Evaluation of the presence of gingivitis as confounding factor in assessing inflammatory status in serum and saliva of dogs with diabetes mellitus.

The aim of this study was to evaluate the changes in the serum and salivary inflammatory markers induced by Diabetes mellitus (DM) in dogs and to assess the possible confounding effect of gingivitis. A panel of 13 cytokines was measured in the serum and saliva of dogs diagnosed with DM and compared with healthy dogs without gingivitis (control group 1; CG1) and dogs with gingivitis but otherwise healthy (control group 2; CG2). The results of the present study showed statistically significantly higher levels of IL-8, KC-like and MCP1 in the serum of dogs with DM compared to CG1 dogs. In the case of saliva, the DM group presented statistically higher GM-CSF, IL6, IL15, and MCP1 levels compared to CG1, and lower KC-like chemokine compared to CG2. Finally, gingivitis produced changes in saliva, with salivary levels of GM-CSF, IL-6, IL-7, IL-15, IP-10, KC-like, IL-10, IL-18, MCP1, TNFα being statistically significantly higher in the saliva of CG2 dogs compared to CG1. The results of the present study indicate that dogs with DM have altered cytokine levels in serum and saliva compared to healthy dogs. In addition, this study highlights the importance of taking oral health into account when determining cytokines in dogs, as gingivitis can significantly alter their concentrations. .

Predictive risk model of recurrence of acute diverticulitis after the first episode.

INTRODUCTION: The recurrence of acute diverticulitis (AD) of the colon is frequent and leads to hospital readmissions and the need for elective surgery in selected cases. It is important to individualize risk factors and develop predictive tools for their identification. MATERIALS AND METHODS: This prospective observational study included 368 patients who were diagnosed with AD between 2016 and 2021 in a tertiary general university hospital during their first episode and who had a good response to antibiotic, percutaneous, or peritoneal lavage treatment. Univariate and multivariate Cox regression analyses of the variables associated with recurrence were performed. Subsequently, a predictive risk score was developed and validated through survival studies. RESULTS: After a median follow-up of 50 months, there were 71 (19.3%) cases of recurrence out of a total of 368 patients. The mean time of recurrence was 15 months, and 73.3% of cases of recurrence occurred before 2 years of follow-up. Recurrence was independently associated with presentation with colonic perforation in the antimesenteric location (HR 3.67 95% CI [1.59-8.4]) and a CRP level greater than 100 mg/dl (HR 1.69 95% CI [1.04-2.77). A score with 5 variables was created that differentiated two risk groups: intermediate risk (0-3 points), with 19% recurrence and high risk (more than 3 points), with 42% recurrence. CONCLUSIONS: The risk of recurrence after the first episode of diverticulitis can be estimated using predictive scores. The detection of high-risk patients facilitates the individualization of follow-up and treatment.

Serum Ferritin in Obese Dogs: Changes and Comparison with Other Analytes.

Canine obesity is the most common nutritional disorder and is associated with decreased quality of life and longevity as well as comorbidities including cardiorespiratory, endocrine, oncologic, or orthopaedic disorders. Ferritin is a major acute-phase protein in dogs, increasing during inflammation; however, it could also be affected by other conditions, including trauma, iron metabolism dysregulations, neoplasia, or hypoxia. Higher ferritin levels have been reported in obese humans, but ferritin has not been explored in canine obesity. To evaluate the possible changes in serum ferritin in canine obesity, ferritin levels from lean/normal weight (CG, n = 55) and overweight/obese dogs (OG, n = 37) were measured, together with complete hemogram and biochemical analyses. Statistically significant higher ferritin levels (1.2-fold) were found in OG (median, (interquartile range), 204 (166-227.5) µg/L) in comparison to CG animals (172 (137-210) µg/L)), with median levels of ferritin in OG dogs above the reference range for healthy animals in our laboratory (60-190 µg/L). In addition, statistically significant higher mean corpuscular volume (MCV), mean cell haemoglobin concentration (MCHC), total proteins, globulins, haptoglobin, total ferric fixation capacity (TIBC), alkaline phosphatase (ALP), butyrylcholinesterase (BChE), triglycerides, and calcium were observed in OG in comparison to CG. The higher levels in ferritin, together with higher TBIC, haematocrit, and MCV, could indicate tissue hypoxia in obese dogs.

Food production in space from CO2 using microbial electrosynthesis.

The current food method in space is launching prepackaged food which is costly and unsustainable. Alternatives include growing crops and microalgae single cell protein (SCP) using artificial light photosynthesis, which are energy inefficient. Prepackaged food and microalgae food were compared to microbial electrosynthesis of acetic acid (MES-AA). Since the dominant cost of a space mission is the cost of launching mass, components of a system were converted to an equivalent mass, including power, heat rejection, and volume. Three-year roundtrip crewed missions were evaluated for the International Space Station, the Moon, and Mars. The average Equivalent System Mass (ESM) of MES-AA is 1.38x and 2.84x lower than prepackaged food and microalgae SCP, respectively. The expected electricity-to-calorie conversion efficiency of MES-AA is 19.8 %, consuming 3.45 kW to fully feed five astronauts; diets would realistically include multiple foods. MES-AA has a higher energy efficiency than any currently investigated resilient food in space. MES-AA can provide diet diversity at a lower cost than customarily storing prepackaged food or growing crops in space. Producing food while contributing to closed loop life support in space can contribute to reducing global catastrophic risk and is relevant in off-grid communities, like in rural Alaska.

Is the prognosis of non-hypertensive, COVID-19 patients treated with renin-angiotensin-aldosterone system inhibitors more uncertain?

Previous studies suggested that ongoing treatment with renin-angiotensin-aldosterone system (RAAS) inhibitor drugs may alter the course of SARS-CoV-2 infection and promote the development of more severe forms of the disease. The authors conducted a comparative, observational study to retrospectively analyze data collected from 394 patients admitted to ICU due to SARS-CoV-2 pneumonia. The primary aim of the study was to establish an association between the use of RAAS inhibitor drugs and mortality in the ICU. The secondary aims of the study were to establish an association between the use of RAAS inhibitor drugs and clinical severity at ICU admission, the need for tracheal intubation, total days of mechanical ventilation, and the ICU length of stay. The authors found no statistically significant difference in ICU mortality between patients on RAAS inhibitor drugs at admission and those who were not (31.3% versus 26.2% mortality, p-value 0.3). However, the group of patients taking RAAS inhibitor drugs appeared to be more critical at ICU admission, and this difference became statistically significant in the subgroup of non-hypertensive patients. ICU mortality in the subgroup of non-hypertensive patients treated with RAAS inhibitor drugs also tended to be higher. Overexpression of the angiotensin-converting enzyme 2 (ACE2) in human cells, induced by RAAS inhibitor drugs, promotes viral entry-replication of SARS-CoV-2 and alters the basal balance of the RAAS, which may explain the findings observed in the present study. These phenomena may be amplified in non-hypertensive patients treated with RAAS inhibitor therapy.

Postoperative Intracranial Hypotension-Associated Venous Congestion after Spinal Surgery Managed with Multiple Blood Patches: Case Report.

BACKGROUND: Postoperative intracranial hypotension-associated venous congestion (PIHV) is a rare event. The authors report the case of a patient presenting with PIHV after spinal surgery following the sudden loss of cerebrospinal fluid (CSF) induced by suction drainage. METHODS: A 69-year-old patient underwent uneventful revision surgery for wound dehiscence after lumbar surgery with placement of a subfascial suction drain. RESULTS: Postoperatively, the patient presented with fluctuating consciousness and a generalized tonic-clonic seizure. Computed tomography (CT) and serial magnetic resonance imaging (MRI) were performed showing convexity subarachnoid hemorrhages (SAHs), diffuse swelling of the brain and thalami and striatum bilaterally without diffusion restriction, and signs of intracranial hypertension resulting in pseudohypoxic brain swelling in PIHV. A dural leak at L3-L4 was treated with several CT-guided patches combining autologous blood and fibrin glue injections. The patient recovered without neurologic deficit and follow-up MRI revealed progressive complete reversal of brain swelling, and re-expansion of CSF spaces. CONCLUSION: PIHV is a rare but potentially fatal entity. Awareness of PIHV after cranial or spinal surgery leads to early treatment of CSF hypovolemia and possibly better clinical outcome. Following acute CSF volume loss, an acute elevation of cerebral blood volume overcoming autoregulatory mechanisms seems a likely explanation for diffuse cerebral vasogenic edema and SAH in PIHV.

Methane Single Cell Protein: Potential to Secure a Global Protein Supply Against Catastrophic Food Shocks.

Global catastrophes such as a supervolcanic eruption, asteroid impact, or nuclear winter could cause global agricultural collapse due to reduced sunlight reaching the Earth's surface. The human civilization's food production system is unprepared to respond to such events, but methane single cell protein (SCP) could be a key part of the solution. Current preparedness centers around food stockpiling, an excessively expensive solution given that an abrupt sunlight reduction scenario (ASRS) could hamper conventional agriculture for 5-10 years. Instead, it is more cost-effective to consider resilient food production techniques requiring little to no sunlight. This study analyses the potential of SCP produced from methane (natural gas and biogas) as a resilient food source for global catastrophic food shocks from ASRS. The following are quantified: global production potential of methane SCP, capital costs, material and energy requirements, ramp-up rates, and retail prices. In addition, potential bottlenecks for fast deployment are considered. While providing a more valuable, protein-rich product than its alternatives, the production capacity could be slower to ramp up. Based on 24/7 construction of facilities, 7%-11% of the global protein requirements could be fulfilled at the end of the first year. Despite significant remaining uncertainties, methane SCP shows significant potential to prevent global protein starvation during an ASRS at an affordable price-US$3-5/kg dry.

Nutrition in Abrupt Sunlight Reduction Scenarios: Envisioning Feasible Balanced Diets on Resilient Foods.

Abrupt sunlight reduction scenarios (ASRS) following catastrophic events, such as a nuclear war, a large volcanic eruption or an asteroid strike, could prompt global agricultural collapse. There are low-cost foods that could be made available in an ASRS: resilient foods. Nutritionally adequate combinations of these resilient foods are investigated for different stages of a scenario with an effective response, based on existing technology. While macro- and micronutrient requirements were overall met, some-potentially chronic-deficiencies were identified (e.g., vitamins D, E and K). Resilient sources of micronutrients for mitigating these and other potential deficiencies are presented. The results of this analysis suggest that no life-threatening micronutrient deficiencies or excesses would necessarily be present given preparation to deploy resilient foods and an effective response. Careful preparedness and planning-such as stock management and resilient food production ramp-up-is indispensable for an effective response that not only allows for fulfilling people's energy requirements, but also prevents severe malnutrition.

Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults.

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.

Development of a health data derived frailty index as a predictor of adverse outcomes in older patients with pancreatic cancer.

Pancreatic cancer is a prevalent disease among older adults. Well-selected patients, based on a geriatric assessment for risk stratification, could be good candidates for chemotherapy and/or curative resection. Deficits accumulation frailty indices (FI) utilize readily available clinical data and easily obtained patient-reported information to predict hospitalization and mortality of older individuals. Retrospective data from 440 older adults (median age 76 years) with pancreatic cancer, obtained from electronic health records, was used to develop a FI and its ability to predict mortality and other geriatric and cancer related outcomes was tested. Fatigue (n = 45), infection (n = 40) and neutropenia (n = 36) were the most common registered adverse events of treatment; 153 subjects had no adverse events. The mean FI score was 0.26, 112 subjects were fit (0.0 < 0.2), 255 pre-frail (0.2 < 0.35), and 73 frail (≥ 0.35). Median survival was twelve months for the whole sample; at one year 62.5% of fit patients, 46.3% of pre-frail, and 26% of frail patients were alive. The FI categories correlated with institutionalization (p < 0.001) and non-planned hospitalization (p < 0.001). The FI categories did not correlate with the presence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 adverse events (p = 0.377). We conclude that patients with pancreatic cancer classified as frail with our FI had worse survival than those fit and pre-frail. Non-fit patients were also more prone to be institutionalized and have non-planned hospitalizations. The items used for this FI can be usually acquired from electronic health records and could be automated in the future, which could simplify its use as a helping tool for decisions in older patients with pancreatic cancer.

Endoscopic Endocautery Polypectomy for the Treatment of Duodenal and Gastric Polyps in a Cat.

Endoscopic polypectomy is commonly performed in human medicine, with large-scale studies reported. However, few reports have described its use in veterinary medicine and, specifically, the procedure in the case of duodenal polyps in cats has not been reported. A 7 kg 14-year-old cat presented with recurrent vomiting for several months. Gastroduodenoscopy revealed a pedunculated polyp at the pyloric antrum and another in the duodenum, with its head protruding into the pylorus. Endoscopic polypectomy was performed using an electrosurgical snare with no recurrence of clinical signs after six months. Duodenal polypectomy in cats may be difficult because of space limitation but it can be safe, minimally invasive, and successful, thus avoiding more invasive surgical techniques. Endoscopic polypectomy may be a viable alternative to surgery in cats with gastric and duodenal polyps.

Economic Burden and Impact on Quality of Life of Herpes Zoster in Spanish Adults Aged 50 Years or Older: A Prospective Cohort Study.

INTRODUCTION: The economic burden of herpes zoster (HZ), including its most common complication, postherpetic neuralgia (PHN), and its impact on health-related quality of life (HRQL) is not well described in Spain. The aim of this study was to estimate HZ-related healthcare costs and impact on HRQL in Spanish adults aged 50 years or older. METHODS: A prospective, observational study was performed with patients with HZ recruited through four general practitioner networks in Spain (NCT01521286). HRQL data were collected using the EuroQoL-5 Dimension (EQ-5D) questionnaire; HZ-related pain and associated interference with activities of daily living (ADL) were assessed using the Zoster Brief Pain Inventory (ZBPI) questionnaire at days 0 (HZ rash onset), 15, 30, 60, and 90; patients with PHN were assessed up until day 270. Medical resource utilization was recorded throughout study follow-up. Work loss for patients/caregivers was also assessed. Costs were calculated from both the payer and societal perspectives. RESULTS: A total of 545 patients with Hz were included, of whom 25 developed PHN. During days 0-30 post HZ diagnosis, the mean EQ-5D utility score was 0.738, equating to a utility loss of 0.138. Sleep was the ADL most affected component. The mean costs for HZ in the overall cohort were €240 and €296 from the payer/societal perspective, respectively; €187/€242 for patients with HZ without any HZ-related complications; and €571/€712 for patients who developed PHN. The majority of costs were incurred during days 0-30. CONCLUSIONS: In Spain, HZ and HZ-related complications such as PHN reduce patient HRQL and increase the economic burden for both payers and society in general. TRAIL REGISTRATION: ClinicalTrials.gov identifier NCT01521286.

Aneurisma coronario de localización inusual asociado a infarto agudo de miocardio / A coronary aneurysm in an unusual location associated with acute myocardial infarction

Resumen Se presenta un caso clínico de difícil abordaje terapéutico. Paciente masculino joven con obesidad tipo II, quien ingresa por síndrome coronario agudo con elevación del segmento ST, se realiza coronariografía que pone en evidencia un aneurisma ubicado en el tronco coronario con imagen sugestiva de trombo en su interior que se trató con inhibidor de glicoproteína IIb/IIIa. En la evolución presenta falla cardiaca aguda manejada con inotrópicos y vasopresores. En segunda coronariografía se observó desaparición completa del componente trombótico. Como prevención secundaria se deja tratamiento antiagregante plaquetario y antitrombótico. El manejo de estos pacientes a la fecha es un reto ante la posibilidad de presentar un nuevo evento trombótico por la alteración en el flujo laminar intracoronario.

Abstract We present a clinical case with difficult treatment. A young male patient with type II obesity was admitted due to acute coronary syndrome with ST elevation. Coronariography showed an aneurysm on the coronary trunk suggestive of having a thrombus inside. It was treated with a glycoprotein IIb/IIIa antagonist. The patient progressed to acute heart failure managed with inotropes and vasopressors. A second coronariography showed complete disappearance of the thrombotic component. He was prescribed antiplatelet and antithrombotic treatment as secondary prevention. To date, the management of these patients has been a challenge, given the possibility of experiencing a new thrombotic event due to altered intracoronary laminar flow.

Potential of microbial protein from hydrogen for preventing mass starvation in catastrophic scenarios.

Human civilization's food production system is currently unprepared for catastrophes that would reduce global food production by 10% or more, such as nuclear winter, supervolcanic eruptions or asteroid impacts. Alternative foods that do not require much or any sunlight have been proposed as a more cost-effective solution than increasing food stockpiles, given the long duration of many global catastrophic risks (GCRs) that could hamper conventional agriculture for 5 to 10 years. Microbial food from single cell protein (SCP) produced via hydrogen from both gasification and electrolysis is analyzed in this study as alternative food for the most severe food shock scenario: a sun-blocking catastrophe. Capital costs, resource requirements and ramp up rates are quantified to determine its viability. Potential bottlenecks to fast deployment of the technology are reviewed. The ramp up speed of food production for 24/7 construction of the facilities over 6 years is estimated to be lower than other alternatives (3-10% of the global protein requirements could be fulfilled at end of first year), but the nutritional quality of the microbial protein is higher than for most other alternative foods for catastrophes. Results suggest that investment in SCP ramp up should be limited to the production capacity that is needed to fulfill only the minimum recommended protein requirements of humanity during the catastrophe. Further research is needed into more uncertain concerns such as transferability of labor and equipment production. This could help reduce the negative impact of potential food-related GCRs.

Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist.

Activation of TRAILR2 has emerged as an important therapeutic concept in cancer treatment. TRAILR2 agonistic molecules have only had limited clinical success, to date, due either to lack of efficacy or hepatotoxicity. BI 905711 is a novel tetravalent bispecific antibody targeting both TRAILR2 and CDH17 and represents a novel liver-sparing TRAILR2 agonist specifically designed to overcome the disadvantages of previous strategies. Here, we show that BI 905711 effectively triggered apoptosis in a broad panel of CDH17-positive colorectal cancer tumor cells in vitro. Efficient induction of apoptosis was dependent on the presence of CDH17, as exemplified by the greater than 1,000-fold drop in potency in CDH17-negative cells. BI 905711 demonstrated single-agent tumor regressions in CDH17-positive colorectal cancer xenografts, an effect that was further enhanced upon combination with irinotecan. Antitumor efficacy correlated with induction of caspase activation, as measured in both the tumor and plasma. Effective tumor growth inhibition was further demonstrated across a series of different colorectal cancer PDX models. BI 905711 induced apoptosis in both a cis (same cell) as well as trans (adjacent cell) fashion, translating into significant antitumor activity even in xenograft models with heterogeneous CDH17 expression. In summary, we demonstrate that BI 905711 has potent and selective antitumor activity in CDH17-positive colorectal cancer models both in vitro and in vivo. The high prevalence of over 95% CDH17-positive tumors in patients with colorectal cancer, the molecule preclinical efficacy together with its potential for a favorable safety profile, support the ongoing BI 905711 phase I trial in colorectal cancer and additional CDH17-positive cancer types (NCT04137289).

Edad y responsabilidades políticas / Age and political responsabilities

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Venous thromboembolism in critically Ill patients with COVID-19: Results of a screening study for deep vein thrombosis.

BACKGROUND: The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and coronavirus disease 2019 (COVID-19), has caused more than 3.9 million cases worldwide. Currently, there is great interest to assess venous thrombosis prevalence, diagnosis, prevention, and management in patients with COVID-19. OBJECTIVES: To determine the prevalence of venous thromboembolism (VTE) in critically ill patients with COVID-19, using lower limbs venous ultrasonography screening. METHODS: Beginning March 8, we enrolled 25 patients who were admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 infections. The presence of lower extremity deep vein thrombosis (DVT) was systematically assessed by ultrasonography between day 5 and 10 after admission. The data reported here are those available up to May 9, 2020. RESULTS: The mean (± standard deviation) age of the patients was 68 ± 11 years, and 64% were men. No patients had a history of VTE. During the ICU stay, 8 patients (32%) had a VTE; 6 (24%) a proximal DVT, and 5 (20%) a pulmonary embolism. The rate of symptomatic VTE was 24%, while 8% of patients had screen-detected DVT. Only those patients with a documented VTE received a therapeutic anticoagulant regimen. As of May 9, 2020, 5 patients had died (20%), 2 remained in the ICU (8%), and 18 were discharged (72%). CONCLUSIONS: In critically ill patients with SARS-CoV-2 infections, DVT screening at days 5-10 of admission yielded a 32% prevalence of VTE. Seventy-five percent of events occurred before screening. Earlier screening might be effective in optimizing care in ICU patients with COVID-19.

Egg oral immunotherapy in children (SEICAP I): Daily or weekly desensitization pattern.

BACKGROUND: Studies are required before incorporating egg oral immunotherapy (OIT) into clinical practice. The Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP) conducted a multicenter, randomized controlled study assessing the effectiveness and safety of the OIT using pasteurized egg white (PEW) in egg-allergic children. METHODS: One hundred and one egg-allergic children (6-9 years) were randomized for 1 year: 25 to an egg-free-diet (CG) and 76 to OIT (target dose 3.3 g PEW proteins), PI (30% weekly plus 5% daily increments) or PII (only 30% weekly increments) buildup patterns. Egg skin prick test, sIgE and sIgG4 serum levels, PEW double-blind placebo-controlled food challenge (DBPCFC), and dosing adverse reactions (DARs) were evaluated in all patients from inclusion (T0) until completing 1 year of follow-up (T12). At T12, egg-allergic control patients could start OIT. The effectiveness and safety of OIT and the effect of the buildup pattern were analyzed. RESULTS: At T12, 4/25 (16.0%) CG patients passed the PEW DBPCFC vs 64/76 (84.2%) OIT that reached total desensitization (P = 0.000); 12 egg-allergic control patients started OIT. Finally, 72/88 (81.81%) patients reached total desensitization, 96.15% PI vs 75.80% on PII (P = 0.01). Induction period (121.12 ± 91.43, median 98.00 days) was longer in patients on PII buildup pattern, and those with allergic asthma, minor threshold dose, or higher egg sIgE (P < 0.05). Most patients (89.06%) developed DARs: 74.53% were mild; 21.90% moderate; and 3.5% requiring adrenaline-treatment. Moderate reactions and those requiring adrenaline were more frequent in patients with allergic asthma, PII pattern, or higher egg sIgE serum antibody levels (P < 0.05). CONCLUSIONS: PEW OIT is an effective treatment for children with persistent egg allergy. A 30% weekly plus 5% daily increment pattern could be more effective and safer than one with only 30% weekly increments.