Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

Endocarditis in patients with ascending aortic prosthetic graft: a case series from a national multicentre registry.

OBJECTIVES: Endocarditis in patients with ascending aortic prosthetic graft (AAPG) is a life-threatening complication. The purpose of this study was to examine the clinical presentation and prognosis of patients with AAPG endocarditis included in a large prospective infectious endocarditis multicentre study. METHODS: From January 2008 to April 2015, 3200 consecutive patients with infectious endocarditis according to the modified Duke criteria, were prospectively included in the 'Spanish Collaboration on Endocarditis Registry (GAMES)' registry. Twenty-seven definite episodes of endocarditis (0.8%) occurred in patients with AAPG. RESULTS: During the study period, 27 cases of endocarditis were detected in patients with AAPG. The median age of patients was 61 years [interquartile range (IQR) 51-68 years] and 23 (85.2%) patients were male. The median time from AAPG surgery to the episode of AAPG infection was 24 months (IQR 6-108 months). The most frequently isolated micro-organisms were coagulase-negative staphylococci and S. aureus (11 patients, 40.7%). Four patients (14.8%) underwent medical treatment, whereas surgery was performed in 21 (77.7%). Two patients (7.4%) died before surgery could be performed. The median hospital stay prior to surgery was 7 days (IQR 4-21 days). Surgery consisted of replacing previous grafts with a composite aortic graft (10 cases) or aortic homograft (2 patients), and removal of a large vegetation attached to the valve of a composite tube (1 case). Nine patients had an infected aortic valve prosthesis without evidence of involvement of the AAPG. Isolated redo-aortic valve replacement was performed in 8 (88.9%) of these patients. Reinfection occurring during 1 year of follow-up was not detected in any patient. Two patients (7.4%) died while awaiting surgery and 6 did so after surgery (22.2%). A New York Heart Association (NYHA) Class IV was associated with mortality in patients undergoing surgery (P < 0.019). CONCLUSIONS: Most cases of endocarditis in patients with AAPG occur late after initial surgery. Mortality rate of patients with AAPG endocarditis who undergo surgery is acceptable. NYHA Class IV before surgery is associated with an increased postoperative mortality.

Hidatidosis: aspectos epidemiológicos, clínicos, diagnósticos y terapéuticos / Hydatidosis: epidemiological, clinical, diagnostic and therapeutic aspects

La hidatidosis o equinococosis quística (EQ) es una zoonosis parasitaria causada por Echinococcus granulosus. Su ciclo vital incluye perros, ovejas y otros animales. La EQ tiene distribución mundial, con mayor prevalencia en zonas templadas. En España, Castilla y León, La Rioja, Navarra, Aragón y la costa mediterránea son las áreas donde se diagnostica más frecuentemente, aunque también se han publicado casos en otras regiones, como Cantabria. Los signos y síntomas de la EQ pueden deberse al efecto masa del quiste, su sobreinfección o reacciones de anafilaxia secundarias a su ruptura. Debido a su lento crecimiento, el diagnóstico habitualmente se realiza en la edad adulta, mediante los síntomas clínicos y las pruebas de imagen y serológicas. No hay consenso universal respecto al tratamiento de la EQ. Éste se basa en tres pilares fundamentales: cirugía, drenaje percutáneo y antiparasitarios (habitualmente albendazol). La elección del tratamiento más apropiado se basa en la sintomatología del paciente y las características del quiste (AU)

Hydatidosis or cystic echinococcosis (CE) is a parasitic zoonosis caused by Echinococcus granulosus. Its life cycle involves dogs, sheep and sometimes other animals. CE has a worldwide distribution, with greater prevalence in temperate zones. In Spain, Castile and León, La Rioja, Navarre, Aragón, and the Mediterranean coast are the areas where it is most commonly diagnosed, although there have also been published cases in other regions, such as Cantabria. Clinical signs and symptoms of EC may be related to the mass effect of the cyst, its superinfection or anaphylactic reactions secondary to its rupture. Because of its slow growth, diagnosis is usually made in adulthood by combining clinical symptoms with imaging and serological tests. There is no universal consensus on the management of CE. Treatment is based mainly on three pillars: medical treatment (mainly albendazole), surgery, and percutaneous drainage. The choice of the most appropriate approach is based on the patient’s symptoms and the characteristics of the cysts (AU)

Epidemiology and risk factors of infections after solid organ transplantation

La infección sigue siendo una complicación significativa tras el trasplante de órgano sólido (TOS). La incidencia de los diferentes patógenos varía ampliamente dependiendo de la presencia de factores específicos y, de acuerdo con esto, los pacientes pueden clasificarse en diferentes categorías de riesgo que precisarán estrategias profilácticas específicas para cada categoría. Deben tenerse en cuenta tanto los microorganismos de origen endógeno (colonización previa o infección latente) como los de nueva adquisición (infección primaria a partir del donante o del entorno). Las infecciones bacterianas predominan en los pacientes con estancias hospitalarias complejas o alteraciones anatómicas. Las infecciones virales, causadas tanto por virus oportunistas (citomegalovirus, virus de Epstein-Barr, virus BK, etc.) como por virus comunes (influenza, virus respiratorios, virus de la varicela zoster, etc.) son esenciales y pueden contribuir al rechazo crónico del trasplante. Las infecciones fúngicas no son habituales hoy en día, pero provocan una alta mortalidad y precisan profilaxis en un subgrupo de pacientes. Las infecciones parasitarias son una clara amenaza, principalmente en pacientes trasplantados que viajen a zonas endémicas. Los médicos que tratan a los receptores de TOS deben ser conscientes de estos factores de riesgo, que incluyen las características específicas del receptor, tipo de trasplante, microorganismo y planes de inmunosupresión (AU)

Infection remains a significant complication after solid organ transplantation (SOT). The incidence of various pathogens varies widely depending on the presence of specific factors, according to which patients can be classified into different risk categories that may merit tailored prophylaxis strategies. Both the endogenous origin of microorganisms (previous colonization or latent infection) and new acquisition (primary infection from donor or environment) should be considered. Bacterial infections predominate in patients with complex hospital stays or anatomical alterations. Viral infections, caused both by opportunistic (CMV, EBV, BKV, etc.) and common viruses (influenza, respiratory virus, VVZ, etc.), are of great importance, and may contribute to chronic rejection. Fungal infections are uncommon nowadays, but cause high mortality and deserve prophylaxis for a subset of patients. Parasitic infections are a clear threat, mainly in transplanted patients or those travelling to endemic areas. Physicians attending SOT recipients should be aware of these risk factors, which include specific host characteristics, type of transplantation, microorganism and immunosuppressive policy (AU)