The SADDEN DEATH Study: Results from a Pilot Study in Non-ICU COVID-19 Spanish Patients

Introduction: The worldwide pandemic, coronavirus disease 2019 (COVID-19) is a novel infection with serious clinical manifestations, including death. Our aim is to describe the first non-ICU Spanish deceased series with COVID-19, comparing specifically between unexpected and expected deaths. Methods: In this single-centre study, all deceased inpatients with laboratory-confirmed COVID-19 who had died from March 4 to April 16, 2020 were consecutively included. Demographic, clinical, treatment, and laboratory data, were analyzed and compared between groups. Factors associated with unexpected death were identified by multivariable logistic regression methods. Results: In total, 324 deceased patients were included. Median age was 82 years (IQR 76–87); 55.9% males. The most common cardiovascular risk factors were hypertension (78.4%), hyperlipidemia (57.7%), and diabetes (34.3%). Other common comorbidities were chronic kidney disease (40.1%), chronic pulmonary disease (30.3%), active cancer (13%), and immunosuppression (13%). The Confusion, BUN, Respiratory Rate, Systolic BP and age ≥65 (CURB-65) score at admission was >2 in 40.7% of patients. During hospitalization, 77.8% of patients received antivirals, 43.3% systemic corticosteroids, and 22.2% full anticoagulation. The rate of bacterial co-infection was 5.5%, and 105 (32.4%) patients had an increased level of troponin I. The median time from initiation of therapy to death was 5 days (IQR 3.0–8.0). In 45 patients (13.9%), the death was exclusively attributed to COVID-19, and in 254 patients (78.4%), both COVID-19 and the clinical status before admission contributed to death. Progressive respiratory failure was the most frequent cause of death (92.0%). Twenty-five patients (7.7%) had an unexpected death. Factors independently associated with unexpected death were male sex, chronic kidney disease, insulin-treated diabetes, and functional independence. Conclusions: This case series provides in-depth characterization of hospitalized non-ICU COVID-19 patients who died in Madrid. Male sex, insulin-treated diabetes, chronic kidney disease, and independency for activities of daily living are predictors of unexpected death

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Las estructuras políticas en las redes de macrocriminalidad en México

Reconocimientos. Este artículo pertenece a una investigación más amplia intitulada "El funcionamiento de las redes de macrocriminalidad en Veracruz", financiado por la Fundación Heinrich Boell y el órgano de cooperación técnica alemán GIZ. Esta publicación da cuenta de los primeros hallazgos con carácter exploratorio.Las redes de macrocriminalidad se conforman por estructuras criminales, empresariales y políticas. En México, la estructura política es relevante para determinar la lógica y funcionamiento de la red. ¿Cuáles son las semejanzas y diferencias de las redes de macrocriminalidad de tres regiones de la entidad federativa de Veracruz considerando sus diferencias políticas? En la medida que los principales operadores de la red son de la entidad federativa, las diferencias políticas municipales no tienen ningún impacto. Pese a lo anterior, hay una división del trabajo por región que tienen consecuencias en el nivel de violencia.Macrocriminal networks are made up of criminal, business and political structures. In Mexico, the political structure is relevant to determine the logic and operation of the network. What are the similarities and differences of the macro-criminality networks of three regions of the federal entity of Veracruz considering their political differences? To the extent that the main network operators are from the federal entity, municipal political differences have no impact. Despite the above, there is a division of labor by region that has consequences for the level of violence.Les réseaux de macrocriminalité sont constitués de structures criminelles, commerciales et politiques. Au Mexique, la structure politique est pertinente pour déterminer la logique et le fonctionnement du réseau. Quelles sont les similitudes et les différences des réseaux de macrocriminalité de trois régions de l'État de Veracruz compte tenu de leurs différences politiques ? Dans la mesure où les principaux opérateurs de réseaux sont issus de l'entité fédérale, les divergences politiques communales n'ont pas d'impact. Malgré ce qui précède, il existe une division du travail par région qui a des conséquences sur le niveau de violence.As redes de macrocriminalidade são constituídas por estruturas criminosas, empresariais e políticas. No México, a estrutura política é relevante para determinar a lógica e o funcionamento da rede. Quais são as semelhanças e diferenças das redes de macrocriminalidade de três regiões do estado de Veracruz considerando suas diferenças políticas? Na medida em que os principais operadores de rede são do ente federal, as diferenças políticas municipais não têm impacto. Apesar do exposto, há uma divisão do trabalho por região que tem consequências no nível de violência

Cancer in patients with heart failure: incidence, risk factors and prognostic impact

Observational study[Abstract] Aims: To assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF). Methods: Observational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory. Results: We studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4-2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1-4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1-1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8-3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26). Conclusion: Patients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population

Assessment of the Molecular Responses of an Ancient Angiosperm against Atypical Insect Oviposition: The Case of Hass Avocados and the Tephritid Fly <i>Anastrepha ludens</i>

Anastrepha spp. (Diptera: Tephritidae) infestations cause significant economic losses in commercial fruit production worldwide. However, some plants quickly counteract the insertion of eggs by females by generating neoplasia and hindering eclosion, as is the case for Persea americana Mill., cv. Hass (Hass avocados). We followed a combined transcriptomics/metabolomics approach to identify the molecular mechanisms triggered by Hass avocados to detect and react to the oviposition of the pestiferous Anastrepha ludens (Loew). We evaluated two conditions: fruit damaged using a sterile pin (pin) and fruit oviposited by A. ludens females (ovi). We evaluated both of the conditions in a time course experiment covering five sampling points: without treatment (day 0), 20 min after the treatment (day 1), and days 3, 6, and 9 after the treatment. We identified 288 differentially expressed genes related to the treatments. Oviposition (and possibly bacteria on the eggs’ surface) induces a plant hypersensitive response (HR), triggering a chitin receptor, producing an oxidative burst, and synthesizing phytoalexins. We also observed a process of cell wall modification and polyphenols biosynthesis, which could lead to polymerization in the neoplastic tissue surrounding the eggs

Fibroblast growth factor 21 and its novel association with oxidative stress

Fibroblast growth factor 21 (FGF21) is an endocrine-member of the FGF family. It is synthesized mainly in the liver, but it is also expressed in adipose tissue, skeletal muscle, and many other organs. It has a key role in glucose and lipid metabolism, as well as in energy balance. FGF21 concentration in plasma is increased in patients with obesity, insulin resistance, and metabolic syndrome. Recent findings suggest that such increment protects tissue from an increased oxidative stress environment. Different types of physical stress, such as strenuous exercising, lactation, diabetic nephropathy, cardiovascular disease, and critical illnesses, also increase FGF21 circulating concentration. FGF21 is now considered a stress-responsive hormone in humans. The discovery of an essential response element in the FGF21 gene, for the activating transcription factor 4 (ATF4), involved in the regulation of oxidative stress, and its relation with genes such as NRF2, TBP-2, UCP3, SOD2, ERK, and p38, places FGF21 as a key regulator of the oxidative stress cell response. Its role in chronic diseases and its involvement in the treatment and follow-up of these diseases has been recently the target of new studies. The diminished oxidative stress through FGF21 pathways observed with anti-diabetic therapy is another clue of the new insights of this hormone. Keywords: FGF21, Oxidative stress, Insulin resistance, Metabolic syndrome, Diabete