Rerouting cardiovascular management following gastric bypass surgery: Dose optimization of carvedilol using population-based analysis.

AIMS: A population-based pharmacokinetic (PK) modeling approach (PopPK) was used to investigate the impact of Roux-en-Y gastric bypass (RYGB) on the PK of (R)- and (S)-carvedilol. We aimed to optimize carvedilol dosing for these patients utilizing a pharmacokinetic/pharmacodynamic (PK/PD) link model. METHODS: PopPK models were developed utilizing data from 52 subjects, including nonobese, obese, and post- RYGB patients who received rac- carvedilol orally. Covariate analysis included anthropometric and laboratory data, history of RYGB surgery, CYP2D6 and CYP3A4 in vivo activity, and relative intestinal abundance of major drug- metabolizing enzymes and transporters. A direct effect inhibitory Emax pharmacodynamic model was linked to the PK model of (S)- carvedilol to simulate the changes in exercise- induced heart rate. RESULTS: A 2-compartmental model with linear elimination and parallel first-order absorptions best described (S)-carvedilol PK. RYGB led to a twofold reduction in relative oral bioavailability compared to nonoperated subjects, along with delayed absorption of both enantiomers. The intestinal ABCC2 mRNA expression increases the time to reach the maximum plasma concentration. The reduced exposure (AUC) of (S)-carvedilol post-RYGB corresponded to a 33% decrease in the predicted area under the effect curve (AUEC) for the 24-hour ß-blocker response. Simulation results suggested that a 50-mg daily dose in post-RYGB patients achieved comparable AUC and AUEC to 25-mg dose in nonoperated subjects. CONCLUSION: Integrated PK/PD modeling indicated that standard dosage regimens for nonoperated subjects do not provide equivalent ß-blocking activity in RYGB patients. This study highlights the importance of personalized dosing strategies to attain desired therapeutic outcomes in this patient cohort.

The Safety and Cost Analysis of Outpatient Laparoendoscopy in the Treatment of Cholecystocholedocholithiasis: A Retrospective Study.

INTRODUCTION: The advantages of single-stage treatment of cholecystocholedocholithiasis are well established, but the conditions for carrying out treatment on an outpatient basis require a review of concepts and practices of medical corporations. OBJECTIVE: To evaluate the practice of treating cholecystocholedocholithiasis by laparoendoscopy on an outpatient basis with cost analysis. METHOD: A retrospective study was conducted on patients with cholecystocholedocholithiasis treated by combined laparoscopic cholecystectomy and endoscopic choledocholithotomy from January 2015 to January 2019. After collecting data from physical and digital medical records, the patients were divided into two groups-AR (n = 42)-ambulatory regimen and HR (n = 28)-hospitalization regimen-which were compared in terms of demographic, clinical and treatment variables and their results, as well as in terms of costs. RESULTS: The mean age of the AR group was lower than that of the HR group and the physical status of the AR patients was better when assessed according to the American Society of Anesthesiologists (ASA) (p = 0.01). There was no difference between groups regarding the risk of choledocholithiasis (p = 0.99). For the AR group, the length of stay was shorter: 11.29 h × 65.21 h (p = 0.02), as was the incidence of postoperative complications assessed by applying the Clavien-Dindo classification: 3 (7.1%) × 11 (39.2%) (p < 0.01). The total mean costs were higher for the HR group (USD 2489.93) than the AR group (USD 1650.98) (p = 0.02). CONCLUSION: Outpatient treatment of cholecystocholedocholithiasis by laparoendoscopy is safe and viable for most cases, has a lower cost and can support the reorientation of training and practice of hepatobiliary surgeons.

mRNA Expression and Methylation of the RAD51, ATM, ATR, BRCA1, and BRCA2 Genes in Gastric Adenocarcinoma.

Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. Objective and design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm. Methods: We evaluated mRNA expression and methylation of RAD51, ATM, ATR, BRCA1, and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features. Results: RAD51, ATR, BRCA1, BRCA2, and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR (P = .027), BRCA1 (P < .001), and BRCA2 (P < .001); ATR with BRCA1 (P = .007), and ATM (P = .001); BRCA1 with BRCA2 (P = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P = .035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P = .010) and death (1.664 vs 0.929, P = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P = .032), and no significant correlation for the other markers. Conclusions: Our results suggest RAD51, BRCA1, and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.

Effect of Roux-En-Y Gastric Bypass in the Pharmacokinetics of (R)-Carvedilol and (S)-Carvedilol.

Roux-en-Y gastric bypass is one of the most common surgical treatments for obesity due to the effective long-term weight loss and remission of associated comorbidities. Carvedilol, a third-generation ß-blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH-dependent solubility and dissolution and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after roux-en-Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux-en-Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n = 15, body mass index < 25 kg/m2 ), obese (n = 19, body mass index ≥ 30), and post-roux-en-Y gastric bypass subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered a single oral dose of 25-mg racemic carvedilol, and blood was sampled for up to 24 hours. Plasma concentrations of (R)- and (S)-carvedilol were determined by liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve (AUC) of (R)-carvedilol were 2- to 3-fold higher than (S)-carvedilol in all groups. Obese subjects have shown reduced Cmax of (R)- and (S)-carvedilol without changing the AUC. Post-roux-en-Y gastric bypass subjects presented a 3.5-fold reduction in the Cmax of the active (S)-carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach Cmax of (S)-carvedilol increased 2.5-fold in post-roux-en-Y gastric bypass subjects compared to obese or nonobese. Although the ß-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-roux-en-Y gastric bypass may be clinically relevant and require dose adjustment.

Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma.

Since the incidence of gastric adenocarcinoma (GA) is high in populations living at high altitudes, we evaluated the influence of altitude on the expression of HIF-1 and survival of Ecuadorian GA patients. METHOD: 155 GA cases were studied: 56 from coastal (GAC) and 99 from mountainous regions (GAM), and 74 non-GA controls (25 coast and 49 mountain). The expression of HIF-1/HER2 was analyzed by immunohistochemistry. Analyses were performed using Fisher's exact and Breslow-Day tests for homogeneity and Kaplan-Meier curves and restricted median survival time ΔRMST. RESULTS: HIF-1 was overexpressed in normal/inflamed gastric mucosa, especially in mountainous non-GA patients (p = 0.001). There was no difference between GAC and GAM in terms of age/gender, HIF-1/HER2 expression, stage/tumor location. Median survival at 120 months was significantly higher among GAC, with a difference (ΔRMST) of 43.7 months (95% CI 29.5, 57.8) (p < 0.001) and those with positive HIF-1 expression: ΔRMST 26.6 months (95% CI 11.0, 42.1) (p < 0.001). Positive HIF-1 expression was associated with better GAM survival, with ΔRMST 33.6 months (95% CI 14.2, 52.9) (p < 0.001). CONCLUSION: Despite the limitations of this retrospective study, GA patients in the coastal region and those who expressed HIF-1 exhibited a better prognosis, but this factor was associated with better survival only in the mountain region.

Chemometric optimization of salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS for the analysis of carvedilol enantiomers in human plasma: Application to clinical pharmacokinetics.

Carvedilol is a commonly used antihypertensive whose oral absorption is limited by low solubility and significant first-pass metabolism. This work aimed to apply chemometrics for the optimization of a salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS to analyze carvedilol enantiomers in plasma samples. Method development and validation were driven for application in pharmacokinetic studies. Parameters that influence the efficiency of SALLE were evaluated using a fractional factorial 24-1 design with 4 factors and a central composite design was used to evaluate the optimal extraction condition. Carvedilol enantiomers and the internal standard lidocaine were separated on an Astec® Chirobiotic® V column and a mixture of methanol:ethanol (90:10, v/v) with 0.02% diethylamine and 0.18% acetic acid as mobile phase. The positive ion mode on electrospray ionization was used to monitor the transitions of m/z 407 > 100 and 235 > 86 for carvedilol enantiomers and lidocaine, respectively. Acetonitrile and ammonium acetate solution were selected for sample preparation by SALLE. Surface graphs and the desirability test were used to define the optimized SALLE conditions which resulted in 93% recovery for both carvedilol enantiomers. The method was linear in the range of 0.5 to 100 ng/mL in plasma, with a lower limit of quantification of 0.5 ng/mL. Within-run and between-run precision (as the relative standard deviation) were all < 9.74% and accuracy (as relative error) did not exceed ± 10.30%. Residual effect and matrix effect were not observed. Carvedilol enantiomers were stable in plasma under the storage, preparation, and analysis conditions. The validated method was successfully applied to analyze carvedilol in plasma samples from patients previously submitted to a Roux-en-Y gastric bypass surgery treated with a single oral dose of 25 mg racemic-carvedilol. Higher plasma concentrations were observed for (R)-(+)-carvedilol when compared to (S)-(-)-carvedilol in two patients post-bariatric surgery.

Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma.

Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma.

The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis.

Diagnosis and treatment of pancreatic ductal adenocarcinoma (PA) remains a challenge in clinical practice. The aim of this study was to assess the role of microRNAs (miRNAs-21, -23a, -100, -107, -181c, -210) in plasma and tissue as possible biomarkers in the diagnosis of PA. Samples of plasma (PAp-n = 13), pancreatic tumors (PAt-n = 18), peritumoral regions (PPT-n = 9) were collected from patients during the surgical procedure. The control group consisted of samples from patients submitted to pancreatic surgery for trauma or cadaveric organs (PC-n = 7) and healthy volunteers donated blood (PCp-n = 6). The expression profile of microRNAs was measured in all groups using RT-PCR, serum CA19-9 levels were determined in PA and PC. In tissue samples, there was a difference in the expression of miRNAs-21, -210 (p < 0.05) across the PAt, PC and PPT groups. The PAp showed overexpression of miRNAs-181c, -210 (p < 0.05) when compared to PCp. The combination of miRNAs-21, -210 tissue expression and serum CA19-9 showed 100% accuracy in the diagnosis of PA, as well as miR-181c expression in the plasma (PApxPCp). The expression of microRNAs in plasma proved to be a promising tool for a noninvasive detection test for PA, as well as further studies will evaluate the utility of microRNAs expression as biomarkers for prognostic and response to therapy in PA.

Clinical outcomes and costs of the use of fibrin sealant in pancreaticojejunal anastomosis after pancreaticoduodenectomy: a retrospective analysis study.

OBJECTIVES: The benefits of using a fibrin sealant to reinforce the pancreaticojejunal anastomosis are still contentious, a fact that justifies the study of its effects on clinical outcomes and costs of pancreaticoduodenectomy. METHODS: Study of 62 consecutive patients submitted to pancreaticoduodenectomy, divided into two groups of 31 patients each: GWS = group with sealant and GWOS = group without sealant that were compared according to demographic, clinical, laboratory aspects, the incidence of postoperative pancreatic fistula (POPF), according to the definition of the International Study Group on Pancreatic Fistula, updated in 2016, and its postoperative complications categorized according to the Clavien classification, as well as hospital costs evaluated by the absorption costing method (with the exception of those related to medications). RESULTS: The groups were homogeneous and there were no significant differences in the postoperative clinical course or in the indicators of hospital care between them. Hard texture of pancreatic tissue was the only protective factor against the development of POPF (RR = 0.29 (95%CI:0,12-0,68); p = 0.005). Moreover, hospital costs were higher in GWS than in GWOS (p < 0.0001). CONCLUSIONS: The use of fibrin sealant to reinforce pancreaticojejunal anastomosis did not improve the clinical and healthcare outcomes and, in addition, increased hospital costs.

IS THE NEW PROCORE 20G DOUBLE FORWARD-BEVEL NEEDLE CAPABLE TO OBTAIN BETTER HISTOLOGICAL SAMPLES BY ENDOSCOPIC ULTRASOUND FOR DIAGNOSING SOLID PANCREATIC LESIONS?

BACKGROUND: Fine needle biopsy (FNB) histological samples by endoscopic ultrasound. It is important to obtain representative histological samples of solid biliopancreatic lesions without a clear indication for resection. The role of new needles in such task is yet to be determined. AIM: To compare performance assessment between 20G double fine needle biopsy (FNB) and conventional 22G fine needle aspiration (FNA) needles for endoscopic ultrasound (EUS)-guided biopsy. METHODS: This prospective study examined 20 patients who underwent the random puncture of solid pancreatic lesions with both needles and the analysis of tissue samples by a single pathologist. RESULTS: The ProCore 20G FNB needle provided more adequate tissue samples (16 vs. 9, p=0.039) with better cellularity quantitative scores (11 vs. 5, p=0.002) and larger diameter of the histological sample (1.51±1.3 mm vs. 0.94±0.55 mm, p=0.032) than the 22G needle. The technical success, puncture difficulty, and sample bleeding were similar between groups. The sensitivity, specificity, and diagnostic accuracy were 88.9%, 100%, and 90% and 77.8%, 100%, and 78.9% for the 20G and 22G needles, respectively. CONCLUSIONS: The samples obtained with the ProCore 20G FNB showed better histological parameters; although there was no difference in the diagnostic performance between the two needles, these findings may improve pathologist performance.

Is the new procore 20g double forward-bevel needle capable to obtain better histological samples by endoscopic ultrasound for diagnosing solid pancreatic lesions? / A nova agulha procore 20g com bisel frontal duplo é capaz de obter melhores amostras histológicas por ecoendoscopia no diagnóstico de lesões sólidas pancreáticas?

ABSTRACT Background: It is important to obtain representative histological samples of solid biliopancreatic lesions without a clear indication for resection. The role of new needles in such task is yet to be determined. Aim: To compare performance assessment between 20G double fine needle biopsy (FNB) and conventional 22G fine needle aspiration (FNA) needles for endoscopic ultrasound (EUS)-guided biopsy. Methods: This prospective study examined 20 patients who underwent the random puncture of solid pancreatic lesions with both needles and the analysis of tissue samples by a single pathologist. Results: The ProCore 20G FNB needle provided more adequate tissue samples (16 vs. 9, p=0.039) with better cellularity quantitative scores (11 vs. 5, p=0.002) and larger diameter of the histological sample (1.51±1.3 mm vs. 0.94±0.55 mm, p=0.032) than the 22G needle. The technical success, puncture difficulty, and sample bleeding were similar between groups. The sensitivity, specificity, and diagnostic accuracy were 88.9%, 100%, and 90% and 77.8%, 100%, and 78.9% for the 20G and 22G needles, respectively. Conclusions: The samples obtained with the ProCore 20G FNB showed better histological parameters; although there was no difference in the diagnostic performance between the two needles, these findings may improve pathologist performance.

RESUMO Racional: As lesões sólidas pancreáticas não ressecáveis cirurgicamente demandam boa amostragem tecidual para definição histológica e condução oncológica . O papel das novas agulhas de ecopunção no aprimoramento diagnóstico ainda necessita elucidação. Objetivo: Comparar as biópsias guiadas por ecoendoscoopia com a nova agulha 20G de bisel frontal duplo (FNB) com a agulha de aspiração fina 22G convencional. Métodos: Este estudo prospectivo avaliou 20 pacientes submetidos à punção de lesões pancreáticas sólidas com ambas agulhas e envolveu análise de amostras teciduais por um único patologista. Resultados: A agulha FNB 20G forneceu amostras de tecido mais adequadas (16 vs. 9, p=0,039) com melhores escores quantitativos de celularidade (11 vs. 5, p=0,002) e maior diâmetro máximo da amostra histológica (1,51±1,3 mm vs. 0,94±0,55 mm, p=0,032) que a agulha 22G. O sucesso técnico, dificuldade de punção e sangramento da amostra foram semelhantes entre os grupos. A sensibilidade, especificidade e acurácia diagnóstica foram 88,9%, 100% e 90% e 77,8%, 100% e 78,9% para as agulhas 20G e 22G, respectivamente. Conclusão: As amostras obtidas com a FNB 20G apresentaram melhores parâmetros histológicos, embora não tenha havido diferença no desempenho diagnóstico entre as duas agulhas.

Adjuvant therapy for gastric cancer: what have we learned since INT0116?

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

Preoperative variables associated with transfusion requirements in orthotopic liver transplantation.

BACKGROUND: Patients with end-stage chronic liver disease (CLD) and submitted to orthotopic liver transplantation (OLT) usually require blood transfusion during the procedure or in the post-operative period due to hemorrhage. Risk factors for transfusion need are not fully known. This study aimed to identify the factors associated with blood components requirements. METHODS: In this retrospective study a total of 166 consecutive patients submitted to OLT with the piggyback technique, between 2001 and 2011, were evaluated for number of blood components transfused during surgical procedure and the four subsequent days (total of 5 days). We evaluated the association between the number of units transfused and clinical variables, such as: Child-Turcotte-Pugh (CTP) and MELD scores, hemoglobin concentration (Hb), INR, serum creatinine, bilirubin and albumin concentrations, and total, hypothermic and normothermic time of graft ischemia. RESULTS: 152 (91.6%) Patients were transfused (median of 24 units of blood components). Risk factors for higher blood transfusion requirements were CTP, INR, Hb and total time of graft ischemia. The group with CTP-A score received less blood components than CTP-B/C (11.5 vs 27; P=0.002). The group with Hb<10 required a higher number of blood units (34.5 vs 23; P=0.003). The group with INR<1.5 received less blood units (20.5 vs 31; P=0.012). The group transplanted with a graft exposed to less than the median of 555 min of ischemia received less transfusion (21 vs 27; P=0.03). MELD score and the other factors were not associated with blood requirements. CONCLUSION: These results demonstrate that CTP, but not MELD score, hemoglobin concentration, INR, and total time of graft ischemia are preoperative variables associated with blood requirements during OLT and in the subsequent days.

A aplicação de um guia de medidas preventivas por médicos de família em um centro de saúde de Ribeirão Preto, São Paulo, Brasil / The application of a guide for disease prevention by family physicians in a health centre of Ribeirão Preto, São Paulo, Brazil / La aplicación de un guía de medidas preventivas por los médicos de familia en un centro de salud de Ribeirão Preto, São Paulo, Brasil

Neste estudo, foi adaptado um protocolo de prevenção, contendo medidas de prevenção primária e secundária, composto por rastreamento, aconselhamento, vacinação e quimioprofilaxia com níveis A e B de recomendação. O estudo foi desenvolvido em uma Unidade de Saúde da Família na qual atuam residentes de Medicina de Família e Comunidade. Os médicos foram treinados quanto à importância e utilização do material preventivo (tabela e encarte-lembrete) e sua adesão foi avaliada por meio do preenchimento do encarte-lembrete. No ano estudado, realizaram-se 3.995 consultas a 1.596 usuários e, em apenas 397 prontuários, encontrou-se o encarte-lembrete com registro de uma medida preventiva, o que representou 25% da população atendida. As medidas encontradas seguiram esta ordem: rastreamento (99%); aconselhamento (90%); quimioprofilaxia (55%); e vacinação (45%). Este protocolo de prevenção norteia o profissional quanto às medidas a serem oferecidas, entretanto faz-se necessário implementar outras ações para que as medidas preventivas possam ser oferecidas de maneira mais efetiva.

In this study, we adapted a protocol for preventive measures containing primary and secondary prevention, comprising screening, counseling, vaccination and chemoprophylaxis with levels A and B of recommendation. This study was conducted in a Family Healthcare Unit where Family and Community Medicine residents are trained. Medical resident students were trained on the importance and use of prevention material (protocol and reminders) and their adherence was assessed by the completion of booklet reminders. During the one-year study period, 3995 consultations were held with 1596 patients. However, the record of at least one preventive measure was found in only 397 booklet reminders, which represents 25% of the population seen. The preventive measures found were screening (99%), counseling (90%), chemoprophylaxis (55%), and vaccination (45%). This protocol provides professionals with a set of preventive measures to be offered; however, other actions are needed so that preventive measures can be provided more effectively.

En este estudio, fué adaptado un un protocolo de medidas de prevención primarias y secundarias, compuesto por selección, consejo, vacunación y quimioprofilaxis con los niveles A y B de recomendación. El estudio se realizó en una Unidad de Salud Familiar, donde trabajan residentes de Medicina Familiar y Comunitaria. Se capacitó a los médicos sobre la importancia y el uso del material de prevención (tabla y folleto recordatorio) y se evaluó su adhesión mediante las respuestas al cuestionario localizado en el folleto recordatorio. En el año de estudio, los médicos realizaron 3995 consultas a 1596 pacientes y en sólo 397 historias clínicas se encontró el folleto recordatorio con registro de una medida preventiva, lo que representa el 25% de la población atendida. Las medidas encontradas siguieron este orden: selección (99%), consejo (90%), quimioprofilaxis (55%) y vacunación (45%). Este protocolo de prevención guía a los profesionales sobre las medidas que se deben ofrecer, sin embargo, es necesario implementar otras acciones para proporcionar las medidas preventivas con mayor efectividad.

Uncomplicated acute cholecystitis: early or delayed laparoscopic cholecystectomy?

Recent meta-analyses suggested that early laparoscopic cholecystectomy (within 1 week of symptom onset) for uncomplicated acute gallbladder disease is safe and feasible. However, surveys on surgical practices indicated that early laparoscopic cholecystectomy is performed by only a minority of surgeons. Furthermore, the exact time-point for performing this procedure as well as its cost-effectiveness remain a matter of debate. The TBE - CiTE Journal Club performed a critical appraisal of the most relevant evidence recently published on timing of laparoscopic cholecystectomy and its cost-effectiveness for the management of uncomplicated acute cholecystitis and provides evidence-based recommendations on the topic. The literature encompasses small trials with high risk of biases. It suggests that early laparoscopic cholecystectomy is safe and shortens hospital stay. There is scarcity of well-designed and large cost-utility analyses. The following main recommendations were generated: (1) Early laparoscopic cholecystectomy should be attempted as the first-line treatment within one week of symptoms onset; and (2) The cost-effectiveness of early laparoscopic cholecystectomy should be evaluated at the individual hospital level, taking into consideration local resources such as the availability of trained personal, operating room and laparoscopic equipment.

Colecistite aguda não-complicada: colecistectomia laparoscópica precoce ou tardia? / Uncomplicated acute cholecystitis: early or delayed laparoscopic cholecystectomy?

Metanálises recentes sugerem que a colecistectomia laparoscópica precoce (dentro de uma semana do início dos sintomas) para a doença aguda, não complicada, da vesícula biliar é segura e viável. No entanto, enquetes sobre as práticas cirúrgicas indicam que a colecistectomia laparoscópica precoce é realizada por apenas uma minoria dos cirurgiões. Além disso, o melhor momento para realização deste procedimento, bem como sua relação custo-eficácia continuam sendo uma questão de debate. A reunião de revista TBE - CiTE realizou uma avaliação crítica dos artigos mais relevantes, publicados recentemente, sobre o momento da colecistectomia laparoscópica e sua relação custo-eficácia para o tratamento da colecistite aguda não complicada e fornece recomendações baseadas em evidências sobre o tema. A literatura engloba pequenos ensaios com alto risco para vieses. Ela sugere que colecistectomia laparoscópica precoce é segura e encurta o período de internação. Há uma escassez de estudos bem desenhados e de grandes séries analisando custo-utilidade. As seguintes recomendações foram geradas: (1) a colecistectomia laparoscópica precoce deve ser tentada como o tratamento de primeira linha dentro de uma semana do início dos sintomas, e (2) O custo-efetividade da colecistectomia laparoscópica precoce deve ser avaliada em cada local, levando-se em consideração os recursos, tais como a disponibilidade de pessoal treinado e de equipamentos laparoscópicos.

Recent meta-analyses suggested that early laparoscopic cholecystectomy (within 1 week of symptom onset) for uncomplicated acute gallbladder disease is safe and feasible. However, surveys on surgical practices indicated that early laparoscopic cholecystectomy is performed by only a minority of surgeons. Furthermore, the exact time-point for performing this procedure as well as its cost-effectiveness remain a matter of debate. The TBE - CiTE Journal Club performed a critical appraisal of the most relevant evidence recently published on timing of laparoscopic cholecystectomy and its cost-effectiveness for the management of uncomplicated acute cholecystitis and provides evidence-based recommendations on the topic. The literature encompasses small trials with high risk of biases. It suggests that early laparoscopic cholecystectomy is safe and shortens hospital stay. There is scarcity of well-designed and large cost-utility analyses. The following main recommendations were generated: (1) Early laparoscopic cholecystectomy should be attempted as the first-line treatment within one week of symptoms onset; and (2) The cost-effectiveness of early laparoscopic cholecystectomy should be evaluated at the individual hospital level, taking into consideration local resources such as the availability of trained personal, operating room and laparoscopic equipment.