Engineered tenorite structure of barium-enriched copper oxide for on-site monitoring of cytotoxic methotrexate in environmental samples.

Emerging pharmaceutical pollutants pose a threat to both human and environmental health. The removal and monitoring of such pollutants necessitate the use of practical on-site monitoring devices; however, the designs of such devices are underdeveloped. This study involves the fabrication of a low-cost sensor based on barium-incorporated copper oxide (Ba-CuO) for the on-site monitoring of the cytotoxic drug methotrexate (MTRX) in water and sediment samples. The tenorite structure of CuO was slightly enriched with Ba ions at the td sites, distorting the tetrahedron and enhancing its electrochemical properties. Ba-CuO was obtained from Cu(NO3)2 and Ba(OH)2 by a ligand exchange protocol and was characterized using X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray analysis. In addition, the Ba-CuO sensor was tested under various conditions, and it could detect MTRX at concentrations as low as 0.4 nM, with a high sensitivity of 1.3567 µA µM-1 cm-2. On-site monitoring yielded recoveries of greater than 93 % from spiked samples, thus exhibiting excellent reproducibility and stability. Therefore, the developed method is practical and has no matrix effect on the MTRX sensor.

Arterial reinforcement following pancreatoduodenectomy: The solution to prevent delayed hemorrhage caused by postoperative pancreatic fistula.

PURPOSE: Delayed hemorrhage (DH) is a rare and yet well-known fatal complication associated with postoperative pancreatic fistula (POPF) in pancreatoduodenectomy (PD). The study aimed to investigate whether arterial reinforcement (AR) using polyglycolic acid sheets (PAS) followed by fibrin sealant (FS) to the hepatic artery could prevent DH in the setting of POPF after PD. METHODS: A total of 345 patients underwent PD for periampullary tumors from March 2011 to March 2022. From March 2011 to March 2018, 225 patients underwent PD, and AR was not performed (non-AR group). From April 2018 to March 2022, 120 patients underwent PD, and AR was performed (AR group). AR was achieved by wrapping the proper hepatic artery all the way down to the celiac artery with PAS followed by coating with FS. Demographic profile and various outcomes including DH of these two groups were compared and analyzed retrospectively. RESULTS: In non-AR group, 48 (21.3%) and 12 (5.3%) patients had grade B and C POPF, respectively. In AR group, 26 (21.7%) and four (3.3%) patients had grade B and C POPF, respectively. The incidence of POPF was not statistically significant (p = .702) between the groups. Among the patients with grade B or C POPF, DH occurred in 14 (23.3%) patients in non-AR group and only one patient in AR group (p = .016). Of the 15 patients with DH, four (26.7%) patients died. CONCLUSION: AR using PAS and FS is effective in preventing DH in the setting of POPF.

Effect of age on the prognosis of intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma and is the second- most-common primary hepatic tumor. Several predictive and prognostic factors have been analyzed; however, in this study we focused on the influence of age. Our aim was to use real-world results to determine the influence of age in iCCA patients. METHODS: A retrospective analysis of patients treated between 2005 and 2016 at Konkuk University Medical Center. In total, 133 patients with iCCA were identified. The mass-forming, periductal-infiltrating, and intraductal-growth types were included; patients with extrahepatic or hilar-type cholangiocarcinoma were excluded. We defined two groups: a younger group, age < 65 years, and an older group, age ≥ 65 years. Statistical analyses using univariate and multivariate Cox regression analyses, including the Kaplan-Meier method, were conducted. RESULTS: In total, 114 patients were enrolled. The two groups differed with regard to treatment options such as surgery with adjuvant chemotherapy or palliative chemotherapy (p = 0.012, p < 0.001). The younger group had significantly longer survival than the older group (p = 0.017). In the younger group, patients who received therapy had longer survival than those who did not (hazard ratio, 3.942; 95% confidence interval, 2.053 to 7.569; p < 0.001). Multivariate analysis indicated that younger age, lower bilirubin, low CA 19-9, and no lymph-node involvement were independent factors for improved survival. CONCLUSION: Younger patients and those who underwent surgery with adjuvant chemotherapy had longer survival. The younger the patient, the more treatments received, including palliative chemotherapy.

Safety of performing distal pancreatosplenectomy in patients who underwent distal gastrectomy previously: a multicenter cohort analysis with systematic literature review.

Purpose: In patients who have previously undergone subtotal gastrectomy (STG), the remnant stomach is supplied with arterial blood through the splenic artery. It is currently unclear whether the remnant stomach can be safely preserved when performing distal pancreatosplenectomy (DPS) in these patients. Thus, this study aimed to evaluate the safety and feasibility of performing DPS in patients who had undergone a previous STG. Methods: A multicenter cohort study was performed to identify patients who underwent DPS. Electronic medical data of Clinical Data Warehouse from 7 representative high-volume centers in 5 cities were retrospectively reviewed. A propensity score-matched analysis was performed to match patients who had no history of upper abdominal surgery with patients who had undergone a previous STG. Results: Fourteen DPS patients who had a history of STG (STG group) were studied and matched to 70 patients who underwent DPS without any history of upper abdominal surgery (non-STG group). All patients in the STG group had the remnant stomach preserved. In most patients, the blood vessel supplying blood to the remnant stomach was the left inferior phrenic artery. There was no significant difference in the incidence of stomach-related complications or length of hospital stay between the 2 groups. Conclusion: Our study results suggest that the remnant stomach could be safely preserved when performing DPS in patients with a prior STG. However, it is necessary to carefully evaluate the vascular structure of the remnant stomach through preoperative imaging study and closely observe changes to the blue stomach during the operation.

Robotic surgery enables safe and comfortable single-incision cholecystectomy: A comparison of robotic and laparoscopic approaches for single-incision surgery.

BACKGROUND: Although single-incision robotic cholecystectomy (SIRC) overcomes various limitations of single-incision laparoscopic cholecystectomy (SILC), it is associated with high cost. In this study, we intended to investigate if SIRC is recommendable and advantageous to patients despite its high cost. MATERIALS AND METHODS: We prospectively collected and analysed data of patients who had undergone either SILC (n = 25) or SIRC (n = 50) for benign gallbladder diseases, with identical inclusion criteria, between November 2017 and February 2019. RESULTS: SILC and SIRC showed similar operative outcomes in terms of intra- and post-operative complications and verbal numerical rating scale (VNRS) for pain. However, the SIRC group exhibited significantly longer operation time than the SILC group (83.2 ± 32.6 vs. 66.4 ± 32.8, P = 0.002). The SIRC group also showed longer hospital stay (2.4 ± 0.7 vs. 2.2 ± 0.6, P = 0.053). Although the SILC and SIRC groups showed no significant difference in VNRS, the SIRC group required a higher amount (126.0 ± 88.8 mg vs. 87.5 ± 79.7 mg, P = 0.063) and frequency (3.0 ± 2.1 vs. 2.0 ± 1.8, P = 0.033) of intravenous opioid analgesic administration. During surgery, the critical view of safety (CVS), the prerequisite for safe cholecystectomy, was identified in only 24% (n = 6) of patients undergoing SILC and in 100% (n = 50) of patients undergoing SIRC (P < 0.05). CONCLUSION: We conclude that although SILC and SIRC have similar operative outcomes, SIRC is advantageous over SILC because of its potential to markedly enhance the safety of patients by proficiently acquiring CVS.

Longstanding postoperative fluid collection influences recurrence of pancreatic malignancy.

BACKGROUND/AIMS: Postoperative abdominal fluid collection (PAFC) is a frequent complication of pancreatobiliary cancer surgery. The effects of the existence and duration of PAFC are not well known. This study aimed to assess the effects of PAFC on patient prognosis after surgery for pancreatobiliary adenocarcinoma and the association of longstanding PAFC with the recurrence of pancreatic cancer. METHODS: We retrospectively analyzed the data of 194 consecutive patients with pancreatobiliary adenocarcinoma who underwent curative operations from August 2005 to December 2019. The presence of PAFC was assessed using computed tomography within a week of surgery; PAFC lasting > 4 weeks was defined as longstanding PAFC. RESULTS: Among 194 patients, PAFC occurred in 165 (85.1%), and 74 of these had longstanding PAFC. The recurrence rate of pancreatobiliary adenocarcinoma was significantly higher in patients with longstanding PAFC than in patients with non-longstanding PAFC (p = 0.025). Recurrence was also significantly associated with high T stage (T3, T4; p = 0.040), lymph node involvement (p < 0.001), perineural invasion (p < 0.006), and non-receipt of adjuvant chemotherapy (p = 0.025). Longstanding PAFC was significantly associated with the recurrence of pancreatic adenocarcinoma (p = 0.016). However, cancer-specific survival was related to neither the presence nor the duration of PAFC. CONCLUSION: The presence of longstanding PAFC was associated with the recurrence of pancreatic adenocarcinoma. However, a larger prospective study is necessary to confirm the findings.

Carbon Dot/Naphthalimide Based Ratiometric Fluorescence Biosensor for Hyaluronidase Detection.

Bladder cancer is the leading cause of death in patients with genitourinary cancer. An elevated level of hyaluronidase (HAase) was found in bladder cancer, which acts as an important biomarker for the early diagnosis of bladder cancer. Hence, there is a need to develop a simple enzymatic assay for the early recognition of HAase. Herein, we report a simple, sensitive, and ratiometric fluorescence assay for HAase detection under physiological conditions. The fluorescence assay was constructed by the adsorption of cationic carbon dots and positively charged naphthalimide on negatively charged hyaluronic acid and the development of a Förster resonance energy transfer (FRET) mechanism from carbon dots to a naphthalimide fluorophores. The hyaluronidase enzyme cleaves the hyaluronic acid in this assay, and breaking down the FRET mechanism induces ratiometric changes. A detection limit of 0.09 U/mL was achieved, which is less than the HAase level found in normal human body fluids. Moreover, this assay may be used for diagnosing HAase-related diseases.

Effect of stent placement on stone recurrence and post-procedural cholangitis after endoscopic removal of common bile duct stones.

BACKGROUND/AIMS: After endoscopic treatment of common bile duct (CBD) stones, recurrence of choledocholithiasis due to small stone fragments and post-endoscopic retrograde cholangiopancreatography (post-ERCP) cholangitis can occur. We determined the effect of biliary stenting after removal of CBD stones on the recurrence of CBD stones and the incidence of post-ERCP cholangitis. METHODS: We performed a retrospective single-center study involving 483 patients who underwent ERCP for the removal of CBD stones. The patients were classified into two groups according to their biliary stenting status. The primary outcome was the rate of CBD stone recurrence and the secondary outcome was the incidence of post-ERCP cholangitis. RESULTS: Among the 483 patients, 219 and 264 did and did not receive a biliary stent after CBD stone removal, respectively. The incidence of stone recurrence was 15.5% and 7.6% in the non-stenting and stenting groups (p = 0.006), respectively, while the incidence of post-ERCP cholangitis was 4.6% and 2.7% (p = 0.256). In a multivariate analysis, biliary stenting significantly reduced the stone recurrence rate (odds ratio, 0.30; p = 0.004). CONCLUSION: Biliary stenting after the removal of CBD stones reduces the stone recurrence rate and assisted recovery. For patients with large and multiple stones who undergo lithotripsy, preventive biliary stent insertion can reduce the rate of stone recurrence.

A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease.

BACKGROUND: Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality. METHODS: Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters. RESULTS: Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (- 11.9% per year [95% CI - 15.3, - 8.5]) compared to females without any comorbidities (- 8.1% per year [95% CI - 13.6, - 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes. CONCLUSIONS: The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.

A single-tube sample preparation method based on a dual-electrostatic interaction strategy for molecular diagnosis of gram-negative bacteria.

A single-tube method based on a dual-electrostatic interaction (EI) strategy for bacteria capture and DNA extraction was designed to enable the highly sensitive detection of nucleic acids. Specially designed magnetic nanoparticles were developed to meet the opposing requirements of a single-tube method, which exist between the strong EI required for efficient bacteria capture and the weak EI required for DNA extraction with minimal DNA adsorption. A dual-EI strategy for the single-tube (DESIGN) method was thus developed to integrate bacteria enrichment, bacteria cell lysis, and DNA recovery in a single tube, thereby minimizing precious sample loss and reducing handling time. Subsequently, we evaluated the performance with a variety of concentrations from 5 to 100 colony-forming units (CFU)/10 mL human urine and milk samples. The DESIGN method achieved the simple and sensitive detection of Salmonella enterica serovar Typhimurium in 10 mL of human urine and milk samples up to 5 CFU by quantitative PCR. Furthermore, the DESIGN method detected Brucella ovis and Escherichia coli from 10 mL of human urine with a detection limit up to 5 CFU/10 mL. Graphical abstract.

Prognostic impact of hepatitis B or C on intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy, arising from the peripheral intrahepatic bile duct epithelium. Hepatitis B virus (HBV) or hepatitis C virus (HCV) may be involved in the development of ICC. We explored the prognostic value of hepatitis virus infection, as well as other prognostic factors affecting survival in patients with ICC. METHODS: A retrospective chart review was performed for patients diagnosed with ICC between August 2005 and December 2018 at Konkuk University Medical Center. We identified a total of 131 patients with ICC. Overall survival rates of patients with and without hepatitis were determined. Univariate and multivariate analyses were used to estimate factors influencing survival outcomes. RESULTS: A total of 17.6% (23/131) of patients were positive for HBV or HCV. Hepatitis B positive ICC patients were significantly younger with higher albumin and higher α-fetoprotein than those without hepatitis viral infections. The median survival of hepatitis-positive and hepatitis-negative groups was 280 and 213 days, respectively. Survival rates were not significantly different between the two groups (p = 0.279). Multivariate analyses indicated that lower serum carbohydrate antigen 19-9 (CA 19-9) (p < 0.001), lower T stage (p = 0.042), the absence of lymph-node metastasis (p = 0.043), and receiving curative surgery (p = 0.033) were independent predictors of better outcomes. CONCLUSION: While hepatitis influenced a number of clinical features in ICC patients, it did not affect survival rate. Prognostic factors influencing survival outcomes with ICC were CA 19-9 level, T stage, the presence of lymph node metastasis, and curative surgery.

Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether.

BACKGROUND: The use of methyl-tertiary butyl ether (MTBE) to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy. The adverse effects of MTBE are largely attributed to its low boiling point, resulting in a tendency to evaporate. Therefore, if there is a material with a higher boiling point and similar or higher dissolubility than MTBE, it is expected to be an attractive alternative to MTBE. AIM: To determine whether tert-amyl ethyl ether (TAEE), an MTBE analogue with a relatively higher boiling point (102 °C), could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity. METHODS: The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents. The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones. RESULTS: The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%, 56.5% and 38.75% for cholesterol, mixed, and pigmented gallstones, respectively, which represented a 1.2-, 1.4-, and 1.3-fold increase in dissolubility compared to that of MTBE. In the in vitro experiment, the 24 h-dissolubility of TAEE was 71.7% and 63.0% for cholesterol and pigmented gallstones, respectively, which represented a 1.4- and 1.9-fold increase in dissolubility compared to that of MTBE. In addition, the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE. CONCLUSION: We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE. As such, TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.

Distinct Clinical Manifestations of Thyroid Cancer After Hematopoietic Stem Cell Transplantation.

BACKGROUND: The incidence of a secondary solid malignancy after hematopoietic cell transplantation (HCT) is increasing in long-term survivors. OBJECTIVE: The aim of this study was to compare the clinicopathological characteristics of HCT recipients with secondary thyroid cancer (STC), with those of non-HCT thyroid cancer patients. METHODS: We retrospectively investigated 5184 patients who received HCT between 1983 and 2016. Of these, 18 patients developed STC and underwent thyroidectomy due to differentiated thyroid cancer. We compared the clinicopathological characteristics of post-HCT thyroid cancer patients (post-HCT group) with those of a primary differentiated thyroid carcinoma cohort (cohort group) from Seoul St. Mary's Hospital. RESULTS: The mean ages at HCT and thyroidectomy after HCT were 22.0 and 31.8 years, respectively, and the median time interval between HCT and thyroidectomy was 5 years (range 1-16). Compared with the cohort group, the post-HCT group was younger at cancer onset and frequently had a palpable mass at initial diagnosis. The post-HCT group had more aggressive features, including larger tumor size, frequent extrathyroidal extension, lymphatic invasion, perineural invasion, and frequent lateral neck node metastasis and distant metastasis, relative to the cohort group; however, most patients (83.2%) in the post-HCT group were stage I or II. Additionally, BRAF V600E mutation was less frequent in the post-HCT group. CONCLUSIONS: We found that STC after HCT showed younger presentation and more aggressive clinical presentation. Therefore, a policy of regular screening, including neck ultrasound examination, may promote early detection and treatment in HCT recipients.

Novel Discovery of LINE-1 in a Korean Individual by a Target Enrichment Method.

Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

Simple and Low-Cost Sampling of Cell-Free Nucleic Acids from Blood Plasma for Rapid and Sensitive Detection of Circulating Tumor DNA.

Cell-free nucleic acids (cfNAs) are emerging diagnostic biomarkers for monitoring the treatment and recurrence of cancers. In particular, the biological role and clinical usefulness of cfNAs obtained from the plasma of patients with various cancers are popular and still intensely explored, yet most studies are limited by technical problems during cfNA isolation. A dimethyl dithiobispropionimidate (DTBP)-based microchannel platform that enables spontaneous cfNA capture in 15 min with minimal cellular background and no requirements for use of bulky instruments is reported first. This platform identified KRAS and BRAF hot-spot mutations following cfDNA isolation from the blood plasma and tissues obtained from 30 colorectal cancer patients. The correlation of mutations between the primary tissues and plasma from the patients was high using this platform with whole genome sequencing compared to the spin-column method. This platform can also be combined with various detection approaches (biooptical sensor, Sanger sequencing, and polymerase chain reaction (PCR)) for rapid, simple, low-cost, and sensitive circulating tumor DNA detection in blood plasma. The efficiency and versatility of this platform in isolating cfNAs from liquid biopsies has applications in cancer treatment and precision medicine.

Endoscopic Submucosal Dissection of Early Gastric Cancer in Patients with Liver Cirrhosis.

BACKGROUND AND OBJECTIVES: Endoscopic submucosal dissection (ESD) has become widely accepted method for treating early gastric cancer (EGC), but little is known about its role in patients with liver cirrhosis (LC). The aims of this study were to evaluate the outcomes of ESD in treating EGC in patients with LC. METHODS: The multicenter retrospective study identified 43 patients with chronic hepatitis B (CHB)-related cirrhosis undergoing ESD for treating EGC. The patients (LC group) were subdivided into two groups based on their Child-Pugh classification (CP-class): 32 with CP-class A (LC-A) and 11 with CP-class B (LC-B). The patients were compared to 47 non-cirrhotic CHB patients who underwent ESD (CHB group). Eight patients had a past history of hepatocellular carcinoma (HCC) prior to ESD, but no patients had viable HCC when ESD was performed. RESULTS: Procedural outcomes (en bloc, lateral/basal margins resection) and post-procedural complications (bleeding or perforation) did not differ significantly between the LC and CHB groups or between the LC-A and LC-B groups. No patients experienced worsening of the Child-Pugh score 1 month after ESD compared with the baseline score. During a median observation period of 66 months, the recurrence rates of gastric cancers were similar between the LC and CHB groups (5-year recurrence rates: 2.4 vs. 2.3%, p = 0.925), and all recurrent gastric cancers were completely resected by additional ESD. The overall mortality rate was increased in the LC group (5-year mortality rates: 17.9 vs. 5.7%, p = 0.034), and 8 of 10 deaths were attributed to liver-related diseases (such as HCC, complications of portal hypertension, hepatic failure). CONCLUSIONS: ESD is feasible in patients with EGC and comorbid LC, even those with CP-class B cirrhosis. Their prognosis depends on LC-related diseases and not recurrent EGC.

Aggressive intravenous hydration with lactated Ringer's solution for prevention of post-ERCP pancreatitis: a prospective randomized multicenter clinical trial.

BACKGROUND AND STUDY AIMS : The present study aimed to determine the type of intravenous hydration that is best suited to reducing the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. PATIENTS AND METHODS: In a prospective randomized multicenter trial, average-to-high risk patients who underwent first-time ERCP were randomly assigned to three groups (1:1:1) who received: aggressive intravenous hydration (3 mL/kg/h during ERCP, a 20-mL/kg bolus and 3 mL/kg/h for 8 hours after ERCP) with either lactated Ringer's solution (LRS) or normal saline solution (NSS), or standard intravenous hydration with LRS (1.5 mL/kg/h during and for 8 hours after ERCP). The primary end point was post-ERCP pancreatitis (PEP). RESULTS: 395 patients were enrolled, and 385 completed the protocols. The three groups showed no significant differences in demographic characteristics. There was a significant difference in the intention-to-treat (ITT) PEP rate between the aggressive LRS group (3.0 %, 95 % confidence interval [CI] 0.1 % - 5.9 %; 4 /132), the aggressive NSS group (6.7 %, 95 %CI 2.5 % - 10.9 %; 9 /134) and the standard LRS group (11.6 %, 95 %CI 6.1 % - 17.2 %; 15 /129; P = 0.03). In the two-group comparisons, the ITT PEP rate was significantly lower for the aggressive LRS group than for the standard LRS group (relative risk [RR] 0.26, 95 %CI 0.08 - 0.76; P = 0.008). There was no significant difference in the ITT PEP rate between the aggressive NSS group and the standard LRS group (RR 0.57, 95 %CI 0.26 - 1.27; P = 0.17). CONCLUSION: Aggressive hydration with LRS is the best approach to intravenous hydration for the prevention of PEP in average-to-high risk patients.

A rapid bio-optical sensor for diagnosing Q fever in clinical specimens.

Recent zoonotic outbreaks, such as Zika, Middle East respiratory syndrome and Ebola, have highlighted the need for rapid and accurate diagnostic assays that can be used to aid pathogen control. Q fever is a zoonotic disease caused by the transmission of Coxiella burnetii that can cause serious illness in humans through aerosols and is considered a potential bioterrorism agent. However, the existing assays are not suitable for the detection of this pathogen due to its low levels in real samples. We here describe a rapid bio-optical sensor for the accurate detection of Q fever and validate its clinical utility. By combining a bio-optical sensor, that transduces the presence of the target DNA based on binding-induced changes in the refractive index on the waveguide surface in a label-free and real-time manner, with isothermal DNA amplification, this new diagnostic tool offers a rapid (<20 min), 1-step DNA amplification/detection method. We confirmed the clinical sensitivity (>90%) of the bio-optical sensor by detecting C. burnetii in 11 formalin-fixed, paraffin-embedded liver biopsy samples from acute Q fever hepatitis patients and in 16 blood plasma samples from patients in which Q fever is the cause of fever of unknown origin.

Rapid and accurate detection of KRAS mutations in colorectal cancers using the isothermal-based optical sensor for companion diagnostics.

Although KRAS mutational status testing is becoming a companion diagnostic tool for managing patients with colorectal cancer (CRC), there are still several difficulties when analyzing KRAS mutations using the existing assays, particularly with regard to low sensitivity, its time-consuming, and the need for large instruments. We developed a rapid, sensitive, and specific mutation detection assay based on the bio-photonic sensor termed ISAD (isothermal solid-phase amplification/detection), and used it to analyze KRAS gene mutations in human clinical samples. To validate the ISAD-KRAS assay for use in clinical diagnostics, we examined for hotspot KRAS mutations (codon 12 and codon 13) in 70 CRC specimens using PCR and direct sequencing methods. In a serial dilution study, ISAD-KRAS could detect mutations in a sample containing only 1% of the mutant allele in a mixture of wild-type DNA, whereas both PCR and direct sequencing methods could detect mutations in a sample containing approximately 30% of mutant cells. The results of the ISAD-KRAS assay from 70 clinical samples matched those from PCR and direct sequencing, except in 5 cases, wherein ISAD-KRAS could detect mutations that were not detected by PCR and direct sequencing. We also found that the sensitivity and specificity of ISAD-KRAS were 100% within 30 min. The ISAD-KRAS assay provides a rapid, highly sensitive, and label-free method for KRAS mutation testing, and can serve as a robust and near patient testing approach for the rapid detection of patients most likely to respond to anti-EGFR drugs.