Lithium salts as a treatment for COVID-19: Pre-clinical outcomes.

INTRODUCTION: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3. AIMS: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19. RESULTS: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls. CONCLUSIONS: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19's patients.

Risk factors associated with postoperative morbidity and mortality in D2 radical gastrectomy for gastric cancer.

INTRODUCTION AND AIMS: Surgery is the main treatment for gastric cancer. D2 radical gastrectomy is associated with a variable postoperative morbidity and mortality rate worldwide. The aim of the present study was to identify the risk factors associated with the postoperative morbidity and mortality of D2 radical gastrectomy, with curative intent, for gastric cancer. MATERIALS AND METHODS: A retrospective case series was conducted, in which the medical records were reviewed of patients with gastric cancer that underwent D2 radical gastrectomy, within the time frame of January 2014 and December 2018. Univariate and multivariate analyses were carried out to identify the risk factors related to postoperative morbidity and mortality within 90 days. RESULTS: The percentages of postoperative morbidity and mortality in 691 patients were 23.3% and 3.3%, respectively. In the multivariate analysis, age ≥70 years (OR = 1.85, 95% CI: 1.25-2.76), ASA III-IV (OR = 2.06, 95% CI: 1.28-3.34), total gastrectomy (OR = 1.96, 95% CI:1.19-3.23), and pancreatosplenectomy (OR = 5.41, 95% CI: 1.42-20.61) were associated with greater postoperative morbidity, and age ≥70 years (OR = 4.92, 95% CI:1.78-13.65), lower BMI (OR = 0.81, 95% CI: 0.71-0.92), and hypoalbuminemia (OR = 0.91, 95% CI: 0.85-0.98) were associated with greater mortality in distal and total D2 radical gastrectomy. CONCLUSIONS: D2 radical gastrectomy for gastric cancer was shown to be a safe treatment, with low postoperative morbidity and mortality rates. Age ≥70 years, ASA III-IV, total gastrectomy, and pancreatosplenectomy were factors associated with a higher complication rate. Age ≥70 years, lower BMI, and hypoalbuminemia were mortality predictors in distal and total radical gastrectomy.

Radiological evaluation of the postsurgical middle ear.

OBJECTIVE: The radiological evaluation of the postsurgical middle ear is complex due to the intricate anatomy of this region and the wide variety of procedures and materials used iin middle ear surgery. Knowledge of these factors will enable normal postsurgical changes to be differentiated from complications. This article describes the most common surgical procedures in the middle ear, their indications, and the normal radiological appearance after these procedures. It reviews the most common causes of failure in stapes surgery, in surgery for chronic otitis media, and in surgery for cholesteatoma, suggesting the best imaging method to assess the middle ear in each case. CONCLUSION: Computed tomography enables the evaluation of prostheses and the aeration of the cavities, whereas magnetic resonance imaging makes it possible to characterize the possible occupation of the cavities and is the technique of choice for the follow-up of closed mastoidectomy for cholesteatomas.

Risk factors associated with postoperative morbidity and mortality in D2 radical gastrectomy for gastric cancer. / Factores de riesgo asociados con morbilidad y mortalidad postoperatoria en gastrectomía radical D2 por cáncer gástrico.

INTRODUCTION AND AIMS: Surgery is the main treatment for gastric cancer. D2 radical gastrectomy is associated with a variable postoperative morbidity and mortality rate worldwide. The aim of the present study was to identify the risk factors associated with the postoperative morbidity and mortality of D2 radical gastrectomy, with curative intent, for gastric cancer. MATERIALS AND METHODS: A retrospective case series was conducted, in which the medical records were reviewed of patients with gastric cancer that underwent D2 radical gastrectomy, within the time frame of January 2014 and December 2018. Univariate and multivariate analyses were carried out to identify the risk factors related to postoperative morbidity and mortality within 90 days. RESULTS: The percentages of postoperative morbidity and mortality in 691 patients were 23.3% and 3.3%, respectively. In the multivariate analysis, age ≥ 70 years (OR=1.85, 95% CI: 1.25-2.76), ASA III-IV (OR=2.06, 95% CI: 1.28-3.34), total gastrectomy (OR=1.96, 95% CI:1.19-3.23), and pancreatosplenectomy (OR=5.41, 95% CI: 1.42-20.61) were associated with greater postoperative morbidity, and age≥70 years (OR=4.92, 95% CI:1.78-13.65), lower BMI (OR=0.81, 95% CI: 0.71-0.92), and hypoalbuminemia (OR=0.91, 95% CI: 0.85-0.98) were associated with greater mortality in distal and total D2 radical gastrectomy. CONCLUSIONS: D2 radical gastrectomy for gastric cancer was shown to be a safe treatment, with low postoperative morbidity and mortality rates. Age≥70 years, ASA III-IV, total gastrectomy, and pancreatosplenectomy were factors associated with a higher complication rate. Age≥70 years, lower BMI, and hypoalbuminemia were mortality predictors in distal and total radical gastrectomy.

Implicación en Cataluña de los Servicios de Anestesiología y Reanimación en la pandemia por SARS-CoV-2. Una solución real coste-efectiva para una crisis sanitaria sin precedentes / Involvement in Catalonia of the Anaesthesiology and Resuscitation Services in the SARS-CoV-2 pandemic. A real, cost-effective solution to an unprecedented health crisis

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Laparoscopic Liver Resection: A South American Experience with 2887 Cases.

BACKGROUND: Laparoscopic liver resections (LLR) have been increasingly performed in recent years. Most of the available evidence, however, comes from specialized centers in Asia, Europe and USA. Data from South America are limited and based on single-center experiences. To date, no multicenter studies evaluated the results of LLR in South America. The aim of this study was to evaluate the experience and results with LLR in South American centers. METHODS: From February to November 2019, a survey about LLR was conducted in 61 hepatobiliary centers in South America, composed by 20 questions concerning demographic characteristics, surgical data, and perioperative results. RESULTS: Fifty-one (83.6%) centers from seven different countries answered the survey. A total of 2887 LLR were performed, as follows: Argentina (928), Brazil (1326), Chile (322), Colombia (210), Paraguay (9), Peru (75), and Uruguay (8). The first program began in 1997; however, the majority (60.7%) started after 2010. The percentage of LLR over open resections was 28.4% (4.4-84%). Of the total, 76.5% were minor hepatectomies and 23.5% major, including 266 right hepatectomies and 343 left hepatectomies. The conversion rate was 9.7%, overall morbidity 13%, and mortality 0.7%. CONCLUSIONS: This is the largest study assessing the dissemination and results of LLR in South America. It showed an increasing number of centers performing LLR with the promising perioperative results, aligned with other worldwide excellence centers.

Does fitness attenuate the relationship between changes in sitting time and health-related quality of life over time in community-dwelling older adults? Evidence from the EXERNET multicenter longitudinal study.

OBJECTIVE: To assess the relationship between fitness levels and components, sitting time and health-related quality of life (HRQoL), over time among community-dwelling older adults. METHODS: Three different sitting trajectories were calculated: (i) no change; (ii) decrease; and (iii) increase in ST, between baseline and follow-up. Fitness was assessed using the aerobic capacity, upper and lower limb strength, and total fitness. Participants were classified into higher (75th percentile or above) or lower (below 75th percentile) fitness levels, using the fitness tests. HRQoL scores at follow-up were compared to the three different sitting time trajectories within and across both the higher and the lower fitness groups for each of the three fitness indexes. RESULTS: Greater HRQoL scores were observed in those participants that decreased their ST as compared with those increasing their sitting time over time for participants classified in the lower end of their aerobic capacity or total fitness index. No differences were detected in HRQoL scores in people classified in the higher fitness level group for any of the fitness indexes. Participants that increased or did not change their sitting time and who were classified in the higher fitness end of aerobic capacity and total fitness index self-reported higher HRQoL scores when compared with those in the lower fitness end. CONCLUSION: Increased sitting time over time is associated with poorer HRQoL in older adults. Higher fitness levels could help attenuate the negative impact of sitting over time.

Correction to: Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.

The original version of the article unfortunately contained an error in the author group. Dr. Isabel Larré was not submitted and published in the original version.

Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.

Studies made in the Madin-Darby canine kidney (MDCK) epithelial cell line showed that ouabain regulates cell adhesion and cell-adhesion-related biological processes, such as migration. Here, we demonstrated that 10 nM ouabain accelerates collective cell migration and heals wounds in cultured MDCK cell monolayers. Ouabain-induced acceleration of cell migration depends on activation of the cSrc-ERK1/2 signaling cascade, as it was inhibited by the kinase inhibitors PP2 and PD98059. Activation of the cSrc-ERK1/2 signaling cascade increased expression and activation of the extracellular matrix metalloproteinase-2 (MMP-2). Inhibition of MMP activity using the generic inhibitor GM6001 or the potent iMMP-2 inhibitor prevented the accelerative effect of ouabain. Likewise, Focal Adhesion Kinase (FAK) inhibition with the transfection of dominant negative peptide FRNK impaired the effect of ouabain. These results suggest that ouabain binding to the Na+,K+-ATPase accelerates collective migration of MDCK cells through activation of the cSrc-ERK1/2-FAK signaling cascade and promoting secretion and MMP activity.

High prevalence of non-alcoholic fatty liver disease and metabolic risk factors in Guatemala: A population-based study.

BACKGROUND: There are no data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in general population samples in Guatemala or in other Central American countries. The prevalence and distribution of NAFLD and its associated risk factors were evaluated in a population-based sample of adults in Guatemala. METHODS: Cross-sectional study of 411 men and women 40 years of age or older residing in urban and rural areas of Guatemala. Metabolic outcomes included obesity, central obesity, hypercholesterolemia, diabetes, and metabolic syndrome (MetS). Liver disease outcomes included elevated liver enzymes, elevated Fatty Liver Index (FLI), and elevated FIB-4 score. RESULTS: The overall prevalence of obesity, central obesity, diabetes, and MetS were 30.9, 74.3, 21.6, and 64.2%, respectively. The fully-adjusted prevalence ratios (95% CI) for obesity, central obesity, diabetes, and MetS comparing women to men were 2.83 (1.86-4.30), 1.72 (1.46-2.02), 1.18 (1.03-1.34), and 1.87 (1.53-2.29), respectively. The overall prevalence of elevated liver enzymes (ALT or AST), elevated FLI, and elevated FIB-4 scores were 38.4, 60.1, and 4.1%, respectively. The fully-adjusted prevalence ratios (95% CI) for elevated liver enzymes (either ALT or AST) and elevated FLI score comparing women to men were 2.99 (1.84-4.86) and 1.47 (1.18-1.84), respectively. CONCLUSIONS: The prevalence of metabolic abnormalities and liver outcomes in this general population study was very high. The prevalence of metabolic and liver abnormalities was particularly high among women, an observation that could explain the atypical 1:1 male to female ratio of liver cancer in Guatemala.

Tropospheric Emissions: Monitoring of Pollution (TEMPO).

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Reparación de defectos complejos de la pared abdominal y cirugía intestinal en un tiempo / Repair of complex abdominal wall defects and intestinal surgery at a time

Introducción: La reparación de la pared abdominal, presenta escenarios complejos, como los abdómenes abiertos con ostomías o fístulas intestinales, que para su tratamiento el cirujano debe buscar la táctica quirúrgica y el manejo ideal para cada caso. Objetivo: Describir los resultados en la reparación de defectos complejos de la pared abdominal y restitución de tránsito intestinal en un solo tiempo. Pacientes y método: Estudio observacional, descriptivo, prospectivo y longitudinal, de una serie de casos de 30 pacientes, ambos sexos, mayores a 18 años, portadores de defectos complejos de la pared abdominal (abdomen abierto cicatrizado por segunda intención y hernias paraestomales) y ostomías que ingresaron para cirugía electiva en la II Cátedra de Clínica Quirúrgica del Hospital de Clínicas de marzo del 2011 a diciembre del 2015. Todos los pacientes fueron evaluados con tomografía axial computarizada, según el caso sometidos a preparación con neumoperitoneo progresivo pre operatorio y manejados por equipo multidisciplinario...

Introduction: Abdominal wall repair, presents complex scenarios, as the bellies open with ostomy or intestinal fistulas, that treatment the surgeon should seek surgical tactics and ideal management for each case. Objective: To describe the results in repair of complex defects of the abdominal wall and return of intestinal transit in a single time. Patients and methods: observational, descriptive, prospective and longitudinal study, a series of 30 patients, both sexes, over 18 years, carriers of complex defects of the abdominal wall (open abdomen healed by second intention and paraestomales herniations) and ostomy admitted for elective surgery at the surgical clinic of the Hospital de Clínicas of March 2011 to2015 December II. All patients were evaluated with axial computed tomography, according to the case subject to progressive pneumoperitoneumprogressive pre operative and managed by a multidisciplinary team...

Diazo dye Congo Red degradation using a Boron-doped diamond anode: An experimental study on the effect of supporting electrolytes.

Diazo dye Congo Red (CR) solutions at 100mg/L, were degraded using different supporting electrolytes in an electrochemical advanced oxidation process (EAOPs), like the anodic oxidation (AOx/BDD). All experiments were carried out in a 3L flow reactor with a Boron-doped diamond (BDD) anode and stainless steel cathode (AISI 304), at 7.5, 15, 30 and 50mA/cm(2) current densities (j). Furthermore, each experiment was carried out under a flow rate of 7L/min. Additionally, HClO4, NaCl, Na2SO4, and H2SO4 were tested as supporting electrolytes at a 50mM concentration. The degradation process was at all times considerably faster in NaCl medium. Solutions containing SO4(2-) or ClO4(-) ions were less prompted to degradation due to the low oxidation power of these species into the bulk. Dissolved organic carbon (DOC) analysis, was carried out to evaluate the mineralization of CR. The degradation of CR, was evaluated with the HPLC analysis of the treated solutions.

Inappropriate prescribing in elderly people with diabetes admitted to hospital.

AIMS: To assess inappropriate prescribing in older people with diabetes mellitus during the month prior to a hospitalization, using tools on potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs) and comparing inappropriate prescribing in patients with without diabetes. METHODS: In an observational, prospective multicentric study, we assessed inappropriate prescribing in 672 patients aged 75 years and older during hospital admission. The Beers, Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert Doctors to Right Treatment (START) criteria and Assessing Care of Vulnerable Elders (ACOVE-3) medicine quality indicators were used. We analysed demographic and clinical factors associated with inappropriate prescribing. RESULTS: Of 672 patients, 249 (mean age 82.4 years, 62.9% female) had a diagnosis of diabetes mellitus. The mean number of prescribing drugs per patient with diabetes was 12.6 (4.5) vs. 9.4 (4.3) in patients without diabetes (P < 0.001). Of those patients with diabetes, 74.2% used 10 or more medications; 54.5% of patients with diabetes had at least one Beers-listed PIM, 68.1% had at least one STOPP-listed PIM, 64.6% had at least one START-listed PPO and 62.8% had at least one ACOVE-3-listed PPO. Except for the Beers criteria, these prevalences were significantly higher in patients with diabetes than in those without. After excluding diabetes-related items from these tools, only STOPP-listed PIMs remained significantly higher among patients with diabetes (P = 0.04). CONCLUSIONS: Polypharmacy is common among older patients with diabetes mellitus. Inappropriate prescribing is higher in older patients with diabetes, even when diabetes-related treatment is excluded from the inappropriate prescribing evaluation.

Comparación entre dexmedetomidina en infusión intravenosa vs. lidocaína en infusión intravenosa para el control de dolor refractario a tratamiento opioide en pacientes de cuidados paliativos / Comparison between dexmedetomidine infusion vs. lidocaine intravenous infusion for treatment of severe pain in palliative care patients under opioid treatment

Introducción: se define dolor refractario como aquel que se mantiene persistente (EVA 6 o más) a pesar de tratamiento con opioides (con 1 o más rotaciones previas) + antiinflamatorios (AINE o corticoides). Para tratamiento se han utilizado agonistas alfa-2 y/o anestésicos locales. La respuesta analgésica a la administración de dexmedetomidina parece producirse a nivel de la neurona de la raíz dorsal, donde los agonistas alfa-2 bloquean la liberación de la sustancia P en la vía nociceptiva. El efecto analgésico central está mediado por la activación de las vías inhibitorias descendentes gracias al bloqueo de los receptores del aspartato y glutamato. La utilización de lidocaína intravenosa puede suprimir descargas neurales ectópicas procedentes de fibras aferentes primarias lesionadas debido a sus propiedades de bloqueo dependiente de canales de voltaje de sodio Además se ha evidenciado la activación endógena del sistema de opioides por infusión de lidocaína por vía sistémica. Objetivo: evaluar el efecto analgésico de la infusión de dexmedetomidina intravenosa comparada con infusión de lidocaína intravenosa para dolor refractario a opioides en pacientes bajo cuidados paliativos. Material y métodos: se trata de un ensayo clínico aleatorizado, triple ciego, con muestreo consecutivo. El análisis de resultados con medidas de tendencia central y de dispersión. Para comparar variables cuantitativas se usó t de Student para muestras independientes. Se construyeron tablas de contingencia y gráficos a través del programa estadístico SPSS versión 17. Población de estudio: pacientes con dolor refractario, hospitalizados dentro del Programa de Cuidados Paliativos asignados aleatoriamente a uno de los 2 grupos cuyo número de muestra (n = 14) se obtuvo por fórmula de diferencia de proporciones. Resultados: en cuanto a la analgesia con ambas infusiones no hubo diferencias significativas. De los 16 pacientes, 18 % (n: 3) requirieron terapia de rescate durante la infusión y 18 % (n: 3) requirieron rescate durante las 48 horas postinfusión. Durante la infusión el 42 % del grupo de lidocaína necesitó rescate (n: 3) y en el tiempo postinfusión antes de 48 horas se administraron 3 rescates: 42 % de los pacientes del grupo de lidocaína (n: 2) y 14 % de los pacientes del grupo dexmedetomidina (n: 1). En cuanto a sedación durante la infusión se reportaron diferencias significativas (p: -0,01) reportándose mayor sedación en el grupo de dexmedetomidina. No se presentaron complicaciones cardiovasculares y/o respiratorias en ninguno de los dos grupos. Conclusiones: el grupo de dexmedetomidina requirió menos rescates con opioides durante la infusión y posterior a ella. Se presentó mayor sedación en el grupo de dexmedetomidina sin presencia de complicaciones cardiovasculares y/o respiratorias durante o posterior a la infusión (AU)

Introduction: Refractory pain is defined as that which remains persistent (EVA 6 or more) despite treatment with opioids (with 1 or more previous rotations) + anti-inflammatory drugs (NSAIDs or corticosteroids). Alpha-2 agonists and/or local anesthetics have been used for treating. Analgesic response to the administration of dexmedetomidine appears to occur at the level of dorsal root neuron, where the alpha-2 agonists block the release of substance P in the nociceptive pathway. The central analgesic effect is mediated by the activation of descending inhibitory pathways, by blocking the receptors of aspartate and glutamate. The use of intravenous lidocaine can suppress ectopic neural discharges primary afferents from injured due to its blocking voltage-dependent sodium channels. Furthermore it has been demonstrated activation of endogenous opioid system lidocaine infusion systemically. Objective: To evaluate the analgesic effect of intravenous dexmedetomidine infusion compared with intravenous lidocaine infusion for pain refractory to opioids in palliative care patients. Material and methods: This is a randomized, triple-blind study with consecutive sampling. The analysis of results with measures of central tendency and dispersion. To compare quantitative variables T test was used for independent samples. Contingency tables were constructed and graphics through SPSS version 17. Study population: Patients with refractory pain, hospitalized within the Palliative Care Program randomly assigned to one of 2 groups whose sample number (n = 14) was obtained by difference formula proportions. Results: For both infusions analgesia with no significant differences. Of the 16 patients, 18 % (n = 3) required rescue therapy during infusion and 18 % (n = 3) required rescue within 48 hours post-infusion. During infusion of the 42 % lidocaine group need rescue (n = 3) and time within 48 hours post infusion was administered three rescues: 42 % of patients in the lidocaine group (n = 2), and 14 % of dexmedetomidine group patients (n: 1). Regarding sedation during the infusion were reported significant differences (p -0.01) increased sedation reporting for dexmedetomidine group. No complications cardiovascular and / or respiratory none of the two groups. Conclusions: The dexmedetomidine group required less opioid bailouts during infusion and after it. Sedation was greater in the group of dexmedetomidine without presence of cardiovascular and/or respiratory during or after the infusion (AU)

Toxins and virulence factors of enterotoxigenic Escherichia coli associated with strains isolated from indigenous children and international visitors to a rural community in Guatemala.

Diarrhoea remains a common cause of illness in Guatemala, with children suffering most frequently from the disease. This study directly compared the frequency, enterotoxin, and colonization factor (CF) profiles of enterotoxigenic Escherichia coli (ETEC) strains isolated from children living in a rural community in Guatemala and from Western visitors to the same location during the same seasons, using similar detection methodologies. We found that ETEC accounted for 26% of severe cases of diarrhoea in children requiring hospitalization, 15% of diarrhoea in the community, and 29% of travellers' diarrhoea in visitors staying ⩾2 weeks. The toxin and CF patterns of the ETEC strains isolated from both groups differed significantly (P < 0·0005) as determined by χ 2 = 60·39 for CFs and χ 2 = 35 for toxins, while ETEC phenotypes found in Guatemalan children were comparable to those found in children from other areas of the world.

Tratamiento de la fisura anal crónica con diltiazem gel 2% seis años de experiencia / Treatment of chronic anal fissure with diltiazem gel 2% six-years experience

Introducción: En la actualidad existe consenso que el tratamiento médico de la fisura anal crónica, es el de elección, como consecuencia de la morbilidad asociada a la esfinterotomía quirúrgica. Objetivo: Valorar la eficacia, seguridad y recidiva del diltiazem tópico en el tratamiento de la fisura anal crónica. Pacientes y Método: Se estudian los pacientes diagnosticados de fisura anal crónica en nuestro hospital, durante el periodo comprendido entre el uno de enero de 2008 y el 31 de diciembre de 2013 (6 años). Criterios de inclusión: edad mayor de 18 años y menor de 65 años, ausencia de otra patología anorrectal asociada, manometría con hipertonía del esfínter anal interno y consentimiento informado firmado. Criterios de exclusión: cirugía anorrectal previa, enfermedad inflamatoria intestinal, hipotensión arterial, intolerancia o alergia a calcio-antagonistas, deterioro cognitivo y bloqueo auriculo- ventricular. Se empleó una fórmula magistral de gel de diltiazem al 2%, en 3 aplicaciones diarias con una duración máxima de 8 semanas. Se realizaron controles clínicos y medida del dolor mediante escala analógica visual (EAV) al final de la cuarta, sexta y octava semanas. Se compararon los grupos con y sin respuesta al diltiazem mediante las pruebas de la -2 y t de Student. Resultados: Se analizaron 265 pacientes (137 mujeres), con una media de edad de 46,7 (18-65) años. Localización de la fisura: posterior en el 96%, anterior 3% y lateral en el 1%. Todos tenían dolor; 231 sangrado y 198, prurito. Al final de las 8 semanas de tratamiento se curó el 65,7% (174 pacientes), con una morbilidad del 11,7%, de los que el 2,6% abandonó el tratamiento por reacciones adversas. De los 174 pacientes que mejoraron con el tratamiento, 142 (81,6%), lo hicieron a las cuatro semanas de iniciado el tratamiento, 27 (15,5%) a las 6 semanas y tan sólo 5 pacientes (2,9 %) mejoraron a la octava semana, con una diferencia estadísticamente significativa (p<0,05) entre los pacientes respondedores a las 4 semanas, con respecto a la sexta y octava semanas de iniciado el tratamiento. No hubo diferencias significativas (p<0,05) entre los grupos con y sin respuesta al diltiazem en relación a la edad, el sexo, la localización, el sangrado o el prurito. Después de una media de seguimiento de 31 (3-72) meses, se detectaron 43 (16,2%) recidivas. El tiempo medio de recidiva tras finalizar el tratamiento con éxito, fue de 5,7 (2,5-32) meses. Conclusiones: El diltiazem gel 2%, es un medicamento eficaz en el tratamiento de la fisura anal crónica, en casos bien seleccionados. Carece de efectos secundarios importantes con un aceptable cumplimiento del tratamiento, evitando la morbilidad que conlleva la esfinterotomía quirúrgica. Aunque las recidivas son relativamente frecuentes, suelen responder a un nuevo tratamiento con diltiazem

Introduction: In recent years, the medical treatment of chronic anal fissure has consolidated as the choice as a result of the morbidity associated to surgical sphincterotomy. Objective: To evaluate the efficacy, safety and recurrence of topical diltiazem in the treatment of chronic anal fissure Patients and Method: We studied patients diagnosed of chronic anal fissure in our hospital during the period January 2008 to December 2013 (6 years). Inclusion criteria: age greater 18 and less than 65 years, manometry with hypertensive internal anal sphincter and signed informed consent. Exclusion criteria: previous anorrectal surgery, inflammatory bowel disease, intolerance or allergy to calcium antagonists, cognitive impairment, immune suppression, hypotension, and atrioventricular block. We used a formulation of diltiazem gel 2% in 3 daily applications for 8 weeks. There was a clinical and an extent of pain evaluation by visual analog scale (VAS) at the end of the fourth, sixth and eighth weeks. We compared the groups with and without response to diltiazem by the -2 and the Student test. Results: 46 patients were excluded, because they could'nt be contacted the follow-up (lost patients). We analyzed 265 patients (137 woman) with a mean age of 46, 7 (18 to 65) years. Localization of the fissure: Posterior 96%, anterior 3% and side 1%. All had pain, 231 bleeding and 198 itching. At the end of 8 weeks of treatment 65.7% (174 patients) were cured, with a morbidity of 11, 7%, of which the 2,6% discontinued the treatment due to adverse effects. Of the 174 patients who improved with treatment, 142 (81,6%) improved after four weeks of treatment, 27 (15,5%) after 6 weeks and only 5 (2, 9%) patients, after the eighth week, with a statistically significant difference (p <0.005) among responders at four weeks, compared to sixth and eighth week of initiation of treatment. There were no significant differences (p< 0,05) between groups with and without response to diltiazem related to age, sex, location, bleeding or itching. After a mean follow up of 31 (7 to72) months, 43 recurrences were detected (16,2%). The median time to recurrence after successful completion of treatment was 5.7 (2.5 to 32) months Conclusions: Diltiazem 2% gel is an effective drug in the treatment of chronic anal fissure, in selected cases. No major side effects were observed with an acceptable compliance, avoiding the morbidity associated to surgical sphincterotomy. Although recurrences are relatively common, they often respond to repeated treatment with diltiazem