Pharmacological interventions for protecting renal function after cardiac surgery: a Bayesian network meta-analysis of comparative effectiveness.

Many drugs have been investigated as potentially protective of renal function after cardiac surgery. However, their comparative effectiveness has not been established. We performed an arm-based hierarchical Bayesian network meta-analysis including 95 randomised controlled trials with 28,833 participants, which allowed us to compare some agents not previously compared directly. Renal outcomes, including: the incidence of postoperative renal dysfunction and haemodialysis; serum creatinine level at 24 hours postoperatively; all-cause mortality; and length of hospital and ICU stay, were compared. Exploratory meta-regression was conducted for potential effect modifiers. A random effects model was selected according to the evaluation of model fit by deviance information criteria. Atrial natriuretic peptide (odds ratio (95%CrI) 0.28 (0.17-0.48); moderate-quality evidence), B-type natriuretic peptide, dexmedetomidine, levosimendan and N-acetyl cysteine significantly decreased the rate of postoperative renal dysfunction compared with placebo. Atrial natriuretic peptide (OR (95%CrI) 0.24 (0.10-0.58); low-quality evidence), B-type natriuretic peptide, and dexamethasone significantly decreased the need for haemodialysis. Levosimendan significantly decreased mortality, OR (95%CrI) 0.49 (0.27-0.91); low-quality evidence). The benefit of atrial natriuretic peptide was still apparent when baseline renal function was normal. None of the potential effect modifiers were significantly correlated with our renal outcomes. Atrial natriuretic peptide was ranked best regarding renal dysfunction, haemodialysis and length of hospital stay. Levosimendan was ranked best regarding mortality and ICU stay. However, our results should be interpreted cautiously given the assumptions made about transitivity and consistency.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

Quantitative proteomic analysis of HER2 expression in the selection of gastric cancer patients for trastuzumab treatment.

Background: A wide range of response rates have been reported in HER2-positive gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted therapies for GC have yet to show efficacy in clinical trials. These findings raise question about the ability of standard HER2 diagnostics to accurately distinguish between GC patients who would and would not benefit from anti-HER2 therapies. Patients and methods: GC patients (n = 237), including a subset from the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2 status and history of treatment with standard chemotherapy or chemotherapy plus trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as a continuous variable, we defined a predictive protein level cutoff to identify which patients would benefit from trastuzumab. We compared quantitated protein level with clinical outcome and HER2 status as determined by conventional HER2 diagnostics. Results: Quantitative proteomics detected a 115-fold range of HER2 protein expression among patients diagnosed as HER2 positive by standard methods. A protein level of 1825 amol/µg was predicted to determine benefit from the addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2 protein levels above this cutoff had twice the median overall survival (OS) of their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011). Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had outcomes similar to HER2-positive patients treated with chemotherapy. (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus 12.6 months: P = 0.520). HER2 levels were not prognostic for response to chemotherapy. Conclusions: Proteomic analysis of HER2 expression demonstrated a quantitative cutoff that improves selection of GC patients for trastuzumab as compared with current diagnostic methods.

Allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease: a pilot clinical trial.

AIM: Many perianal fistulae in Crohn's disease do not respond to conventional surgical and medical management and recurrence rates are high. The study evaluated the safety and feasibility of allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease. METHOD: A multicentre, open-label, dose escalation pilot study was performed. The first three patients (group 1) were administered 1 × 10(7) cells/ml based on the size of the fistula tract. Four weeks later, after which time this dose had been confirmed to be safe, the next three patients (group 2) were administered 3 × 10(7) cells/ml. The end-point was complete closure at 8 weeks after the injection. Patients who attended for the 8 week assessment were followed for an additional 6 months. RESULTS: There were no adverse events of Grade 3 or 4 severity and no adverse events related to the treatment with allogeneic adipose-derived stem cells. Two patients in group 1 achieved complete closure of the fistula at month 4 and month 6, and one patient in group 2 achieved complete closure at 8 weeks. The closure was sustained up to month 8 in all three of those patients. CONCLUSION: These data suggest that allogeneic adipose-derived stem cells may be a feasible treatment option for perianal fistula in Crohn's disease.

Using genomics to identify novel antimicrobials.

There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the challenges of antimicrobial resistance. High-throughput gene expression analysis is providing new tools that are enabling the discovery of host-derived antimicrobial peptides. Examples of gene-encoded natural antibiotics that have gained attention include antimicrobial peptides such as human granulysin and its multi-species homolog, namely NK-lysin, which provide a protective response against a broad range of microbes and are a principal component of innate immunity in vertebrates. Both granulysin and NK-lysin are localised in cytolytic granules in natural killer and cytotoxic T lymphocytes. Host-derived NK-lysins that were first described in mammals are also found in avian species, and they have been shown to have antimicrobial activities that could potentially be used to control important poultry pathogens. Morphological alterations observed following chicken NK-lysin binding to Eimeria sporozoites and Escherichia coli membranes indicate damage and disruption of cell membranes, suggesting that NK-lysin kills pathogenic protozoans and bacteria by direct interaction. Genotype analysis revealed that chicken NK-lysin peptides derived from certain alleles were more effective at killing pathogens than those derived from others, which could potentially affect susceptibility to diseases. Although the host-derived antimicrobial peptides described in this paper may not, by themselves, be able to replace the antibiotics currently used in animal production, their use as specific treatments based on their known mechanisms of action is showing promising results.

Il est devenu impératif de développer de nouveaux agents antimicrobiens utilisables en production animale et de mettre au point des stratégies alternatives permettant de réduire l'utilisation des antibiotiques et de faire face aux enjeux de la résistance aux agents antimicrobiens. Les nouveaux outils rendus possibles par l'analyse à haut débit de l'expression génique permettent de découvrir les peptides antimicrobiens synthétisés par l'hôte. Parmi les antibiotiques naturels codés par des gènes qui suscitent actuellement le plus d'intérêt figurent les peptides antimicrobiens tels que la granulysine humaine et son homologue pluriespèces, la NK-lysine, qui déclenchent une réponse protectrice contre un large éventail d'agents microbiens et constituent l'une des principales composantes de l'immunité innée chez les vertébrés. La granulysine et la NK-lysine sont toutes deux localisées dans les granules cytolytiques des lymphocytes cytotoxiques T et des cellules NK (natural killer). Décrites dans un premier temps chez des mammifères, les NK-lysines synthétisées par l'hôte sont également présentes chez les oiseaux et il a été démontré qu'elles présentent des propriétés antimicrobiennes qui pourraient être utilisées pour contrôler d'importants agents pathogènes affectant les volailles. Les modifications morphologiques observées suite à la fixation de la NK-lysine du poulet aux sporozoïtes d'Eimeria et aux membranes d'Escherichia coli sont le signe d'un endommagement et d'une rupture des membranes cellulaires qui semblent indiquer que la NK-lysine tue les protozoaires et bactéries pathogènes par interaction directe. L'analyse génotypique a révélé que les peptides des NK-lysines de poulet encodés par certains allèles sont plus efficaces pour tuer les agents pathogènes que ceux encodés par d'autres allèles, ce qui pourrait avoir une influence sur la sensibilité aux maladies. Bien que les peptides antimicrobiens synthétisés par l'hôte décrits dans cet article ne puissent remplacer à eux seuls les antibiotiques utilisés actuellement en production animale, leur utilisation en tant que traitements spécifiques basés sur leurs propres mécanismes d'action connus, donne déjà des résultats prometteurs.

En el ámbito de la producción animal es ahora imperativo no solo dar con nuevos antimicrobianos, sino también concebir estrategias alternativas que ayuden a reducir el uso de antibióticos y a afrontar los problemas derivados de la resistencia a los antimicrobianos. El análisis de alto rendimiento de la expresión génica proporciona nuevas herramientas que están propiciando el descubrimiento de péptidos antimicrobianos sintetizados por los organismos anfitriones. Entre los ejemplos de antibióticos naturales codificados por genes que vienen suscitando interés están péptidos antimicrobianos como la granulisina humana y su homólogo multiespecífico, la NK-lisina, que inducen una respuesta protectora contra muy diversos microbios y son un componente básico de la inmunidad innata de los vertebrados. Tanto la granulisina como la NK-lisina están localizadas en el interior de los gránulos citolíticos de las células NK (natural killer) y los linfocitos T citotóxicos. Las NK-lisinas sintetizadas por el anfitrión, descritas en un principio en mamíferos, también se encuentran en especies aviares, y se ha demostrado que presentan propiedades antimicrobianas que podrían ser útiles para luchar contra importantes patógenos de las aves de corral. Las alteraciones morfológicas observadas después de que la NK-lisina de pollo se uniera a esporozoítos de Eimeria y a membranas de Escherichia coli son indicativas de deterioro y desorganización de la membrana celular, de donde se infiere que la NK-lisina mata a los patógenos protozoarios y bacterianos por interacción directa. El análisis genotípico en pollos reveló que ciertos alelos codificaban NK-lisinas que mataban a los patógenos con más eficacia que los péptidos codificados por otros alelos, lo que podría tener influencia en la sensibilidad a las enfermedades. Aunque tal vez los péptidos antimicrobianos sintetizados por el anfitrión que los autores describen en estas líneas no puedan, por sí solos, sustituir a los antibióticos actualmente utilizados en producción animal, su utilización en tratamientos específicos basados en sus mecanismos de acción conocidos está deparando resultados prometedores.

Acute gastroenteritis outbreaks associated with ground-waterborne norovirus in South Korea during 2008-2012.

Epidemiological and virological studies indicate that noroviruses-contaminated groundwater was the primary source of four acute gastroenteritis outbreaks in South Korea between 2008 and 2012. Furthermore, cabbage kimchi was first identified as the vehicle of transmission between groundwater and infected patients in an outbreak in 2011. The proper treatment of groundwater sources prior to use for drinking or in food preparation is necessary to prevent further outbreaks.

Lateral spread response monitoring during microvascular decompression for hemifacial spasm. Comparison of two targets of partial neuromuscular blockade.

AIM: The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal. MATERIAL AND METHODS: A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T1/Tc ratio of 50 % (T1: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups. RESULTS: Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n = 15 (50.0 %) in group TOF versus n = 24 (82.8 %) in group T1 (P = 0.008), corresponding to a 32.8 % higher success rate in group T1 than group TOF (95 % CI: 13.9-51.7 %). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count = 2 (1) in group TOF versus 3 (1) in group T1 (P = 0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group. CONCLUSION: Maintenance of partial NMB with a target T1/Tc ratio of 50 % resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T1/Tc ratio of 50 % rather than TOF count of two during LSR monitoring for MVD can therefore be recommended.

Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study.

The incidence and severity of Clostridium difficile infections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.

Comparison of motor-evoked potentials monitoring in response to transcranial electrical stimulation in subjects undergoing neurosurgery with partial vs no neuromuscular block.

BACKGROUND: There have been no evidence-based comparisons of motor-evoked potential (MEP) monitoring with no and partial neuromuscular block (NMB). We compared the effects of different levels of NMB including no NMB on MEP parameters. METHODS: MEP-monitored 120 patients undergoing neurosurgery were enrolled. The patients were randomly allocated to four groups: Group A was to maintain two train-of-four (TOF) counts; Group B was to maintain a T(1)/Tc of 0.5; Group C was to maintain a T(2)/Tc of 0.5 (T(1,2), first or second twitch height of TOF; Tc, control twitch height); Group D did not maintain NMB. The mean MEP amplitude, coefficient of variation (CV), the incidence of spontaneous respiration or movement, the efficacy of MEP, and haemodynamic parameters were compared. RESULTS: The median [inter-quartile range (IQR)] amplitudes of the left leg for Groups A, B, C, and D were 0.23 (0.15-0.57), 0.44 (0.19-0.79), 0.28 (0.15-0.75), and 0.75 (0.39-1.35) mV, respectively. The median (IQR) CVs of the left leg were 71.1 (56.9-88.8), 76.1 (54.2-93.1), 59.8 (48.6-95.6), and 25.2 (17.3-35.0), respectively. The differences between groups of the mean amplitudes of the left arm and both legs were statistically significant (Kruskal-Wallis test, P=0.011 for the left leg). For all limbs, the differences between groups of the CVs were significant (P<0.001, for the left leg). Other parameters were not different. CONCLUSIONS: If NMB is used during MEP monitoring, a target T(2)/Tc of 0.5 is recommended. In terms of the MEP amplitude and variability, no NMB was more desirable than any level of partial NMB.

Prolonged inspiratory time produces better gas exchange in patients undergoing laparoscopic surgery: A randomised trial.

BACKGROUND: Laparoscopic surgery performed with a patient in the Trendelenburg position is known to have adverse effects on pulmonary gas exchange and respiratory mechanics. We supposed that prolonged inspiratory time can improve gas exchange at lower airway pressure. METHODS: One hundred patients undergoing gynaecologic laparoscopic surgery were randomly assigned to one of four groups: conventional inspiratory-to-expiratory (I : E) ratio (Group 1 : 2), I : E ratio of 1 : 1 (Group 1 : 1), 2 : 1 (Group 2 : 1), or 1 : 2 with external positive end-expiratory pressure (PEEP) of 5 cmH2 O (Group 1 : 2 PEEP). Tidal volume was set to 6 ml/kg, and I : E ratio was adjusted at the onset of pneumoperitoneum. Arterial blood gas analysis with measurements of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2 /FiO2 ), and physiologic dead space-to-tidal volume ratio (VD /VT ) was performed 15 min after anaesthetic induction (T1), and 30 (T2) and 60 min (T3) after onset of CO2 insufflation. RESULTS: PaO2 /FiO2 at T3 in Groups 1 : 1, 2 : 1, and 1 : 2 PEEP were higher than Group 1 : 2. The partial pressure of arterial carbon dioxide at T3 in Group 2 : 1 was lower than the other groups. The VD /VT at T2 and T3 were lower in Groups 1 : 1 and 2 : 1 than Groups 1 : 2 and 1 : 2 PEEP. Peak or plateau airway pressure was higher in Group 1 : 2 PEEP than the other groups. CONCLUSIONS: A prolonged inspiratory time demonstrated a beneficial effect on oxygenation. Furthermore, it showed better CO2 elimination without elevating the peak or plateau airway pressure compared with applying external PEEP. In terms of gas exchange and respiratory mechanics, a prolonged inspiratory time appears to be superior to applying external PEEP in patients undergoing laparoscopic surgery in the Trendelenburg position.

The effects of prolonged inspiratory time during one-lung ventilation: a randomised controlled trial.

We evaluated the effects of a prolonged inspiratory time on gas exchange in subjects undergoing one-lung ventilation for thoracic surgery. One hundred patients were randomly assigned to Group I:E = 1:2 or Group I:E = 1:1. Arterial blood gas analysis and respiratory mechanics measurements were performed 10 min after anaesthesia induction, 30 and 60 min after initiation of one-lung ventilation, and 15 min after restoration of conventional two-lung ventilation. The mean (SD) ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen after 60 min of one-lung ventilation was significantly lower in Group I:E = 1:2 compared with Group I:E = 1:1 (27.7 (13.2) kPa vs 35.2 (22.1) kPa, respectively, p = 0.043). Mean (SD) physiological dead space-to-tidal volume ratio after 60 min of one-lung ventilation was significantly higher in Group I:E = 1:2 compared with Group I:E = 1:1 (0.46 (0.04) vs 0.43 (0.04), respectively, p = 0.008). Median (IQR [range]) peak inspiratory pressure was higher in Group I:E = 1:2 compared with Group I:E = 1:1 after 60 min of one-lung ventilation (23 (22-25 [18-29]) cmH2O vs 20 (18-21 [16-27]) cmH2O, respectively, p < 0.001) and median (IQR [range]) mean airway pressure was lower in Group I:E = 1:2 compared with Group I:E = 1:1 (10 (8-11 [5-15]) cmH2O vs 11 (10-13 [5-16]) cmH2O, respectively, p < 0.001). We conclude that, compared with an I:E ratio of 1:2, an I:E ratio of 1:1 resulted in a modest improvement in oxygenation and decreased shunt fraction during one-lung ventilation.

Arthroscopic shoulder surgery under general anesthesia with brachial plexus block: postoperative respiratory dysfunction of combined obstructive and restrictive pathology.

OBJECTIVE: Changes in respiratory parameters and pulmonary function tests were evaluated after shoulder arthroscopic surgery with brachial plexus block (BPB). The purpose of this study was to identify the mechanism of respiratory dysfunction after this type of surgery. METHODS: Patients undergoing arthroscopic rotator cuff repair under general anesthesia (GA) with BPB were enrolled in the arthroscopy group (n = 30) while those undergoing open reduction of a clavicle or humerus fracture under GA were enrolled in the control group (n = 30). Forced vital capacity (FVC) and forced expiratory volume 1 s (FEV(1)) were measured at the outpatient clinic stage (#1) before (#2) and 20 min after BPB (#3) and 1 h after extubation (#4). Respiratory variable measurements along with the cuff leak test were performed 5 min after surgical positioning (T1) and at the start of skin closure (T2). Respiratory discomfort was evaluated after extubation. The upper airway diameters and soft tissue depth of chest wall were also measured by ultrasonography at stages #3 and #4. RESULTS: Static compliance decreased significantly at T2 in the arthroscopy group (50 ± 11 at T1 vs. 44 ± 9 ml/cm H(2)O at T2, p =0.035) but not in the control group. The incidence of positive cuff leak tests at T2 was significantly higher in the arthroscopy group than in the control group (47% in the arthroscopy group vs. 17% in controls, p =0.010). While FEV(1) and FVC remained stable at stages #1 and #2, FVC and FEV(1) decreased at stages #3 and #4 only in the arthroscopy group (FVC in arthroscopy group, #2: 3.26 ± 0.77 l; #3: 2.55 ± 0.63 l, p =0.015 vs. #2; #4: 2.66 ± 0.41 l, p =0.040 vs. #2). The subglottic diameter decreased at #4 in the arthroscopy group, while no changes occurred in the control group (0.70 ± 0.21 cm vs. 0.85 ± 0.23 cm in the arthroscopy and control groups, respectively, p =0.011). Depth of skin to pleura increased at both intercostal spaces 1-2 and 3-4 in the arthroscopy group. There were three cases of hypoxia (S(p)O(2) < 95%) with room air in the arthroscopy group while none occurred in the controls. CONCLUSION: Shoulder arthroscopic surgery under GA with BPB induced both restrictive and obstructive pathologies. It is important to maintain a high level of awareness for the potential negative respiratory effects of this surgery especially for subjects with pre-existing cardiopulmonary disease. The measurements in this study would be useful to monitor the risk of respiratory dysfunction in these patients.

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.

BACKGROUND: The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas. METHODS: MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma. RESULTS: Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis. CONCLUSION: MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.

Radiotolerance of phosphatases of a Serratia sp.: potential for the use of this organism in the biomineralization of wastes containing radionuclides.

Aqueous wastes from nuclear fuel reprocessing present special problems of radiotoxicity of the active species. Cells of Serratia sp. were found previously to accumulate high levels of hydrogen uranyl phosphate (HUP) via the activity of a phosphatase enzyme. Uranium is of relatively low radiotoxicity whereas radionuclide fission products such as (90)Sr and (137)Cs are highly radiotoxic. These radionuclides can be co-crystallized, held within the bio-HUP "host" lattice on the bacterial cells and thereby removed from contaminated solution, depending on continued phosphatase activity. Radiostability tests using a commercial (60)Co γ-source showed that while cell viability and activity of purified phosphatase were lost within a few hours on irradiation, whole-cell phosphatase retained 80% of the initial activity, even after loss of cell culturability, which was increased to 100% by the incorporation of mercaptoethanol as an example radioprotectant, beyond an accumulated dose of >1.3 MGy. Using this co-crystallization approach (without mercaptoethanol) (137)Cs(+) and (85)Sr(2+) were removed from a simulated waste selectively against a 33-fold excess of Na(+).

Colloid coload versus crystalloid coload to prevent maternal hypotension in women receiving prophylactic phenylephrine infusion during caesarean delivery: a randomised controlled trial.

BACKGROUND: The optimal fluid strategy to prevent maternal hypotension during caesarean delivery remains unclear. This study aim was to compare the incidence of post-spinal anaesthesia hypotension in women receiving either colloid or crystalloid coload in the setting of prophylactic phenylephrine infusion during caesarean delivery. METHODS: Healthy mothers undergoing elective caesarean delivery under spinal anaesthesia were randomised to receive a rapid intravenous coload with 6% hydroxyethyl starch 130/0.4 10 mL/kg (colloid group) or balanced crystalloid solution (Plasma Solution A) 10 mL/kg (crystalloid group) during spinal anaesthesia. All women had a prophylactic phenylephrine infusion initiated at 25 µg/min immediately after the subarachnoid block and titrated to systolic blood pressure using a standardised protocol. The primary outcome was the incidence of hypotension (systolic blood pressure <80% of baseline) until delivery. RESULTS: The incidence of hypotension was 50% in the colloid group and 62% in the crystalloid group (absolute difference, -12% [95% CI -33% to 9%]; relative risk, 0.8 [95% CI 0.56 to 1.14]; P=0.314). No significant difference between groups was found in the number of hypotensive episodes (median 0.5 [IQR 0 to 1] vs 1 [0 to 2], P=0.132) or phenylephrine dose (675 [IQR 425 to 975] µg vs 750 [625 to 950] µg, P=0.109). The incidence of severe hypotension, symptomatic hypotension, bradycardia, nausea, and the neonatal outcomes were not significantly different. CONCLUSIONS: This study found no benefit of colloid coload compared with crystalloid coload for preventing maternal hypotension in the presence of prophylactic phenylephrine infusion during caesarean delivery.

High FOXP3+ regulatory T-cell density in the sentinel lymph node is associated with downstream non-sentinel lymph-node metastasis in gastric cancer.

BACKGROUND: We aimed to evaluate the immunologic nature of sentinel lymph nodes (SLNs) in gastric cancer patients and to determine whether it can predict non-SLN metastasis. METHODS: Sentinel lymph node samples were collected from 64 gastric carcinoma patients who had undergone gastrectomy with SLN biopsy. One representative SLN sample was selected from each patient and was subjected to immunostaining for CD8, CD57, FOXP3, and DC-LAMP. The numbers of marker-positive cells in each sample were counted. The relationships between various immune cell densities and clinicopathologic parameters or metastasis status of SLNs and non-SLNs were sought. RESULTS: High FOXP3+ Treg density of the SLN was found to be significantly associated with the presence of metastasis in either SLNs or non-SLNs. DC-LAMP+ cell density of the SLN was the highest at the isolated tumours cell level, and this decreased along with an increase in tumour metastasis in either SLNs or non-SLNs. Univariate and multivariate logistic regression models revealed that high FOXP3+ Treg density of the SLN was an independently significant predictor of non-SLN metastasis. CONCLUSIONS: This study is the first to indicate an important role of SLNs in metastatic dissemination of gastric cancer. Our findings suggest that Tregs could be a new therapeutic target for regulating the metastasis of gastric cancer.

A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κB promotes gastric tumour growth and angiogenesis.

BACKGROUND: The underlying mechanisms involved in the activation of hypoxia-inducible factor-1 (HIF-1) in gastric cancer remain unclear. As nuclear factor-κB (NF-κB) as well as HIF-1 have been implicated in angiogenesis of various cancers, we investigated their relationship in gastric cancer. METHODS: Nuclear expressions of HIF-1α and NF-κB/RelA were assessed in 251 human gastric carcinoma specimens by immunohistochemical tissue array analysis. Stable human gastric cancer cells, infected with a retroviral vector containing super-suppressive mutant form of IκBα (IκBαM), were used for animal studies as well as cell culture experiments. Xenografted tumours were measured and IκBαM effects on angiogenesis and HIF-1α activation were assessed by immunohistochemistry, western blotting, luciferase reporter assay, and semiquantitative reverse transcription-polymerase chain reaction. In addition, NF-κB effects on the HIF-1α degradation and synthesis were examined. RESULTS: Hypoxia-inducible factor-1α activation positively correlated with RelA activation in clinical gastric cancer samples (P<0.001). The IκBαM overexpression suppressed tumour growth, microvessel density, and HIF-1α activation in xenografted tumours. Cell culture experiments showed that hypoxia-induced HIF-1α expression was reduced by NF-κB inhibition under hypoxic conditions at the translational level. CONCLUSION: The hypoxia-dependent activation of the NF-κB/HIF-1α/VEGF pathway contributes, at least in part, to gastric cancer promotion via enhancement of angiogenesis.

Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis.

BACKGROUND: Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects. METHODS: From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering. RESULTS: In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P=0.003) and subsite (P=0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period. CONCLUSION: Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity.