Davide Paolo Bernasconi

Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials.

Abstract The role of glutamine (GLN) supplementation in critically ill patients is controversial. Our aim was to analyze its potential effect in patients admitted to intensive care unit (ICU). We performed a systematic literature review through Medline, Embase, Pubmed, Scopus, Ovid, ISI Web of Science, and the Cochrane-Controlled Trials Register searching for randomized clinical trials (RCTs) published from 1983 to 2014 and comparing GLN supplementation to no supplementation in patients admitted to ICU. A random-effect meta-analysis for each outcome (hospital and ICU mortality and rate of infections) of interest was carried out. The effect size was estimated by the risk ratio (RR). Thirty RCTs were analyzed with a total of 3696 patients, 1825 (49.4%) receiving GLN and 1859 (50.6%) no GLN (control groups). Hospital mortality rate was 27.6% in the GLN patients and 28.6% in controls with an RR of 0.93 (95% CI = 0.81–1.07; P = 0.325, I2 = 10.7%). ICU mortality was 18.0 % in the patients receiving GLN and 17.6% in controls with an RR of 1.01 (95% CI = 0.86–1.19; P = 0.932, I2 = 0%). The incidence of infections was 39.7% in GLN group versus 41.7% in controls. The effect of GLN was not significant (RR = 0.88; 95% CI = 0.76–1.03; P = 0.108, I2 = 56.1%). These results do not allow to recommend GLN supplementation in a generic population of critically ills. Further RCTs are needed to explore the effect of GLN in more specific cohort of patients.

Preoperative Computed Tomography to Predict and Stratify the Risk of Severe Pancreatic Fistula After Pancreatoduodenectomy

Abstract The aim of this article is to assess whether measures of abdominal fat distribution, visceral density, and antropometric parameters obtained from computed tomography (CT) may predict postoperative pancreatic fistula (POPF) occurrence. We analyzed 117 patients who underwent pancreatoduodenectomy (PD) and had a preoperative CT scan as staging in our center. CT images were processed to obtain measures of total fat volume (TFV), visceral fat volume (VFV), density of spleen, and pancreas, and diameter of pancreatic duct. The predictive ability of each parameter was investigated by receiver-operating characteristic (ROC) curves methodology and assessing optimal cutoff thresholds. A stepwise selection method was used to determine the best predictive model. Clinically relevant (grades B and C) POPF occurred in 24 patients (20.5%). Areas under ROC-curves showed that none of the parameters was per se significantly predictive. The multivariate analysis revealed that a VFV >2334 cm3, TFV >4408 cm3, pancreas/spleen density ratio <0.707, and pancreatic duct diameter <5 mm were predictive of POPF. The risk of POPF progressively increased with the number of factors involved and age. It is possible to deduce objective information on the risk of POPF from a simple and routine preoperative radiologic workup.

Effect of glutamine dipeptide supplementation on primary outcomes for elective major surgery: systematic review and meta-analysis.

To evaluate if glutamine (GLN) supplementation may affect primary outcomes in patients undergoing major elective abdominal operations, we performed a systematic literature review of randomized clinical trials (RCTs) published from 1983 to 2013 and comparing intravenous glutamine dipeptide supplementation to no supplementation in elective surgical abdominal procedures. A meta-analysis for each outcome (overall and infectious morbidity and length of stay) of interest was carried out. The effect size was estimated by the risk ratio (RR) or by the weighted mean difference (WMD). Nineteen RCTs were identified with a total of 1243 patients (640 receiving GLN and 603 controls). In general, the studies were underpowered and of medium or low quality. GLN supplementation did not affect overall morbidity (RR = 0.84, 95% CI 0.51 to 1.36; p = 0.473) and infectious morbidity (RR = 0.64; 95% CI = 0.38 to 1.07; p = 0.087). Patients treated with glutamine had a significant reduction in length of hospital stay (WMD = −2.67; 95% CI = −3.83 to −1.50; p < 0.0001). In conclusion, GLN supplementation appears to reduce hospital stay without affecting the rate of complications. The positive effect of GLN on time of hospitalization is difficult to interpret due to the lack of significant effects on surgery-related morbidity.

Stillbirths in singletons, dichorionic and monochorionic twins: a comparison of risks and causes

OBJECTIVES To estimate the risk of stillbirth in dichorionic and monochorionic twins compared with singletons, and to evaluate the relevant causes of stillbirth in each group. STUDY DESIGN A retrospective cohort analysis of all pregnancies ≥22 weeks of gestation was performed at a tertiary care center from January 1995 to June 2011. The overall fetal survival and the prospective risk of stillbirth were compared in monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins, and singletons. Causes of stillbirth were classified using the ReCoDe classification and were compared among the three study groups. RESULTS A total of 46,200 singletons, 462 MCDA twins and 1108 DCDA twins were included in the study. Both Kaplan-Meier analysis and prospective risk calculation showed that MCDA twins had the highest risk of stillbirth (OR ranging between 13.5 95% CI 8.7-20.7 at 22.0-24.6 weeks and 4.0 95% CI 1.1-13.1 at 31.0-33.6 weeks, compared to singletons), while singletons had the lowest. Main causes of stillbirth were major congenital malformations in singletons (25.1%) and in DCDA twins (75%), and twin-twin transfusion syndrome in MCDA twins (81.5%). When excluding fetuses affected by major congenital anomalies, MCDA twins (p<0.001) but not DCDA twins (p=0.2) remained at increased risk for stillbirth compared with singletons. CONCLUSION The risk of stillbirth is significantly higher both in MCDA and DCDA twins compared with singletons. Stillbirths are mainly due to twin-twin transfusion syndrome in MCDA twins and major congenital anomalies in DCDA twins. When major congenital anomalies are excluded, DCDA twins have a similar in utero mortality to singletons.

Simultaneous liver iron and fat measures by magnetic resonance imaging in patients with hyperferritinemia

Abstract Objective. Hyperferritinemia is frequent in chronic liver diseases of any cause, but the extent to which ferritin truly reflects iron stores is variable. In these patients, both liver iron and fat are found in variable amount and association. Liver biopsy is often required to quantify liver fat and iron, but sampling variability and invasiveness limit its use. We aimed to assess single breath-hold multiecho magnetic resonance imaging (MRI) for the simultaneous lipid and iron quantification in patients with hyperferritinemia. Material and methods. We compared MRI results for both iron and fat with their respective gold standards – liver iron concentration and computer-assisted image analysis for steatosis on biopsy. We prospectively studied 67 patients with hyperferritinemia and other 10 consecutive patients were used for validation. We estimated two linear calibration equations for the prediction of iron and fat based on MRI. The agreement between MRI and biopsy was evaluated. Results. MRI showed good performances in both the training and validation samples. MRI information was almost completely in line with that obtained from liver biopsy. Conclusion. Single breath-hold multiecho MRI is an accurate method to obtain a valuable measure of both liver iron and steatosis in patients with hyperferritinemia.

Preoperative Oral Carbohydrate Load Versus Placebo in Major Elective Abdominal Surgery (PROCY): A Randomized, Placebo-controlled, Multicenter, Phase III Trial

Objective: To explore whether preoperative oral carbohydrate (CHO) loading could achieve a reduction in the occurrence of postoperative infections. Background: Hyperglycemia may increase the risk of infection. Preoperative CHO loading can achieve postoperative glycemic control. Methods: This was a randomized, controlled, multicenter, open-label trial. Nondiabetic adult patients who were candidates for elective major abdominal operation were randomized (1:1) to a CHO (preoperative oral intake of 800 mL of water containing 100 g of CHO) or placebo group (intake of 800 mL of water). The blood glucose level was measured every 4 hours for 4 days. Insulin was administered when the blood glucose level was >180 mg/dL. The primary endpoint was the occurrence of postoperative infection. The secondary endpoint was the number of patients needing insulin. Results: From January 2011 through December 2015, 880 patients were randomly allocated to the CHO (n = 438) or placebo (n = 442) group. From each group, 331 patients were available for the analysis. Postoperative infection occurred in 16.3% (54/331) of CHO group patients and 16.0% (53/331) of placebo group patients (relative risk 1.019, 95% confidence interval 0.720–1.442, P = 1.00). Insulin was needed in 8 (2.4%) CHO group patients and 53 (16.0%) placebo group patients (relative risk 0.15, 95% confidence interval 0.07–0.31, P < 0.001). Conclusions: Oral preoperative CHO load is effective for avoiding a blood glucose level >180 mg/dL, but without affecting the risk of postoperative infectious complication.

Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment

Background Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear. Methods Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89–60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates). Results 2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2–3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8–2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4–6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF. Conclusions Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage.

Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis

AIM To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. METHODS We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. RESULTS Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P < 0.05 for both comparisons). Mesalamine administration was also associated with an earlier reintroduction of food intake (median 1.5 d and 3 d, study group vs controls respectively, P < 0.001) and with a shorter hospital stay (median 5 d and 5.5 d, study group vs controls respectively, P = 0.03). CONCLUSION Despite its limitations, this study suggests that mesalamine may allow for a faster recovery and for a reduction of inflammatory response in acute uncomplicated diverticulitis.

Description of survival data extended to the case of competing risks: A teaching approach based on frequency tables

Survival analysis is a powerful statistical tool to study failure-time data. In introductory courses students learn how to describe right-censored survival time data using the product-limit estimator of the survival function on a given end-point relying on a product of conditional survival probabilities. In the case of a composite end-point , the next step is to account for the presence of competing risks. The complement to one of the survival function is decomposed into the sum of cause-specific incidences, which are obtained as sum of unconditional probabilities due to the single competing risk. However, this algebraic decomposition is not straightforward, given the difference between the structure of the involved estimators. In addition, one is tempted to use the Kaplan-Meier estimator, leading to an erroneous decomposition of the overall incidence. Here we discuss a simple reinterpretation of the Kaplan-Meier formula in terms of sum of non-conditional probabilities of developing the end-point in time, adjusted for the presence of censoring. This approach could be used for describing survival data through simple frequency tables which are directly generalized to the case of competing risks. In addition, it makes clear how the estimation of the single cause-specific incidence through the Kaplan-Meier estimator, simply considering the occurrence of competing events as censored data, leads to an overestimation of the cause-specific incidence. Two examples are provided to support the explanation: the first one, could help to clarify the procedure described by the formulas; the second one, simulates real data in order to present graphically the results.