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Introduction and objectives Noninvasive ventilation (NIV) has been shown to reduce the rate of endotracheal intubation and mortality in patients with acute heart failure (AHF). However, patients with AHF secondary to acute coronary syndrome/acute myocardial infarction (ACS-AMI) have been excluded from many clinical trials. The purpose of this study was to compare the effectiveness of NIV between patients with AHF triggered by ACS-AMI and by other etiologies. Methods Prospective cohort study of all patients with AHF treated with NIV admitted to the intensive care unit for a period of 20 years. Patients were divided according to whether they had ACS-AMI as the cause of the AHF episode. NIV failure was defined as the need for endotracheal intubation or death. Results A total of 1009 patients were analyzed, 403 (40%) showed ACS-AMI and 606 (60%) other etiologies. NIV failure occurred in 61 (15.1%) in the ACS-AMI group and in 64 (10.6%) in the other group (P = .031), without differences in in-hospital mortality (16.6% and 14.9%, respectively; P = .478). Conclusions The presence of ACS-AMI as the triggering cause of AHF did not influence patients with acute respiratory failure requiring noninvasive respiratory support .

Objective To evaluate the influence of ABO and Rh blood groups on morbidity among SARS-CoV-2 infected pregnancies. Design Prospective observational study. Setting 78 centers of the Spanish Obstetric Emergency Group. Population Pregnant women with SARS-CoV-2 tested with polymerase-chain-reaction between 26-February and 5-November 2020. A cohort of 1278 SARS-CoV-2(+) pregnant women was analyzed and a concurrent comparison group of 1453 SARS-COV-2(−) patients was established. Methods Data were collected from medical charts. SARS-COV-2(+) was compared with SARS-COV-2(−) for differences in distribution of blood groups. We performed multivariate analysis, controlling for maternal age and ethnicity, to evaluate association of ABO and Rh blood groups with maternal and perinatal outcomes in SARS-CoV-2(+) patients with adjusted odds ratios (aOR) and 95% confidence intervals (CI). Main outcomes measures Medical morbidity: Symptomatic COVID-19 and medical complications. Obstetric outcomes: caesarean delivery, preterm deliveries, preterm premature rupture of membranes (PPROM), hemorrhagic events, pre-eclampsia, maternal and neonatal mortality, stillbirth. Results Differences were noted between blood types and Rh for age and ethnicity comparing SARS-CoV-2(+) and SARS-CoV-2(−) groups (p

Resumo Objetivo Definir a eficácia da biópsia vertebral percutânea guiada por fluoroscopia. Métodos Este é um estudo prospectivo de pacientes com síndrome de destruição vertebral em uma instituição. Os pacientes foram submetidos a biópsias vertebrais transpediculares percutâneas guiadas por fluoroscopia, com obtenção de tecido ósseo e tecido do disco intervertebral, para estudo histopatológico e microbiológico. Idade, sexo, segmento vertebral, estado neurológico, e resultados de biópsia e de cultura foram analisados. Resultados A idade média dos pacientes foi de 53,8 anos (gama: 2 a 83 anos), e o principal local acometido da coluna foi a segmento lombar, em 62% dos casos. Segundo a escala de disfunção da American Spinal Injury Association (ASIA), no pré-operatório, 49% dos pacientes foram classificados como ASIA E, e 100% apresentavam dor. A etiologia definitiva foi identificada em 83% dos pacientes. A etiologia foi agrupada em três categorias: infecciosa, neoplásica, e degenerativa (osteoporótica). O grupo infeccioso era composto por 36% dos pacientes da amostra, e Staphylococcus aureus foi o agente mais comumente identificado; em 34,9% dos casos, a etiologia era neoplásica, principalmente mieloma múltiplo e doença metastática por câncer de próstata; 21,7% dos pacientes apresentavam osteoporose. O tempo cirúrgico médio foi de 47,5 minutos, e a perda média de sangue foi de 10 mL. Nenhuma complicação foi relatada. Conclusão Nesta série, a biópsia percutânea transpedicular guiada por fluoroscopia teve 83% de eficácia no diagnóstico etiológico da síndrome de destruição vertebral. Este procedimento minimamente invasivo deve ser considerado bom, fácil, barato e reprodutível, com baixo risco de complicações em curto e longo prazos.

To prospectively assess the diagnostic value of intestinal ultrasound (US) compared to computerized tomography (CT) in differentiating uncomplicated and complicated acute colonic diverticulitis (ACD). During a period of 14 months patients referred to the department of Radiology with clinical suspicion of ACD underwent an US examination. All confirmed US ACD diagnosis were included and subsequently underwent an emergency abdominal CT, used as gold standard. The WSES (World Society for Emergent Surgery) classification of diverticulitis was used. Diverticulitis was prospectively classified as either uncomplicated or complicated. Sensitivity, specificity, positive predictive value, and negative predictive values of US were evaluated. Before CT scan, the radiologist indicated whether they would have required or not a complementary CT scan, based on US findings. Of the 240 patients included in our study, 71 (29.6%) were Stage 0, 127 (53%) Stage 1A, and 42 (17.5%) were moderate-severe ACD (stages 1B, 2A, 2B, 3 and 4). The sensitivity of US for diagnosing complicated ACD was 84% and specificity of 95.8%. Most patients (24 of 27) misclassified by US as uncomplicated diverticulitis were classified on CT as stage 1A. From the 148 cases in which the radiologist considered CT unnecessary, only 3 of these revealed signs of complicated ACD on CT; none of them required emergency surgery. US is an effective technique to differentiate complicated from uncomplicated ACD. Our results suggest that US, may be a valuable alternative to CT for the initial radiologic evaluation in patients with clinical suspicion of ACD.

Ceftobiprole is a broad-spectrum, fifth-generation cephalosporin currently approved for community-acquired and non-ventilator-associated hospital-acquired pneumonia. High bactericidal and anti-biofilm activity has been exhibited in in vitro and animal models. This, together with its synergism with other antibiotics against gram-positive bacteria, makes it an ideal candidate for treatment of complex infections, such as those associated with devices or infective endocarditis. More clinical data are needed to achieve drug positioning.

espanolLa ecografia tiene un excelente rendimiento diagnostico tanto cuando se sospecha una enfermedad de Crohn como en la valoracion de la actividad o en determinar su extension y localizacion, muy similar a otras exploraciones como resonancia magnetica o tomografia computarizada. Tiene una buena correlacion con las lesiones endoscopicas y permite la deteccion de complicaciones como estenosis, fistulas o abscesos. Complementa a la colonoscopia en el diagnostico y dada su tolerancia, coste e inmediatez, es una buena herramienta para la monitorizacion de la enfermedad. En la colitis ulcerosa su papel es menos relevante, limitandose a valorar la extension y actividad cuando no sea posible o haya dudas con otras tecnicas diagnosticas. A pesar de sus ventajas, su empleo en la enfermedad inflamatoria intestinal (EII) no esta muy extendido en nuestro pais. Por este motivo, el presente documento revisa las virtudes e inconvenientes de la tecnica para favorecer su conocimiento e implantacion en las Unidades de EII. EnglishUltrasound has an excellent diagnostic performance when Crohn's disease is suspected, when performing an activity assessment, or determining the extension and location of Crohn's disease, very similar to other examinations such as MRI or CT. It has a good correlation with endoscopic lesions and allows the detection of complications such as strictures, fistulas or abscesses. It complements colonoscopy in the diagnosis and, given its tolerance, cost and immediacy, it can be considered as a good tool for disease monitoring. In ulcerative colitis, its role is less relevant, being limited to assessing the extent and activity when it is not possible with other diagnostic techniques or if there are doubts with these. Despite its advantages, its use in inflammatory bowel disease (IBD) is not widespread in Spain. For this reason, this document reviews the advantages and disadvantages of the technique to promote knowledge about it and implementation of it in IBD Units.

Ultrasound has an excellent diagnostic performance when Crohn's disease is suspected, when performing an activity assessment, or determining the extension and location of Crohn's disease, very similar to other examinations such as MRI or CT. It has a good correlation with endoscopic lesions and allows the detection of complications such as strictures, fistulas or abscesses. It complements colonoscopy in the diagnosis and, given its tolerance, cost and immediacy, it can be considered as a good tool for disease monitoring. In ulcerative colitis, its role is less relevant, being limited to assessing the extent and activity when it is not possible with other diagnostic techniques or if there are doubts with these. Despite its advantages, its use in inflammatory bowel disease (IBD) is not widespread in Spain. For this reason, this document reviews the advantages and disadvantages of the technique to promote knowledge about it and implementation of it in IBD Units. (C) 2020 The Authors. Published by Elsevier Espana, S.L.U.

Imaging techniques play a fundamental role in the initial diagnosis and follow-up of inflammatory bowel disease. Intestinal ultrasound has high sensitivity and specificity in patients with suspected Crohn's disease and in the detection of inflammatory activity. This technique enables the early diagnosis of intra-abdominal complications such as stenosis, fistulas, and abscesses. It has also proven useful in monitoring the response to treatment and in detecting postsurgical recurrence. Technical improvements in ultrasound scanners, technological advances such as ultrasound contrast agents and elastography, and above all increased experience have increased the role of ultrasound in the evaluation of the gastrointestinal tract. The features that make ultrasound especially attractive include its wide availability, its noninvasiveness and lack of ionizing radiation, its low cost, and its good reproducibility, which is important because it is easy to repeat the study and the study is well tolerated during follow-up. This review summarizes the role of intestinal ultrasound in the detection and follow-up of inflammatory bowel disease.

Cryptococcus species are environmental yeasts, with a worldwide distribution and remarkable environmental adaptation. Although many species do not cause disease, C. neoformans and C. gattii are causative agents of cryptococcosis, a life threatening infection and a significant public health problem worldwide. Infection especially affects immunocompromised animals and humans. In wildlife, cryptococcosis appears to be more prevalent in captive populations. The objective of this study was to assess whether apparently healthy quokkas (Setonix brachyurus) harbor Cryptococcus spp. Using cultural and molecular methods, we studied yeasts isolated from nasal swabs collected from 130 free-ranging quokkas on Rottnest Island (RI, n = 97) and the mainland (n = 33) of Western Australia. Unspeciated Cryptococcus spp. (from four quokkas), C. neoformans var. grubii (serotype A) (two quokkas) and C. magnus (one quokka) were isolated from the nasal lining of apparently healthy quokkas from RI. Cryptococcus neoformans var. grubii was isolated from animals captured in a human-populated area on RI. There was no significant effect of the presence of Cryptococcus on the results of haematology, blood chemistry, peripheral blood cell morphology or clinical examination. To the best of our knowledge, this is the first documented isolation of C. neoformans var. grubii (serotype A) and C. magnus in a free-ranging macropod in Western Australia. The public health implications of this finding should be further explored.

Introduction The present study aimed to evaluate the short- and mid-term outcomes of laparoscopic colon-first staged resection for colorectal cancer (CRC) and colorectal cancer liver metastases (CRCLM). Methods This study included patients with metastatic CRC who underwent laparoscopic surgical staged resection for the primary tumor and CRCLM between June 2013 and December 2018. Data collection included the baseline patient's and tumor features, the perioperative and histopathologic outcomes from both surgical procedures, and the oncologic follow-up. Results Twenty-five patients were eligible for the study. Three major and 22 minor laparoscopic liver resections were performed following laparoscopic CRC surgery. Five patients required conversion to laparotomy during CRCLM resection, but no conversion was needed for the colorectal procedures. The rate of severe intraoperative complications (CLASSIC grade III-IV) was 8% and 16% during CRC and CRCLM resection, respectively. Three patients (12%) developed major postoperative complications (Clavien-Dindo grade > III) after both interventions, including one death due to intraoperative bleeding. During a median follow-up of 30 months, 15 patients were diagnosed with disease recurrence. The 3-year disease-free survival and overall survival were 33.3% and 73.9%, respectively. Conclusions Laparoscopic staged resection for CRC and CRCLM is safe, feasible, and offers acceptable midterm oncological outcomes in patients with metastatic colorectal cancer.

Background. Bilateral traumatic hip dislocation in children is a very rare orthopedic emergency. Few case reports are available in literature. Clinical case. A 4-year-old male child case with a trivial mechanism of injury is presented. Closed reduction in emergency department was achieved after 24 hours of injury, he was placed on Bucks skin traction for 4 days and during 4 weeks in a spica cast. There was not either clinical sign nor images of early or late complications during follow up until he reached skeletal maturity. Discussion. Hip dislocation in children is a rare emergency with an incidence of 0.8 cases per million per year, its treatment should not be delayed to minimize late complications such as osteonecrosis, recurrent dislocations, osteoarthritis, neurological lesions, coxa magna and heterotopic ossification. The reported incidence for hip osteonecrosis is 36.4% for late (6 hours) and 8.2% after early (6 hours) reduction. After 12 years of follow up no complication was found although the reduction was made 24 hours later. Conclusions. After immediate reduction a 4 to 6 weeks immobilization period is an effective treatment. Close monitoring to timely identify and treat any further complication is mandatory.

Crohn's disease is a chronic inflammatory bowel disease characterized by periods of relative inactivity alternating with acute flare-ups. Imaging techniques play a fundamental role in the diagnosis and follow-up of Crohn's disease, providing information on the extent of disease, disease activity, and the presence of extramural complications. Because of the frequent re-evaluation required by the relapsing nature of Crohn's disease and the relative young age at which most patients are diagnosed, techniques that use ionizing radiation are best avoided in monitoring this population. Thus, magnetic resonance enterography (MRE) and ultrasonography (US) are the preferable techniques. Various studies have demonstrated that US is accurate in assessing the gut. Despite some clear advantages over MRE, US has long been underused in the evaluation of intestinal disease. This review presents an overview of the main imaging findings in Crohn's disease, correlating representative US images with MRE and surgical pathology specimens. We conclude that US reliably depicts both bowel-related and mesenteric features of Crohn's disease and US findings correlate strongly with MRE findings.

Esta investigación es de carácter cuantitativo, con un nivel descriptivo y correlacional cuyo objetivo fue analizar la relación entre el componente intelectual y nutricional en un grupo de 76 menores escolarizados de una institución educativa de carácter oficial seleccionada por conveniencia, 38 sujetos hicieron parte del grupo control (sin desnutrición) y 38 conformaron el grupo caso (con desnutrición crónica). La evaluación clínica de la capacidad intelectual se realizó a través de la prueba RIAS; además de la valoración nutricional; de acuerdo con los resultados se encontró un menor desempeño en los sujetos tanto del grupo caso como del control a nivel de las escalas de inteligencia verbal, no verbal e índice de memoria; sin embargo, no se presentaron diferencias significativas en los grupos en funcion del componente intelectual. Por lo anterior se concluye que al investigar el factor de implicación nutricional en los menores se debe tener en cuenta el análisis de otro tipo de variables como es el psicosocial la cual podría estar explicando el desempeño análogo obtenido por los grupos evaluados.

Human TPI (HsTPI) is a central and essential glycolytic enzyme for energy supply and is overexpressed in cancer cells. Here, we investigated HsTPI as a potential target for inducing cell death in triple-hormone receptor-negative breast cancer, which is highly dependent on glycolysis, and therapies for its treatment are limited. We found endogenous accumulation of deamidated HsTPI in human breast cancer cells, which might be caused by the lower activity of the HsTPI-degrading caspase-1 in breast cancer cells.In silicoandin vitroanalyses of deamidated HsTPI demonstrated the efficacy of thiol-reactive drugs in blocking enzyme activity. The cancer cells were selectively programmed to undergo apoptosis with thiol-reactive drugs by inducing the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs).In vivoin mice, the thiol-reactive drug effectively inhibited the growth of human tumors by targeting HsTPI as underlying mechanism. Our findings demonstrate deamidated HsTPI as a novel target to develop therapeutic strategies for treating cancers and other pathologies in which this post-translationally modified protein accumulates.

SUMMARYBackgroundSOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralizing IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralizing antibodies.MethodsFrom March 8th to September 30th, 2021 we conducted in Havana, Cuba a multicentre randomized, double-blind, placebo-controlled, phase-3 trial evaluating two doses of SOBERANA-02 and a heterologous scheme with one dose SOBERANA-Plus added to it. Participants 19–80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 occurring at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose.FindingWe included 44·031 participants in a context of Beta VOC predominance, with this variant being gradually replaced by Delta near the trial end. Vaccine efficacy in the heterologous combination was 92·0% (95%CI 80·4–96·7) against symptomatic and 100% against severe COVID-19. Two doses of SOBERANA-02 was 69·7% (95%CI 56·5-78·9) and 74·9% (95%CI 33·7-90·5) efficacious to protect against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe AEs was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient.InterpretationOur results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC dominance and that they constitute an attractive, feasible option for low- and middle-income countries, where besides financial constraints ease of vaccine storage and distribution is of concern.FundingThis study received funds from Finlay Vaccine Institute and National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020–20). of Ministry of Science, Technology and the Environment (Contract Project-2020-20) in Cuba.

Axillary lymph node involvement is still an important predictor of recurrence and survival in breast cancer. Axillary staging was classically done by axillary lymph node dissection (ALND), but the introduction of sentinel lymph node biopsy (SLNB) has led to a progressive and continuing de-escalation in its use. Therefore, SLNB can now be considered the standard procedure for axillary staging in clinically N0 patients. Different studies have also begun to report that a positive sentinel node does not always require ALND, reducing the morbidity derived from this technique. Fears that this sentinel node approach might not be accurate for neoadjuvant chemotherapy have been allayed by several studies showing that post-neoadjuvant SLNB in clinical N0 patients reduces the rate of ALND. This approach benefits from axillary pathological complete response with an acceptable false-negative rate. By contrast, however, cN1 disease still requires that we optimise the technique to reduce the rate of false negatives. Currently, SLNB is the best method for axillary staging in breast cancer, allowing patients to be treated according to risk of recurrence, and with good evidence that morbidity is lower than with other more radical techniques.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses ( 800 mg), either at the viral (1–7 days post-symptom onset), early inflammatory (8–15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37–4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4–15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400–800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Introduction: Diabetes Mellitus type 2 (DM2) is a chronic disease characterized by absolute or relative failure of a hormone produced by the pancreas, called insulin and is characterized by an alteration in the metabolism of proteins, fats and carbohy- drates [1-3]. Objective: Identify whether the high birth weight in children aged 7 to 11 years is a predictor for the association of overweight and obesity with diabetes mellitus. Methods: A descriptive study was conducted with a design case - control with children born between January 1992 and December 1995. Results: Encontramos in the study group that overweight 2.85% is pre diabetic and 1, 44% diabetic, in obese 1.42% is pre-diabetic and diabetic 3.56%, where there Fisher’s P = 0.0002 association between nutritional status (overweight, obesity) pre diabetes and diabetes; in the control group, in overweight we found that 3.00% diabetic and diabetic pre 0.00% in obese diabetic pre 1.00% and 2.00% with a diabetic Fisher’s P = 0, 0343, existing association between nutritional status and pre-diabetes and diabetes in this group association between nutritional status and diabetes was also found, so there is no difference in the two groups, but we must note that in the study group his association was stronger. In our study is not high birth weight per, association for diabetes. Conclusion: The high birth weight (macrosomia) does not constitute per se a predic- tor for the association of malnutrition by excess and diabetes, association for excess malnutrition and diabetes in both groups.

Hospitalizations for ischemic heart disease have an uneven distribution throughout Spain, in which Asturias is the community with the highest rates of acute myocardial infarction (AMI) and angina pectoris (AP). Cardiovascular diseases are related to environmental, socioeconomic and previous medical conditions, which result in geographical differences in the incidence of hospital admissions and mortality. The goal of this study was to describe the spatial distribution of hospital admissions in the central area of Asturias and explore the existence of spatial patterns or clusters. Urgent hospital admissions for AMI and angina AP in the hospitals of the central area of Asturias were registered, geocoded and grouped by census tracts. Standardized admission ratio, smoothed relative risk, posterior risk probability and analysis of spatial clusters between relative risks throughout the study area were calculated and mapped. Geographical differences were found in the distribution of hospital admissions for AMI and AP across the area and between men and women. The cluster analysis indicated contiguous census tracts with high relative risk values in the northwest region of the study area and low relative risk in the east, particularly for men. The geographical analysis shows the existence of patterns and spatial clusters in the incidence of AMI and AP, for both men and women, in the central area of Asturias.

Background In 2012, the central government of Spain enacted Royal Decree-Law (RDL) 16/2012 and Royal Decree (RD) 1192/2012, which abolished universal healthcare coverage, thus limiting access to care for undocumented immigrants. Free health care was also no longer granted to anyone who has never been employed. In this context, this study investigated the prevalence of late HIV diagnoses (LHDs) among immigrants living in Spain vs. native-born Spaniards. Methods Data (n = 5943) from the 2010 to 2015 Cohort of the Spanish AIDs Research Network were used, including HIV-positive and antiretroviral therapy (ART)-naïve patients throughout Spain. Multivariate logistic models were fitted to compare the prevalence of LHD among the groups, adjusting for covariates. Results The prevalence of LHD in the total sample was 39.5%. Compared with native-born Spaniards (n = 4445), immigrants (n = 1488) were more likely to have LHD (37.4% vs. 45.7%, respectively; P < 0.001). Multivariate analysis showed that the prevalence ratio of LHD among immigrants vs. native-born Spaniards was 1.15 [95% confidence interval (CI), 1.02–1.28], after adjusting for covariates. This disparity widened from 2010 to 2011 (APR = 1.14, 95% CI, 1.02–1.29) to 2012–15 (APR = 1.28, 95% CI, 1.17–1.39), although the change was not statistically significant. Conclusions Immigrants in Spain had a higher risk of LHD compared with native-born counterparts. LHD is an important healthcare marker due to the positive benefits of early HIV diagnosis, including prevention, improvements in health outcomes and decreases in overall cost of treatment. More research is needed on the causes of the disparity and potential social and policy interventions to reduce the prevalence of LHD among immigrants.

Coronavirus disease-19 (COVID-19) is perhaps the most worrisome pandemic in the 21st century, having entailed devastating consequences for the whole society during the last year. Different studies have displayed an existing association between pregnancy and COVID-19 severity due to the various physiological changes that occur during gestation. Recent data identified maternal country of origin as an important determinant of COVID-19 presentation in pregnant women. However, the explanation of this fact remains to be fully elucidated. Therefore, the purpose of this work is to analyze the possible relationship between Human Development Index (HDI) of maternal country of origin with the morbimortality of pregnant women and their newborns. Here, we conducted a multicentric, ambispective, observational case-control study (1:1 ratio) and compare with the HDI of each country (group 1—very high HDI, group 2—high HDI, group 3—medium HDI, and group 4—low HDI). In total, 1347 pregnant women with confirmed SARV-CoV-2 infection (cases) were enrolled, and each was paired with one control to give a total number of 2694 participants from 81 tertiary care centers. Among the women with SARS-CoV-2 infection, more cases were produced of perinatal mortality, overall maternal morbidity, COVID-19 maternal morbidity, C-sections, hypertensive maternal morbidity, and perinatal morbidity. Our results described an inverse association between HDI and maternofetal morbidity and mortality. Moreover, the countries with an HDI lower than 1 showed higher rates of patients with maternal COVID-19-related morbidity (6.0% vs. 2.4%, p &lt, 0.001), a need for oxygen therapy (4.7% vs. 1.8%, p &lt, 0.001), and maternal ICU admission (2.6% vs. 1.0%, p = 0.007). Compared to other risk factors such as overweight, obesity, preexisting and obstetric comorbidities, HDI emerged as an independent risk factor explaining much of the increased maternal–perinatal morbidity and mortality detected in our group of cases. Further research is needed to establish to confirm the real impact of this factor and its components on pregnancy outcomes.

Free-range pigs are in the highest risk to acquire cysticercosis in endemic rural locations, although the behavioral and physiological responses to the infection are known to vary widely between pigs. Those animals reared in semi-confinement showed a group behavior that allows us to follow the herd to assess the risks of contact with the parasite. This study is aimed to determine the movement and feeding habits of pig groups raised under semi-confinement conditions, using minimally invasive procedures, applying trajectory analysis to different herds in rural settings. Pig population and subpopulations were characterized, and their movement was evaluated in two seasons of the year, using a global positioning system (GPS). Our results indicate that pig groups are formed based on human ownership and the establishment of family bonds with each other. Each group interacts with other groups in specific sites of the village. Significant differences were found in the time and distance covered by pigs in the dry and rainy seasons (P < 0.05), and the distance travelled by different groups were found to take place in repetitive, well-defined spaces that include moving through sewage, landfills, and open defecation sites. Due to this stability, the trajectories covered by pigs could be useful as indicators of risk factors linked to the exposure of pigs to Taenia solium

[Background] The aim of this study was to describe the natural history of acute Q fever, including its clinical and serological evolution and progression to chronic Q fever., [Methods] Observational cohort study (January 2011–September 2020) performed at Valme University Hospital (Seville, Spain). Inclusion criteria: (1) patients aged ≥18 years; (2) acute Q fever diagnosis, defined as suggestive symptoms in the presence of phase II immunoglobulin G (IgG) titer >1:256; (3) at least 6 months’ follow-up after the acute Q fever episode. The incidence of seroconversion to a chronic Q fever serological pattern, defined as phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis, was assessed., [Results] During the study period, 117 patients were included. Thirty-four (29%) patients showed phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis. All patients with classic serological criteria for chronic Q fever diagnosis remained asymptomatic despite no specific treatment, with a median (quartile 1–quartile 3 [Q1–Q3]) follow-up of 26.5 (14–44) months in this subgroup. No cases of Q fever endocarditis nor other persistent focalized infection forms were observed during the study period., [Conclusions] A significant proportion of acute Q fever patients develop classic serological criteria for chronic Q fever diagnosis in the absence of additional data of chronic Q fever. Consequently, phase I IgG cutoff titers >1:800 should not be used as a criterion to consider such a diagnosis. The incidence of persistent focalized infection forms after acute Q fever is extremely low and does not justify the use of prophylaxis strategies.

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

During 2020, Coronavirus Disease-19 (COVID-19) incidence fluctuated in two clear waves across the spring and autumn periods. This study was designed to compare the maternal and perinatal clinical outcomes in obstetrics patients with COVID-19 between the two waves of infection in Spain. We conducted an observational, analytical, ambispective cohort study with longitudinal follow-up of mothers with confirmed SARV-CoV-2 infection from different hospitals in our country between March–November 2020. We recruited 1295 pregnant women with SARS-CoV2 infection from 78 hospitals, 846 (65.3%) of whom were diagnosed during the first wave and 449 (34.7%) during the second wave. Our results show that patients developing COVID-19 during the first wave had more symptoms at triage, early in pregnancy with greater rates of COVID-19-related maternal morbidity, caesarean section and preterm birth in the first wave. We register two cases of maternal mortality and only during the first wave. Maternal morbidity events showed a strong link to perinatal mortality events in the first wave compared to the second wave, in which maternal morbidity was more associated with pneumonia. Likewise, maternal morbidity showed a strong correlation with perinatal morbidity events in both waves. We describe the differences between the patients’ profiles and management between the two waves and related to maternal and perinatal outcomes. Differences were also observed in the management of pregnant women with COVID-19. Thus, there were fewer caesarean sections, and maternal and perinatal morbidity events were reduced in the second wave, while the impacts of respiratory symptoms and their severity, including a greater need for maternal treatment, were greater in this last period. Identifying the impact that changes in the profile as well as in the treatment have on maternal–perinatal morbidity and mortality will help improve the well-being of our patients and their newborns.

Introduction The prognosis of lung cancer (LC) correlates directly with the stage of the disease at the time of diagnosis. Material and methods We performed low-dose CT (LDCT) in asymptomatic individuals ≥50 years old, smokers or former smokers of ≥10 pack-years, with no history of cancer. We followed an evaluation algorithm, according to the size and morphology of the nodules. The appropriate treatment for the LC diagnosis was given and patients were followed up for 5 years. Results We studied 4951 individuals (65.4% males) with an average age of 56.89±5.26 years; 550 presented nodules. Of the 3891 nodules detected, 692 (19.57%) were considered positive, and 38 tumors (36 LC) were identified. In the annual follow-up, nodules were found in 224 subjects, 288 (7.91%) of which were positive (13 LC). In 80%, the study was performed with LDCT, and biopsy was indicated in 5.8% (baseline) and in 7.6% (annual) of the positive nodules. Prevalence was 0.89 and incidence was 0.1%. The sensitivity, specificity, PPV and NPV in the baseline study were 92.31, 89.54, 6.55 and 99.93%, respectively, and in the annual study, they were 76.92, 95.7, 4.52 and 99.94%, respectively. A total of 52 tumors were detected (49 LC), 25 (52.08%) in stage I. The 5-year overall survival rate for LC was 58.5% and cancer-specific survival was 67.1% (75.8% in surgical patients). Conclusion LDCT integrated into an elaborate nodule detection and evaluation program is a useful tool for diagnosing early-stage LC.

espanolIntroduccion La pancreatectomia izquierda laparoscopica (PIL) es una tecnica quirurgica cada vez mas utilizada para el tratamiento de lesiones benignas y malignas del pancreas izquierdo. Analizamos los resultados de nuestra serie de PIL para el tratamiento de las lesiones primarias de cuerpo y cola pancreaticos. Metodos Desde noviembre de 2011 a noviembre de 2017 se han intervenido 18pacientes por lesiones primarias del pancreas realizandose una pancreatectomia distal laparoscopica. En todos los casos se dejo un drenaje intraabdominal y se siguieron las recomendaciones del International Study Group for Pancreatic Fistula (ISGPF). Resultados La mediana de edad fue de 66,5anos (RIQ46-74). De las 18 pancreatectomias izquierdas, cuatro se realizaron con preservacion esplenica, una de ellas una pancreatectomia central. Hubo dos conversiones. La mediana del tiempo operatorio fue de 247,5min (RIQ242-275). La mediana de estancia hospitalaria fue de 7dias (RIQ6-8). A los 90dias se detectaron complicaciones en cinco pacientes: tres gradoII, una gradoIII y una gradoV segun la clasificacion modificada de Clavien-Dindo. Hubo una fistula pancreatica gradoB y cuatro pacientes reingresaron por colecciones peripancreaticas. La anatomia patologica evidencio malignidad en el 38,9% de los casos, presentando todos ellos margenes negativos. Conclusiones La PIL puede ser considerada tecnica de eleccion para el tratamiento de las lesiones pancreaticas benignas y una alternativa al abordaje abierto para pacientes seleccionados diagnosticados de neoplasias malignas, siempre que la realicen cirujanos con experiencia en cirugia pancreatica y laparoscopica avanzada. EnglishIntroduction Laparoscopic left-sided pancreatectomy (LLP) is an increasingly used surgical technique for the treatment of benign and malignant lesions of the left side of the pancreas. The results of LLP as a treatment for primary pancreatic lesions of the head and tail of the pancreas were evaluated. Methods From November 2011 to November 2017, 18 patients underwent surgery for primary lesions of the pancreas by means of a laparoscopic distal pancreatectomy. An intra-abdominal drain tube was used in all cases, and the recommendations of the International Study Group for Pancreatic Fistula (ISGPF) were followed. Results The mean age was 66.5years (IQR 46-74). Among the 18 left pancreatectomies performed, four were with splenic preservation, and one was a central pancreatectomy. There were two conversions. The median surgical time was 247.5minutes (IQR 242-275). The median postoperative hospital stay was 7days (IQR 6-8). After 90days, complications were detected in five patients: three gradeII, one gradeIII and one gradeV according to the modified Clavien-Dindo classification. There was one gradeB pancreatic fistula, and four patients had to be readmitted to hospital because of peripancreatic collections. The anatomic pathology diagnosis was malignant neoplasm in 38.9% of cases, all of them with negative resection margins. Conclusions LLP can be considered the technique of choice in the treatment of primary benign pancreatic lesions and an alternative to the open approach in selected patients diagnosed with malignant pancreatic lesions.

Malignant tumors originate from somatic mutations and other genomic and epigenomic alterations, which lead to loss of control of the cellular circuitry. These alterations present patterns of co‐occurrence and mutual exclusivity that can influence prognosis and modify response to drugs, highlighting the need for multitargeted therapies. Studies in this area have generally focused in particular malignancies and considered whole genes instead of specific mutations, ignoring the fact that different alterations in the same gene can have widely different effects. Here, we present a comprehensive analysis of co‐dependencies of individual somatic mutations in the whole spectrum of human tumors. Combining multitesting with conditional and expected mutational probabilities, we have discovered rules governing the codependencies of driver and nondriver mutations. We also uncovered pairs and networks of comutations and exclusions, some of them restricted to certain cancer types and others widespread. These pairs and networks are not only of basic but also of clinical interest, and can be of help in the selection of multitargeted antitumor therapies. In this respect, recurrent driver comutations suggest combinations of drugs that might be effective in the clinical setting, while recurrent exclusions indicate combinations unlikely to be useful. Fil: Ochoa, Soledad. Fundación Instituto Leloir; Argentina Fil: Martinez Perez, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina Fil: Zea, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina Fil: Molina Vila, Miguel Angel. Hospital Universitario Quirón Dexeus; España Fil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina

Purpose To investigate the association of keratoconus (KC) with meibomian gland dysfunction (MGD) and to describe the epidemiological characteristics of MGD in this disease. Methods In this observational study, 120 KC patients seen in the Department of Ophthalmology of the Complexo Hospitalario Universitario de Santiago de Compostela and 87 controls were analyzed. The Ocular surface disease index (OSDI) questionnaire was administered and several DED tests and an evaluation of the meibomian glands and lid margin were performed. MGD signs and DED tests were compared between the groups. Symptoms were further analyzed in patients and controls with and without MGD. Results KC was significantly associated with MGD after adjusting for age and sex [adjusted odds ratio (ORa), 2.40]. The frequency of MGD in KC patients [59 (49.2%) KC patients and 25 (28.7%) controls had MGD] correlated with the severity of KC (r = 0.206) (P = 0.020). Mean OSDI score in KC patients with and without MGD was 31.1 ± 24.1 and 35.2 ± 26.0 (P = 0.326), and 17.2 ± 22.7 and 13.3 ± 14.1 in controls with and without it (P = 0.366). The most common MGD signs coincided in both groups. Staining with fluorescein (P = 0.000) and lissamine green (P = 0.019) was higher in KC patients, but no differences were detected with TBUT (P = 0.116) or the Schirmer test (P = 0.637). Hypersecretory MGD was the most prevalent variant in both groups. Conclusions MGD and DED are common in KC patients. MGD correlates with the severity of KC and is indistinguishable from MGD in patients without KC. No association was found with symptoms. Patients with KC should be screened for MGD because of its possible clinical implications. Further research is needed to clarify the role of MGD in KC patients.

Background and aims Contrast-enhanced ultrasound [CEUS] is reported to be superior to wall thickness or colour Doppler imaging [CDI] in predicting disease activity using endoscopy as the reference standard. Our aims were to determine in patients with Crohn's disease [CD] whether the evaluation of wall thickness or CDI before CEUS examination could help to decide when the injection of contrast agent is justified as a means for detecting disease activity as determined at endoscopy, without reducing the accuracy of ultrasound. Methods In total, 180 patients with CD underwent both colonoscopy and ultrasound, including mural thickness, CDI and CEUS evaluation, prospectively as part of clinical care. A receiver operating characteristic curve was constructed to determine the area under the curve and the best cutoff of wall thickness and ultrasound enhancement value to discriminate between endoscopically active and inactive disease. Several analyses were carried out to determine which parameter or combination of parameters best detected endoscopic activity. Results Comparative evaluation of the different analysis showed that wall thickness alone classified 76.6% of patients correctly, CDI alone 72.7%, and thickness plus CDI 72.2%. The use of CEUS significantly improved the diagnosis of active disease: CEUS alone correctly classified 164 of 180 patients [91.1%], combined analysis of CDI and CEUS 165 of 180 [91.7%], and combined analysis of thickness, CDI and CEUS 164 of 180 [91.1%], without significant differences. Patients with CDI grade 2 or 3 showed a predictive positive value of 97% to detect disease activity, similar to CEUS [100%]. Conclusion CEUS is the most reliable ultrasound criterion for endoscopic disease activity. However, the use of a contrast agent is probably not justified to assess disease activity for patients with CDI grade 2/3.

Objective Sphenopetroclival (SPC) meningiomas are considered among the most complex skull-base neoplasms to approach surgically. We aim to determine whether some SPC meningiomas can be safely and effectively treated using a modified minimally invasive pterional posterolateral transcavernous-transtentorial approach (MIPLATTA). Methods Fourteen patients harboring SPC meningiomas were surgically treated through a MIPLATTA. MIPLATTA includes a minipterional craniotomy, anterior extradural clinoidectomy, peeling of the temporal fossa, decompression of cranial nerves (CNs) in the cavernous sinus, and sectioning of the tentorium to reach the upper part of the posterior fossa. Results Gross total resection was achieved in 11 of 14 patients (78%), whereas near-total resection was accomplished in the other 3 patients (22%), each of whom underwent a further complementary retrosigmoid approach for gross total tumor resection. There were no deaths, and 13 of 14 patients were independent at 6 months follow-up (modified Rankin Scale score ≤2). One patient had pontine infarction after the procedure and experienced moderate disability at follow-up (modified Rankin Scale score 3). All patients had some degree of CN impairment. Of 38 cranial neuropathies, 15 (39%) improved, 20 (53%) remained stable, and 3 (8%) worsened postoperatively. Four new CN deficits were observed postoperatively in 3 patients (fourth CN, 2 patients; third CN, 1; fifth CN, 1). Conclusions MIPLATTA is a useful and safe treatment alternative that allows resection of large SPC tumors with dominant invasion of cavernous sinus and middle fossa, preserves hearing and facial motor function, and provides good chances of recovery of visual and oculomotor deficits.

A 53-year-old man with a known allergy to metamizole presented for acute gonalgia, receiving metamizole by mistake. He suffers a severe allergy reaction accompanied by chest pain and signs of acute lower myocardial infarction, which subsides with treatment of anaphylactic shock and fibrinolysis, without observing intracoronary thrombus or signs of complication of atherosclerotic plaque. LEARNING OBJECTIVE An exceptional clinical case is presented illustrating an acute myocardial infarction related to a severe allergic reaction. In addition, a review of the optimal management of this entity is carried out. We intend to make this entity known, which should be suspected in the appropriate clinical setting

Background The effectiveness of surgical treatment for splenic flexure carcinomas (SFCs) in emergency settings remains unexplored. This study aims to compare the perioperative and long-term outcomes of different alternatives for emergency SFC resection. Method This multicenter retrospective study was based on the SFC Study Group database. For the present analysis, SFC patients were selected if they had received emergency surgical resection with curative intent between 2000 and 2018. Extended right colectomy (ERC), left colectomy (LC), and segmental left colectomy (SLC) were evaluated and compared. Results The study sample was composed of 90 SFC patients who underwent emergency ERC (n = 55, 61.1%), LC (n = 18, 20%), or SLC (n = 17, 18.9%). Bowel obstruction was the most frequent indication for surgery (n = 75, 83.3%), and an open approach was chosen in 81.1% of the patients. A higher incidence of postoperative complications was observed in the ERC group (70.9%) than in the LC (44.4%) and SLC groups (47.1%), with a significant procedure-related difference for severe postoperative complications (Dindo-Clavien ≥ III; adjusted odds ratio for ERC vs. LC:7.23; 95% CI 1.51-34.66; p = 0.013). Anastomotic leakage occurred in 8 (11.2%) patients, with no differences between the groups (p = 0.902). R0 resection was achieved in 98.9% of the procedures, and ≥ 12 lymph nodes were retrieved in 92.2% of patients. Overall and disease-free survival rates at 5 years were similar between the groups and were significantly associated with stage pT4 and the presence of synchronous metastases. Conclusion In the emergency setting, ERC and open surgery are the most frequently performed procedures. ERC is associated with increased odds of severe postoperative complications when compared to more conservative SFC resections. Nonetheless, all the alternatives seem to provide similar pathologic and long-term outcomes, supporting the oncological safety of more conservative resections for emergency SFCs.

Periodontal disease refers to inflammation of the tissues that support the tooth. It is of multifactorial etiology. Innate and adaptive immune cells participate jointly through the release of their molecules and mechanisms of action in order to maintain homeostasis in periodontal tissues, so the host's immune response plays an essential role in defense against microorganisms. However, bacterial persistence and the dysregulation of the immune system as an exaggerated response can lead to the worsening of periodontal disease, leading to loss of gingival tissue and alveolar bone and thereby loss of teeth. Therefore, a better understanding of the cellular mechanisms involved in the development of periodontal disease is necessary to design new treatments and prophylactic measures in order to decrease the prevalence of this disease that afflicts a large part of the world population.

Background: We analyzed the immediate effects of a Telerehabilitation Program (TP) based on aerobic exercise in women with fibromyalgia (FM) syndrome during the lockdown declared in Spain due to the COVID-19 pandemic. Methods: A single-blind randomized controlled trial was designed. Thirty-four women with FM were randomized into two groups: TP group and Control group. The intervention lasted 15 weeks, with 2 sessions per week. The TP based on aerobic exercise was guided by video and the intensity of each session was monitored using the Borg scale. Pain intensity (Visual Analogue Scale), mechanical pain sensitivity (algometer), number of tender points, FM impact (Revised Fibromyalgia Impact Questionnaire), pain catastrophizing (Pain Catastrophizing Scale), physiological distress (Hospital Anxiety and Depression Scale), upper (Arm Curl Test) and lower-limb physical function (6-min Walk Test) were measured at baseline and after the intervention. Results: The TP group improved pain intensity (p = 0.022), mechanical pain sensitivity (p &lt, 0.05), and psychological distress (p = 0.005), compared to the Control group. The Control group showed no statistically significant changes in any variable (p &gt, 0.05). Conclusion: A TP based on aerobic exercise achieved improvements on pain intensity, mechanical pain sensitivity, and psychological distress compared to a Control group during the lockdown declared in Spain due to COVID-19 pandemic.

Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP.MEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration.A total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29-0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27-0.54, p 0.001) and organ failure (RR 0.30; 95%CI 0.21-0.44, p 0.001) in comparison with hydroxyethyl starch (HES). High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41-5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04-1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51-5.19, p = 0.001) compared to moderate fluid rate infusion.In patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.

Deciphering protection mechanisms against Mycobacterium tuberculosis (Mtb) remains a critical challenge for the development of new vaccines and therapies. We analyze the phenotypic and transcriptomic profile in lung of a novel tuberculosis (TB) nanoparticle-based boosting mucosal vaccine Nano-FP1, which combined to BCG priming conferred enhanced protection in mice challenged with low-dose Mtb. We analyzed the vaccine profile and efficacy at short (2 weeks), medium (7 weeks) and long term (11 weeks) post-vaccination, and compared it to ineffective Nano-FP2 vaccine. We observed several changes in the mouse lung environment by both nanovaccines, which are lost shortly after boosting. Additional boosting at long-term (14 weeks) recovered partially cell populations and transcriptomic profile, but not enough to enhance protection to infection. An increase in both total and resident memory CD4 and CD8 T cells, but no pro-inflammatory cytokine levels, were correlated with better protection. A unique gene expression pattern with differentially expressed genes revealed potential pathways associated to the immune defense against Mtb. Our findings provide an insight into the critical immune responses that need to be considered when assessing the effectiveness of a novel TB vaccine. Xunta de Galicia | Ref. ED431C 2016/041 Xunta de Galicia | Ref. ED431G2019/06 Xunta de Galicia | Ref. ED481A-2018/230 Fundação para a Ciência e a Tecnologia | Ref. PTDC/SAU-INF/28463/2017 Fundação para a Ciência e a Tecnologia | Ref. UIDB/50026/2020 Fundação para a Ciência e a Tecnologia | Ref. UIDP/50026/2020

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Background/Aim: The aim of this study was to compare the ability of different lymph nodal staging systems to predict cancer recurrence in a multicenter European series of patients who underwent proctectomy after neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Patients and Methods: Data on 170 consecutive patients undergoing proctectomy after neoadjuvant therapy for cT3-4 or cN+ rectal adenocarcinoma were retrieved from the European MRI and Rectal Cancer Surgery database. The prognostic role of the number of retrieved and examined nodes, nodal ratio, and log odds of positive lymph nodes (LODDS) was analyzed and compared by receiver operating characteristic curves, Pearson test, and univariate and multivariate analysis. Results: At multivariate analysis, ypN, nodal ratio, and LODDS were all significantly associated with disease-free survival, but LODDS showed the strongest association (hazard ratio(HR)=2.39; 95% confidence interval(CI)=1.05-5.48; p=0.039). Conclusion: LODDS appears to be a useful prognostic indicator in the prediction of disease-free survival of patients undergoing neoadjuvant chemoradiotherapy and proctectomy for locally advanced rectal cancer.

Treating individual patients on the basis of specific factors, such as biomarkers, molecular signatures, phenotypes, environment and lifestyle is what differentiates the precision medicine initiative from standard treatment regimens. Although precision medicine can be applied to almost any branch of medicine, it is perhaps most easily applied to the field of oncology. Cancer is a heterogeneous disease, meaning that even though patients may be histologically diagnosed with the same cancer type, their tumours may have different molecular characteristics, genetic mutations or tumour microenvironments that can influence prognosis or treatment response. In this review, we describe what methods are currently available to clinicians that allow them to monitor key tumour microenvironmental parameters in a way that could be used to achieve precision medicine for cancer patients. We further describe exciting novel research involving the use of implantable medical devices for precision medicine, including those developed for mapping tumour microenvironment parameters (e.g. O2, pH and cancer biomarkers), delivering local drug treatments, assessing treatment responses and monitoring for recurrence and metastasis. Although these research studies have predominantly focused on and were tailored to humans, the results and concepts are equally applicable to veterinary patients. While veterinary clinical studies that have adopted a precision medicine approach are still in their infancy, there have been some exciting success stories. These have included the development of a receptor tyrosine kinase inhibitor for canine mast cell tumours and the production of a PCR assay to monitor the chemotherapeutic response of canine high-grade B-cell lymphomas. Although precision medicine is an exciting area of research, it currently has failed to gain significant translation into human and veterinary healthcare practices. In order to begin to address this issue, there is increasing awareness that cross-disciplinary approaches involving human and veterinary clinicians, engineers and chemists may be needed to help advance precision medicine towards its full integration into human and veterinary clinical practices

Introduction Postoperative pancreatic fistula (POPF) is the most dreadful complication of pancreaticoduodenectomy (PD) and previous literature focused on technical modifications of pancreatic remnant reconstruction. We developed a multifactorial mitigation strategy (MS) and the aim of the study is to assess its clinical impact in patients at high-risk of POPF. Methods All patients candidate to PD between 2012 and 2018 were considered. Only patients with a high Fistula Risk Score (FRS 7–10) were included. Patients undergoing MS were compared to patients receiving Standard Strategy (SS). Clinical outcomes were compared between the two groups. Multivariate hierarchical logistic regression analyses were performed to detect independent predictors of POPF. Results Out of 212 patients, 33 were finally included in MS Group and 29 in SS Group. POPF rate was significantly lower in MS Group (12.1% vs 44.8%, p = 0.005). Delayed gastric emptying, postoperative pancreatitis, complications and hospital stay were also significantly lower in MS Group. Hierarchical logistic regression analyses showed that Body Mass Index (OR = 1.196, p = 0.036) and MS (OR = 0.187, p = 0.032) were independently associated with POPF. Conclusion A multifactorial MS can be helpful to reduce POPF rate in patients with high FRS following PD. Personalized approach for vulnerable patients should be investigated in the future.

Objective To demonstrate that delayed cord clamping (DCC) is safe in mothers with confirmed SARS‐CoV‐2 infection. Design, setting and participants Prospective observational study involving epidemiological information from 403 pregnant women with SARS‐CoV‐2 between 1 March and 31 May 2020. Data were collected from 70 centres that participate in the Spanish Registry of COVID‐19. Methods Patients' information was collected from their medical chart. Main outcomes and measures The rate of perinatal transmission of SARS‐CoV‐2 and development of the infection in neonates within 14 days postpartum. Results The early cord clamping (ECC) group consisted of 231 infants (57.3%) and the DCC group consisted of 172 infants (42.7%). Five positive newborns (1.7% of total tests performed) were identified with the nasopharyngeal PCR tests performed in the first 12 hours postpartum, two from the ECC group (1.7%) and three from the DCC group (3.6%). No significant differences between groups were found regarding neonatal tests for SARS‐CoV‐2. No confirmed cases of vertical transmission were detected. The percentage of mothers who made skin‐to‐skin contact within the first 24 hours after delivery was significantly higher in the DCC group (84.3% versus 45.9%). Breastfeeding in the immediate postpartum period was also significantly higher in the DCC group (77.3% versus 50.2%). Conclusions The results of our study show no differences in perinatal outcomes when performing ECC or DCC, and skin‐to‐skin contact, or breastfeeding. Tweetable abstract This study demonstrates that delayed cord clamping is safe in mothers with confirmed SARS‐CoV‐2 infection., Tweetable abstract This study demonstrates that delayed cord clamping is safe in mothers with confirmed SARS‐CoV‐2 infection.

PROBAC REIPI/GEIH-SEIMC/SAEI., [Background] Catheter-related bloodstream infections (CRBSIs) increase morbidity and mortality, prolong hospitalization and generate considerable medical costs. Recent guidelines for CRBSI recommend empirical therapy against Gram-positive bacteria (GPB) and restrict coverage for Gram-negative bacteria (GNB) only to specific circumstances., [Objectives]To investigate predictors of GNB aetiology in CRBSI and to assess the predictors of outcome in patients with CRBSI., [Methods] Patients with CRBSI were selected from the PROBAC cohort, a prospective, observational, multicentre national cohort study including patients with bloodstream infections consecutively admitted to 26 Spanish hospitals in a 6 month period (October 2016–March 2017). Outcome variables were GNB aetiology and 30 day mortality. Adjusted analyses were performed by logistic regression., [Results] Six hundred and thirty-one episodes of CRBSI were included in the study. Risk factors independently related to GNB aetiology were central venous catheter (CVC) [OR 1.60 (95% CI: 1.05–2.44), P = 0.028], sepsis/septic shock [OR: 1.76 (95% CI: 1.11–2.80), P = 0.016], antibiotic therapy in the previous 30 days [OR: 1.56 (95% CI: 1.02–2.36), P = 0.037], neutropenia, [Conclusions] Our study reinforces the recommendation that empirical coverage should cover GNB in patients presenting with sepsis/septic shock and in neutropenic patients. Catheter removal and adequate empirical treatment were both protective factors against mortality in patients with CRBSI., This study was funded by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, through the following grants: Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; RD16/0016/0007; RD16/0016/0008; RD16/0016/0012), co-financed by European Development Regional Fund ‘A way to achieve Europe’, Operative Program Intelligent Growth 2014–2020, and PI16/01432. F. Caló enjoyed an ESCMID Observership grant at Hospital Universitario Virgen Macarena to develop this research.

Factor XI (FXI) deficiency, also known as hemophilia C, is included in the rare bleeding disorders (RBDs). It is distinct from other coagulation factor deficiencies because it rarely presents as spontaneous hemorrhage, but rather as bleeding after trauma or surgery; in addition, the severity of bleeding does not correlate with FXI levels. Most delayed traumatic intracerebral hemorrhage (DTICH) occurs during the first 72 hours of the trauma. Factors that contribute to its formation include local or systemic coagulopathy, among others. Hemorrhagic cases of FXI deficiency related to the central nervous system (CNS) are very rare, with only 13 reported cases. To the best of our knowledge, this is the first reported case of a DTICH in a patient with undiagnosed FXI deficiency.

Research using in vitro canine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast cancer is commonly treated with radiotherapy; however, tumor response depends on both innate radiosensitivity and on tumor repopulation by cells that develop radioresistance. Comparative canine and human studies investigating the mechanisms of radioresistance may lead to novel cancer treatments that benefit both species. In this study, we developed a canine mammary cancer (REM-134) radioresistant (RR) cell line and investigated the cellular mechanisms related to the development of acquired radioresistance. We performed a comparative analysis of this resistant model with our previously developed human breast cancer radioresistant cell lines (MCF-7 RR, ZR-751 RR, and MDA-MB-231 RR), characterizing inherent differences through genetic, molecular, and cell biology approaches. RR cells demonstrated enhanced invasion/migration capabilities, with phenotypic evidence suggestive of epithelial-to-mesenchymal transition. Similarities were identified between the REM-134 RR, MCF-7 RR, and ZR-751 RR cell lines in relation to the pattern of expression of both epithelial and mesenchymal genes, in addition to WNT, PI3K, and MAPK pathway activation. Following the development of radioresistance, transcriptomic data indicated that parental MCF-7 and ZR-751 cell lines changed from a luminal A classification to basal/HER2-overexpressing (MCF-7 RR) and normal-like/HER2-overexpressing (ZR-751 RR). These radioresistant subtypes were similar to the REM-134 and REM-134 RR cell lines, which were classified as HER2-overexpressing. To our knowledge, our study is the first to generate a canine mammary cancer RR cell line model and provide a comparative genetic and phenotypic analysis of the mechanisms of acquired radioresistance between canine and human cancer cell lines. We demonstrate that the cellular processes that occur with the development of acquired radioresistance are similar between the human and canine cell lines; our results therefore suggest that the canine model is appropriate to study both human and canine radioresistant mammary cancers, and that treatment strategies used in human medicine may also be applicable to veterinary patients.

RESUMEN Objetivo: establecer la asociación entre el retraso en el diagnóstico de cáncer de mama con un estadio clínico avanzado y explorar factores que influyen en dicho retraso. Materiales y métodos: estudio de corte transversal con mujeres mayores de 18 años con cáncer de mama que consultaron en cuatro centros oncológicos de Medellín, Colombia, en 2017. Se usó el Breast Cancer Delay Questionnaire que incluye variables sociodemográficas, clínicas y de tiempos de atención. Se estimó el odds ratio (OR) crudo y ajustado por medio de una regresión logística con el estadio clínico avanzado como desenlace y el retraso diagnóstico como exposición. Resultados: se incluyeron 242 pacientes. La mediana del tiempo entre identificar el problema y la biopsia diagnóstica fue 104,5 días; entre identificar el problema y la primera consulta médica, 20 días, y de la primera consulta a la biopsia diagnóstica fue de 53 días. El 52,1 % se diagnosticó en estadio avanzado. Hubo asociación del retraso diagnóstico con estadio clínico avanzado (OR = 2,15; IC 95 %: 1,21-3,79). Se encontró que la edad mayor a 40 años es un factor protector contra una lesión avanzada (OR = 0,35; IC 95 %: 0,14-0,83). El retraso diagnóstico se asoció con estar afiliada al régimen subsidiado por el Estado (OR = 9,67; IC 95 %: 2,76-33,9) y tener edad mayor a 40 años (OR = 2,75; IC 95 %: 1,16-6,53). Conclusión: se requieren intervenciones educativas en las pacientes para adherir a los programas de tamización temprana o la consulta oportuna al identificar un signo o síntoma, para lograr un diagnóstico en estadios tempranos de la enfermedad. Además, se requieren estudios prospectivos para determinar los factores relacionados con la demora en recibir el tratamiento una vez diagnosticado el cáncer de seno y evaluar las intervenciones destinadas a disminuir las dilaciones en la atención de este cáncer. ABSTRACT Objective: To determine the association between delayed diagnosis and advanced clinical stage breast cancer, and to explore the factors that influence this delay. Materials and methods: Cross-sectional study of women over 18 years of age with breast cancer who attended 4 oncology centers in Medellín, Colombia, in 2017. The “Breast Cancer Delay Questionnaire” which includes sociodemographic and clinical variables as well as time intervals was used. Crude and adjusted odds ratio (OR) were estimated, using advanced clinical stage as outcome and delayed diagnosis as exposure. Results: 242 patients were included. The median time interval between the identification of the problem and the diagnostic biopsy was 104.5 days; between the identification of the problem and the first medical visit, 20 days; and between the first visit and the diagnostic biopsy, 53 days. Of all the cases, 52.1 % were diagnosed at an advanced stage. An association was found between delayed diagnosis and advanced clinical stage (OR = 2.15 95 % CI 1.21-3.79). Age above 40 was found to be a protective factor against having an advanced-stage lesion (OR = 0.35; 95 % CI: 0.14-0.83). Delayed diagnosis was associated with affiliation to the government subsidized health system (OR = 9.67; 95 % CI 2.76- 33.9) and age over 40 years (OR = 2.75; 95 % CI: 1.16-6.53). Conclusion: Patient education is required in order to ensure adherence to early screening programs or timely consultation whenever a sign or symptom is identified, thus allowing diagnosis at an early stage of the disease. Moreover, prospective studies are needed in order to identify factors associated with delays in treatment after the diagnosis of breast cancer, and to assess interventions designed to reduce delays in the care of this form of cancer.

Amoebiasis is a human parasitic disease caused by Entamoeba histolytica. The parasite can invade the large intestine and other organs such as liver; resistance to the host tissue oxygen is a condition for parasite invasion and survival. Thioredoxin reductase of E. histolytica (EhTrxR) is a critical enzyme mainly involved in maintaining reduced the redox system and detoxifying the intracellular oxygen; therefore, it is necessary for E. histolytica survival under both aerobic in vitro and in vivo conditions. In the present work, it is reported that rabeprazole (Rb), a drug widely used to treat heartburn, was able to inhibit the EhTrxR recombinant enzyme. Moreover, Rb affected amoebic proliferation and several functions required for parasite virulence such as cytotoxicity, oxygen reduction to hydrogen peroxide, erythrophagocytosis, proteolysis, and oxygen and complement resistances. In addition, amoebic pre-incubation with sublethal Rb concentration (600 μM) promoted amoebic death during early liver infection in hamsters. Despite the high Rb concentration used to inhibit amoebic virulence, the wide E. histolytica pathogenic-related functions affected by Rb strongly suggest that its molecular structure can be used as scaffold to design new antiamoebic compounds with lower IC50 values.

Appendicitis-related hospitalizations linked with peritonitis or postoperative complications result in longer lengths of stay and higher costs. The aim of the present study was to assess the independent association between potential predictors and prolonged hospitalization after laparoscopic appendectomy (LA) for complicated acute appendicitis (CAA). A retrospective cohort study was conducted on adult patients diagnosed with CAA in which LA was attempted. The primary outcome was a prolonged length of stay (LOS) after surgery, defined as hospitalizations longer than or equal to the 75th percentile for LOS, including the day of discharge. Hierarchical regression models were run to elucidate the independent predictors for the variable of interest. The present study involved 160 patients with a mean age of 50.71 years. The conversion rate was 1.9%, and the overall postoperative morbidity rate was 23.8%. The median length of stay (LOS) was 5 days (75th percentile: 7 days). Multivariate analyses included nine variables that are statistically and/or clinically relevant to assess its relationship with a prolonged LOS: three preoperative (age, sex, and comorbidity), four intraoperative (appendix gangrene, perforation, degree of peritonitis, and drain placement), and two postoperative (immediate ICU admission and complications). The development of postoperative complications (OR 6.162, 95% CI 2.451–15.493; p = 0.000) and the placement of an abdominal drain (OR 3.438, 95% CI 1.107–10.683; p = 0.033) were found to be independent predictors for prolonged LOS. For patients not presenting postoperative complications, drain placement was the only independent predictor for the outcome (OR 7.853, 95% CI 1.520–40.558; p = 0.014). Sensitivity analyses showed confirmatory results. The intraoperative process of care has a clear impact on LOS after LA for CAA in adults; therefore, the decision of whether to drain in these situations should be made more restrictively yet with judicious caution.

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumour heterogeneity, tumour radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumour type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to the gross tumour volume, it is proving more difficult to personalise radiotherapy regimens based on tumour biology. Biomarkers that provide prognostic or predictiveinformation regarding a tumour’s intrinsic radiosensitivity or its response to treatment could prove valuable in helping to personalise radiation dosing, enabling clinicians to make decisions between different treatment options whilst avoiding radiationinduced toxicity in patients unlikely to gain therapeutic benefit. Studies have investigated numerous ways in which both patientand tumour radiosensitivities can be assessed. Tumour molecular profiling has been used to develop radiosensitivity gene signatures, while the assessment of specific intracellular or secreted proteins, including circulating tumour cells, exosomes and DNA, has been performed to identify prognostic or predictive biomarkers of radiation response. Finally, the investigation of biomarkers related to radiation-induced toxicity could provide another means by which radiotherapy could become personalised. In this review, we discuss studies that have used these methods to identify or develop prognostic/predictive signatures of radiosensitivity, and how such assays could be used in the future as a means of providing personalised radiotherapy.