A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species

Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries. A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications. In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit. The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers. The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device "Spin-Tube", as each of them creates a specific spot pattern. Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay. The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per μL with single mismatch specificity. The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries.This research work has received funding from Junta de Andalucía, Consejería de Economía e Innovación (project number 2012-BIO1778), the Spanish Ministerio de Economía y Competitividad (Grants CTQ2012-34778, BIO2016-80519-R, FPI Grant BES-2013- 063020). This research was partially supported by the 7th European Community Framework Program (FP7-PEOPLE-2012-CIG-Project Number 322276)

Metal-Substituted Microporous Aluminophosphates

This chapter aims to present the zeotypes aluminophosphates (AlPOs) as a complementary alternative to zeolites in the isomorphic incorporation of metal ions within all-inorganic microporous frameworks as well as to discuss didactically the catalytic consequences derived from the distinctive features of both frameworks. It does not intend to be a compilation of either all or the most significant publications involving metal-substituted microporous aluminophosphates. Families of AlPOs and zeolites, which include metal ion-substituted variants, are the dominant microporous materials. Both these systems are widely used as catalysts, in particular through aliovalent metal ions substitution. Here, some general description of the synthesis procedures and characterization techniques of the MeAPOs (metal-contained aluminophosphates) is given along with catalytic properties. Next, some illustrative examples of the catalytic possibilities of MeAPOs as catalysts in the transformation of the organic molecules are given. The oxidation of the hardly activated hydrocarbons has probably been the most successful use of AlPOs doped with the divalent transition metal ions Co2+, Mn2+, and Fe2+, whose incorporation in zeolites is disfavoured. The catalytic role of these MeAPOs is rationalized based on the knowledge acquired from a combination of the most advanced characterization techniques. Finally, the importance of the high specificity of the structure-directing agents employed in the preparation of MeAPOs is discussed taking N,N-methyldicyclohexylamine in the synthesis of AFI-structured materials as a driving force. It is shown how such a high specificity could be predicted and how it can open great possibilities in the control of parameters as critical in catalysis as crystal size, inter-and intracrystalline mesoporosity, acidity, redox properties, incorporation of a great variety of heteroatom ions or final environment of the metal site (surrounding it by either P or Al)

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies

Amongst the various demyelinating diseases that affect the central nervous system, those induced by an inflammatory response stand out because of their epidemiological relevance. The best known inflammatory-induced demyelinating disease is multiple sclerosis, but the immune response is a common pathogenic mechanism in many other less common pathologies (e.g., acute disseminated encephalomyelitis and acute necrotizing haemorrhagic encephalomyelitis). In all such cases, modulation of the immune response seems to be a logical therapeutic approach. Cannabinoids are well known immunomodulatory molecules that act through CB1 and CB2 receptors. While activation of CB1 receptors has a psychotropic effect, activation of CB2 receptors alone does not. Therefore, to bypass the ethical problems that could result from the treatment of inflammation with psychotropic molecules, considerable effort is being made to study the potential therapeutic value of activating CB2 receptors. In this review we examine the current knowledge and understanding of the utility of cannabinoids as therapeutic molecules for inflammatory-mediated demyelinating pathologies. Moreover, we discuss how CB2 receptor activation is related to the modulation of immunopathogenic states

Predictors of active cancer thromboembolic outcomes: RIETE experience of the Khorana score in cancer-associated thrombosis

158sinoneEven though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1-2 points and 1145 (14 %) scored ≥points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99-7.63), 11.2 (95 %CI: 9.91-12.7) and 19.4 (95 %CI: 15.4-24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13-6.56), 10.3 (95 %CI: 9.02-11.7) and 19.4 (95 %CI: 15.4-24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8-28.0), 58.5 (95 %CI: 55.5-61.7) and 120 (95 %CI: 110-131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50-0.56) for recurrent VTE, 0.56 (95 %CI: 0.54-0.59) for major bleeding and 0.54 (95 %CI: 0.52-0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.noneTafur A.J.; Caprini J.A.; Cote L.; Trujillo-Santos J.; del Toro J.; Garcia-Bragado F.; Tolosa C.; Barillari G.; Visona A.; Monreal M.; Adarraga M.D.; Aibar M.A.; Alfonso M.; Arcelus J.I.; Ballaz A.; Barba R.; Barron M.; Barrn-Andres B.; Bascunana J.; Blanco-Molina A.; Canas I.; Chic N.; del Pozo R.; Diaz-Pedroche M.C.; Diaz-Peromingo J.A.; Falga C.; Fernandez-Aracil C.; Fernandez-Capitan C.; Fidalgo M.A.; Font C.; Font L.; Gallego P.; Garcia I.; Garcia M.A.; Garcia-Rodenas M.; Gavin O.; Gomez C.; Gomez V.; Gonzalez J.; Grau E.; Grimon A.; Guijarro R.; Guirado L.; Gutierrez J.; Hernandez-Comes G.; Hernandez-Blasco L.; Jara-Palomares L.; Jaras M.J.; Jimenez D.; Jimenez J.; Joya M.D.; Llamas P.; Lobo J.L.; Lopez P.; Lopez-Jimenez L.; Lopez-Reyes R.; Lopez-Saez J.B.; Lorente M.A.; Lorenzo A.; Lumbierres M.; Marchena P.J.; Martin-Martos F.; Mellado M.; Nieto J.A.; Nieto S.; Nunez A.; Nunez M.J.; Otalora S.; Otero R.; Ovejero A.; Pedrajas J.M.; Perez G.; Perez-Ductor C.; Peris M.L.; Pons I.; Porras J.A.; Reig O.; Riera-Mestre A.; Riesco D.; Rivas A.; Rodriguez M.; Rodriguez-Davila M.A.; Rosa V.; Ruiz-Artacho P.; Ruiz-Gimenez N.; Sahuquillo J.C.; Sala-Sainz M.C.; Samperiz A.; Sanchez-Martinez R.; Sanz O.; Soler S.; Sopena B.; Surinach J.M.; Torres M.I.; Uresandi F.; Usandizaga E.; Valero B.; Valle R.; Vela J.; Velez-Mendizabal E.; Vidal G.; Vila M.; Villalobos A.; Xifre B.; Vanassche T.; Verhamme P.; Yoo H.H.B.; Wells P.; Hirmerova J.; Maly R.; Salgado E.; Bertoletti L.; Bura-Riviere A.; Falvo N.; Farge-Bancel D.; Hij A.; Mahe I.; Moustafa F.; Braester A.; Brenner B.; Tzoran I.; Antonucci G.; Bilora F.; Bortoluzzi C.; Brandolin B.; Bucherini E.; Candeloro G.; Cattabiani C.; Ciammaichella M.; Dentali F.; Di Micco P.; Duce R.; Giorgi-Pierfranceschi M.; Grandone E.; Imbalzano E.; Lessiani G.; Maida R.; Mastroiacovo D.; Pace F.; Parisi R.; Pellegrinet M.; Pesavento R.; Pinelli M.; Poggio R.; Prandoni P.; Quintavalla R.; Rocci A.; Tiraferri E.; Tonello D.; Tufano A.; Visona A.; Gibietis V.; Skride A.; Vitola B.; Bosevski M.; Zdraveska M.; Bounameaux H.; Mazzolai L.Tafur, A. J.; Caprini, J. A.; Cote, L.; Trujillo-Santos, J.; del Toro, J.; Garcia-Bragado, F.; Tolosa, C.; Barillari, G.; Visona, A.; Monreal, M.; Adarraga, M. D.; Aibar, M. A.; Alfonso, M.; Arcelus, J. I.; Ballaz, A.; Barba, R.; Barron, M.; Barrn-Andres, B.; Bascunana, J.; Blanco-Molina, A.; Canas, I.; Chic, N.; del Pozo, R.; Diaz-Pedroche, M. C.; Diaz-Peromingo, J. A.; Falga, C.; Fernandez-Aracil, C.; Fernandez-Capitan, C.; Fidalgo, M. A.; Font, C.; Font, L.; Gallego, P.; Garcia, I.; Garcia, M. A.; Garcia-Rodenas, M.; Gavin, O.; Gomez, C.; Gomez, V.; Gonzalez, J.; Grau, E.; Grimon, A.; Guijarro, R.; Guirado, L.; Gutierrez, J.; Hernandez-Comes, G.; Hernandez-Blasco, L.; Jara-Palomares, L.; Jaras, M. J.; Jimenez, D.; Jimenez, J.; Joya, M. D.; Llamas, P.; Lobo, J. L.; Lopez, P.; Lopez-Jimenez, L.; Lopez-Reyes, R.; Lopez-Saez, J. B.; Lorente, M. A.; Lorenzo, A.; Lumbierres, M.; Marchena, P. J.; Martin-Martos, F.; Mellado, M.; Nieto, J. A.; Nieto, S.; Nunez, A.; Nunez, M. J.; Otalora, S.; Otero, R.; Ovejero, A.; Pedrajas, J. M.; Perez, G.; Perez-Ductor, C.; Peris, M. L.; Pons, I.; Porras, J. A.; Reig, O.; Riera-Mestre, A.; Riesco, D.; Rivas, A.; Rodriguez, M.; Rodriguez-Davila, M. A.; Rosa, V.; Ruiz-Artacho, P.; Ruiz-Gimenez, N.; Sahuquillo, J. C.; Sala-Sainz, M. C.; Samperiz, A.; Sanchez-Martinez, R.; Sanz, O.; Soler, S.; Sopena, B.; Surinach, J. M.; Torres, M. I.; Uresandi, F.; Usandizaga, E.; Valero, B.; Valle, R.; Vela, J.; Velez-Mendizabal, E.; Vidal, G.; Vila, M.; Villalobos, A.; Xifre, B.; Vanassche, T.; Verhamme, P.; Yoo, H. H. B.; Wells, P.; Hirmerova, J.; Maly, R.; Salgado, E.; Bertoletti, L.; Bura-Riviere, A.; Falvo, N.; Farge-Bancel, D.; Hij, A.; Mahe, I.; Moustafa, F.; Braester, A.; Brenner, B.; Tzoran, I.; Antonucci, G.; Bilora, F.; Bortoluzzi, C.; Brandolin, B.; Bucherini, E.; Candeloro, G.; Cattabiani, C.; Ciammaichella, M.; Dentali, F.; Di Micco, P.; Duce, R.; Giorgi-Pierfranceschi, M.; Grandone, E.; Imbalzano, E.; Lessiani, G.; Maida, R.; Mastroiacovo, D.; Pace, F.; Parisi, R.; Pellegrinet, M.; Pesavento, R.; Pinelli, M.; Poggio, R.; Prandoni, P.; Quintavalla, R.; Rocci, A.; Tiraferri, E.; Tonello, D.; Tufano, A.; Visona, A.; Gibietis, V.; Skride, A.; Vitola, B.; Bosevski, M.; Zdraveska, M.; Bounameaux, H.; Mazzolai, L