Rapid in vitro activity of telavancin against Bacillus anthracis and in vivo protection against inhalation anthrax infection in the rabbit model.

Inhalation anthrax is the most severe form of Bacillus anthracis infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess in vitro potency of telavancin against 17 B. anthracis isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 µg/mL). Further, telavancin conveyed 100% survival in this model and cleared B. anthracis from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal in vivo activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.

Mistakes in the diagnosis and treatment of Helicobacter pylori infection in daily clinical practice.

BACKGROUND: An adequate diagnostic and therapeutic approach to Helicobacter pylori (H. pylori) infection is the cornerstone to avoid overdiagnosis, overuse of health resources, and increase in antibiotic resistances. The aim of the study was to evaluate the most common errors in clinical practice and the associated risk factors. MATERIALS AND METHODS: This is a retrospective observational study including patients with H. pylori infection and no previous treatment belonging to two defined areas of the National Health System in Spain; some of them were enrolled in the European Registry on H. pylori management (Hp-EuReg). Patients were attended by gastroenterologists between 2010 and 2019. According to current guidelines, we evaluated indications for H. pylori investigation, appropriateness of diagnostic test used in dyspeptic patients and discontinuation of surveillance after treatment. RESULTS: A total of 1730 patients were included, receiving 2260 eradication regimens. H. pylori infection was investigated in 1.7% cases in absence of a formal indication. Oral endoscopy was incorrectly used in 56% of patients with dyspepsia under 55 years without alarm signs, and urea breath test (UBT) was incorrectly used in 22.4% of patients with dyspepsia ≥55 years or red flags. Levofloxacin containing regimens were used as first-line therapy in 7.5% of non-allergic to penicillin patients. After first-line failure, clarithromycin was repeated in 2.6% of the patients who received second-line therapy. Confirmatory test of H. pylori status was absent in 2.5% cases. Men, patients under 55 years, and patients diagnosed by UBT had a higher risk of not undergoing a confirmatory test. CONCLUSIONS: Investigation of H. pylori infection by gastroenterologists is rare in absence of a formal indication; however, endoscopy is commonly used for dyspeptic patients <55 years without red flags and non-invasive tests are still used for dyspeptic patients ≥55 years or presenting alarm signs. Men, patients under 55 years, and patients diagnosed by UBT have an increased risk of being lost to follow-up after eradication treatment.

[Analysis of the broadcasting and perceived utility through the implementation of a virtual training platform during the pandemic]. / Análisis de la difusión y utilidad percibida a través de la implementación de una plataforma de formación virtual durante la pandemia por COVID-19.

Introduction: The SARS-CoV-2 pandemic has affected training opportunities for healthcare professionals partly because face to face courses were cancelled. This study analyzes the results of participation and satisfaction of the AEC Virtual Classroom sessions during the first year. Methods: The AEC Virtual Classroom includes a combined format of weekly Webinar broadcast live that can be viewed on a delayed basis in a virtual platform. In this study, the results in its first year are evaluated considering the number of live participants, the delayed views and the global reach; as well as the results of the satisfaction survey in each of the sessions (0-10). Results: From 16/04/2020 to 15/04/2021, 50 sessions of the Virtual Classroom AEC were held. The average scope of the sessions was 509 ± 288 views with a range between 196 and 149. At the times of highest incidence of cases during the pandemic, a decrease in live participants was observed 275 ± 135 vs. 391 ± 233 (p = 0.032). The mean score on the format was 8.46 ± 0.31/10. The best-scored sessions were those of the subject related to coloproctology with a statistically significant difference in the mean score 8.79 ± 0.42 vs. 8.39 ± 0.27 (p = 0.035). 90% of users considered the sessions useful. 97.2% of respondents believe that the sessions should be maintained after the pandemic. Conclusions: The AEC Virtual Classroom has a very good results in the first year, proving to be a useful surgical teaching tool that will foreseeably survive once the pandemic is over.

Patient-Reported Outcome Measures in Colorectal Surgery: Construction of Core Measures Using Open-Source Research Method.

Purpose. The primary aim of the study was to review the existing literature about patient-reported outcome measures (PROMs) in colorectal cancer and IBD. The secondary aim was to present a road map to develop a core outcome set via opinion gathering using social media. Method. This study is the first step of a three-step project aimed at constructing simple, applicable PROMs in colorectal surgery. This article was written in a collaborative manner with authors invited both through Twitter via the #OpenSourceResearch hashtag. The 5 most used PROMs were presented and discussed as slides/images on Twitter. Inputs from a wide spectrum of participants including researchers, surgeons, physicians, nurses, patients, and patients' organizations were collected and analyzed. The final draft was emailed to all contributors and 6 patients' representatives for proofreading and approval. Results. Five PROM sets were identified and discussed: EORTC QLQ-CR29, IBDQ short health questionnaire, EORTC QLQ-C30, ED-Q5-5L, and Short Form-36. There were 315 tweets posted by 50 tweeters with 1458 retweets. Awareness about PROMs was generally limited. The general psycho-physical well-being score (GPP) was suggested and discussed, and then a survey was conducted in which more than 2/3 of voters agreed that GPP covers the most important aspects in PROMs. Conclusion. Despite the limitations of this exploratory study, it offered a new method to conduct clinical research with opportunity to engage patients. The general psycho-physical well-being score suggested as simple, applicable PROMs to be eventually combined procedure-specific, disease-specific, or symptom-specific PROMs if needed.

[National survey on the treatment of cholelitiasis in Spain during the initial period of the COVID-19 pandemic]. / Encuesta nacional sobre el tratamiento de la colelitiasis en España durante la fase inicial de la pandemia por COVID-19.

Introduction: The extraordinary impact of COVID-19 pandemic on Spanish hospitals has led to a redistribution of resources for the treatment of these patients, with a decreased capacity of care for other common diseases. The aim of the present study is to analyse how this situation has affected the treatment of cholecystitis and cholelythiasis. Methods: It is a descriptive national study after online voluntary distribution of a specific questionnaire with Google Drive™ to members of the Spanish Association of Surgeons (AEC). Results: We received 153 answers (one per hospital). Elective cholecystectomies have been cancelled in 96.7% of centres. Conservative treatment for acute cholecystitis has been selected in 90% (previously 18%), and if operated, 95% have been performed laparoscopically. Globally, only 49% perform preoperative diagnostic tests for SARS-CoV-2, and 58.5% recognize there have been cases confirmed postoperatively after other surgeries, with worse surgical outcomes in 54%. Conclusions: This survey shows that most of the Spanish centers are following the surgical societies suggestions during the pandemic. However, some data requires to be taken into account for the next phase of the pandemic.

Ligand-Constraint-Induced Peroxide Activation for Electrophilic Reactivity.

µ-1,2-peroxo-bridged diiron(III) intermediates P are proposed as reactive intermediates in various biological oxidation reactions. In sMMO, P acts as an electrophile, and performs hydrogen atom and oxygen atom transfers to electron-rich substrates. In cyanobacterial ADO, however, P is postulated to react by nucleophilic attack on electrophilic carbon atoms. In biomimetic studies, the ability of µ-1,2-peroxo-bridged dimetal complexes of Fe, Co, Ni and Cu to act as nucleophiles that effect deformylation of aldehydes is documented. By performing reactivity and theoretical studies on an end-on µ-1,2-peroxodicobalt(III) complex 1 involving a non-heme ligand system, L1, supported on a Sn6 O6 stannoxane core, we now show that a peroxo-bridged dimetal complex can also be a reactive electrophile. The observed electrophilic chemistry, which is induced by the constraints provided by the Sn6 O6 core, represents a new domain for metal-peroxide reactivity.

Temperature Dependence of the Catalytic Two- versus Four-Electron Reduction of Dioxygen by a Hexanuclear Cobalt Complex.

The synthesis and characterization of a hexanuclear cobalt complex 1 involving a nonheme ligand system, L1, supported on a Sn6O6 stannoxane core are reported. Complex 1 acts as a unique catalyst for dioxygen reduction, whose selectivity can be changed from a preferential 4e-/4H+ dioxygen-reduction (to water) to a 2e-/2H+ process (to hydrogen peroxide) only by increasing the temperature from -50 to 25 °C. A variety of spectroscopic methods (119Sn-NMR, magnetic circular dichroism (MCD), electron paramagnetic resonance (EPR), SQUID, UV-vis absorption, and X-ray absorption spectroscopy (XAS)) coupled with advanced theoretical calculations has been applied for the unambiguous assignment of the geometric and electronic structure of 1. The mechanism of the O2-reduction reaction has been clarified on the basis of kinetic studies on the overall catalytic reaction as well as each step in the catalytic cycle and by low-temperature detection of intermediates. The reason why the same catalyst can act in either the two- or four-electron reduction of O2 can be explained by the constraint provided by the stannoxane core that makes the O2-binding to 1 an entropically unfavorable process. This makes the end-on µ-1,2-peroxodicobalt(III) intermediate 2 unstable against a preferential proton-transfer step at 25 °C leading to the generation of H2O2. In contrast, at -50 °C, the higher thermodynamic stability of 2 leads to the cleavage of the O-O bond in 2 in the presence of electron and proton donors by a proton-coupled electron-transfer (PCET) mechanism to complete the O2-to-2H2O catalytic conversion in an overall 4e-/4H+ step. The present study provides deep mechanistic insights into the dioxygen reduction process that should serve as useful and broadly applicable principles for future design of more efficient catalysts in fuel cells.

A Highly Reactive Oxoiron(IV) Complex Supported by a Bioinspired N3 O Macrocyclic Ligand.

The sluggish oxidants [FeIV (O)(TMC)(CH3 CN)]2+ (TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and [FeIV (O)(TMCN-d12 )(OTf)]+ (TMCN-d12 =1,4,7,11-tetra(methyl-d3 )-1,4,7,11-tetraazacyclotetradecane) are transformed into the highly reactive oxidant [FeIV (O)(TMCO)(OTf)]+ (1; TMCO=4,8,12-trimethyl-1-oxa-4,8,12-triazacyclotetradecane) upon replacement of an NMe donor in the TMC and TMCN ligands by an O atom. A rate enhancement of five to six orders of magnitude in both H atom and O atom transfer reactions was observed upon oxygen incorporation into the macrocyclic ligand. This finding was explained in terms of the higher electrophilicity of the iron center and the higher availability of the more reactive S=2 state in 1. This rationalizes nature's preference for using O-rich ligand environments for the hydroxylation of strong C-H bonds in enzymatic reactions.

Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.

Executive summary: Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.

Negative-Pressure Therapy to Reduce the Risk of Wound Infection Following Diverting Loop Ileostomy Reversal: An Initial Study.

OBJECTIVE: To evaluate if the application of a negative-pressure therapy system (Prevena Incision Management System, Kinetics Concepts Inc, [KCI] an Acelity Company, San Antonio, Texas) on ileostomy-closure surgical wounds would reduce surgical site infections (SSIs) in comparison with conventional closure and dressing. DESIGN: Prospective interventional pilot study. SETTING: La Paz University Hospital, tertiary care academic hospital in Madrid, Spain. PATIENTS: The Prevena device was applied on the wounds of 17 consecutive patients undergoing ileostomy reversal. Control subjects were 43 patients undergoing the same procedure, in which conventional dressings were used for the wound. INTERVENTION: The device was applied on the wound immediately after surgery (under sterile conditions) and maintained for 5 to 7 days. Patients were evaluated daily, and on the seventh postoperative day, the device was removed and wounds carefully inspected. Another evaluation was performed a month after the surgical intervention in the outpatient clinic. MAIN OUTCOME MEASURE: The primary end point of the study was the detection of SSI (defined according to the Centers for Disease Control and Prevention definitions). Other intervention-related complications were also registered. MAIN RESULTS: There were no significant differences in demographic variables between groups. In the control group, 9 patients (21%) presented SSI, with statistical significance (P < .038) when compared with the intervention group (0%). There were no complications associated with the application of the Prevena device. Other complications (for example, ileus or obstruction) occurred in 30% of patients. CONCLUSIONS: The negative-pressure Prevena System was safe and easy to use and may prevent SSIs in dirty wounds, such as those from ileostomy closure.

Surgical protocol for confirmed or suspected cases of Ebola and other highly transmissible diseases.

Outbreaks of viral haemorrhagic fevers such as Ebola can lead to imported cases in Europe and America. The eventuality of surgery in the setting of Ebola Virus Disease (EVD) is low, but the Spanish Association of Surgeons elaborated a surgical protocol for EVD. INDICATION: Elective surgical procedures are not indicated. Emergency cases can be considered in: persons under investigation, possible cases and early confirmed cases. In some conditions usually treated by surgery a medical treatment can be tested. HOSPITALS AND TEAMS: All cases must be treated in high technology hospitals. These hospitals must be equipped with adequate means for healthcare provider's protection. All members of the healthcare team should practice thorough simulation prior to caring for a possible Ebola patient. SURGICAL PROTOCOL: This protocol is based on international guidelines on use of Personal Protective Equipment, protocols of other scientific societies, and specific recommendations for the operating room environment.

Oxidation Reactions with Bioinspired Mononuclear Non-Heme Metal-Oxo Complexes.

The selective functionalization of strong C-H bonds and the oxidation of water by cheap and nontoxic metals are some of the key targets of chemical research today. It has been proposed that high-valent iron-, manganese-, and copper-oxo cores are involved as reactive intermediates in important oxidation reactions performed by biological systems, thus making them attractive targets for biomimetic synthetic studies. The generation and characterization of metal-oxo model complexes of iron, manganese, and copper together with detailed reactivity studies can help in understanding how the steric and electronic properties of the metal centers modulate the reactivity of the metalloenzymes. This Review provides a focused overview of the advances in the chemistry of biomimetic high-valent metal-oxo complexes from the last 5-10 years that can be related to our understanding of biological systems.

Peptidylarginine deiminase 3 modulates response to neratinib in HER2 positive breast cancer.

Neratinib is a tyrosine kinase inhibitor that is used for the therapy of patients with HER2+ breast tumors. However, despite its clinical benefit, resistance to the drug may arise. Here we have created cellular models of neratinib resistance to investigate the mechanisms underlying such resistance. Chronic neratinib exposure of BT474 human HER2+ breast cancer cells resulted in the selection of several clones resistant to the antiproliferative action of the drug. The clones were characterized biochemically and biologically using a variety of techniques. These clones retained HER2 levels similar to parental cells. Knockdown experiments showed that the neratinib-resistant clones retained oncogenic dependence on HER2. Moreover, the tyrosine phosphorylation status of BT474 and the resistant clones was equally sensitive to neratinib. Transcriptomic and Western analyses showed that peptidylarginine deiminase 3 was overexpressed in the three neratinib-resistant clones studied but was undetectable in BT474 cells. Experiments performed in the neratinib-resistant clones showed that reduction of PADI3 or inhibition of its function restored sensitivity to the antiproliferative action of neratinib. Moreover, overexpression of FLAG-tagged PADI3 in BT474 cells provoked resistance to the antiproliferative action of neratinib. Together, these results uncover a role of PADI3 in the regulation of sensitivity to neratinib in breast cancer cells overexpressing HER2 and open the possibility of using PADI3 inhibitors to fight resistance to neratinib.

Surgical Infection Reduction Program of the Observatory of Surgical Infection (PRIQ-O): Delphi prioritization and consensus document on recommendations for the prevention of surgical site infection.

Surgical site infection is the most frequent and avoidable complication of surgery, but clinical guidelines for its prevention are insufficiently followed. We present the results of a Delphi consensus carried out by a panel of experts from 17 Scientific Societies with a critical review of the scientific evidence and international guidelines, to select the measures with the highest degree of evidence and facilitate their implementation. Forty measures were reviewed and 53 recommendations were issued. Ten main measures were prioritized for inclusion in prevention bundles: preoperative shower; correct surgical hand hygiene; no hair removal from the surgical field or removal with electric razors; adequate systemic antibiotic prophylaxis; use of minimally invasive approaches; skin decontamination with alcoholic solutions; maintenance of normothermia; plastic wound protectors-retractors; intraoperative glove change; and change of surgical and auxiliary material before wound closure.

Prophylactic use of incisional negative pressure wound therapy for the prevention of surgical site occurrences in general surgery: Consensus document.

BACKGROUND: Surgical site occurrences pose a threat to patient health, potentially resulting in significant increases in health care spending caused by using additional resources. The objective of this study was to reach a consensus among a group of experts in incisional negative pressure wound therapy to determine the indications for using this type of treatment prophylactically and to analyze the associated risk factors of surgical site occurrences in abdominal surgery. METHODS: A group of experts in incisional negative pressure wound therapy from Spain and Portugal was formed among general surgery specialists who frequently perform colorectal, esophagogastric, or abdominal wall surgery. The Coordinating Committee performed a bibliographic search to identify the most relevant publications and to create a summary table to serve as a decision-making protocol regarding the use of prophylactic incisional negative pressure wound therapy based on factors related to the patient and type of procedure. RESULTS: The patient risk factors associated with surgical site occurrence development such as age, immunosuppression, anticoagulation, hypoalbuminemia, smoking, American Society of Anesthesiologists classification, diabetes, obesity, and malnutrition were analyzed. For surgical procedure factors, surgical time, repeated surgeries, organ transplantation, need for blood transfusion, complex abdominal wall reconstruction, surgery at a contaminated site, open abdomen closure, emergency surgery, and hyperthermic intraperitoneal chemotherapy were analyzed. CONCLUSION: In our experience, this consensus has been achieved on a tailored set of recommendations on patient and surgical aspects that should be considered to reduce the risk of surgical site occurrences with the use of prophylactic incisional negative pressure wound therapy, particularly in areas where the evidence base is controversial or lacking.