Postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography pancreatitis (ERCP). No randomized controlled trial (RCT) has compared the efficacy of the American Society of Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy recommended interventions for PEP prevention. We assessed the effectiveness of these interventions using network meta-Analysis. PubMed, EMBASE, and Cochrane databases were searched to identify RCTs investigating guideline-recommended interventions and their combinations [rectal nonsteroidal anti-inflammatory drugs (NSAIDs): indomethacin or diclofenac, pancreatic stent (PS), aggressive hydration (AH), sublingual nitrate) for PEP prevention. We performed direct and Bayesian network meta-Analysis, and the surface under the cumulative ranking curve to rank interventions. Subgroup network meta-Analysis for high-risk populations was also performed. We identified a total of 38 RCTs with 10 different interventions. Each intervention was protective against PEP on direct and network meta-Analysis compared with controls. Except AH+diclofenac and NSAIDs+ sublingual nitrate, AH+indomethacin was associated with a significant reduction in risk of PEP compared with PS [odds ratio (OR), 0.09; credible interval (CrI), 0.003-0.71], indomethcin+PS (OR, 0.09; CrI, 0.003-0.85), diclofenac (OR, 0.09; CrI, 0.003-0.65), AH (OR, 0.09; CrI, 0.003-0.65), sublingual nitrate (OR, 0.07; CrI, 0.002-0.63), and indomethacin (OR, 0.06; CrI, 0.002-0.43). AH with either rectal NSAIDs or sublingual nitrate had similar efficacy. AH+indomethacin was the best intervention for preventing PEP with 95.3% probability of being ranked first. For high-risk patients, although the efficacy of PS and indomethacin were comparable, PS had an 80.8% probability of being ranked first. AH+indomethacin seems the best intervention for preventing PEP. For high-risk patients, PS seems the most effective strategy. The potential of combination of interventions need to be explored further.

Purpose: Use of ampicillin in outpatient parenteral antimicrobial therapy (OPAT) has historically been complicated by frequent dosing and short beyond use dates. However historic stability data relied on inaccurate testing methods. The purpose of this study is to evaluate the stability of ampicillin using high-pressure liquid chromatography (HPLC), the gold standard, in a real-world OPAT dosing model using continuous infusion at room temperature over 24 hours immediately following preparation compared to batches stored under refrigeration for 24 hours, 72 hours, and 7 days. Methods: An HPLC method was developed and validated as stability – indicating according to guidance in USP general Chapter < 1225 >. Method development included linearity, precision, accuracy, repeatability and forced degradation. Four batches were prepared using 4 different lots from 2 different manufacturers for each storage condition (immediate, 24 hours, 72 hours, and 7 days). Three 2-gram vials were each reconstituted with 10 mL of sterile water for injection (SWFI) and added to 250 mL of normal saline by a licensed pharmacist and stored in a laboratory refrigerator (2 – 8oC). A pump system was used to continuously circulate the solutions through medical grade tubing at room temperature. One milliliter aliquots were removed from each batch at time 0, 4 hours, 8 hours, 12 hours and 24 hours and analyzed for ampicillin concentration using the aforementioned HPLC method. The samples were filtered prior to analysis using a 0.22-micron syringe filter and analyzed in triplicates along with freshly prepared calibration samples (24 – 12 mg/mL). Peak area was used to determine percent recovery for each sample. Results:Each batch was assayed for initial concentration (20.34 – 21.50 mg/mL) upon preparation, and percent recovery was compared to that initial concentration thereafter. Acceptable recovery was defined as 90 – 110% of initial concentration. On the day of product preparation (immediate use), the average percent recovery over 24 hours was 96.4%. The other average percent recoveries were as follows: 95.8% (24-hour storage), 94.6% (72-hour storage) and 90.3% (7-day storage). These data represent the average percent recovery for all time points during the 24 hours sampling (n = 60 for each experiment). When evaluating individual time points, the percent recovery remained above 90% for all batches and time points except for the 7-day storage experiment. Under 7-day storage conditions, the percent recovery fell below 90% after 4 hours of circulation through the medical grade tubing. Furthermore, 95% confidence interval for percent recovery for ampicillin in the samples stayed within 90 – 110% of the initial concentration for the duration of the experiment for all test groups except 7-day storage. Conclusion:Ampicillin can be prepared and stored in a refrigerator for up to 72-hours prior to continuously infusing at room temperature over 24 hours with less than a 10% loss of potency over the dosing period. This model supports twice weekly OPAT delivery of ampicillin.

No / The aim of this prospective randomized study was to evaluate the role of carbon dioxide (CO2) and normal saline for diagnostic accuracy in out-patient hysteroscopy. Women admitted to our Department in order to undergo total abdominal hysterectomy also underwent diagnostic hysteroscopy, 12¿24 h prior to surgery. The selection of distending medium was made after randomization. Two groups of patients were formed, group A (CO2; n=39) and group B (normal saline; n=35). More than half of the women in the study population were post-menopausal. Post-hysteroscopy, all women were asked to rank any symptom that they felt during the procedure on a 4-point scale (0 = none; 1 = mild; 2 = severe; 3 = inability to perform hysteroscopy). The hysteroscopic diagnosis was compared with the macroscopic findings and the histological examination of the surgical specimen after hysterectomy. The percentage who completed hysteroscopy was 89.74% within group A and 97.14% within group B. Most patients of both groups felt some pain of mild intensity. The diagnostic accuracy of hysteroscopy was similar for both media when major pathology [large polyps (group A 91.7%; group B 92.7%), myomas (group A 81.25%; group B 92.7%) and/or hyperplasia (group A 87.5%; group B 90.2%)] of the endometrial cavity was detected. In contrast, in cases of minor pathology (small polyps, mucosal elevations, crypts, hypervascularization), hysteroscopy with saline presented with significantly higher diagnostic accuracy (85.4%) compared with hysteroscopy with CO2 (64.6%). In out-patient hysteroscopy, CO2 and normal saline were comparable with regard to patient discomfort and for the detection of major pathology of the endometrial cavity. Normal saline seems to be the most appropriate medium for the detection of minor pathology of the endometrial cavity.

Background: Periprocedural intravenous hydration is suggested to decrease the risk of post-ERCP pancreatitis (PEP). However, quality of evidence supporting this suggestion remains poor. Here we hypothesized that aggressive hydration(AH) could be an effective preventive measure. Methods: Pubmed, EMBASE, CINAHL, Google Scholar, Clinical Trials. gov, Clinical Key, International Standard Randomized Trial Number registry as well as secondary sources were searched through January 2019 to identify randomized controlled studies comparing AH to standard hydration (SH) for prevention of PEP. Pooled odds ratio (OR) and 95% confidence intervals (CIs) were calculated using the random-effects model. RevMan 5.3 was used for analysis. Results: A total of 9 RCTs, with 2094 patients, were included in the meta-analysis. AH reduced incidence of PEP by 56% compared to SH (OR = 0.44, CI:0.28–0.69; p = 0.0004). The incidence of post-ERCP hyperamylasemia also decreased with AH compared to SH (OR = 0.51; p = 0.001). Length of stay decreased by 1 day with AH (Mean Difference (MD): −0.89 d; p = 0.00002). There was no significant difference in adverse events related to fluid overload between two groups (OR:1.29; p = 0.81) and post-ERCP abdominal pain (OR:0.35; p = 0.17). Numbers of patient to be treated with AH to prevent one episode of PEP was 17. Final results of the meta-analysis were not affected by alternative effect measures or statistical models of heterogeneity. Conclusion: Aggressive hydration is associated with a significantly lower incidence of PEP and it appears to be an effective and safe strategy for the prevention of Post ERCP pancreatitis.

Introdução: A Hemodiluição normovolêmica Aguda (HNA) envolve a retirada do sangue total e concomitante infusão de fluidos de reposição volêmica para manutenção da normovolemia. É uma estratégia que restringe a transfusão de sangue e evita a transmissão de doenças, imunossupressão e outras complicações associadas à transfusão sanguínea. Objetivos: O objetivo deste estudo foi determinar os efeitos de diversos fluidos na resposta inflamatória durante o procedimento de HNA. Métodos: Foram utilizados 28 suínos (n=28; 7/grupo) randomizados nos seguinte grupos: Controle, grupo anestesiado sem HNA; HNA + Amido, os animais foram submetidos a HNA sendo a reposição volêmica realizada com amido hidroxietílico 6% (130/0,4) na taxa de 1 ml de fluido para 1 ml de sangue retirado; HNA + NaCl, animais submetidos a HNA com reposição volêmica realizada com solução de cloerto de sódio 0,9% na proporção de 3:1; HNA + GEL, procedimento de HNA realizado com infusão da gelatina fluida modificada na taxa de 1:1. Os animais foram hemodiluídos durante 30 minutos para o hematócrito de 15%. Foram mensurados os parâmetros hemodinâmicos e foram coletados sangue para realização da hemogasometria e determinação dos níveis plasmáticos de IL-1b, TNF-a, IL-6 e IL-10, além do burst oxidativo de neutrófilos e monócitos circulantes. O lavado broncoalveolar foi coletado para mensuração dos níveis da IL-8 e do burst oxidativo de células pulmonares. O tecido pulmonar foi coletado para análise histológica e para imunoistoquímica para detecção da expressão de COX-2 e Eselectina. A análise estatística foi realizada por meio de provas paramétricas como a análise de variância com medidas repetidas (ANOVA), seguido do teste de Tukey- Kramer e de provas não paramétricas, o teste de Kruskal-Wallis. O grau de significância estabelecido foi de 5% (p < 0,05). Resultados: Os principais resultados deste estudo demonstraram que os animais hemodiluídos tanto com gelatina, como solução de cloreto de sódio 0,9% apresentaram resposta inflamatória mais pronunciada quando comparado aos outros grupos, traduzida no aumento de citocinas (TNF-, IL-6 e IL-10), na expressão de COX-2 e E-selectina no tecido pulmonar, além da observação de edema pulmonar, congestão e colapso alveolar. Apesar destes fatos, a resposta inflamatória estudada no sangue foi considerada de baixa magnitude. Conclusão: Durante a HNA, tanto a gelatina quanto a solução de cloreto de sódio 0,9% promove resposta inflamatória mais intensa quando comparada ao amido hidroxietílico 6% / Background: Acute normovolemic hemodilution (ANH) involves intentional withdrawal of the whole blood with concurrent infusion of fluids to maintain normovolemia. ANH avoids blood transfusion and deleterious effects related with transfusion. Objective: The aim of this study was to determine the effects of diverse fluids on the inflammatory response during ANH. Methods: Twenty-eight pigs (n=28; 7/group) were randomized as follows: (Control) control group without ANH; (ANH + HES) ANH with 6% hydroxyethyl starch at a ratio of 1:1; (ANH + NS) ANH with normal saline at a ratio of 3:1; (ANH + GEL) ANH with gelatin 1:1. Animals were hemodiluted to a hematocrit of 15% in 30 min. Hemodynamic parameters were recorded, and blood samples were collected to determine plasma levels of IL-1, IL-6, TNF-, IL-10, as well as gas analysis. IL-8 was measured in the bronchoalveolar lavage fluid (BALF). Neutrophil and macrophage oxidative burst activity were determined in the peripheral blood and BALF. Histophatological and immunohistochemistry to COX-2 and E-selectin expression were performed with the lung tissue. Data were submitted to analysis of Variance for repeated measures followed by the Tukey-Kramer test. To immunohistochemistry and histophatological scores the Kruskal-Wallis test was used to assess the significance. The p < 0.05 was considered significant. Results: The principal findings of this investigation showed that animals hemodiluted with GEL and NS had a more pronounced inflammatory response when compared to those hemodiluted with HES. The animals in the GEL and NS groups showed an increase in cytokines (TNF-, IL-6, IL-10), a strong expression of COX-2 and Eselectin in the lung tissue and pulmonary edema, congestion and alveoli collapse. However, the magnitude of this response was quite small showing that ANH does not substantially activate the inflammatory system. Conclusion: During ANH, GEL and NS but not HES could elicit an inflammatory response besides the effective plasma volume therapy

Introdução: A Hemodiluição normovolêmica Aguda (HNA) envolve a retirada do sangue total e concomitante infusão de fluidos de reposição volêmica para manutenção da normovolemia. É uma estratégia que restringe a transfusão de sangue e evita a transmissão de doenças, imunossupressão e outras complicações associadas à transfusão sanguínea. Objetivos: O objetivo deste estudo foi determinar os efeitos de diversos fluidos na resposta inflamatória durante o procedimento de HNA. Métodos: Foram utilizados 28 suínos (n=28; 7/grupo) randomizados nos seguinte grupos: Controle, grupo anestesiado sem HNA; HNA + Amido, os animais foram submetidos a HNA sendo a reposição volêmica realizada com amido hidroxietílico 6% (130/0,4) na taxa de 1 ml de fluido para 1 ml de sangue retirado; HNA + NaCl, animais submetidos a HNA com reposição volêmica realizada com solução de cloerto de sódio 0,9% na proporção de 3:1; HNA + GEL, procedimento de HNA realizado com infusão da gelatina fluida modificada na taxa de 1:1. Os animais foram hemodiluídos durante 30 minutos para o hematócrito de 15%. Foram mensurados os parâmetros hemodinâmicos e foram coletados sangue para realização da hemogasometria e determinação dos níveis plasmáticos de IL-1b, TNF-a, IL-6 e IL-10, além do burst oxidativo de neutrófilos e monócitos circulantes. O lavado broncoalveolar foi coletado para mensuração dos níveis da IL-8 e do burst oxidativo de células pulmonares. O tecido pulmonar foi coletado para análise histológica e para imunoistoquímica para detecção da expressão de COX-2 e Eselectina. A análise estatística foi realizada por meio de provas paramétricas como a análise de variância com medidas repetidas (ANOVA), seguido do teste de Tukey- Kramer e de provas não paramétricas, o teste de Kruskal-Wallis. O grau de significância estabelecido foi de 5% (p < 0,05). Resultados: Os principais resultados deste estudo demonstraram que os animais hemodiluídos tanto com gelatina, como solução de cloreto de sódio 0,9% apresentaram resposta inflamatória mais pronunciada quando comparado aos outros grupos, traduzida no aumento de citocinas (TNF-, IL-6 e IL-10), na expressão de COX-2 e E-selectina no tecido pulmonar, além da observação de edema pulmonar, congestão e colapso alveolar. Apesar destes fatos, a resposta inflamatória estudada no sangue foi considerada de baixa magnitude. Conclusão: Durante a HNA, tanto a gelatina quanto a solução de cloreto de sódio 0,9% promove resposta inflamatória mais intensa quando comparada ao amido hidroxietílico 6% / Background: Acute normovolemic hemodilution (ANH) involves intentional withdrawal of the whole blood with concurrent infusion of fluids to maintain normovolemia. ANH avoids blood transfusion and deleterious effects related with transfusion. Objective: The aim of this study was to determine the effects of diverse fluids on the inflammatory response during ANH. Methods: Twenty-eight pigs (n=28; 7/group) were randomized as follows: (Control) control group without ANH; (ANH + HES) ANH with 6% hydroxyethyl starch at a ratio of 1:1; (ANH + NS) ANH with normal saline at a ratio of 3:1; (ANH + GEL) ANH with gelatin 1:1. Animals were hemodiluted to a hematocrit of 15% in 30 min. Hemodynamic parameters were recorded, and blood samples were collected to determine plasma levels of IL-1, IL-6, TNF-, IL-10, as well as gas analysis. IL-8 was measured in the bronchoalveolar lavage fluid (BALF). Neutrophil and macrophage oxidative burst activity were determined in the peripheral blood and BALF. Histophatological and immunohistochemistry to COX-2 and E-selectin expression were performed with the lung tissue. Data were submitted to analysis of Variance for repeated measures followed by the Tukey-Kramer test. To immunohistochemistry and histophatological scores the Kruskal-Wallis test was used to assess the significance. The p < 0.05 was considered significant. Results: The principal findings of this investigation showed that animals hemodiluted with GEL and NS had a more pronounced inflammatory response when compared to those hemodiluted with HES. The animals in the GEL and NS groups showed an increase in cytokines (TNF-, IL-6, IL-10), a strong expression of COX-2 and Eselectin in the lung tissue and pulmonary edema, congestion and alveoli collapse. However, the magnitude of this response was quite small showing that ANH does not substantially activate the inflammatory system. Conclusion: During ANH, GEL and NS but not HES could elicit an inflammatory response besides the effective plasma volume therapy