Modelo animal de ectasia corneal en conejo mediante inyección intraestromal de colagenasa tipo ii / Animal model of corneal ectasia in rabbits by intrastromal injection of type II collagenase

Introducción La colagenasa ii ha sido utilizada para inducir queratocono experimental en modelos animales. Sin embargo, no ha sido estudiado su efecto cuando se administra por inyección intraestromal, por lo que el propósito de este estudio fue estudiar los efectos de la inyección intraestromal de colagenasa ii sobre la superficie corneal y la morfología de la córnea. Método Se trabajó con 6 conejos Nueva Zelanda, se administró colagenasa ii por inyección intraestromal (5μL de 2,5mg/mL) en los ojos derechos y solución salina balanceada en los ojos izquierdos. Se realizaron queratometrías para evaluar la alteración de la curvatura, también al séptimo día se obtuvieron las córneas y se realizó tinción hematoxilina-eosina para examinar los cambios morfológicos. Asimismo, se investigaron los cambios en la expresión de colágeno tipo i por tinción rojo sirio y PCR semicuantitativa. Resultados K1, K2 y Km presentaron diferencias en los promedios con cambios estadísticamente significativos. Los cambios morfológicos que se demostraron fueron degradación y disposición irregular del estroma corneal, incremento en la densidad celular de queratocitos y ligera infiltración celular. Finalmente se demostró que hay mayor expresión de fibras de colágeno tipo i en el grupo experimental a diferencia de los controles y el grosor de las fibras también aumentó por acción de la colagenasa ii; sin embargo, en cuestión génica no hubo cambios en la expresión de colágeno tipo i a nivel molecular entre el grupo control y experimental. Conclusiones La colagenasa ii administrada por inyección intraestromal es capaz de inducir cambios en la superficie corneal y el estroma, pudiendo simular un modelo de queratocono (AU)

Introduction Collagenase II has been used to induce experimental keratoconus in animal models. However, its effect when administered by intrastromal injection has not been studied, so the purpose of this study was to study the effects of intrastromal injection of collagenase II on corneal surface and corneal morphology. Method Six New Zealand rabbits were used, collagenase II was administered by intrastromal injection (5μL of 2.5mg/mL) in the right eyes and balanced salt solution in the left eyes. Keratometry was performed to evaluate curvature alteration, also at day 7 corneas were obtained and hematoxylin–eosin staining was performed to examine morphologic changes. Likewise, changes in type I collagen expression were investigated by Sirius Red staining and semi-quantitative PCR. Results K1, K2, and Km presented differences in the means with statistically significant changes. The morphological changes that were demonstrated were degradation and irregular arrangement of the corneal stroma, increase in the cellular density of keratocytes and slight cellular infiltration. Finally, it was demonstrated that there is greater expression of type I collagen fibers in the experimental group as opposed to the controls and the thickness of the fibers also increased due to the action of collagenase II, however, in terms of genetics there were no changes in the expression of type I collagen at molecular level between the control and experimental groups. Conclusions Collagenase II administered by intrastromal injection is able to induce changes in the corneal surface and stroma, being able to simulate a model of keratoconus (AU)

Animal model of corneal ectasia in rabbits by intrastromal injection of type II collagenase.

INTRODUCTION: Collagenase II has been used to induce experimental keratoconus in animal models. However, its effect when administered by intrastromal injection has not been studied, so the purpose of this study was to study the effects of intrastromal injection of collagenase II on corneal surface and corneal morphology. METHODS: Six New Zealand rabbits were used, collagenase II was administered by intrastromal injection (5µL of 2.5mg/mL) in the right eyes and balanced salt solution in the left eyes. Keratometry was performed to evaluate curvature alteration, also at day 7 corneas were obtained and Hematoxylin-Eosin staining was performed to examine morphologic changes. Likewise, changes in type I collagen expression were investigated by Sirius Red staining and semiquantitative PCR. RESULTS: K1, K2 and Km presented differences in the means with statistically significant changes. The morphological changes that were demonstrated were degradation and irregular arrangement of the corneal stroma, increase in the cellular density of keratocytes and slight cellular infiltration. Finally, it was demonstrated that there is greater expression of type I collagen fibers in the experimental group as opposed to the controls and the thickness of the fibers also increased due to the action of collagenase II, however, in terms of genetics there were no changes in the expression of type I collagen at molecular level between the control and experimental groups. CONCLUSIONS: Collagenase II administered by intrastromal injection is able to induce changes in the corneal surface and stroma, being able to simulate a model of keratoconus.

Formulation and development of paediatric orally disintegrating carbamazepine tablets.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

Signatures of a magnetic-field-induced Lifshitz transition in the ultra-quantum limit of the topological semimetal ZrTe5.

The quantum limit (QL) of an electron liquid, realised at strong magnetic fields, has long been proposed to host a wealth of strongly correlated states of matter. Electronic states in the QL are, for example, quasi-one dimensional (1D), which implies perfectly nested Fermi surfaces prone to instabilities. Whereas the QL typically requires unreachably strong magnetic fields, the topological semimetal ZrTe5 has been shown to reach the QL at fields of only a few Tesla. Here, we characterize the QL of ZrTe5 at fields up to 64 T by a combination of electrical-transport and ultrasound measurements. We find that the Zeeman effect in ZrTe5 enables an efficient tuning of the 1D Landau band structure with magnetic field. This results in a Lifshitz transition to a 1D Weyl regime in which perfect charge neutrality can be achieved. Since no instability-driven phase transitions destabilise the 1D electron liquid for the investigated field strengths and temperatures, our analysis establishes ZrTe5 as a thoroughly understood platform for potentially inducing more exotic interaction-driven phases at lower temperatures.

Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination After Cytoreductive Surgery and HIPEC.

BACKGROUND: Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). PATIENTS AND METHODS: Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). RESULTS: The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. CONCLUSIONS: An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.

Defining stage in mucinous tumours of the appendix with peritoneal dissemination: the importance of grading terminology: systematic review.

BACKGROUND: Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but no universally accepted histological grading has been established. The aim of this systematic review was to provide historical insight to understand current grading classifications, basic histopathological features of each category, and to define which classification correlates best with prognosis. METHODS: MEDLINE and the Cochrane Library were searched for studies that reported survival across different pathological grades in patients with mucinous neoplasm of the appendix with PD treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PRISMA guidelines were followed. RESULTS: Thirty-eight studies were included. Ronnett's classification was the most common (9 studies). Classifications proposed by the Peritoneal Surface Oncology Group International (PSOGI) (6 studies) and the seventh or eighth edition of the AJCC (7 studies) are gaining in popularity. Nine studies supported a two-tier, 12 a three-tier, and two a four-tier classification system. Three studies demonstrated that acellular mucin had a better prognosis than low-grade pseudomyxoma peritonei in the PSOGI classification or M1bG1 in the eighth edition of the AJCC classification. Four studies demonstrated that the presence of signet ring cells was associated with a worse outcome than high-grade pseudomyxoma peritonei in the PSOGI classification and M1bG2 in the eighth edition of the AJCC. CONCLUSION: There is a great need for a common language in describing mucinous neoplasms of the appendix with PD. Evolution in terminology as a result of pathological insight turns the four-tiered PSOGI classification system into a coherent classification option.

Origin of the quasi-quantized Hall effect in ZrTe5.

The quantum Hall effect (QHE) is traditionally considered to be a purely two-dimensional (2D) phenomenon. Recently, however, a three-dimensional (3D) version of the QHE was reported in the Dirac semimetal ZrTe5. It was proposed to arise from a magnetic-field-driven Fermi surface instability, transforming the original 3D electron system into a stack of 2D sheets. Here, we report thermodynamic, spectroscopic, thermoelectric and charge transport measurements on such ZrTe5 samples. The measured properties: magnetization, ultrasound propagation, scanning tunneling spectroscopy, and Raman spectroscopy, show no signatures of a Fermi surface instability, consistent with in-field single crystal X-ray diffraction. Instead, a direct comparison of the experimental data with linear response calculations based on an effective 3D Dirac Hamiltonian suggests that the quasi-quantization of the observed Hall response emerges from the interplay of the intrinsic properties of the ZrTe5 electronic structure and its Dirac-type semi-metallic character.

A light-induced phononic symmetry switch and giant dissipationless topological photocurrent in ZrTe5.

Dissipationless currents from topologically protected states are promising for disorder-tolerant electronics and quantum computation. Here, we photogenerate giant anisotropic terahertz nonlinear currents with vanishing scattering, driven by laser-induced coherent phonons of broken inversion symmetry in a centrosymmetric Dirac material ZrTe5. Our work suggests that this phononic terahertz symmetry switching leads to formation of Weyl points, whose chirality manifests in a transverse, helicity-dependent current, orthogonal to the dynamical inversion symmetry breaking axis, via circular photogalvanic effect. The temperature-dependent topological photocurrent exhibits several distinct features: Berry curvature dominance, particle-hole reversal near conical points and chirality protection that is responsible for an exceptional ballistic transport length of ~10 µm. These results, together with first-principles modelling, indicate two pairs of Weyl points dynamically created by B1u phonons of broken inversion symmetry. Such phononic terahertz control breaks ground for coherent manipulation of Weyl nodes and robust quantum transport without application of static electric or magnetic fields.

Unconventional Hall response in the quantum limit of HfTe5.

Interacting electrons confined to their lowest Landau level in a high magnetic field can form a variety of correlated states, some of which manifest themselves in a Hall effect. Although such states have been predicted to occur in three-dimensional semimetals, a corresponding Hall response has not yet been experimentally observed. Here, we report the observation of an unconventional Hall response in the quantum limit of the bulk semimetal HfTe5, adjacent to the three-dimensional quantum Hall effect of a single electron band at low magnetic fields. The additional plateau-like feature in the Hall conductivity of the lowest Landau level is accompanied by a Shubnikov-de Haas minimum in the longitudinal electrical resistivity and its magnitude relates as 3/5 to the height of the last plateau of the three-dimensional quantum Hall effect. Our findings are consistent with strong electron-electron interactions, stabilizing an unconventional variant of the Hall effect in a three-dimensional material in the quantum limit.

Study of tocopherol content and its potential antioxidant activity in commercial lipid emulsions for parenteral nutrition.

The objective of this study was to determine the content and evaluate the potential antioxidant effect of tocopherols in commercially available lipid emulsions, using a simple validated method adequate for further routine use. During the study, variability between manufacturers as well as between three non-consecutive batches of the same emulsion was observed. Furthermore, addition of α-tocopherol to lipid emulsions as excipient yields more stable emulsions and potentially a beneficial clinical effect. It was concluded that the variation of the tocopherol content between batches implies the importance of control and specification of tocopherol content by the manufacturers.

Cost-benefit analysis of funding smoking cessation before surgery.

BACKGROUND: Smoking at the time of surgery is associated with postoperative complications. Quitting smoking before surgery is linked to fewer complications during the hospital stay. This work analysed whether a smoking cessation intervention before surgery is economically worthwhile when funded by the National Health System (NHS) in Spain. METHODS: The economic analysis considered costs and benefits of the intervention to the NHS for the year 2016. The population who would benefit comprised adult smokers who were ready to quit and for whom surgery requiring admission to hospital was planned. The intervention, a combination of medical counselling and use of a smoking cessation drug which should occur 12 weeks before surgery, considered one attempt only to quit smoking. Benefits were costs avoided by averting postoperative complications if cessation was successful. The analysis compared the net economic outcome (benefit minus cost of intervention) and the return on investment, for intervention funded by the NHS versus the current situation without funding. RESULTS: Smoking cessation increased by 21·7 per cent with funding; the rate was 32·5 per cent when funded versus 10·7 per cent without funding, producing 9611 extra quitters. The cost per averted smoker was €1753 with a benefit of €503, achieving a net economic benefit of €4·8 million per year. Given the annual cost of the intervention (€17·4 million, of which €5·6 million (32·5 per cent) represents drugs), the return on investment was 28·7 per cent annually, equivalent to €1·29 per €1 of investment. CONCLUSION: From the perspective of the Spanish NHS, the benefit of funding smoking cessation before surgery, in terms of healthcare cost savings, appears to greatly outweigh the costs.

ANTECEDENTES: Ser fumador activo hasta el momento de la cirugía se asocia con complicaciones postoperatorias. Se ha descrito una disminución de las complicaciones durante la hospitalización al abandonar el hábito de fumar antes de la cirugía. Este trabajo analizó si una intervención preoperatoria para dejar de fumar es económicamente beneficiosa cuando se financia por el Sistema Nacional de Salud (SNS) en España. MÉTODOS: En el análisis económico se consideraron tantos los costes como los beneficios de la intervención para el SNS, en euros, correspondientes al año 2016. La población que se beneficiaría eran fumadores adultos dispuestos a dejar de fumar, en los que se programase una intervención quirúrgica con hospitalización. La intervención, una combinación de asesoramiento médico y tratamiento farmacológico para dejar de fumar, se llevó a cabo a las 12 semanas antes de la cirugía, considerando únicamente un intento para dejar de fumar. Los beneficios fueron los costes evitados por una reducción en la tasa de complicaciones postoperatorias en los casos en los que se hubiese conseguido la eliminación del hábito. El análisis comparó el resultado económico neto (beneficio menos coste de la intervención) y el retorno de la inversión (return on investment, ROI), cuando la intervención era financiada por el SNS en comparación con la situación actual sin financiamiento público. RESULTADOS: La tasa de abandono del hábito tabáquico aumentó en un 21,8%; 32,5% cuando se financiaba frente al 10,7% sin financiación, consiguiendo un extra de 9.611 personas que dejaron de fumar. El coste por fumador rescatado fue de €1753 con un beneficio de €503, por lo que el beneficio económico neto conseguido fue de €4,8 millones por año. Dado que el coste anual de la intervención (€17,4 millones, de los cuales €5,6 millones corresponden a fármacos (32%)), el ROI anual fue del 28,7% con un beneficio de €1,29 por cada €1 de inversión. CONCLUSIÓN: Desde la perspectiva del SNS español, los beneficios de financiar el abandono del hábito de fumar en el preoperatorio de los pacientes, en términos de ahorro de costes parecen ser muy superiores a los costes de la intervención.

Evaluation of Plasma Disappearance Rate Indocyanine Green Clearance as a Predictor of Liver Graft Rejection in Donor Brain Death.

INTRODUCTION: There currently exist no quantitative methods to assess graft viability before the donor procurement procedure. In Europe, around 20% of liver grafts evaluated "in situ" by an experienced surgeon are discarded. The aim of this study is to evaluate the use of the plasma disappearance rate indocyanine green (PDR-ICG) clearance in predicting liver graft rejection to avoid this 20% of futile surgeries. OBJECTIVES: To evaluate PDR-ICG as a predictor of liver graft rejection in death brain donors compared with the gold standard evaluation by an experienced surgeon. MATERIAL AND METHODS: Prospective observational single center study. From March 2017 to July 2019, 29 donors were included in the study, 17 were men and 12 women with a median age of 68 years ± 16.9 years. Donors had an intensive care unit stay of 2 days ± 4 days. PDR-ICG was measured with PICCO2 monitor. Indocyanine green clearance dose was 0.25 mg/kg injected intravenously in the operating room just before donor procurement procedure is initiated. The surgeon was unaware of the PDR-ICG measure until the decision of graft acceptance was taken. Data regarding the donors and biopsy results were included in a prospective database. RESULTS: PDR-ICG measure could be obtained in 10 minutes in all of the cases included. The median PDR-ICG obtained was 18%/min (range, 2.4-31%/min). Graft rejection took place in 15 out of the 29 donors. PDR-ICG value was less than 10%/min in 6 of these rejected grafts and less than 15%/min in 10 donors. All donor grafts with PDR-ICG <15% were discarded. The graft had been discarded in 5 donors with a PDR-ICG >15%. CONCLUSIONS: In our study a plasma disappearance rate <10 would have identified the grafts that would be rejected, thus avoiding the displacement work and expense of the surgical team. These results should be confirmed in a multicentric study.

20 años en tabaquismo / 20 years in smoking

No disponible

20 años en enfermería respiratoria / 20 years in respiratory nursing

No disponible

Donor Risk Index Has an Impact in Intraoperative Measure of Hepatic Artery Flow and in Clearance of Indocyanine Green: An Observational Cohort Study.

BACKGROUND: The increase in indications for liver transplantation has led to acceptance of donors with expanded criteria. The donor risk index (DRI) was validated with the aim of being a predictive model of graft survival based on donor characteristics. Intraoperative arterial hepatic flow and indocyanine green clearance (plasma clearance rate of indocyanine green [ICG-PDR]) are easily measurable variables in the intraoperative period that may be influenced by graft quality. Our aim was to analyze the influence of DRI on intraoperative liver hemodynamic alterations and on intraoperative dynamic liver function testing (ICG-PDR). METHODS: This investigation was an observational study of a single-center cohort (n = 228) with prospective data collection and retrospective data analysis. Measurement of intraoperative flow was made with a VeriQ flowmeter based on measurement of transit time (MFTT). The ICG-PDR was obtained from all patients with a LiMON monitor (Pulsion Medical Systems AG, Munich, Germany). DRI was calculated using a previously validated formula. Normally distributed variables were compared using Student's t test. Otherwise, the Mann-Whitney U test or Kruskal-Wallis test was applied, depending on whether there were 2 or more comparable groups. The qualitative variables and risk measurements were analyzed using the chi-square test. P < .05 was considered statistically significant. RESULTS: DRI score (mean ± SD) was 1.58 ± 0.31. The group with DRI >1.7 (poor quality) had an intraoperative arterial flow of 234.2 ± 121.35 mL/min compared with the group having DRI < 1.7 (high quality), with an intraoperative arterial flow of 287.24 ± 156.84 mL/min (P = .02). The group with DRI >1.70 had an ICG-PDR of 14.75 ± 6.52%/min at 60 minutes after reperfusion compared to the group with DRI <1.70, with an ICG-PDR of 16.68 ± 6.47%/min at 60 minutes after reperfusion (P = .09). CONCLUSION: Poor quality grafts have greater susceptibility to ischemia-reperfusion damage. Decreased intraoperative hepatic arterial flow may represent an increase in intrahepatic resistance early in the intraoperative period.

The Moving to Health (M2H) approach to natural experiment research: A paradigm shift for studies on built environment and health.

Improving the built environment (BE) is viewed as one strategy to improve community diets and health. The present goal is to review the literature on the effects of BE on health, highlight its limitations, and explore the growing use of natural experiments in BE research, such as the advent of new supermarkets, revitalized parks, or new transportation systems. Based on recent studies on movers, a paradigm shift in built-environment health research may be imminent. Following the classic Moving to Opportunity study in the US, the present Moving to Health (M2H) strategy takes advantage of the fact that changing residential location can entail overnight changes in multiple BE variables. The necessary conditions for applying the M2H strategy to Geographic Information Systems (GIS) databases and to large longitudinal cohorts are outlined below. Also outlined are significant limitations of this approach, including the use of electronic medical records in lieu of survey data. The key research question is whether documented changes in BE exposure can be linked to changes in health outcomes in a causal manner. The use of geo-localized clinical information from regional health care systems should permit new insights into the social and environmental determinants of health.

Topical Analgesia with Lidocaine Plus Diclofenac Decreases Pain in Benign Anorectal Surgery: Randomized, Double-blind, and Controlled Clinical Trial.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a topical formulation containing lidocaine plus diclofenac (CLIFE1) compared to lidocaine (CLIFE2), to decrease pain in benign anorectal surgery (BARS) to date not evaluated. More than 50% of patients undergoing BARS, especially hemorrhoidectomy, suffer from moderate and severe postoperative pain. This remains an unresolved problem that could be addressed with the new CLIFE1 topical treatment. METHODS: A multicenter, randomized double-blind, active-controlled parallel-group superiority trial, was conducted in two Spanish hospitals. Patients undergoing BARS (hemorrhoids, anal fistula and anal fissure) were randomized at the end of surgery at a 1:1 ratio to receive first dose either CLIFE1 (n = 60) or CLIFE2 (n = 60) anorectal topical treatment, and after every 12 h for the first three postoperative days and once a day from the fourth to sixth. The primary outcome was average of pain decrease after topical treatment, measured with visual analogue scale (VAS) by the patients themselves, the evening in the surgery day and four times daily for the first three postoperative days. RESULTS: The results of 120 patients included out of 150 selected undergoing BARS show a decrease in pain after CLIFE1 topical treatment (7.47 ± 13.09) greater than with CLIFE2 (4.38 ± 6.75), difference -3.21 95% CI (-5.75; -0.68), p = 0.008, decreasing significantly postoperative pain ( ≥ 9 mm, VAS) in 35% of patients undergoing benign anorectal surgery, compared to 18.33 % treated with lidocaine. CONCLUSIONS: The CLIFE1 topical treatment shows better analgesic efficacy than CLIFE2 in BARS.