Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020. OBJECTIVES: To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report POPF, quality of life, or cost-effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.

Experimental Verification for Numerical Simulation of Thalamic Stimulation-Evoked Calcium-Sensitive Fluorescence and Electrophysiology with Self-Assembled Multifunctional Optrode.

Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method for mediating neural activity and neural function, the relationship between DBS-evoked neural Ca2+ change and DBS-evoked neural electrophysiology remains unknown. Therefore, in this study, a self-assembled optrode was demonstrated as a DBS stimulator and an optical biosensor capable of concurrently recording Ca2+ fluorescence and electrophysiological signals. Before the in vivo experiment, the volume of tissue activated (VTA) was estimated, and the simulated Ca2+ signals were presented using Monte Carlo (MC) simulation to approach the realistic in vivo environment. When VTA and the simulated Ca2+ signals were combined, the distribution of simulated Ca2+ fluorescence signals matched the VTA region. In addition, the in vivo experiment revealed a correlation between the local field potential (LFP) and the Ca2+ fluorescence signal in the evoked region, revealing the relationship between electrophysiology and the performance of neural Ca2+ concentration behavior. Concurrent with the VTA volume, simulated Ca2+ intensity, and the in vivo experiment, these data suggested that the behavior of neural electrophysiology was consistent with the phenomenon of Ca2+ influx to neurons.

Prophylactic abdominal drainage for pancreatic surgery.

BACKGROUND: The use of surgical drains is a very common practice after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. This is the third update of a previously published Cochrane Review to address the uncertain benifits of prophylactic abdominal drainage in pancreatic surgery. OBJECTIVES: To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal. SEARCH METHODS: In this updated review, we re-searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and the Chinese Biomedical Literature Database (CBM) on 08 February 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We conducted the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. We used GRADE to assess the certainty of the evidence for important outcomes. MAIN RESULTS: We identified a total of nine RCTs with 1892 participants. Drain use versus no drain use We included four RCTs with 1110 participants, randomised to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. Low-certainty evidence suggests that drain use may reduce 90-day mortality (RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants). Compared with no drain use, low-certainty evidence suggests that drain use may result in little to no difference in 30-day mortality (RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants), wound infection rate (RR 0.98, 95% CI 0.68 to 1.41; four studies, 1055 participants), length of hospital stay (MD -0.14 days, 95% CI -0.79 to 0.51; three studies, 876 participants), the need for additional open procedures for postoperative complications (RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants), and quality of life (105 points versus 104 points; measured with the pancreas-specific quality of life questionnaire (scale 0 to 144, higher values indicating a better quality of life); one study, 399 participants). There was one drain-related complication in the drainage group (0.2%). Moderate-certainty evidence suggests that drain use probably resulted in little to no difference in morbidity (RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants). The evidence was very uncertain about the effect of drain use on intra-abdominal infection rate (RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-certainty evidence), and the need for additional radiological interventions for postoperative complications (RR 0.87, 95% CI 0.40 to 1.87; three studies, 660 participants; very low-certainty evidence). Active versus passive drain We included two RCTs involving 383 participants, randomised to the active drain group (N = 194) and the passive drain group (N = 189) after pancreatic surgery. Compared with a passive drain, the evidence was very uncertain about the effect of an active drain on 30-day mortality (RR 1.23, 95% CI 0.30 to 5.06; two studies, 382 participants; very low-certainty evidence), intra-abdominal infection rate (RR 0.87, 95% CI 0.21 to 3.66; two studies, 321 participants; very low-certainty evidence), wound infection rate (RR 0.92, 95% CI 0.44 to 1.90; two studies, 321 participants; very low-certainty evidence), morbidity (RR 0.97, 95% CI 0.53 to 1.77; two studies, 382 participants; very low-certainty evidence), length of hospital stay (MD -0.79 days, 95% CI -2.63 to 1.04; two studies, 321 participants; very low-certainty evidence), and the need for additional open procedures for postoperative complications (RR 0.44, 95% CI 0.11 to 1.83; two studies, 321 participants; very low-certainty evidence). There was no drain-related complication in either group. Early versus late drain removal We included three RCTs involving 399 participants with a low risk of postoperative pancreatic fistula, randomised to the early drain removal group (N = 200) and the late drain removal group (N = 199) after pancreatic surgery. Compared to late drain removal, the evidence was very uncertain about the effect of early drain removal on 30-day mortality (RR 0.99, 95% CI 0.06 to 15.45; three studies, 399 participants; very low-certainty evidence), wound infection rate (RR 1.32, 95% CI 0.45 to 3.85; two studies, 285 participants; very low-certainty evidence), hospital costs (SMD -0.22, 95% CI -0.59 to 0.14; two studies, 258 participants; very low-certainty evidence), the need for additional open procedures for postoperative complications (RR 0.77, 95% CI 0.28 to 2.10; three studies, 399 participants; very low-certainty evidence), and the need for additional radiological procedures for postoperative complications (RR 1.00, 95% CI 0.21 to 4.79; one study, 144 participants; very low-certainty evidence). We found that early drain removal may reduce intra-abdominal infection rate (RR 0.44, 95% CI 0.22 to 0.89; two studies, 285 participants; very low-certainty evidence), morbidity (RR 0.49, 95% CI 0.30 to 0.81; two studies, 258 participants; very low-certainty evidence), and length of hospital stay (MD -2.20 days, 95% CI -3.52 to -0.87; three studies, 399 participants; very low-certainty evidence), but the evidence was very uncertain. None of the studies reported on drain-related complications. AUTHORS' CONCLUSIONS: Compared with no drain use, it is unclear whether routine drain use has any effect on mortality at 30 days or postoperative complications after pancreatic surgery. Compared with no drain use, low-certainty evidence suggests that routine drain use may reduce mortality at 90 days. Compared with a passive drain, the evidence is very uncertain about the effect of an active drain on mortality at 30 days or postoperative complications. Compared with late drain removal, early drain removal may reduce intra-abdominal infection rate, morbidity, and length of hospital stay for people with low risk of postoperative pancreatic fistula, but the evidence is very uncertain.

Branched hybridization chain reaction-using highly dimensional DNA nanostructures for label-free, reagent-less, multiplexed molecular diagnostics.

The specific and multiplexed detection of DNA underpins many analytical methods, including the detection of microorganisms that are important in the medical, veterinary, and environmental sciences. To achieve such measurements generally requires enzyme-mediated amplification of the low concentrations of the target nucleic acid sequences present, together with the precise control of temperature, as well as the use of enzyme-compatible reagents. This inevitably leads to compromises between analytical performance and the complexity of the assay. The hybridization chain reaction (HCR) provides an attractive alternative, as a route to enzyme-free DNA amplification. To date, the linear nucleic acid products, produced during amplification, have not enabled the development of efficient multiplexing strategies, nor the use of label-free analysis. Here, we show that by designing new DNA nanoconstructs, we are able, for the first time, to increase the molecular dimensionality of HCR products, creating highly branched amplification products, which can be readily detected on label-free sensors. To show that this new, branching HCR system offers a route for enzyme-free, label-free DNA detection, we demonstrate the multiplexed detection of a target sequence (as the initiator) in whole blood. In the future, this technology will enable rapid point-of-care multiplexed clinical analysis or in-the-field environmental monitoring.

Prophylactic abdominal drainage for pancreatic surgery.

BACKGROUND: The use of surgical drains has been considered mandatory after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. OBJECTIVES: To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal. SEARCH METHODS: For the last version of this review, we searched CENTRAL (2016, Issue 8), and MEDLINE, Embase, Science Citation Index Expanded, and Chinese Biomedical Literature Database (CBM) to 28 August 2016). For this updated review, we searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and CBM from 2016 to 15 November 2017. SELECTION CRITERIA: We included all randomized controlled trials that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included randomized controlled studies that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We identified six studies (1384 participants). Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. MAIN RESULTS: Drain use versus no drain useWe included four studies with 1110 participants, who were randomized to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. There was little or no difference in mortality at 30 days between groups (1.5% with drains versus 2.3% with no drains; RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants; moderate-quality evidence). Drain use probably slightly reduced mortality at 90 days (0.8% versus 4.2%; RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants; moderate-quality evidence). We were uncertain whether drain use reduced intra-abdominal infection (7.9% versus 8.2%; RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-quality evidence), or additional radiological interventions for postoperative complications (10.9% versus 12.1%; RR 0.87, 95% CI 0.79 to 2.23; three studies, 660 participants; very low-quality evidence). Drain use may lead to similar amount of wound infection (9.8% versus 9.9%; RR 0.98 , 95% CI 0.68 to 1.41; four studies, 1055 participants; low-quality evidence), and additional open procedures for postoperative complications (9.4% versus 7.1%; RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants; low-quality evidence) when compared with no drain use. There was little or no difference in morbidity (61.7% versus 59.7%; RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants; moderate-quality evidence), or length of hospital stay (MD -0.66 days, 95% CI -1.60 to 0.29; three studies, 711 participants; moderate-quality evidence) between groups. There was one drain-related complication in the drainage group (0.2%). Health-related quality of life was measured with the pancreas-specific quality-of-life questionnaire (FACT-PA; a scale of 0 to 144 with higher values indicating a better quality of life). Drain use may lead to similar quality of life scores, measured at 30 days after pancreatic surgery, when compared with no drain use (105 points versus 104 points; one study, 399 participants; low-quality evidence). Hospital costs and pain were not reported in any of the studies.Type of drainWe included one trial involving 160 participants, who were randomized to the active drain group (N = 82) and the passive drain group (N = 78) after pancreatic surgery. An active drain may lead to similar mortality at 30 days (1.2% with active drain versus 0% with passive drain; low-quality evidence), and morbidity (22.0% versus 32.1%; RR 0.68, 95% CI 0.41 to 1.15; low-quality evidence) when compared with a passive drain. We were uncertain whether an active drain decreased intra-abdominal infection (0% versus 2.6%; very low-quality evidence), wound infection (6.1% versus 9.0%; RR 0.68, 95% CI 0.23 to 2.05; very low-quality evidence), or the number of additional open procedures for postoperative complications (1.2% versus 7.7%; RR 0.16, 95% CI 0.02 to 1.29; very low-quality evidence). Active drain may reduce length of hospital stay slightly (MD -1.90 days, 95% CI -3.67 to -0.13; one study; low-quality evidence; 14.1% decrease of an 'average' length of hospital stay). Additional radiological interventions, pain, and quality of life were not reported in the study.Early versus late drain removalWe included one trial involving 114 participants with a low risk of postoperative pancreatic fistula, who were randomized to the early drain removal group (N = 57) and the late drain removal group (N = 57) after pancreatic surgery. There was no mortality in either group. Early drain removal may slightly reduce morbidity (38.6% with early drain removal versus 61.4% with late drain removal; RR 0.63, 95% CI 0.43 to 0.93; low-quality evidence), length of hospital stay (MD -2.10 days, 95% CI -4.17 to -0.03; low-quality evidence; 21.5% decrease of an 'average' length of hospital stay), and hospital costs (MD -EUR 2069.00, 95% CI -3872.26 to -265.74; low-quality evidence; 17.0% decrease of 'average' hospital costs). We were uncertain whether early drain removal reduced additional open procedures for postoperative complications (0% versus 1.8%; RR 0.33, 95% CI 0.01 to 8.01; one study; very low-quality evidence). Intra-abdominal infection, wound infection, additional radiological interventions, pain, and quality of life were not reported in the study. AUTHORS' CONCLUSIONS: It was unclear whether routine abdominal drainage had any effect on the reduction of mortality at 30 days, or postoperative complications after pancreatic surgery. Moderate-quality evidence suggested that routine abdominal drainage probably slightly reduced mortality at 90 days. Low-quality evidence suggested that use of an active drain compared to the use of a passive drain may slightly reduce the length of hospital stay after pancreatic surgery, and early removal may be superior to late removal for people with low risk of postoperative pancreatic fistula.

Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction for the prevention of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Pancreatoduodenectomy is a surgical procedure used to treat diseases of the pancreatic head and, less often, the duodenum. The most common disease treated is cancer, but pancreatoduodenectomy is also used for people with traumatic lesions and chronic pancreatitis. Following pancreatoduodenectomy, the pancreatic stump must be connected with the small bowel where pancreatic juice can play its role in food digestion. Pancreatojejunostomy (PJ) and pancreatogastrostomy (PG) are surgical procedures commonly used to reconstruct the pancreatic stump after pancreatoduodenectomy. Both of these procedures have a non-negligible rate of postoperative complications. Since it is unclear which procedure is better, there are currently no international guidelines on how to reconstruct the pancreatic stump after pancreatoduodenectomy, and the choice is based on the surgeon's personal preference. OBJECTIVES: To assess the effects of pancreaticogastrostomy compared to pancreaticojejunostomy on postoperative pancreatic fistula in participants undergoing pancreaticoduodenectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 9), Ovid MEDLINE (1946 to 30 September 2016), Ovid Embase (1974 to 30 September 2016) and CINAHL (1982 to 30 September 2016). We also searched clinical trials registers (ClinicalTrials.gov and WHO ICTRP) and screened references of eligible articles and systematic reviews on this subject. There were no language or publication date restrictions. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) assessing the clinical outcomes of PJ compared to PG in people undergoing pancreatoduodenectomy. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We performed descriptive analyses of the included RCTs for the primary (rate of postoperative pancreatic fistula and mortality) and secondary outcomes (length of hospital stay, rate of surgical re-intervention, overall rate of surgical complications, rate of postoperative bleeding, rate of intra-abdominal abscess, quality of life, cost analysis). We used a random-effects model for all analyses. We calculated the risk ratio (RR) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes (using PG as the reference) with 95% confidence intervals (CI) as a measure of variability. MAIN RESULTS: We included 10 RCTs that enrolled a total of 1629 participants. The characteristics of all studies matched the requirements to compare the two types of surgical reconstruction following pancreatoduodenectomy. All studies reported incidence of postoperative pancreatic fistula (the main complication) and postoperative mortality.Overall, the risk of bias in included studies was high; only one included study was assessed at low risk of bias.There was little or no difference between PJ and PG in overall risk of postoperative pancreatic fistula (PJ 24.3%; PG 21.4%; RR 1.19, 95% CI 0.88 to 1.62; 7 studies; low-quality evidence). Inclusion of studies that clearly distinguished clinically significant pancreatic fistula resulted in us being uncertain whether PJ improved the risk of pancreatic fistula when compared with PG (19.3% versus 12.8%; RR 1.51, 95% CI 0.92 to 2.47; very low-quality evidence). PJ probably has little or no difference from PG in risk of postoperative mortality (3.9% versus 4.8%; RR 0.84, 95% CI 0.53 to 1.34; moderate-quality evidence).We found low-quality evidence that PJ may differ little from PG in length of hospital stay (MD 1.04 days, 95% CI -1.18 to 3.27; 4 studies, N = 502) or risk of surgical re-intervention (11.6% versus 10.3%; RR 1.18, 95% CI 0.86 to 1.61; 7 studies, N = 1263). We found moderate-quality evidence suggesting little difference between PJ and PG in terms of risk of any surgical complication (46.5% versus 44.5%; RR 1.03, 95% CI 0.90 to 1.18; 9 studies, N = 1513). PJ may slightly improve the risk of postoperative bleeding (9.3% versus 13.8%; RR 0.69, 95% CI: 0.51 to 0.93; low-quality evidence; 8 studies, N = 1386), but may slightly worsen the risk of developing intra-abdominal abscess (14.7% versus 8.0%; RR 1.77, 95% CI 1.11 to 2.81; 7 studies, N = 1121; low quality evidence). Only one study reported quality of life (N = 320); PG may improve some quality of life parameters over PJ (low-quality evidence). No studies reported cost analysis data. AUTHORS' CONCLUSIONS: There is no reliable evidence to support the use of pancreatojejunostomy over pancreatogastrostomy. Future large international studies may shed new light on this field of investigation.

Prophylactic abdominal drainage for pancreatic surgery.

BACKGROUND: The use of surgical drains has been considered mandatory after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. OBJECTIVES: To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal. SEARCH METHODS: For the initial version of this review, we searched the Cochrane Library (2015, Issue 3), MEDLINE (1946 to 9 April 2015), Embase (1980 to 9 April 2015), Science Citation Index Expanded (1900 to 9 April 2015), and Chinese Biomedical Literature Database (CBM) (1978 to 9 April 2015). For this updated review, we searched the Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded, and CBM from 2015 to 28 August 2016. SELECTION CRITERIA: We included all randomized controlled trials that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included randomized controlled trials that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We identified five trials (of 985 participants) which met our inclusion criteria. Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we employed the random-effects model. MAIN RESULTS: Drain use versus no drain useWe included three trials involving 711 participants who were randomized to the drainage group (N = 358) and the no drainage group (N = 353) after pancreatic surgery. There was inadequate evidence to establish the effect of drains on mortality at 30 days (2.2% with drains versus 3.4% no drains; RR 0.78, 95% CI 0.31 to 1.99; three studies; low-quality evidence), mortality at 90 days (2.9% versus 11.6%; RR 0.24, 95% CI 0.05 to 1.10; one study; low-quality evidence), intra-abdominal infection (7.3% versus 8.5%; RR 0.89, 95% CI 0.36 to 2.20; three studies; very low-quality evidence), wound infection (12.3% versus 13.3%; RR 0.92, 95% CI 0.63 to 1.36; three studies; low-quality evidence), morbidity (64.8% versus 62.0%; RR 1.04, 95% CI 0.93 to 1.16; three studies; moderate-quality evidence), length of hospital stay (MD -0.66 days, 95% CI -1.60 to 0.29; three studies; moderate-quality evidence), or additional open procedures for postoperative complications (11.5% versus 9.1%; RR 1.18, 95% CI 0.55 to 2.52; three studies). There was one drain-related complication in the drainage group (0.6%). Type of drainWe included one trial involving 160 participants who were randomized to the active drain group (N = 82) and the passive drain group (N = 78) after pancreatic surgery. There was no evidence of differences between the two groups in mortality at 30 days (1.2% with active drain versus 0% with passive drain), intra-abdominal infection (0% versus 2.6%), wound infection (6.1% versus 9.0%; RR 0.68, 95% CI 0.23 to 2.05), morbidity (22.0% versus 32.1%; RR 0.68, 95% CI 0.41 to 1.15), or additional open procedures for postoperative complications (1.2% versus 7.7%; RR 0.16, 95% CI 0.02 to 1.29). The active drain group was associated with shorter length of hospital stay (MD -1.90 days, 95% CI -3.67 to -0.13; 14.1% decrease of an 'average' length of hospital stay) than in the passive drain group. The quality of evidence was low, or very low. Early versus late drain removalWe included one trial involving 114 participants with a low risk of postoperative pancreatic fistula who were randomized to the early drain removal group (N = 57) and the late drain removal group (N = 57) after pancreatic surgery. There was no evidence of differences between the two groups in mortality at 30 days (0% for both groups) or additional open procedures for postoperative complications (0% with early drain removal versus 1.8% with late drain removal; RR 0.33, 95% CI 0.01 to 8.01). The early drain removal group was associated with lower rates of postoperative complications (38.5% versus 61.4%; RR 0.63, 95% CI 0.43 to 0.93), shorter length of hospital stay (MD -2.10 days, 95% CI -4.17 to -0.03; 21.5% decrease of an 'average' length of hospital stay), and hospital costs (17.0% decrease of 'average' hospital costs) than in the late drain removal group. The quality of evidence for each of the outcomes was low. AUTHORS' CONCLUSIONS: It is unclear whether routine abdominal drainage has any effect on the reduction of mortality and postoperative complications after pancreatic surgery. In case of drain insertion, low-quality evidence suggests that active drainage may reduce hospital stay after pancreatic surgery, and early removal may be superior to late removal for people with low risk of postoperative pancreatic fistula.

Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database.

BACKGROUND/PURPOSE: The National Health Insurance Research Database, which uses claims data from hospitals contracted with the National Health Insurance (NHI) program in Taiwan, has been widely used for stroke research. The diagnostic accuracy of the NHI claims data with regard to acute ischemic stroke (AIS) has rarely been validated. The aim of this study was to validate the diagnosis of AIS in NHI claims data using the Taiwan Stroke Registry (TSR) as a reference. METHODS: We retrieved patients' data with a discharge diagnosis of AIS [five-digit International Classification of Diseases Code, 9(th) version (ICD-9 code): 433xx or 434xx] in a single medical center from August 2006 to December 2008. We then linked these patients to the TSR to validate their AIS diagnosis in the claims data. The positive predictive value (PPV) and sensitivity were determined. RESULTS: We reviewed the claims data of 1736 consecutive AIS patients, of whom 1299 (74.8%) were linked successfully to the stroke registry database. After reviewing the medical records and imaging results of other patients not linked to the registry database (n = 437), 235 patients were found to have had an AIS. The PPV was 88.4% [95% confidence interval (CI): 86.8-89.8%] and sensitivity was 97.3% (95% CI: 96.4-98.1%). Forty-four (21.8%) of the false-positive cases (n = 202) were coded as 433x0 or 434x0. CONCLUSION: The PPV of a diagnosis of AIS in the NHI claims data was high. Using five-digit ICD-9 codes to identify AIS cases will markedly decrease the false-positive rate compared with using the commonly used three-digit method.

Studies on pharmacokinetic mechanism of phenytoin resistance in refractory epilepsy.

P-glycoprotein (P-gp) is a drug efflux pump in many organs, including the intestine and liver. Two single nucleotide polymorphisms (SNPs) of P-gp gene, 2677G>T and 3435C>T, were reported to influence function and expression of P-gp and have the controversial effects on drug disposition. Phenytoin is one substrate of P-gp. Persistent low phenytoin levels in plasma and P-gp overexpression in brain in several refractory epilepsy patients were reported. P-gp polymorphisms may also affect phenytoin efficacy by altering its bioavailability (F). Because two P-gp SNPs, 2677G>T and 3435C>T, may affect P-gp expression in tissue, we examined phenytoin disposition in patients of different P-gp haplotypes, G/G2677C/C3435 and T/T2677T/T3435. We found that the mean absolute F of phenytoin in T/T2677T/T3435 subjects (91%) is slightly higher than in G/G2677C/C3435 subjects (82%). There was no difference in the maximum concentration (Cmax ) and the area under the serum concentration-time curve of phenytoin administered orally between two genotypic groups. However, the time of maximum concentration was higher in T/T2677T/T3435 subjects (10 h) than in G/G2677C/C3435 subjects (6 h). The study ruled out the possibility that genetic polymorphisms of P-gp may affect phenytoin efficacy through the decreased absorption or the increased elimination. P-gp SNPs could affect phenytoin efficacy in refractory epilepsy patients probably because of central nervous system.

The dilemma of treating vertebrobasilar dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a common phenomenon among people over 50 years old, and the related clinical expressions are varied. One of our VBD patients presented with brainstem infarction initially, received low molecular weight heparin treatment, and developed rupture of the dolichoectasia segment. Another patient with a similar-sized VBD experienced recurrent brainstem infarction three times over 2 years, despite higher bleeding tendency and long-term antiplatelet treatment. The third patient with a smallersized VBD, had left hemiplegia and received intravenous recombinant tissue plasminogen activator within 3 h, totally recovered with no lesions detected on brain Magnetic Resonance Imaging (MRI). The pathophysiology of VBD is unique, its prevalence and risks of ischemic stroke and intracranial hemorrhage both increase as the degree of arterial dolichoectasia extends, making the strategy of management quite a challenge. The best management of VBD is controlling arterial hypertension and following up with image studies regularly to detect the early extension of VBD degree.

Reversible postvaccination paraneoplastic encephalomyelitis in a patient with lung adenocarcinoma.

Encephalomyelitis occurs in paraneoplastic syndrome and acute disseminated encephalomyelitis through different autoimmune mechanisms. No postvaccinal encephalomyelitis other than acute disseminated encephalomyelitis has been reported in patients with malignancy. A 68-year-old woman was admitted because of a headache followed by a gait disturbance and psychomotor retardation 2 days after she had received an influenza vaccination followed by abulia, limb rigidity and hyperreflexia of both legs, and meningeal irritation. Cerebrospinal fluid studies showed increased intracranial pressure, elevated immunoglobulins G and A, and pleocytosis. Contrasted brain magnetic resonance imaging revealed ventriculomegaly and multiple symmetric leptomeningeal enhancement, without demyelinating changes or cortical ribbon signs. Somatosensory evoked potentials and nerve conduction velocity studies suggested myelitis. Encephalomyelitis was diagnosed on the basis of clinical and laboratory examinations. The etiological survey identified a lung adenocarcinoma. Both the encephalomyelitis and the lung adenocarcinoma simultaneously progressed after the vaccination and then, after targeted therapy for lung cancer, simultaneously subsided. In conclusion, postinfluenza-vaccination paraneoplastic encephalomyelitis may occur in patients with lung adenocarcinoma.

Get With the Guidelines-Stroke performance indicators: surveillance of stroke care in the Taiwan Stroke Registry: Get With the Guidelines-Stroke in Taiwan.

BACKGROUND: Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. The Taiwan Stroke Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess the applicability of GWTG-Stroke in Taiwan, which spends ≈ 1/10 of what the United States does in medical costs per new or recurrent stroke. METHODS AND RESULTS: Taiwan Stroke Registry, sponsored by the Taiwan Department of Health, engages 39 academic and community hospitals and covers the entire country with 4 steps of quality control to ensure the reliability of entered data. Five GWTG-Stroke performance measures and 1 safety indicator are applicable to assess Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3 other indicators (intravenous tissue plasminogen activator, anticoagulation for atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall behind. Preliminary analysis shows that compliance with selected GWTG-Stroke guidelines is associated with better outcomes. CONCLUSIONS: Results suggest that GWTG-Stroke performance measures, with modification for ethnic factors, can become global standards across national and economic boundaries for assessing and improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated into ongoing stroke registries across nations.

Inhibition of CYP3A4 expression by ketoconazole is mediated by the disruption of pregnane X receptor, steroid receptor coactivator-1, and hepatocyte nuclear factor 4alpha interaction.

BACKGROUND: Earlier studies have shown that ketoconazole inhibits CYP3A4 expression through pregnane X receptor (PXR)-mediated transcription and coactivator interaction. The involvement of other nuclear receptors remains to be elucidated. It was recently reported that hepatocyte nuclear receptor 4alpha (HNF4alpha), a master regulator of several nuclear receptors, associates with PXR thus regulates the expression of CYP3A4 under rifampin treatment. We therefore focused on the role of PXR-HNF4alpha interaction in the transcriptional regulation of CYP3A4 under rifampin-mediated ketoconazole inhibition. METHODS AND RESULTS: Several approaches were used to characterize this role and to investigate the relation between the regulatory function of the PXR-HNF4alpha complex and CYP3A4 expression, including a mammalian two-hybrid system, DNA affinity precipitation assay, co-immunoprecipitation, and HNF4alpha silencing by RNA interference. Here, we report that HNF4alpha plays a critical role in CYP3A4 promoter activation, and the interaction between PXR and HNF4alpha, which is closely related to the expression of CYP3A4, might be involved in ketoconazole-mediated inhibition of CYP3A4 gene expression. These observations indicate that the inhibition of the interaction of PXR with HNF4alpha is likely an important mechanism of drug-drug interaction.

The effects of ergoloid mesylates and ginkgo biloba on the pharmacokinetics of ticlopidine.

Ticlopidine is sometimes coadministered with ergoloid mesylates or ginkgo biloba in clinical situations. Our objective was to examine the effect of ergoloid mesylates and ginkgo biloba on ticlopidine pharmacokinetics. Ticlopidine, ergoloid mesylates, and ginkgo biloba significantly inhibited the organic anion transporting polypeptide (OATP-B)-mediated uptake of [(3)H]-estrone-3-sulfate in a concentration-dependent manner. When ergoloid mesylates was coadministered with ticlopidine, the ticlopidine area under the plasma drug concentration-time profile (AUC) from 0 to 12 hours was decreased 30% and the peak plasma drug concentration (C(max)) was decreased 29%, compared with ticlopidine administration alone. There were no significant changes in the pharmacokinetic parameters of ticlopidine when it was coadministered with ginkgo biloba. In summary, ergoloid mesylates is a more potent inhibitor of OATP-B than is ginkgo biloba, and it can reduce the oral bioavailability of drugs transported by OATP-B. Ergoloid mesylates markedly decreased the AUC and C(max) of ticlopidine, probably by inhibiting the OATP-B-mediated uptake of ticlopidine during the intestinal absorption phase. The results support a new model of intestinal drug-drug interaction.

Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells.

Arsenic is an established human carcinogen. The role of aquaglyroporins (AQPs) in arsenic disposition was recently identified. In order to examine whether organic anion transporting polypeptide-C (OATP-C) also plays a role in arsenic transport, OATP-C cDNA was transfected into cells of a human embryonic kidney cell line (HEK-293). Transfection increased uptake of the model OATP-C substrate, estradiol-17beta-D-glucuronide, by 10-fold. In addition, we measured uptake and cytotoxicity of arsenate, arsenite, monomethylarsonate(MMA(V)), and dimethylarsinate (DMA(V)). Transfection of OATP-C increased uptake and cytotoxicity of arsenate and arsenite, but not of MMA(V) or DMA(V). Rifampin and taurocholic acid (a substrate of OATP-C) reversed the increased toxicity of arsenate and arsenite seen in OATP-C-transfected cells. The increase in uptake of inorganic arsenic was not as great as that of estradiol-17beta-D-glucuronide. Our results suggest that OATP-C can transport inorganic arsenic in a (GSH)-dependent manner. However, this may not be the major pathway for arsenic transport.

Screening CYP3A single nucleotide polymorphisms in a Han Chinese population with a genotyping chip.

Human cytochrome P450 (CYP)3A is a major P450 enzyme found in the liver and gastrointestinal tract. It plays an important role in the metabolism of a wide variety of drugs, some endogenous steroids and harmful environmental contaminants. It has been shown that CYP3A alleles encoding enzymes with little or no activity are largely created by single nucleotide polymorphisms (SNPs) in the sequences of these genes. The most prevalent of these SNPs are often of low allelic frequency, and many are specific to certain ethnic groups. Therefore, an accurate determination of their frequency in any given ethnic population requires investigations involving large sample sizes. A genotyping chip with enzyme-colorimetric detection was developed and used for simultaneous analysis of 22 known CYP3A SNPs in 451 Han Chinese subjects. Following multiplex polymerase chain reaction and allele-specific primer extension labeling, an enzymatic colorimetry detection system was employed to visualize genotype patterns on a nylon membrane. With this robust system, accurate discrimination ratios were obtained, and approximately 9,922 genotypes were determined. We found that the major CYP3A SNPs in the Chinese subjects were CYP3A4*4 (allele frequency 2.4%), CYP3A4*5 (0.7%), CYP3A4*18A (2.7%) and CYP3A5*3C (70.2%). Most of the major CYP3A4 SNPs found in other ethnicities were not found in this study. Using these SNPs, 11 haplotypes were identified. Comparison between present and previous studies shows that CYP3A4*4 and CYP3A4*5 alleles were Chinese-specific. The genotyping chip developed in this study is an efficient, economic and accurate system for screening multiple SNPs in a large population. Application of such technology is expected to be less labor intensive and easier to adapt to specific searches when compared with other methodologies.

Platelet glycoprotein Ia C807T, Ib C3550T, and IIIa Pl(A1/A2) polymorphisms and ischemic stroke in young Taiwanese.

Platelet plays a pivotal role in the pathogenesis of thrombotic cardiovascular diseases. Recently, the polymorphism of platelet glycoprotein (GP) genes has been reported to be associated with an increased risk for ischemic stroke. The purpose of this study is to evaluate the association between platelet GP genetic variants and ischemic stroke in young Taiwanese. We conducted a case-control study in 157 young ischemic stroke patients recruited between September 2001 and March 2003 and 157 age- and sex-matched controls. The genotypes of platelet GP Ia C807T, GP Ib C3550T, and GP IIIa Pl(A1/A2) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Student's t-test, chi-square test, and logistic regression modeling were used for data analyses. The GP Ia C807T CC, CT and TT genotype frequencies were similar between patients (50.3%, 43.9%, 5.7%) and controls (53.5%, 38.9%, 7.6%; p=0.58). There were no significant differences in GP Ib C3550T CC and CT genotype distributions between patients (91.1%, 8.9%) and controls (91.7%, 8.3%; p=0.84). Of all subjects, none carries GP IIIa Pl(A2) mutation. In conclusion, platelet GP Ia C807T and GP Ib C3550T polymorphisms in our population are less common compared with Caucasians, and GP IIIa Pl(A1/A2) genetic mutation is not found, and all of them are not associated with ischemic stroke in young Taiwanese.

4G/5G promoter polymorphism of plasminogen activator inhibitor-1, lipid profiles, and ischemic stroke.

The 4G allele of common 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with increased PAI-1 transcription and has been proposed as a candidate genetic risk factor for thrombotic diseases. We investigated the relationship between this polymorphism and lipid profiles and stroke risk. One hundred patients with ischemic stroke and 150 age- and sex-matched control subjects were enrolled. PAI-1 genotype was determined with the use of polymerase chain reaction and restriction-length analysis. Genotype distribution in the stroke group was 40% 4G/4G, 46% 4G/5G, and 14% 5G/5G; in the control group it was 38.7% 4G/4G, 45.3% 4G/5G, and 16% 5G/5G. The allele and genotype frequencies of 4G/5G polymorphism were not different between the stroke and control groups. Control subjects who were homozygous for the 4G allele had significantly lower high-density lipoprotein (HDL) cholesterol levels than did those carrying the 5G allele (51.2 +/- 11.8 vs 58.4 +/- 15.8 mg/dL; P =.002). In the control group, regression analysis revealed a significant contribution of 4G/4G genotype to increased triglyceride (P =.042) and to decreased HDL cholesterol (P <.001) levels. Our findings suggest that PAI-1 4G/5G promoter polymorphism alone is not associated with ischemic stroke. However, this polymorphism influences lipid levels, and the underlying mechanism must be determined.