Microbiological etiology and current resistance patterns in acute calculous cholecystitis.

INTRODUCTION: The current treatment for acute calculous cholecystitis (ACC) is early laparoscopic cholecystectomy, in association with appropriate empiric antibiotic therapy. In our country, the evolution of the prevalence of the germs involved and their resistance patterns have been scarcely described. The aim of the study was to analyze the bacterial etiology and the antibiotic resistance patterns in ACC. METHODS: We conducted a single-center, retrospective, observational study of consecutive patients diagnosed with ACC between 01/2012 and 09/2019. Patients with a concomitant diagnosis of pancreatitis, cholangitis, postoperative cholecystitis, histology of chronic cholecystitis or carcinoma were excluded. Demographic, clinical, therapeutic and microbiological variables were collected, including preoperative blood cultures, bile and peritoneal fluid cultures. RESULTS: A total of 1104 ACC were identified, and samples were taken from 830 patients: bile in 89%, peritoneal fluid and/or blood cultures in 25%. Half of the bile cultures and less than one-third of the blood and/or peritoneum samples were positive. Escherichia coli (36%), Enterococcus spp (25%), Klebsiella spp (21%), Streptococcus spp (17%), Enterobacter spp (14%) and Citrobacter spp (7%) were isolated. Anaerobes were identified in 7% of patients and Candida spp in 1%. Nearly 37% of patients received inadequate empirical antibiotic therapy. Resistance patterns were scrutinized for each bacterial species. The main causes of inappropriateness were extended-spectrum beta-lactamase-producing bacteria (34%) and Enterococcus spp (45%), especially in patients older than 80 years. CONCLUSIONS: Updated knowledge of microbiology and resistance patterns in our setting is essential to readjust empirical antibiotic therapy and ACC treatment protocols.

In Vitro and Ex Vivo Synergistic Effect of Pyrvinium Pamoate Combined with Miltefosine and Paromomycin against Leishmania.

One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines and whose pharmacological treatments are scarce and unsafe. Combination therapy is a strategy that could solve the above-mentioned problems, due to the participation of several mechanisms of action and the reduction in the amount of drug necessary to obtain the therapeutic effect. In addition, this approach also increases the odds of finding an effective drug following the repurposing strategy. From the previous screening of two collections of repositioning drugs, we found that pyrvinium pamoate had a potent leishmanicidal effect. For this reason, we decided to combine it separately with two clinically used leishmanicidal drugs, miltefosine and paromomycin. These combinations were tested in axenic amastigotes of Leishmania infantum obtained from bone marrow cells and in intramacrophagic amastigotes obtained from primary cultures of splenic cells, both cell types coming from experimentally infected mice. Some of the combinations showed synergistic behavior, especially in the case of the combination of pyrvinium pamoate with paromomycin, and exhibited low cytotoxicity and good tolerability on intestinal murine organoids, which reveal the potential of these combinations for the treatment of leishmaniasis.

Impact of empiric antibiotic therapy on the clinical outcome of acute calculous cholecystitis.

PURPOSE: Although mortality and morbidity of severe acute calculous cholecystitis (ACC) are still a matter of concern, the impact of inadequate empirical antibiotic therapy has been poorly studied as a risk factor. The objective was to assess the impact of the adequacy of empirical antibiotic therapy on complication and mortality rates in ACC. METHODS: This observational retrospective cohort chart-based single-center study was conducted between 2012 and 2016. A total of 963 consecutive patients were included, and pure ACC was selected. General, clinical, postoperative, and microbiological variables were collected, and risk factors and consequences of inadequate treatment were analyzed. RESULTS: Bile, blood, and/or exudate cultures were obtained in 76.3% of patients, more often in old, male, and severely ill patients (P < 0.001). Patients who were cultured had a higher overall rate of postoperative complications (47.4% vs. 29.7%; P < 0.001), as well as of severe complications (11.6% vs. 4.7%; P = 0.008). Patients with positive cultures had more overall complications (54.8% vs. 39.6%; P = 0.001), more severe complications (16.3% vs. 6.7%; P = 0.001), and higher mortality rates (6% vs. 1.9%; P = 0.012). Patients who received inadequate empirical antibiotic therapy had a fourfold higher mortality rate than those receiving adequate therapy (n = 283; 12.8% vs. 3.4%; P = 0.003). This association was especially marked in severe ACC TG-III patients (n = 132; 18.2 vs. 5.1%; P = 0.018) and remained a predictor of mortality in a binary logistic regression (OR 4.4; 95% CI 1.3-15.3). CONCLUSION: Patients with positive cultures developed more complications and faced higher mortality. Adequate empirical antibiotic therapy appears to be of paramount importance in ACC, particularly in severely ill patients.

Análisis de los factores de riesgo para complicaciones en la colecistitis aguda litiásica. Deconstrucción de las Tokyo Guidelines / Risk factors for complications in acute calculous cholecystitis. Deconstruction of the Tokyo Guidelines

Introducción: Analizar los factores de riesgo de complicaciones para colecistitis aguda litiásica confrontándolos a las Tokyo Guidelines. Métodos: Estudio retrospectivo de 963 pacientes con colecistitis aguda durante 5 años. Se seleccionaron 725 pacientes con colecistitis aguda litiásica «pura», y analizaron 166 variables mediante regresión logística, incluyendo todos los factores de riesgo de las Tokyo Guidelines. Mediante el Propensity Score Matching, se seleccionaron subpoblaciones comparables de 75 pacientes y se analizaron las complicaciones según el tratamiento realizado (quirúrgico/no quirúrgico) y se utilizó el fallo en el rescate como indicador de calidad del tratamiento en la colecistitis aguda litiásica. Resultados: La mediana de edad fue de 69 años (RIQ 53-80). La mayoría de los pacientes fueron ASA II o III (85,1%). El 21% de las colecistitis fueron leves, el 39% moderadas y el 40% graves. Se colecistectomizó al 95% de los pacientes. El 43% de los pacientes se complicaron y la mortalidad fue del 3,6%. Los factores de riesgo independientes para complicaciones graves fueron ASA>II, tumor sólido sin metástasis e insuficiencia renal. El fallo en el rescate (8%) fue mayor en los no operados (32% vs. 7%; P=0,002). Tras realizar el Propensity Score Matching, la tasa de complicaciones graves fueron comparables entre operados y no operados (48,5% vs. 62,5%; P=0,21). Conclusiones: La colecistectomía precoz es el tratamiento preferente para la colecistitis aguda litiásica. Solo tres de los factores de las Tokyo Guidelines son variables independientes para predecir complicaciones graves. El fallo en el rescate es mayor en los pacientes no intervenidos quirúrgicamente. (AU)

Introduction: To challenge the risk factors described in Tokyo Guidelines in acute calculous cholecystitis. Methods: Retrospective single center cohort study with 963 patients with acute cholecystitis during a period of 5 years. Some 725 patients with a “pure” Acute calculous cholecystitis were selected. The analysis included 166 variables encompassing all risk factors described in Tokyo Guidelines. The Propensity Score Matching method selected two subgroups of patients with equal comorbidities, to compare the severe complications rate according to the initial treatment (Surgical vs. non-surgical). We analyzed the failure-to-rescue as a quality indicator in the treatment of acute calculous cholecystitis. Results: The median age was 69 years (IQR 53-80). 85.1% of the patients were ASA II or III. The grade of the acute calculous cholecystitis was mild in a 21%, moderate in 39% and severe in 40% of the patients. Cholecystectomy was performed in 95% of the patients. The overall complications rate was 43% and the mortality was 3.6%. The Logistic Regression model isolated 3 risk factor for severe complication: ASA>II, cancer without metastases and moderate to severe renal disease. The failure-to-rescue (8%) was higher in patients with non-surgical treatment (32% vs. 7%; P=.002). After Propensity Score Matching, the number of severe complications was similar between Surgical and Non-Surgical treatment groups (48.5% vs 62.5%; P=.21). Conclusions: The recommended treatment for acute calculous cholecystitis is the laparoscopic cholecystectomy. Only three risk factors from the Tokyo Guidelines list appeared as independent predictors of severe complications. The failure-to-rescue is higher in non-surgically treated patients. (AU)

Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis.

Visceral leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania donovani and Leishmania infantum that is endemic not only in East African countries, but also in Asia, regions of South America and the Mediterranean Basin. For the pharmacological control of this disease, there is a limited number of old and, in general, poorly adherent drugs, with a multitude of adverse effects and low oral bioavailability, which favor the emergence of resistant pathogens. Pentavalent antimonials are the first-line drugs, but due to their misuse, resistant Leishmania strains have emerged worldwide. Although these drugs have saved many lives, it is recommended to reduce their use as much as possible and replace them with novel and more friendly drugs. From a commercial collection of anti-infective drugs, we have recently identified nifuratel-a nitrofurantoin used against vaginal infections-as a promising repurposing drug against a mouse model of visceral leishmaniasis. In the present work, we have tested combinations of miltefosine-the only oral drug currently used against leishmaniasis-with nifuratel in different proportions, both in axenic amastigotes from bone marrow and in intracellular amastigotes from infected Balb/c mouse spleen macrophages, finding a potent synergy in both cases. In vivo evaluation of oral miltefosine/nifuratel combinations using a bioimaging platform has revealed the potential of these combinations for the treatment of this disease.

Risk factors for complications in acute calculous cholecystitis. Deconstruction of the Tokyo Guidelines.

OBJECTIVE: To challenge the risk factors described in Tokyo Guidelines in Acute Calculous Cholecystitis. METHODS: Retrospective single center cohort study with 963 patients with Acute Cholecystitis during a period of 5 years. Some 725 patients with a "pure" Acute Calculous Cholecystitis were selected. The analysis included 166 variables encompassing all risk factors described in Tokyo Guidelines. The Propensity Score Matching method selected two subgroups of patients with equal comorbidities, to compare the severe complications rate according to the initial treatment (Surgical vs Non-Surgical). We analyzed the Failure-to-rescue as a quality indicator in the treatment of Acute Calculous Cholecystitis. RESULTS: the median age was 69 years (IQR 53-80). 85.1% of the patients were ASA II or III. The grade of the Acute Calculous Cholecystitis was mild in a 21%, moderate in 39% and severe in 40% of the patients. Cholecystectomy was performed in 95% of the patients. The overall complications rate was 43% and the mortality was 3.6%. The Logistic Regression model isolated 3 risk factor for severe complication: ASA > II, cancer without metastases and moderate to severe renal disease. The Failure-to-Rescue (8%) was higher in patients with non-surgical treatment (32% vs. 7%; P = 0.002). After Propensity Score Matching, the number of severe complications was similar between Surgical and Non-Surgical treatment groups (48.5% vs 62.5%; P = 0.21). CONCLUSIONS: the recommended treatment for Acute Calculous Cholecystitis is the Laparoscopic Cholecystectomy. Only three risk factors from the Tokyo Guidelines list appeared as independent predictors of severe complications. The failure-to-rescue is higher in non-surgically treated patients.

Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines.

In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration, the associated adverse effects and the generation of resistance. In this work we have evaluated the antileishmanial effect of 1,5- and 1,8-substituted fused naphthyridines through in vitro and ex vivo assays, using genetically modified axenic and intramacrophagic Leishmania infantum amastigotes. The toxicity of these compounds has been tested in the mammalian host cell using murine splenic macrophages, as well as in murine intestinal organoids (miniguts) in order to assess their potential for oral administration. The 1,8- derivatives showed greater leishmanicidal activity and the presence of a nitrogen atom in the fused ring to the naphthyridine was important to increase the activity of both types of molecules. The aromatization of the pyridine ring also had marked differences in the activity of the compounds.

Evidencia científica de la duración del tratamiento antibiótico en las infecciones intraabdominales con control de foco quirúrgico / Scientific evidence of the duration of antibiotic treatment in intra-abdominal infections with surgical focus control

El aumento progresivo de las resistencias antibióticas apremia el tener estrategias para disminuir la presión sobre la microbiota. La duración del tratamiento antibiótico empírico es variable, a pesar de las recomendaciones de las guías. Se ha realizado una revisión bibliográfica de la evidencia científica publicada sobre la duración del tratamiento antibiótico empírico en las infecciones intraabdominales quirúrgicas con control de foco efectivo. Se analizan las guías americanas realizadas por Mazuski et al. de 2017 como eje central en las recomendaciones de la duración de tratamiento antibiótico empírico en infecciones intraabdominales con control del foco y se añade una búsqueda bibliográfica de todos los artículos que contuviesen las palabras claves en Pubmed y Google Scholar. Se recopilan 21 artículos referentes en la duración del tratamiento antibiótico empírico en la infección intraabdominal con control del foco. Con las guías americanas y estos artículos se ha elaborado una propuesta de duración del tratamiento antibiótico empírico en pacientes sin factores de riesgo entre 24 y 72 h. Y en los que presentan factores de riesgo se habría de individualizar el mismo con monitorización activa cada 24 h de fiebre, íleo paralítico y leucocitosis, ante una detección precoz de complicaciones o de necesidad de cambios en el espectro antibiótico. Los tratamientos cortos son igual de eficaces que los de duraciones más prolongadas y se asocian a menos tasa de efectos adversos, por tanto, ajustar y revaluar diariamente la duración del tratamiento antibiótico empírico es fundamental para una mejor praxis (AU)

A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 2017, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72h. And in those who present risk factors, it should be individualized with active monitoring every 24h of fever, paralytic ileus and leukocytosis, before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice (AU)

Antibiotic desensitization as a potential tool in antimicrobial stewardship programs: retrospective data analysis and systematic literature review.

OBJECTIVES: Antibiotic allergy labels (AAL) are related to worse therapeutic results. Strategies to improve the management of these patients, such as the implementation of antibiotic desensitization, are essential for Antimicrobial Stewardship Programs (ASP). The aim of our study is to evaluate the efficacy and safety of antibiotic desensitization procedures for the management of patients with AAL. METHODS: A retrospective study from 2015 to 2022 was performed to describe all antibiotic desensitization conducted in our institution, within the framework of ASP. A systematic literature review using electronic databases, such as PubMed, was also done to identify studies describing antibiotic desensitization between 2000 and 2022. RESULTS: Sixteen antibiotic desensitization protocols were carried out in our institution. In fourteen cases, the desensitization was successfully completed, and the antibiotic could be used to treat the infection. In the systematic review, twenty-two studies were included, with a total of 202 desensitization episodes . In 97% of them, the desensitization was completed successfully. No desensitization-related mortality was observed neither in our cohort nor in literature review. CONCLUSIONS: Antibiotic desensitization strategies should be considered a safe and effective tool that can be included in ASP for patients with a high risk of or confirmed allergy to penicillin.

Scientific evidence of the duration of antibiotic treatment in intra-abdominal infections with surgical focus control.

A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections (IIA) with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 20171, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72 h. And in those who present risk factors, it should be individualized with active monitoring every 24 h of fever, paralytic ileus and leukocytosis (FIL), before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice.

Design, synthesis and evaluation of novel ß-carboline ester analogues as potential anti-leishmanial agents.

Leishmaniasis is one of today's most neglected diseases. The emergence of new anti-leishmanial therapies emphasizes several study groups funded by the World Health Organization. The present investigation will focus on the research to determine a few new potential derivatives of ß-carboline ester derivatives against leishmaniasis. The in-silico predicted ADMET properties of most of the titled compounds are in an acceptable range and having drug like properties. Among all the tested analogs, compound ES-3 (EC50 3.36 µM; SI > 29.80) showed comparable and equipotent anti-leishmanial activity as that of standard drug miltefosine (EC50 4.80 µM; SI > 20.80) against amastigote forms of the tested L. infantum strain. Two compounds ES-6 and ES-10 exhibited significant activity with EC50 10.16, 13.56 µM; SI > 4.90, 7.37, respectively. In-silico based molecular docking and dynamics study of the significantly active analog also performed to study the putative binding mode, interaction pattern at the active site of the target leishmanial trypanothione reductase enzyme as well as stability of the target-ligand complex. The changes in the conformation of molecules during MD (frame wise trajectory analysis) provided new insights for the development of novel potent molecules. These findings will further give insight that will help modify the compound ES-3 for better potency and the design of novel inhibitors for leishmaniasis.Communicated by Ramaswamy H. Sarma.

Novel phenanthridine amide analogs as potential anti-leishmanial agents: In vitro and in silico insights.

In the current work, sixteen novel amide derivatives of phenanthridine were designed and synthesized using 9-fluorenone, 4-Methoxy benzyl amine, and alkyl/aryl acids. The characterization of the title compounds was performed using LCMS, elemental analysis, 1HNMR, 13CNMR and single crystal XRD pattern was also developed for compounds A8. All the final analogs were screened in vitro for anti-leishmanial activity against promastigote form of L. infantum strain. Among the tested analogs, four compounds (A-06, A-11, A-12, and A-15) exhibited significant anti-leishmanial activity with EC50 value ranges from 8.9 to 21.96 µM against amastigote forms of tested L. infantum strain with SI ranges of 1.0 to 4.3. From the activity results it was found that A-11 was the most active compound in both promastigote and amastigotes forms with EC50 values 8.53 and 8.90 µM respectively. In-silico ADME prediction studies depicted that the titled compounds obeyed Lipinski's rule of five as that of the approved marketed drugs. The predicted in-silico toxicity profile also confirmed that the tested compounds were non-toxic. Finally, molecular docking and molecular dynamics study was also performed for significantly active compound (A-11) in order to study it's putative binding pattern at the active site of the selected leishmanial trypanothione reductase target as well as to understand the stability pattern of target-ligand complex for 100 ns. Single crystal XRD of compound A-08 revealed that the compound crystallizes in monoclinic C2/c space group and showed interesting packing arrangements.

Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B).

This work describes, for the first time, the synthesis of dialkyl (2-arylquinolin-8-yl)phosphonate derivatives. The preparation was carried out through a direct and simple process as a multicomponent Povarov reaction of aminophenylphosphonates, aldehydes, and styrenes and subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or, alternatively, by a cycloaddition reaction between phosphonate aldimines and acetylenes. Based on phosphonate group structural characteristics, considered as phosphorous isosteres of carboxylic heterocycles, they may present interesting biological properties related to cell proliferation. In the current report, a new series of dialkyl (2-arylquinolin-8-yl)phosphonates have been synthesized and their antiproliferative effect evaluated on different human cancer and embryonic cells, as well as on Leishmania infantum parasites, a eukaryotic protist responsible for visceral leishmaniasis. Thereby, the antitumor effect was assessed in human lung adenocarcinoma cells (A549), human ovarian carcinoma cells (SKOV3), and human embryonic kidney cells (HEK293) versus the non-cancerous lung fibroblasts cell line (MRC5). On the other hand, the antileishmanial activity was tested against both stages of L. infantum cell cycle, namely free-living promastigotes and intramacrophage amastigotes, using a primary culture of Balb/c splenocytes to calculate the selectivity index. Besides the antiproliferative and antileishmanial capacities, their behavior as topoisomerase 1B inhibitors has been evaluated as a possible mechanism of action.

Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry.

(1) Background: The inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. (2) Methods: Retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. (3) Results: A total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. (4) Conclusion: The present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters.

Mortality risk estimation in acute calculous cholecystitis: beyond the Tokyo Guidelines.

BACKGROUND: Acute calculous cholecystitis (ACC) is the second most frequent surgical condition in emergency departments. The recommended treatment is the early laparoscopic cholecystectomy; however, the Tokyo Guidelines (TG) advocate for different initial treatments in some subgroups of patients without a strong evidence that all patients will benefit from them. There is no clear consensus in the literature about who is the unfit patient for surgical treatment. The primary aim of the study is to identify the risk factors for mortality in ACC and compare them with Tokyo Guidelines (TG) classification. METHODS: Retrospective unicentric cohort study of patients emergently admitted with and ACC during 1 January 2011 to 31 December 2016. The study comprised 963 patients. Primary outcome was the mortality after the diagnosis. A propensity score method was used to avoid confounding factors comparing surgical treatment and non-surgical treatment. RESULTS: The overall mortality was 3.6%. Mortality was associated with older age (68 + IQR 27 vs. 83 + IQR 5.5; P = 0.001) and higher Charlson Comorbidity Index (3.5 + 5.3 vs. 0+2; P = 0.001). A logistic regression model isolated four mortality risk factors (ACME): chronic obstructive pulmonary disease (OR 4.66 95% CI 1.7-12.8 P = 0.001), dementia (OR 4.12; 95% CI 1.34-12.7, P = 0.001), age > 80 years (OR 1.12: 95% CI 1.02-1.21, P = 0.001) and the need of preoperative vasoactive amines (OR 9.9: 95% CI 3.5-28.3, P = 0.001) which predicted the mortality in a 92% of the patients. The receiver operating characteristic curve yielded an area of 88% significantly higher that 68% (P = 0.003) from the TG classification. When comparing subgroups selected using propensity score matching with the same morbidity and severity of ACC, mortality was higher in the non-surgical treatment group. (26.2% vs. 10.5%). CONCLUSIONS: Mortality was higher in ACC patients treated with non-surgical treatment. ACME identifies high-risk patients. The validation to ACME with a prospective multicenter study population could allow us to create a new alternative guideline to TG for treating ACC. TRIAL REGISTRATION: Retrospectively registered and recorded in Clinical Trials. NCT04744441.

Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas / iPCSK9 treatment of Familial Hypercholesterolemia in a patient diagnosed as Congenital Muscular Dystrophy with contraindication for statin use

Las estatinas están contraindicadas en pacientes con miopatías. Hasta hace unos años, la alternativa en pacientes con hipercolesterolemia familiar que tenían distrofias musculares y no conseguían niveles adecuados de colesterol era la lipoaféresis. Cuando surgieron los inhibidores de PCSK9, se consiguió suspender la lipoaféresis en algunos de estos pacientes y mantenerlos con concentraciones plasmáticas de colesterol adecuadas. Presentamos el caso de un varón, diagnosticado en la infancia de distrofia muscular congénita. A los 27 años se remitió a la unidad de lípidos por hipercolesterolemia, donde tras estudio genético se confirmó una hipercolesterolemia familiar heterocigota. A pesar del tratamiento con dieta y ezetimiba continuó con cifras elevadas de cLDL por lo que se incluyó en programa de lipoaféresis. Con esto se alcanzaron niveles de cLDL de 70 mg/dl. Al disponer de los iPCSK9, se suspendió la lipoaféresis y se inició tratamiento con alirocumab 150 mg quincenal, con buena respuesta y manteniendo valores de cLDL en torno a 75 mg/dl

Statins are contraindicated in patients with myopathies. Until a few years ago, in those patients with Familial Hypercholesterolemia who also presented muscular dystrophies and didńt reach adequate cholesterol plasmatic levels, the next therapeutic ladder was lipoapheresis. When iPCSK9 first appeared, lipoapheresis could be suspended in some of these patients, sustaining nevertheless proper levels of cholesterol. We present the case of a 27 year-old male, diagnosed with Congenital Muscular Dystrophy in the early childhood. He was referred to the Unit of Lipidology presenting hypercholesterolemia which, after genetic test, was assessed as Heterozygous Familial Hypercholesterolemia. Despite of treatment with diet and ezetimibe, cLDL blood levels abide high, being consequently included in lipoapheresis programme, therewith obtained levels of cLDL of 70 mg/dl. In providing iPCSK9, lipoapheresis was withdrawn and treatment with alirocumab 150 mg fortnightly introduced, unveiling a positive response, and sustaining cLDL levels around 75 mg/dl

iPCSK9 treatment of Familial Hypercholesterolemia in a patient diagnosed as Congenital Muscular Dystrophy with contraindication for statin use. / Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas.

Statins are contraindicated in patients with myopathies. Until a few years ago, in those patients with Familial Hypercholesterolemia who also presented muscular dystrophies and didnt reach adequate cholesterol plasmatic levels, the next therapeutic ladder was lipoapheresis. When iPCSK9 first appeared, lipoapheresis could be suspended in some of these patients, sustaining nevertheless proper levels of cholesterol. We present the case of a 27 year-old male, diagnosed with Congenital Muscular Dystrophy in the early childhood. He was referred to the Unit of Lipidology presenting hypercholesterolemia which, after genetic test, was assessed as Heterozygous Familial Hypercholesterolemia. Despite of treatment with diet and ezetimibe, cLDL blood levels abide high, being consequently included in lipoapheresis programme, therewith obtained levels of cLDL of 70mg/dl. In providing iPCSK9, lipoapheresis was withdrawn and treatment with alirocumab 150mg fortnightly introduced, unveiling a positive response, and sustaining cLDL levels around 75mg/dl.

The role of the laparoscopic approach in the surgical management of acute adhesive small bowel obstruction.

BACKGROUND: Postoperative adhesions represent 75% of all acute small bowel obstructions. Although open surgery is considered the standard approach for adhesiolysis, laparoscopic approach is gaining popularity. METHODS: A retrospective study with data from a prospectively maintained data base of all patients undergoing surgical treatment for adhesive small bowel obstruction (ASBO) from January 2007 to May 2016 was conducted. Postoperative outcomes comparing open vs laparoscopic approaches were analysed. An intention to treat analysis was performed. The aim of the study was to evaluate the potential benefits of the laparoscopic approach in the treatment of ASBO. RESULTS: 262 patients undergoing surgery for ASBO were included. 184 (70%) and 78 (30%) patients were operated by open and laparoscopic approach respectively. The conversion rate was 38.5%. Patients in the laparoscopic group were younger (p < 0.001), had fewer previous abdominal operations (p = 0.001), lower ASA grade (p < 0.001), and less complex adhesions were found (p = 0.001). Operative time was longer in the open group (p = 0.004). Laparoscopic adhesiolysis was associated with a lower overall complication rate (43% vs 67.9%, p < 0.001), lower mortality (p = 0.026), earlier oral intake (p < 0.001) and shorter hospital stay (p < 0.001). Specific analysis of patients with single band and/or internal hernia who did not need bowel resection, also demonstrated fewer complications, earlier oral intake and shorter length of stay. In the multivariate analysis, the open approach was an independent risk factor for overall complications compared to the laparoscopic approach (Odds Ratio = 2.89; 95% CI 1.1-7.6; p = 0.033). CONCLUSIONS: Laparoscopic management of ASBO is feasible, effective and safe. The laparoscopic approach improves postoperative outcomes and functional recovery, and should be considered in patients in whom simple band adhesions are suspected. Patient selection is the strongest key factor for having success.

Tuberculosis intestinal / Intestinal tuberculosis

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