Bacterial profiling of head lice isolated from the Orang Asli: A first report in Malaysia.

This study was carried out to determine from bacterial profiling to the bacterial profiles of head lice among the Orang Asli communities. The head lice were collected from Orang Asli community volunteers. The surface sterilized head lice pools were subjected to genomic DNA extraction while next generation sequencing of the 16S rRNA gene was performed using the Illumina MiSeq platform. Six female and three male head lice identified as Pediculus humanus capitis were collected. A total of 111 368 number of NGS sequencing reads were recorded while another 223 bacterial taxa sequences were obtained. Symbiotic bacteria showed the highest number of reads, with Arsenophonus and Rhodococcus sequences being the most abundant genera in the female and male samples, respectively. The female head lice contained a more distinct microbial diversity. Amongst the pathogenic bacterial species sequences noted were the methicillin-resistant Staphylococcus aureus, Streptobacillus moniliformis, Haemophilus influenzae, Bordetella pertussis and Acinetobacter baumannii. The 16S rRNA genome sequencing revealed a number of rare and pathogenic bacterial species within the head lice of the Orang Asli. The socio-economic practices of the community which involved forest foraging and hunting, and their poor living conditions potentially facilitated the transmission of zoonotic bacterial pathogens, including those found within the head lice. Hence, there is the possibility that the head lice could serve as vectors for the transmission of pathogenic bacteria. This study highlighted the diverse microbial community found within the head lice's gut of the Orang Asli, with the detection of multiple rare and pathogenic bacteria capable of causing severe infections.

Computational wear prediction of insert conformity and material on mobile-bearing unicompartmental knee arthroplasty.

OBJECTIVES: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty with isolated medial or lateral compartment osteoarthritis. However, polyethylene wear can significantly reduce the lifespan of UKA. Different bearing designs and materials for UKA have been developed to change the rate of polyethylene wear. Therefore, the objective of this study is to investigate the effect of insert conformity and material on the predicted wear in mobile-bearing UKA using a previously developed computational wear method. METHODS: Two different designs were tested with the same femoral component under identical kinematic input: anatomy mimetic design (AMD) and conforming design inserts with different conformity levels. The insert materials were standard or crosslinked ultra-high-molecular-weight polyethylene (UHMWPE). We evaluated the contact pressure, contact area, wear rate, wear depth, and volumetric wear under gait cycle loading conditions. RESULTS: Conforming design inserts had the lower contact pressure and larger contact area. However, they also had the higher wear rate and volumetric wear. The improved wear performance was found with AMD inserts. In addition, the computationally predicted volumetric wear of crosslinked UHMWPE inserts was less than half that of standard UHMWPE inserts. CONCLUSION: Our results showed that increasing conformity may not be the sole predictor of wear performance; highly crosslinked mobile-bearing polyethylene inserts can also provide improvement in wear performance. These results provide improvements in design and materials to reduce wear in mobile-bearing UKA.Cite this article: Bone Joint Res 2019;8:563-569.

Influence of tibiofemoral congruency design on the wear of patient-specific unicompartmental knee arthroplasty using finite element analysis.

OBJECTIVES: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty for patients who require treatment of single-compartment osteoarthritis, especially for young patients. To satisfy this requirement, new patient-specific prosthetic designs have been introduced. The patient-specific UKA is designed on the basis of data from preoperative medical images. In general, knee implant design with increased conformity has been developed to provide lower contact stress and reduced wear on the tibial insert compared with flat knee designs. The different tibiofemoral conformity may provide designers the opportunity to address both wear and kinematic design goals simultaneously. The aim of this study was to evaluate wear prediction with respect to tibiofemoral conformity design in patient-specific UKA under gait loading conditions by using a previously validated computational wear method. METHODS: Three designs with different conformities were developed with the same femoral component: a flat design normally used in fixed-bearing UKA, a tibia plateau anatomy mimetic (AM) design, and an increased conforming design. We investigated the kinematics, contact stress, contact area, wear rate, and volumetric wear of the three different tibial insert designs. RESULTS: Conforming increased design showed a lower contact stress and increased contact area. In addition, increased conformity resulted in a reduction of the wear rate and volumetric wear. However, the increased conformity design showed limited kinematics. CONCLUSION: Our results indicated that increased conformity provided improvements in wear but resulted in limited kinematics. Therefore, increased conformity should be avoided in fixed-bearing patient-specific UKA design. We recommend a flat or plateau AM tibial insert design in patient-specific UKA.Cite this article: Y-G. Koh, K-M. Park, H-Y. Lee, K-T. Kang. Influence of tibiofemoral congruency design on the wear of patient-specific unicompartmental knee arthroplasty using finite element analysis. Bone Joint Res 2019;8:156-164. DOI: 10.1302/2046-3758.83.BJR-2018-0193.R1.

Comparison of Core Temperature Changes Between Pediatric Patients Lying on Regular Operating Room Linen Drapes and Water-Repellent Sheepskin Rug in Living Donor Liver Transplantation.

OBJECTIVES: The aims of this study were to compare the core temperature changes between pediatric patients lying on regular operating room linen drapes and a water-repellent sheepskin rug during living donor liver transplantation (LDLT) and to evaluate the effectiveness of using a water-repellent sheepskin rug in preventing profound hypothermia due to fluid overflow from the abdominal cavity during LDLT. PATIENTS AND METHODS: The operative records of pediatric patients who underwent LDLT from June 1994-September 2003 were reviewed retrospectively. The nasopharyngeal temperature (NT) changes during the LDLT procedure between patients lying on regular operating room drapes (GI) and water-repellent sheepskin rug (GII) were compared and analyzed using the Mann-Whitney U test. A P value <.05 was regarded as significant. RESULTS: Thirty-two patients were included in GI and 56 in GII. Profound hypothermia was not observed in any recipients lying on a water-repellent sheepskin rug (GII). The NT after induction and the following 4 hours into the LT procedure were significantly higher in GII than GI. CONCLUSION: Pediatric patients lying on water-repellent sheepskin preserved their core temperature better in comparison to patients lying on linen drapes. The use of a water-repellent sheepskin rug seems to be effective in preventing profound hypothermia related to physical contact with abdominal fluid overflow during the LDLT.

Eye Protection in Liver Transplantation Patients Under General Anesthesia.

BACKGROUND: Opsite (Smith & Nephew, Hull, UK) is widely used in wound care but its use in eye protection against corneal abrasion during major surgery is rarely reported. The purpose of the current study is to compare the effectiveness of using Opsite in eye protection with either wet gauze alone or with wet gauze following application of eye ointment in patients undergoing living donor liver transplantation (LDLT). METHODS: This is a prospective, double-blinded, randomized controlled trial. Forty-one patients undergoing liver transplantation were enrolled. One eye of each patient was protected with sterile gauze soaked with normal saline solution and covered with Opsite. Duratears (ALCON, Fort Worth, Tex, United States) ointment was applied to the other eye before covering it with sterile wet gauze and Opsite (ointment group). The corneal examination was carried out after fluorescein staining before and at the end of surgery by the same doctor. A Student t-test and a χ2 test were used for the statistical analyses. RESULTS: Forty-one patients with 82 eyes were observed in this study. No corneal epithelial defects were found in either the normal saline group or the ointment group. CONCLUSION: Opsite combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing LDLT.

Pharmacokinetic modelling and validation of the half-life extension needed to reduce the burden of infusions compared with standard factor VIII.

INTRODUCTION: Currently, no universally accepted definition of extended half-life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half-life extension ratio required for a reduction in dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII. AIM: To identify the half-life extension ratio required to decrease rFVIII dosing frequency by at least 1 day while maintaining the proportion of patients with plasma rFVIII levels above 1 IU/dL and without increasing the total weekly dose. METHODS: A previously published population pharmacokinetic model for standard rFVIII was used to estimate the percentage of patients with factor VIII (FVIII) levels always >1 IU/dL using various benchmark regimens. Using modelling, dosing frequency was reduced while rFVIII half-life was extended until the percentage of patients with FVIII >1 IU/dL equalled that of the benchmark regimen. RESULTS: Benchmark 3×/wk dosing totalling 100 IU/kg/wk of rFVIII resulted in 56.6% of patients with FVIII levels always >1 IU/dL. With 2×/wk dosing, totalling 80 or 90 IU/kg/wk, half-life extensions required to maintain 56.6% of patients at FVIII levels >1 IU/dL were 1.30 and 1.26, respectively. A half-life extension ratio of 1.33 was required to change dosing from every 48 hours to every 72 hours (both at 105 IU/kg/wk) while maintaining 92.8% of patients with FVIII >1 IU/dL. CONCLUSION: Based on this investigation, EHL rFVIII products should have a minimum half-life extension ratio of 1.3 to provide a reduction in dosing frequency from 3× to 2×/wk compared with standard rFVIII products while maintaining the same minimum FVIII trough level.

Extensively drug-resistant tuberculosis in Myanmar: burden and mutations causing second-line drug resistance.

SETTING: Two tuberculosis (TB) reference laboratories in Myanmar. OBJECTIVES: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar. DESIGN: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing. Genotypes were determined to explain relationships between drug resistance patterns and genotypes. RESULTS: Of 89 MDR-TB isolates, 12 were XDR-TB and 24 were pre-XDR-TB, with 21 resistant to fluoroquinolones (FQs) and 3 to second-line injectable agents (SLIDs). High rates of cross-resistance among second-line drugs were observed. Correlations between phenotypic and molecular DST against FQs and SLIDs were 91% in both cases. The most frequent mutation in FQ-resistant isolates was D94G (8/21) in gyrA and A1401G (11/15) in rrs in those resistant to SLIDs. The dominant genotype was the Beijing type (76/89). CONCLUSION: There were high proportions of XDR-TB and pre-XDR-TB among MDR-TB cases; cross-resistance among second-line drugs was high, with various types of genetic mutations. These data suggest that resistance to second-line anti-tuberculosis drugs should be monitored intensively, and molecular DST should be employed.

Signal self-enhancement by coordinated assembly of gold nanoparticles enables accurate one-step-immunoassays.

Current immunoassays are in general performed through time-consuming multi-step procedures that depend on the use of premade signal-producing reporters and often cause assay inaccuracy. Here we report an advanced immunoassay technology that resolves the delayed, complex, and inaccurate assay problems of conventional immunoassays. We have developed an accurate, rapid, simple, and label-free one-step-immunoassay based on the self-enhancement of sensitive immunoassay signals in an assay solution. The nano-scale protein particles (hepatitis B virus capsid and human ferritin heavy chain particles) were genetically engineered to present many well-oriented antibody (or antigen) probes and multi-copies of poly-histidine peptides on their surface, resulting in the construction of 3-dimensional (3D) bioprobes that chemisorb gold ions via coordination bonding and sensitively detect both antigen and antibody analytes. Systematic numerical and experimental analyses show that the signal self-enhancement happens through two coupled reactions under reducing conditions: (1) 3D bioprobe-based sensitive immuno-detection of analytes and (2) coordinated assembly of free and chemisorbed gold nanoparticles around the 3D bioprobe-analyte-associated complexes, which is followed by the quick generation of apparent optical signals. This advanced one-step-immunoassay was successfully applied to diagnostic assays requiring high accuracy and/or speed, i.e. diagnosis of acute myocardial infarction and hepatitis C through detecting a cardiac protein (troponin I) and anti-hepatitis C virus antibodies in patient sera, indicating that it is applicable to the accurate and rapid detection of both antigen and antibody markers of a wide range of diseases.

What happened to patients with RMP-resistant/MDR-TB in Zambia reported as lost to follow-up from 2011 to 2014?

SETTING: University Teaching Hospital, Lusaka, and Ndola Central Hospital, Ndola, Zambia, which implemented active tracing of multidrug-resistant tuberculosis (MDR-TB) patients reported as lost to follow-up (LTFU). OBJECTIVE: To determine 1) the number of patients treated for MDR-TB between 2011 and 2014; 2) the number, proportion, month when LTFU and characteristics of patients registered as LTFU; and 3) final outcomes observed following active patient tracing. DESIGN: Retrospective cohort study. RESULTS: Of 184 patients treated for confirmed MDR-TB, 76 (41%) were reported as LTFU. From 2011 to 2014, the proportions reported each year as LTFU were respectively 21%, 47%, 51% and 39%. Of patients who were LTFU, 43 (57%) had stopped attending the clinic during the intensive phase. These patients were predominantly male, aged 15-44 years, had pulmonary disease and had failed previous treatment. Of 57 (75%) patients with known human immunodeficiency virus (HIV) status, 42 (74%) were HIV-positive, 57% of whom were on antiretroviral treatment. After active patient tracing, 29 (38%) patients could not be found and the observed outcome remained LTFU. Of the remaining 47 patients, 29 (62%) were alive and had completed or were still on treatment, 14 (30%) were alive but had stopped treatment and 4 (8%) had died. CONCLUSION: Zambia has been underreporting its favourable outcomes for MDR-TB treatment and should continue with active tracing of LTFU patients.

Early infant diagnosis and outcomes in HIV-exposed infants at a central and a district hospital, Northern Malawi.

Setting: Mzuzu Central Hospital (MZCH), Mzuzu, and Chitipa District Hospital (CDH), Chitipa, Malawi. Objective: To compare management and outcomes of human immunodeficiency virus (HIV) exposed infants in early infant diagnosis (EID) programmes at MZCH, where DNA polymerase chain reaction (PCR) testing is performed on site, and CDH, where samples are sent to MZCH, between 2013 and 2014. Design: Retrospective cohort study. Results: Of infants enrolled at MZCH (n = 409) and CDH (n = 176), DNA PCR results were communicated to the children's guardians in respectively 56% and 51% of cases. The median time from sample collection to guardians receiving results was 34 days for MZCH and 56 days for CDH. In both hospitals, only half of the dried blood spot (DBS) samples were collected between 6 and 8 weeks. More guardians from MZCH than CDH received test results within 1 month of sample collection (25% vs. 10%). Among the HIV-positive infants, a higher proportion at MZCH (92%) started antiretroviral therapy than at CDH (46%). The relative risk (RR) of death was higher among infants with late DBS collection (RR 1.3, 95%CI 1.0-1.7) or no collection (RR 5.8, 95%CI 4.6-7.2), and when guardians did not receive test results (RR 8.3, 95%CI 5.7-11.9). Conclusion: EID programmes performed equally poorly at both hospitals, and might be helped by point-of-care DNA PCR testing. Better programme implementation and active follow-up might improve infant outcome and retention in care.

Contexte: Hôpital central Mzuzu (MZCH), Mzuzu, et hôpital de district de Chitipa (CDH), Chitipa, Malawi.Objectif: Comparer la prise en charge et les résultats des nourrissons exposés au virus de l'immunodéficience humaine (VIH) dans les programmes de Diagnostic précoce du nourrisson (EID) au MZCH (test ADN réaction polymérase en chaîne [PCR] fait sur place) et au CDH (échantillons envoyés au MZCH) entre 2013 et 2014.Schéma: Etude rétrospective de cohorteRésultats: Parmi les nourrissons enrôlés au MZCH (n = 409) et au CDH (n = 176), les résultats d'ADN PCR ont été communiqués aux responsables des enfants dans 56% et 51% des cas, respectivement. Le délai médian du recueil de l'échantillon à la réception des résultats par les parents a été de 34 jours pour le MZCH et de 56 jours pour le CDH. Dans les deux hôpitaux, seulement la moitié des échantillons de sang séché (DBS) a été recueillie entre 6 et 8 semaines. Plus de parents du MZCH que du CDH ont reçu les résultats du test dans le mois suivant le recueil de l'échantillon (25% contre 10%). Parmi les nourrissons VIH positifs, une proportion plus élevée au MZCH (92%) a mis en route le traitement antirétroviral comparée au CDH (46%). Le risque relatif de décès a été plus élevé parmi les nourrissons ayant eu un recueil tardif de DBS (RR 1,3 ; IC95% 1,0­1,7) ou pas de recueil (RR 5,8 ; IC95% 4,6­7,2) et quand les parents n'ont pas reçu les résultats du test (RR 8,3 ; IC95% 5,7­11,9).Conclusion: Les programmes d'EID ont été aussi peu performants dans les deux hôpitaux et pourraient être améliorés par la possibilité de réaliser sur place le test PCR ADN. Une meilleure mise en œuvre du programme et un suivi actif pourraient améliorer les résultats pour les nourrissons et leur rétention en soins.

Marco de referencia: El Hospital Central de Mzuzu (MZCH) y el Hospital Distrital de Chitipa (CDH), en Malawi.Objetivo: Comparar el manejo y los desenlaces clínicos de los lactantes expuestos al virus de la inmunodeficiencia humana (VIH) en los programas de diagnóstico temprano del lactante (EID) en el MZCH (realización local de pruebas mediante la reacción en cadena de la polimerasa a partir de ADN [PCR-ADN]) y el CDH (muestras enviadas al MZCH) del 2013 al 2014.Método: Fue este un estudio retrospectivo de cohortes.Resultados: De los lactantes inscritos en el MZCH (n = 409), el resultado de la prueba PCR-ADN se comunicó a la persona encargada del niño en un 56% de los casos; esta proporción fue 51% en los lactantes inscritos en el CDH (n = 176). La mediana del lapso entre la obtención de la muestra y la entrega de los resultados a los encargados fue 34 días en el MZCH y 56 días en el CDH. En ambos hospitales, solo la mitad de las muestras de sangre seca (DBS) se recogió en 6 a 8 semanas. Más tutores de los lactantes en el MZCH que en el CDH recibieron el resultado de la prueba en el primer mes después de haber aportado la muestra (25% contra 10%). De los lactantes con resultado positivo frente al VIH, inició tratamiento antirretrovírico una mayor proporción de los niños atendidos en el MZCH (92%) que en el CDH (46%). El riesgo relativo (RR) de mortalidad fue más alto en los lactantes en quienes se obtuvo la muestra de DBS tardíamente (RR 1,3; IC95% de 1,0 a 1,7), en quienes no se obtuvo (RR 5,8; IC95% de 4,6 a 7,2) y cuando los tutores no recibieron los resultados (RR 8,3; IC95% de 5,7 a 11,9).Conclusión: El desempeño de los programas EID fue igualmente deficiente en ambos hospitales y se podría mejorar con la práctica de la prueba PCR-ADN en el momento de la atención. Una mejor ejecución del programa y un seguimiento activo contribuiría a obtener desenlaces clínicos más favorables en los lactantes y a retenerlos en los servicios de atención.

Essential role of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors (HDIs) are promising anticancer therapies and have been clinically used for the treatment of hematological malignancy. However, their efficacy in solid tumors is marginal and drug resistance hampers their further clinical utility. To develop novel strategies for the HDI-based anticancer therapeutics in non-small cell lung cancer (NSCLC), in the present study, we investigated the mechanisms underlying resistance to HDI treatment in NSCLC cells. We show the STAT3-mediated IGF2/IGF-1R signaling cascade as a key modulator for both acquired and primary HDI resistance. The treatment with HDI upregulated IGF2 transcription in NSCLC cells carrying intrinsic or acquired drug resistance via direct binding of STAT3 in IGF2 P3 and P4 promoters. Acetylated STAT3 emerged upon HDAC inhibition was protected from the proteasome-mediated degradation of STAT3 and functioned as a direct transcription factor for IGF2 expression. Genomic or pharmacological strategies targeting STAT3 diminished the HDI-induced IGF2 mRNA expression and overcame the resistance to HDI treatment in HDI-resistant NSCLC- or patient-derived tumor xenograft models. These findings provide new insights into the role of acetylated STAT3-mediated activation of IGF2 transcription in HDI resistance, suggesting IGF2 or STAT3 as novel targets to overcome HDI resistance in NSCLC.

Mortality and predictors in pulmonary tuberculosis with respiratory failure requiring mechanical ventilation.

OBJECTIVE: To analyse the predictors and mortality rate among patients receiving mechanical ventilation (MV) for respiratory failure due to pulmonary tuberculosis (TB). DESIGN: We retrospectively compared patients who required MV for TB with patients who required MV for community-acquired pneumonia (CAP). RESULTS: In-hospital mortality was significantly different between the two groups: 95.1% in TB vs. 62.7% in CAP (P < 0.001 using the χ(2) test). TB patients had a higher 30-day mortality (P = 0.040 using log-rank test), although the median sequential organ failure assessment (SOFA) (7.0 vs. 6.0, P = 0.842) and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores (20.0 ± 6.7 vs. 21.2 ± 6.7, P = 0.379) for TB and CAP patients were not different. TB patients were more likely to have increased lung lesion intrusions (OR 1.307, 95%CI 1.042-1.641, P = 0.021), and reduced albumin (OR 0.073, 95%CI 0.016-0.335, P = 0.001), C-reactive protein (OR 0.324, 95%CI 0.146-0.716, P = 0.005) and CURB-65 score (confusion, uraemia, respiratory rate, blood pressure and age ⩾65 years) (OR 0.916, 95%CI 0.844-0.995, P = 0.037). CONCLUSIONS: TB patients showed identical SOFA and APACHE II scores, but higher mortality than CAP patients. The higher mortality was not related to severity, but suggested an association with the extent of destructive lung lesions.

Changes in lung function according to disease extent before and after pulmonary tuberculosis.

OBJECTIVE: To evaluate changes in lung function in individuals before and after treatment for pulmonary tuberculosis (PTB) in relation to extent of disease. DESIGN: Using a retrospective cohort design, changes in and predictors of lung function were evaluated. RESULTS: A total of 41 patients were included in the final analysis. The median decline in annualised forced expiratory volume in 1 sec (FEV1) was 180.0 ml/year (95%CI 118.9-356.1) in advanced PTB and 94.7 ml/year (95%CI 33.4-147.3) in localised PTB (ΔFEV1% predicted/year 9.4%, 95%CI 4.4-14.0 vs. 3.8%, 95%CI 1.8-6.2). The median decline in annualised forced vital capacity (FVC) was 309.6 ml/year (95%CI 137.0-359.0) in advanced PTB and 101.1 ml/year (95%CI 30.3-219.6) in localised PTB (ΔFVC % predicted/year 7.3%, 95%CI 5.3-12.3 vs. 2.9%, 95%CI 0.9-6.5). CONCLUSIONS: As the sample size of our study was small, the conclusions could be biased. Nevertheless, our findings show that PTB causes a significant decline in lung function even in localised PTB, whereas advanced PTB was associated with excessive or even higher decline. This study suggests that early diagnosis and treatment of PTB is needed to preserve lung function.

Heparin bridging in warfarin anticoagulation therapy initiation could increase bleeding in non-valvular atrial fibrillation patients: a multicenter propensity-matched analysis.

BACKGROUND: The efficacy of heparin-bridging therapy during the initiation of oral anticoagulation therapy (OAC) in non-valvular atrial fibrillation (NVAF) is unclear. OBJECTIVES: To evaluate the efficacy and the safety of heparin-bridging therapy during OAC initiation in NVAF patients. PATIENTS/METHODS: This study included 5327 consecutive warfarin-naïve NVAF patients who received OAC that was initiated with (n = 1053) or without (n = 4274) heparin bridging at four tertiary hospitals. Stroke and bleeding events within 30 days of OAC were evaluated. RESULTS: While there was no difference in the incidence of stroke (0.5% vs. 0.3%, P = 0.381), major bleeding rate (0.9% vs. 0.3%, P = 0.004) was higher in heparin-bridged than in non-bridged patients. This trend remained in the propensity score-matched population (stroke 0.5% vs. 0.6%, P = 0.762; major bleeding 0.8% vs. 0.1%, P = 0.019). A high CHA2 DS2 -VASc score was an independent predictor for stroke, whereas bridging therapy had no beneficial effect in preventing stroke regardless of CHADS2 or CHA2 DS2 -VASc scores. The HAS-BLED score had a predictive value for major bleeding (odds ratio 1.80, 95% confidence interval 1.11-2.92, P = 0.018), and heparin-bridging therapy was associated with a higher major bleeding rate (odds ratio 4.44, 95% confidence interval 1.68-11.72, P = 0.003), especially in patients with a HAS-BLED score of ≥ 1. CONCLUSIONS: The heparin-bridging therapy increased bleeding without the benefit of preventing stroke at the initiation of OAC in NVAF. Our data suggest that heparin bridging should not be considered at the initiation of OAC in NVAF patients.

Prospective evaluation of the feasibility of sentinel lymph node biopsy in breast cancer patients with negative axillary conversion after neoadjuvant chemotherapy.

PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. (18)Fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both (18)F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both (18)F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.

Effect of endoscopy screening on stage at gastric cancer diagnosis: results of the National Cancer Screening Programme in Korea.

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.

Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis.

BACKGROUND: Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated. OBJECTIVES: The hemostatic activity of Reelin is investigated and defined in this study. METHODS: The interplay of Reelin with coagulation components was elucidated by far-Western and liposome/platelet binding assays. In vivo and ex vivo hemostasis-related analyses of Reelin-deficient mice and plasma were also performed. RESULTS: Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin ß1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated with the Kd of 11.7 and 21.2 nm, respectively. Reelin-deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency. Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern. CONCLUSIONS: By interacting with platelet phospholipids and the coagulation factors, thrombin and FXa, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.

Long-term survival analysis of korean breast cancer patients at a single center: improving outcome over time.

PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.

Clinical outcomes of bacteraemia in cellulitis of the leg.

BACKGROUND: Infections of the blood are associated with high mortality and morbidity. In cellulitis, the utility of blood cultures remains controversial because of their relatively low bacterial yield. However, some important but less well studied aspects include risk factors for bacteraemia, the effects of bacteraemia on the length of hospitalization and on morbidity and mortality rates. AIM: To determine the incidence of bacteraemia in cellulitis in an inpatient cohort; to identify risk factors for bacteraemia in cellulitis; and to assess length of hospitalization stay, rate of recurrence of cellulitis, and mortality in patients with cellulitis and bacteraemia. METHODS: Records of 214 patients diagnosed with cellulitis were reviewed. Blood cultures, length of hospitalization stay, rate of recurrence of cellulitis, mortality, coexistent dermatoses and local factors predisposing to cellulitis and comorbidities were analyzed. RESULTS: The incidence of bacteraemia was 10.8%. Mean duration of hospitalization was longer (P < 0.01) and recurrence (P < 0.01) was higher in patients with bacteraemia. There was no difference in mortality between patients with and patients without bacteraemia (P = 0.47). Risk factors for bacteraemia included lymphoedema (P < 0.01), presence of an ipsilateral orthopaedic implant (P < 0.01), total white blood cell (WBC) count > 13.5 × 10(6) µL (P < 0.01, liver cirrhosis (P = 0.02) and chronic kidney disease (P = 0.04). CONCLUSIONS: Blood cultures should be performed for patients with cellulitis who have factors increasing the risk of bacteraemia, such as presence of lymphoedema, ipsilateral orthopaedic device implantation, leucocytosis of > 13.5 × 10(6) µL, liver cirrhosis or chronic kidney disease, and other forms of immunosuppression. Bacteraemia in cases of cellulitis of the leg is a prognostic factor for increased length of hospitalization stay and recurrence of cellulitis.

Giardia lamblia binding immunoglobulin protein triggers maturation of dendritic cells via activation of TLR4-MyD88-p38 and ERK1/2 MAPKs.

Much remains unknown about the mammalian immune response to Giardia lamblia, a protozoan pathogen that causes diarrhoeal outbreaks. We fractionated protein extracts of G. lamblia trophozoites by Viva-spin centrifugation, DEAE ion exchange and gel filtration chromatography. Resultant fractions were screened for antigenic molecules by western blots analysis using anti-G. lamblia antibodies (Abs), resulting in identification of G. lamblia binding immunoglobulin protein (GlBiP). Maturation of mouse dendritic cells (DCs) in response to recombinant GlBiP (rGlBiP) was detected by increased expression of surface molecules such as CD80, CD86 and MHC class II; these mature DCs, produced pro-inflammatory cytokines (TNF-α, IL-12 and IL-6). Especially, the truncated rGlBiP containing the heat-shock protein 70 domain-induced cytokine production from mouse DCs. rGlBiP-induced DC activation was initiated by TLR4 in a MyD88-dependent way and occurred through activation of p38 and ERK1/2 MAPKs as well as increased activity of NF-κB and AP-1. Moreover, CD4(+) T cells stimulated with rGlBiP-treated DCs produced high levels of IL-2 and IFN-γ. Together, our results suggest that GlBiP contributes to maturation of DCs via activation of TLR4-MyD88-p38, ERK1/2 MAPK, NF-κB and AP-1.