Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 µg/mL in human plasma, 2 µg/mL in rat plasma, and 0.5 and 0.025 µg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.

Efficacious Cefazolin Prophylactic Dose for Morbidly Obese Women Undergoing Bariatric Surgery Based on Evidence from Subcutaneous Microdialysis and Populational Pharmacokinetic Modeling.

PURPOSE: To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. METHODS: A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation. RESULTS: CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA ≥ 90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%). CONCLUSIONS: Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.

Revisional Malabsorptive Bariatric Surgery: 29-Year Follow-up in a Brazilian Public Hospital.

BACKGROUND: This study aimed to evaluate the outcomes of 67 patients who underwent revisional bariatric surgeries over a 29-year period in a Brazilian public hospital. METHODS: The records of all patients who underwent revisional bariatric surgery from January 1987 to December of 2016 at our hospital were analyzed for weight loss and complications. Descriptive statistics and paired t tests were computed. RESULTS: Sixty-seven patients were included in the study. The primary surgeries previously performed on these patients were biliopancreatic diversion with duodenal switch (BPD-DS) (37 cases, 55.2%), jejunoileal bypass (JIB) (24 cases, 35.8%), sleeve gastrectomy (4 cases, 5.9%), Roux-en-Y gastric bypass (RYGB) (1 case, 1.5%), and laparoscopic adjustable gastric band (1 case, 1.5%). The indications for revisional surgery were as follows: malnutrition in 29 cases (43.3%), failure to lose weight in 27 cases (40.3%), weight regain in 5 cases (7.5%), and untreatable diarrhea in 6 cases (9.2%). Most revisional surgeries were performed using JIB or BPD-DS. Operative mortality was higher after the revisional procedures compared with that following the primary bariatric surgeries. CONCLUSIONS: Most patients requiring a revisional surgery had undergone a primary BPD-DS or JIB. Severe and untreatable malnutrition and diarrhea were the main indications for the revisional procedures. RYGB produced significant and sustainable weight loss and exhibited a low risk of malnutrition or requiring revisional surgery.

Adipokine Levels Versus Hepatic Histopathology in Bariatric Surgery Patients.

BACKGROUND: Obesity is a worldwide prevalent disease and is an underlying factor of non-alcoholic fatty liver disease (NAFLD). It has been understood as a chronic inflammatory state, being associated with the production of adipokines. The aim of this study was to analyze the levels of adipokines in the serum, visceral, and subcutaneous fat and to compare them with hepatic histopathology in morbidly obese patients. METHODS: This is a cross-sectional observational study, which analyzed the findings of liver biopsy in patients undergoing bariatric surgery and who had performed analysis of adipokines mRNA expression (adiponectin-ADIPOQ, leptin-LEP, and resistin-RETN) in subcutaneous and visceral adipose tissue and circulating adipokines in serum. Liver biopsies performed were evaluated according to Kleiner criteria. RESULTS: The study analyzed 25 patients undergoing bariatric surgery. The sample was composed exclusively of women. There was a predominance of NAFLD, with 21 patients (84%) with intrahepatic fat accumulation. Twelve patients presented non-alcoholic steatohepatitis (NASH). Glycated hemoglobin levels (HbA1c) were elevated in NASH patients. ADIPOQ levels were directly correlated with high-density lipoprotein (HDL) cholesterol levels and inversely correlated with triglycerides and total cholesterol. LEP levels showed an inverse relationship with the degree of steatosis, and RETN levels showed an inverse relationship with fibrosis stages. CONCLUSION: Serum LEP levels were reduced in the presence of increased levels of intrahepatic fat, and serum levels of RETN were diminished in the presence of NASH. HbA1c levels were higher in the presence of NASH, indirectly reflecting insulin resistance. Moreover, ADIPOQ levels were related to blood lipid profile.

Impact of bariatric surgery on the oral health of patients with morbid obesity.

BACKGROUND: The present study assessed the impact of bariatric surgery on the oral health. METHODS: All of the patients who underwent Roux-en-Y gastric bypass at Nossa Senhora da Conceição Hospital between October 2009 and January 2011 were invited to participate. In this longitudinal study, oral examinations and interviews were conducted in two stages. A descriptive analysis, McNemar's test, Student's t test for paired samples, and the Wilcoxon test were performed. RESULTS: Thirty-nine patients completed the protocol. There was a statistically significant reduction in the number of medications taken daily, sensation of dry mouth, and increased stimulated salivary flow rate. CONCLUSIONS: The oral health of patients who underwent bariatric surgery improved; moreover, the sensation of dry mouth decreased.

Antibiotic prophylaxis in obese patients submitted to bariatric surgery. A systematic review.

PURPOSE: To review the use of cefazolin in prophylaxis of surgical wound infection (SSI) in bariatric surgery (BS). METHODS: A systematic review was performed from October to November, 2013 using the following databases: The Cochrane Library, Medline, LILACS, and EMBASE. The inclusion criteria were randomized clinical trials and observational studies that were evaluated by two independent reviewers. RESULTS: Nine hundred and sixty one titles were recovered after preliminary analysis (title and abstract), seven studies remained for final analysis. There were three clinical trials (one with SSI, and two with antibiotic levels as the outcome), and four were observational studies (three cohorts and one case-control, all had SSI as the outcome). After administration of 1g or 2 g, levels of cefazolin in serum and tissue were suboptimal according to two studies. Results from observational studies indicated that different antibiotics were used for prophylaxis of SSI in BS and that use of other drugs may be associated with higher rates of SSI. CONCLUSION: The use of cefazolin for surgical wound infection prophylaxis in bariatric surgery is recommended, however further studies are needed in order to refine parameters as initial dose, redose, moment of administration and lasting of prophylaxis.

Antibiotic prophylaxis in obese patients submitted to bariatric surgery. A systematic review

To review the use of cefazolin in prophylaxis of surgical wound infection (SSI) in bariatric surgery (BS). METHODS: A systematic review was performed from October to November, 2013 using the following databases: The Cochrane Library, Medline, LILACS, and EMBASE. The inclusion criteria were randomized clinical trials and observational studies that were evaluated by two independent reviewers. RESULTS: Nine hundred and sixty one titles were recovered after preliminary analysis (title and abstract), seven studies remained for final analysis. There were three clinical trials (one with SSI, and two with antibiotic levels as the outcome), and four were observational studies (three cohorts and one case-control, all had SSI as the outcome). After administration of 1g or 2 g, levels of cefazolin in serum and tissue were suboptimal according to two studies. Results from observational studies indicated that different antibiotics were used for prophylaxis of SSI in BS and that use of other drugs may be associated with higher rates of SSI. CONCLUSION: The use of cefazolin for surgical wound infection prophylaxis in bariatric surgery is recommended, however further studies are needed in order to refine parameters as initial dose, redose, moment of administration and lasting of prophylaxis.

Prevalence of upper digestive endoscopy and gastric histopathology findings in morbidly obese patients.

CONTEXT: The prevalence of obesity has been increasing in modern society. Roux-en-y gastric bypass is a bariatric surgery that involves the exclusion of significant part of the stomach. Atrophy, intestinal metaplasia and gastric cancer have been associated with infection by Helicobacter pylori. OBJECTIVES: To evaluate the presence of endoscopy findings and histological changes in morbid obese patients for the presence of inflammatory cells, inflammatory activity, lymphoid hyperplasia, H. pylori infection, atrophy and intestinal metaplasia in the gastric mucosa. METHODS: Upper digestive endoscopy and gastric histopathological were studied in 126 obese patients in the preoperative evaluation for bariatric surgery. RESULTS: Upper digestive endoscopy abnormalities were diagnosed in 73/126 (57.9%) patients. In three patients (2.4%) the upper gastrointestinal endoscopy diagnosed gastric ulcer and one patient (0.8%) had duodenal ulcer. The histopathological from gastric biopsies of these obese patients showed 65.1% of mucosa inflammation, inflammatory activity in 50.0%, infection by H. pylori in 53.2%, lymphoid hyperplasia in 50.0% and atrophy and/or intestinal metaplasia in 16.7%. CONCLUSIONS: In present study, with routine preoperative upper gastrointestinal endoscopy and histopathological examination, were detected 57.9% patients with endoscopy abnormalities, high prevalence of infection by H. pylori (53%) and 16.7% of gastric atrophy and/or intestinal metaplasia.

Prevalence of upper digestive endoscopy and gastric histopathology findings in morbidly obese patients / Prevalência de achados gástricos endoscópicos e histopatológicos em pacientes obesos

CONTEXT: The prevalence of obesity has been increasing in modern society. Roux-en-y gastric bypass is a bariatric surgery that involves the exclusion of significant part of the stomach. Atrophy, intestinal metaplasia and gastric cancer have been associated with infection by Helicobacter pylori. OBJECTIVES: To evaluate the presence of endoscopy findings and histological changes in morbid obese patients for the presence of inflammatory cells, inflammatory activity, lymphoid hyperplasia, H. pylori infection, atrophy and intestinal metaplasia in the gastric mucosa. METHODS: Upper digestive endoscopy and gastric histopathological were studied in 126 obese patients in the preoperative evaluation for bariatric surgery. RESULTS: Upper digestive endoscopy abnormalities were diagnosed in 73/126 (57.9%) patients. In three patients (2.4%) the upper gastrointestinal endoscopy diagnosed gastric ulcer and one patient (0.8%) had duodenal ulcer. The histopathological from gastric biopsies of these obese patients showed 65.1% of mucosa inflammation, inflammatory activity in 50.0%, infection by H. pylori in 53.2%, lymphoid hyperplasia in 50.0% and atrophy and/or intestinal metaplasia in 16.7%. CONCLUSIONS: In present study, with routine preoperative upper gastrointestinal endoscopy and histopathological examination, were detected 57.9% patients with endoscopy abnormalities, high prevalence of infection by H. pylori (53%) and 16.7% of gastric atrophy and/or intestinal metaplasia.

CONTEXT: A prevalência de obesidade tem aumentado significativamente nos últimos anos. Bypass gástrico em Y-de-Roux, uma das técnicas cirúrgicas realizadas no tratamento da obesidade, envolve exclusão de parte do estômago. Atrofia, metaplasia intestinal e câncer gástrico têm sido associados com infecção pelo Helicobacter pylori. OBJETIVOS: Avaliar a prevalência de achados endoscópicos e alterações histopatológicas em pacientes obesos mórbidos em relação à presença de células inflamatórias, atividade inflamatória, hiperplasia linfóide, infecção pelo H. pylori, atrofia e metaplasia intestinal na mucosa gástrica. MÉTODOS: Achados na endoscopia digestiva alta e histopatologia gástrica foram analisados em 126 pacientes obesos na avaliação pré-operatória de cirurgia bariátrica. RESULTADOS: Anormalidades endoscópicas do trato digestivo superior foram diagnosticadas em 73/126 pacientes, com três pacientes (2,4%) apresentando úlcera gástrica e um paciente (0,8%) com úlcera duodenal. A histopatologia das biopsias gástricas dos obesos estudados revelou 65,1% de processo inflamatório na mucosa, atividade inflamatória em 50,0%; infecção pelo H. pylori em 53,2%, hiperplasia linfóide em 50,0%, atrofia e/ou metaplasia intestinal em 16,7%. CONCLUSÕES: No presente estudo, através de endoscopia digestiva alta e histopatologia de biopsias gástricas, foram detectados 57,9% de pacientes com anormalidades endoscópicas, prevalência de infecção pelo H. pylori em 53% e atrofia e/ou metaplasia intestinal em 16,7%.

Inferior vena cava syndrome and morbid obesity.

A case is reported of inferior vena cava syndrome in a patient with extreme obesity (BMI: >70 kg/m(2)), treated at a public hospital. The inferior vena cava obstruction was diagnosed during an attempt at inferior vena cava filter percutaneous insertion, in prebariatric surgery period. The diagnosis occurred after a hepatic scintillography, and was confirmed with a femoral venography and celiac trunk arteriography. The patient underwent a biliopancreatic diversion-duodenal switch and has lost weight. A venography 7 months after the surgery did not show any inferior vena cava rechanneling evidence.

Hepatic outcomes after jejunoileal bypass: is there a publication bias?

BACKGROUND: One of the reasons why jejunoileal bypass (JIB) was abandoned were reports of liver failure. The aim of this study was to describe histological findings in the intraoperative and follow-up liver biopsies of a cohort of super-obese patients who had undergone JIB. METHODS: 50 consecutive patients underwent JIB. Samples of liver biopsies performed intraoperatively (41 patients) and in the follow-up (31 patients) were evaluated. Brunt's scale was used. RESULTS: Mean age at operation was 37.9 +/- 7.6 years, and 15 patients (30.6%) had diabetes type 2, 20 (40.8%) had dyslipidemia, 29 (59.2%) had high blood pressure, and one (0.5%) had hepatitis C. Mean BMI preoperatively was 52.8 +/- 7.5 kg/m(2). Mean follow-up time was 67.0 +/- 42.8 months. At the time of the latest liver biopsy, the mean BMI was 35.7 +/- 7.5 kg/m(2). The % excess weight loss (%EWL) was 62.4 +/- 20.0%. 8 deaths (16%) have occurred, none from liver-related complications. At liver biopsy during the JIB operation, NAFLD was confirmed in 36 patients (86.7%) and NASH in 13 (31.7%). In 25 patients with mean follow-up of 4.8 +/- 4.0 years, there was no statistically significant change in the liver histology regarding the extent of steatosis (P=0.20), steatohepatitis (P=0.74) and fibrosis (P=0.71). CONCLUSIONS: There was a significant metabolic improvement, maintenance of the %EWL, and no worsening of liver histology. There has possibly been a publication bias concerning liver outcomes, where the type of JIB and the concomitance of hepatitis C were not taken into account.

Evaluation of quality of life and metabolic improvement after jejunoileal bypass in a community of low socioeconomic status.

BACKGROUND: Bariatric operations are currently the only effective treatment for morbid obesity The first operation, jejunoileal bypass (JIB), has been superceded. However, JIB has left a heritage which must be followed. We report the long-term follow-up of a series of patients who had undergone JIB in south Brazil. METHODS: 49 super-obese patients (85% female) from a poor community were submitted to JIB from 1987 to 2001. 5 deaths occurred and 4 patients were lost during follow-up. Quality of life was evaluated by means of the Bariatric Analysis and Reporting Outcome System (BAROS) applied to 40 patients. RESULTS: Preoperatively, 11 patients (22.4%) were diabetic,13 (26.5%) were dyslipidemic, and 23 (46.9%) had high blood pressure. After a mean postoperative period of 64.3 +/- 40.0 months, there was complete resolution of co-morbidites in all patients. Mean preoperative BMI was 52.8 +/- 10.3 kg/m(2), and the postoperative mean excess weight loss was 58.9% +/- 18.9%. CONCLUSION: JIB was adequate in reduction of weight, resolution of co-morbidites, and improvement in the quality of life as measured by BAROS. Since February 2001, we perform biliopancreatic diversion with duodenal switch, but we continue to follow our patients with JIB.