electrocardiographic parameters (AU)

COVID-19: Some unresolved issues.

Two years after the COVID-19 pandemic, many uncertainties persist about the causal agent, the disease and its future. This document contains the reflection of the COVID-19 working group of the Official College of Physicians of Madrid (ICOMEM) in relation to some questions that remain unresolved. The document includes considerations on the origin of the virus, the current indication for diagnostic tests, the value of severity scores in the onset of the disease and the added risk posed by hypertension or dementia. We also discuss the possibility of deducing viral behavior from the examination of the structure of the complete viral genome, the future of some drug associations and the current role of therapeutic resources such as corticosteroids or extracorporeal oxygenation (ECMO). We review the scarce existing information on the reality of COVID 19 in Africa, the uncertainties about the future of the pandemic and the status of vaccines, and the data and uncertainties about the long-term pulmonary sequelae of those who suffered severe pneumonia.

COVID in Pediatric Age: an opinion paper.

The incidence of COVID in pediatrics was underestimated during the first months of the pandemic due to the oligosymptomatic nature of the infection in many children and the scarcity of diagnostic tests applied to this population. It is now accepted that children are infected and transmit the disease in the same way as adults. On the contrary, children have less severe and less lethal COVID, probably due to a lower maturity of the child's immune system, a lower number of ACE2 receptors and the lower presence of comorbidities in this population group. The development of a multisystemic inflammatory syndrome after SARS-CoV-2 infection in children, despite its rarity, is a very serious condition that frequently requires intensive care. Other less severe post-COVID manifestations have been described in children but are not yet well defined. COVID has had and continues to have a significant psychological impact on the children themselves, on their caregivers and on the exacerbation of pre-existing psychiatric conditions. We apply adult therapeutic principles to children but with very low levels of evidence. Information on the tolerability of the available medications in this population group is still scarce. The mortality of COVID in children is very low and generally affects children with significant comorbidities. There are, at present, three vaccines licensed for pediatric use which are compatible with all other vaccines applicable to children. In these circumstances, there has been much speculation about the indication for vaccination in the pediatric age group, but given its good tolerance, there are clinical and ethical reasons that, in our opinion, justify it.

Resultados del retrasplante cardiaco: subanálisis del Registro Español de Trasplante Cardiaco / Results of heart retransplantation: subanalysis of the Spanish Heart Transplant Registry

Introducción y objetivos: El retrasplante cardiaco (ReTC) representa un tema controvertido actualmente. Nuestro objetivo es describir y analizar los resultados del ReTC en España. Métodos: Análisis retrospectivo del Registro Español de Trasplante Cardiaco de 1984 a 2018. Se recogieron datos sobre donante, receptor, cirugía, inmunosupresión y supervivencia. La mortalidad por todas las causas o la necesidad de ReTC postrasplante fueron el objetivo principal. Se estudiaron diferencias en supervivencia según indicación, tiempo entre trasplantes y época del ReTC. Resultados: Se estudiaron en total 7.592 trasplantes cardiacos (TxC) y 173 (2,3%) ReTC (mediana de edad, 52,0 y 55,0 años respectivamente). La enfermedad vascular del injerto fue la indicación de ReTC más frecuente (42,2%) y 59 pacientes (80,8%) recibieron el ReTC más de 5 años después del trasplante inicial. El rechazo agudo y el fallo primario del injerto disminuyeron como indicaciones durante el periodo estudiado. La insuficiencia renal, la hipertensión, la necesidad de ventilación mecánica o balón intraaórtico y la mayor duración de la isquemia fría fueron más frecuentes en el ReTC. La mediana de seguimiento del ReTC fue 5,8 años. El ReTC tuvo peor supervivencia que el TxC (HR ponderado=1,43; IC95%, 1,17-1,44; p<0,001). El rechazo agudo (HR=2,49; IC95%, 1,45-4,27; p<0,001) se relacionó con el peor resultado. El ReTC más allá de 5 años del trasplante inicial presagia resultados similares a los del TxC primario (HR ponderado=1,14; IC95%, 0,86-1,50; p<0,001). Conclusiones: El ReTC se asoció con mayor mortalidad que el TxC, especialmente por rechazo agudo. El pronóstico del ReTC realizado más de 5 años después es similar al del TxC primario (AU)

Introduction and objectives: Heart retransplantation (ReHT) is controversial in the current era. The aim of this study was to describe and analyze the results of ReHT in Spain. Methods: We performed a retrospective cohort analysis from the Spanish Heart Transplant Registry from 1984 to 2018. Data were collected on donors, recipients, surgical procedure characteristics, immunosuppression, and survival. The main outcome was posttransplant all-cause mortality or need for ReHT. We studied differences in survival according to indication for ReHT, the time interval between transplants and era of ReHT. Results: A total of 7592 heart transplants (HT) and 173 (2.3%) ReHT were studied (median age, 52.0 and 55.0 years, respectively). Cardiac allograft vasculopathy was the most frequent indication for ReHT (42.2%) and 59 patients (80.8%) received ReHT >5 years after the initial transplant. Acute rejection and primary graft failure decreased as indications over the study period. Renal dysfunction, hypertension, need for mechanical ventilation or intra-aortic balloon pump and longer cold ischemia time were more frequent in ReHT. Median follow-up for ReHT was 5.8 years. ReHT had worse survival than HT (weighted HR, 1.43; 95%CI, 1.17-1.44; P<.001). The indication of acute rejection (HR, 2.49; 95%CI, 1.45-4.27; P<.001) was related to the worst outcome. ReHT beyond 5 years after initial HT portended similar results as primary HT (weighted HR, 1.14; 95%CI, 0.86-1.50; P<.001). Conclusions: ReHT was associated with higher mortality than HT, especially when indicated for acute rejection. ReHT beyond 5 years had a similar prognosis to primary HT (AU)

Pharmacological treatment of COVID-19: an opinion paper.

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.