Gender differences in how physicians access and process information.

There is an absence of information on how physicians make surgical decisions, and on the effect of gender on the processing of information. A novel web based decision-matrix software was designed to trace experimentally the process of decision making in medical situations. The scenarios included a crisis and non-crisis simulation for endometrial cancer surgery. Gynecologic oncologists, fellows, and residents (42 male and 42 female) in Canada participated in this experiment. Overall, male physicians used more heuristics, whereas female physicians were more comprehensive in accessing clinical information (p < 0.03), utilized alternative-based acquisition processes in the non-crisis scenario (p = 0.01), were less likely to consider procedure-related costs (p = 0.04), and overall allocated more time to evaluate the information (p < 0.01). Further experiments leading to a better understanding of the cognitive processes involved in medical decision making could influence education and training and impact on patient outcome.

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

Clinical predictors and outcomes of Klebsiella pneumoniae bacteraemia in a regional hospital in Hong Kong.

BACKGROUND: Klebsiella pneumoniae (KP) infection is associated with high morbidity and mortality. Multidrug resistance, especially extended-spectrum ß-lactamase (ESBL) production, in KP is endemic worldwide. AIM: To evaluate the clinical characteristics and outcomes of patients with KP bacteraemia in critical care and general ward settings. METHODS: Adult patients admitted to a regional hospital in Hong Kong from January 1st, 2009 to June 30th, 2016 (7.5 years) with KP bacteraemia were included. Demographics, clinical features, microbiological characteristics, and outcomes were analysed. FINDINGS: Among 853 patients, 178 (20.9%) required critical care and 176 (20.6%) died within 30 days of hospital admission. Thirty-day survivors were younger (P<0.001), had milder disease (defined by Sequential Organ Failure Assessment score) (P<0.001), presented with hepatobiliary sepsis (P<0.001) or urosepsis (P<0.001), less septic shock (P=0.013), fewer invasive organ supports (P<0.001), and had appropriate empirical antibiotics (P<0.001). Cox regression analysis showed that respiratory tract infection (hazard ratio: 2.99; 95% confidence interval: 2.061-4.337; P≤0.001), gastrointestinal tract infection (excluding hepatobiliary system) (2.763; 1.761-4.337; P≤0.001), mechanical ventilation (2.202; 1.506-3.221; P≤0.001), medical case (1.830; 1.253-2.672; P=0.002), inappropriate empirical antibiotics (1.716; 1.267-2.324; P≤0.001), female (1.699; 1.251-2.307; P<0.001), age >65 years (1.692; 1.160-2.467; P=0.006), and presence of solid tumour (1.457; 1.056-2.009; P=0.022) were independent risk factors for 30-day mortality. Unexpectedly, diabetes mellitus was associated with better 30-day survival (P=0.002). A total of 102 patients (12.0%) had infections with ESBL-producing strains, which were not associated with higher 30-day mortality. CONCLUSION: KP bacteraemia is associated with high 30-day mortality. Site of infection, patients' comorbidities and appropriate use of empirical antibiotic are important predictors of patients' outcomes.

Use of the human colorectal adenocarcinoma (Caco-2) cell line for isolating respiratory viruses from nasopharyngeal aspirates.

The human colorectal adenocarcinoma-derived Caco-2 cell line was evaluated as a means isolating common respiratory viruses from nasopharyngeal aspirates for the diagnosis of respiratory diseases. One hundred eighty-nine direct immunofluorescence positive nasopharyngeal aspirates obtained from patients with various viral respiratory diseases were cultured in the presence of Caco-2 cells or the following conventional cell lines: LLC-MK2, MDCK, HEp-2, and A549. Caco-2 cell cultures effectively propagated the majority (84%) of the viruses present in nasopharyngeal aspirate samples compared with any positive cultures obtained using the panel cells (78%) or individual cell line MDCK (38%), HEp-2 (21%), LLC-MK2 (27%), or A549 (37%) cell lines. The differences against individual cell line were statistically significant (P = < 0.000001). Culture in Caco-2 cells resulted in the isolation of 85% (36/42) of viruses which were not cultivated in conventional cell lines. By contrast, 80% (24/30) of viruses not cultivated in Caco-2 cells were isolated using the conventional panel. The findings indicated that Caco-2 cells were sensitive to a wide range of viruses and can be used to culture a broad range of respiratory viruses.

A phase I/II prospective, single arm trial of gefitinib, trastuzumab, and docetaxel in patients with stage IV HER-2 positive metastatic breast cancer.

Inhibition of the HER-2 pathway via the monoclonal antibody trastuzumab has had a major impact in treatment of HER-2 positive breast cancer, but de novo or acquired resistance may reduce its effectiveness. The known interplay between the epidermal growth factor receptor (EGFR) and HER-2 receptors and pathways creates a rationale for combined anti-EGFR and anti-HER-2 therapy in HER-2 positive metastatic breast cancer (MBC), and toxicities associated with the use of multiple chemotherapeutic agents together with biological therapies may also be reduced. We conducted a prospective, single arm, phase I/II trial to determine the efficacy and toxicity of the combination of trastuzumab with the EGFR inhibitor gefitinib and docetaxel, in patients with HER-2 positive MBC. The maximum tolerated dose (MTD) was determined in the phase I portion. The primary end point of the phase II portion was progression-free survival (PFS). Immunohistochemical analysis of biomarker expression of the PKA-related proteins cAMP response element-binding protein (CREB), phospho-CREB and DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa) plus t-DARPP (the truncated isoform of DARPP-32); PTEN; p-p70 S6K; and EGFR was conducted on tissue from metastatic sites. Nine patients were treated in the phase I portion of the study and 22 in the phase II portion. The MTD was gefitinib 250 mg on days 2-14, trastuzumab 6 mg/kg, and docetaxel 60 mg/m(2) every 21 days. For the 29 patients treated at the MTD, median PFS was 12.7 months, with complete and partial response rates of 18 and 46%, and a stable disease rate of 29%. No statistically significant correlation was found between response and expression of any biomarkers. We conclude that the combination of gefitinib, trastuzumab, and docetaxel is feasible and effective. Expression of the biomarkers examined did not predict outcome in this sample of HER-2 overexpressing metastatic breast cancer.

The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring.

BACKGROUND: This study aimed to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy. PATIENTS AND METHODS: Patients with ovarian cancer were randomized to receive either TCM or placebo in addition to standard chemotherapy. The primary outcome was global health status (GHS) score, assessed by European Organization for Research and Treatment of Cancer questionnaire, while the secondary outcomes were other QOL items, chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells. RESULTS: There was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group. CONCLUSIONS: TCM did not improve QOL but did have some effects in terms of maintaining immune function.

Oncogenic Ras/Src cooperativity in pancreatic neoplasia.

Pancreas cancer is one of the most lethal malignancies and is characterized by activating mutations of Kras, present in 95% of patients. More than 60% of pancreatic cancers also display increased c-Src activity, which is associated with poor prognosis. Although loss of tumor suppressor function (for example, p16, p53, Smad4) combined with oncogenic Kras signaling has been shown to accelerate pancreatic duct carcinogenesis, it is unclear whether elevated Src activity contributes to Kras-dependent tumorigenesis or is simply a biomarker of disease progression. Here, we demonstrate that in the context of oncogenic Kras, activation of c-Src through deletion of C-terminal Src kinase (CSK) results in the development of invasive pancreatic ductal adenocarcinoma (PDA) by 5-8 weeks. In contrast, deletion of CSK alone fails to induce neoplasia, while oncogenic Kras expression yields PDA at low frequency after a latency of 12 months. Analysis of cell lines derived from Ras/Src-induced PDA's indicates that oncogenic Ras/Src cooperativity may lead to genomic instability, yet Ras/Src-driven tumor cells remain dependent on Src signaling and as such, Src inhibition suppresses growth of Ras/Src-driven tumors. These findings demonstrate that oncogenic Ras/Src cooperate to accelerate PDA onset and support further studies of Src-directed therapies in pancreatic cancer.

Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses.

BACKGROUND: The novel swine-origin influenza A H1N1 virus (S-OIV) causes the current pandemic. Its tissue tropism and replication in different cell lines are not well understood. OBJECTIVE: Compare the growth characteristics of cell lines infected by S-OIV, seasonal influenza A H1N1 (sH1N1) and avian influenza A H5N1 (H5N1) viruses and the effect of temperature on viral replication. STUDY DESIGN: Cytopathic effect (CPE), antigen expression by immunofluorescence (IF) and viral load profile by quantitative RT-PCR in 17 cell lines infected by S-OIV, sH1N1 and H5N1 were examined. Comparison of their replication efficiency in chick embryo was performed. The effect of temperature on viral replication in Madin-Darby canine kidney (MDCK) cells was determined by TCID(50) at 33 degrees C, 37 degrees C and 39 degrees C for 5 consecutive days. RESULTS: S-OIV replicated in cell lines derived from different tissues or organs and host species with comparable viral load to sH1N1. Among 13 human cell lines tested, Caco-2 has the highest viral load for S-OIV. S-OIV showed a low viral load with no CPE or antigen expression in pig kidney cell PK-15, H5N1 demonstrated the most diverse cell tropism by CPE and antigen expression, and the highest viral replication efficiency in both cell lines and allantoic fluid. All three viruses demonstrated best growth at 37 degrees C in MDCK cells. CONCLUSION: Cell line growth characteristics of S-OIV, sH1N1 and H5N1 appear to correlate clinically and pathologically with involved anatomical sites and severity. Low replication of S-OIV in PK-15 suggests that this virus is more adapted to human than swine.

Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus.

BACKGROUND: Human coronavirus HKU1 (HCoV-HKU1) is a recently identified coronavirus with a global distribution and known to cause mainly respiratory infections. OBJECTIVES: To investigate the seroepidemiology of HKU1 infections in our local population. STUDY DESIGN: An ELISA-based IgG antibody detection assay using recombinant HCoV-HKU1 nucleocapsid and spike (S) proteins (genotype A) were developed for the diagnosis of CoV-HKU1 infections, Additionally, a neutralization antibody assay using the HCoV-HKU1 pseudotyped virus was developed to detect the presence of neutralizing antibodies in serum with antibody positivity in an S protein-based ELISA. RESULTS: Results of the recombinant S protein-based ELISA were validated with Western blot, immunofluorescence analysis and flow cytometry. The coupled results demonstrated good correlation with Spearmen's coefficient of 0.94. Seroepidemiological study in a local hospital-based setting using this newly developed ELISA showed steadily increasing HCoV-HKU1 seroprevalence in childhood and early adulthood, from 0% in the age group of <10 years old to a plateau of 21.6% in the age group of 31-40 years old. CONCLUSIONS: Our study demonstrated the usefulness of the S-based ELISA which could be applied to future epidemiological studies of HCoV-HKU1 in other localities.

An oral mucosal DNA vaccine for SARS coronavirus infections.

1. When different forms of SARS coronavirus (SARS-CoV) spike protein-based vaccines for generation of a neutralising antibody response to SARS-CoV were injected into a mouse model, all the mice immunised with intramuscular tPA-optimised 800 DNA vaccine boosted with intraperitoneal recombinant spike polypeptide generated by Escherichia coli and intramuscular CTLA4Hinge SARS800 DNA vaccine boosted with intraperitoneal S-peptide had neutralising antibody titres of>1:1280.2. This observation may have major practical value for field studies, such as the immunisation of civet cats, as the cost of recombinant proteins produced by E coli is much lower than those produced by eukaryotic systems.3. This study indicates that the type of vaccine used for priming is crucial for determining the type of immune response developed.Subsequent doses will boost the immune response generated by the first dose of vaccine.

Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma.

The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 146 non-small cell lung carcinoma (NSCLC) patients were analysed for relative expression of DDR1 and DDR2 using quantitative real-time PCR (qRT-PCR). An additional 23 matched tumour and normal tissues were tested for differential expression of DDR1 and DDR2, and previously reported somatic mutations. Discoidin domain receptor 1 was found to be significantly upregulated by 2.15-fold (P=0.0005) and DDR2 significantly downregulated to an equivalent extent (P=0.0001) in tumour vs normal lung tissue. Discoidin domain receptor 2 expression was not predictive for patient survival; however, DDR1 expression was significantly associated with overall (hazard ratio (HR) 0.43, 95% CI=0.22-0.83, P=0.014) and disease-free survival (HR=0.56, 95% CI=0.33-0.94, P=0.029). Multivariate analysis revealed DDR1 is an independent favourable predictor for prognosis independent of tumour differentiation, stage, histology, and patient age. However, contrary to previous work, we did not observe DDR mutations. We conclude that whereas altered expression of DDRs may contribute to malignant progression of NSCLC, it is unlikely that this results from mutations in the DDR1 and DDR2 genes that we investigated.

Gemella bacteraemia characterised by 16S ribosomal RNA gene sequencing.

AIMS: To define epidemiology, clinical disease, and outcome of gemella bacteraemia by 16S rRNA gene sequencing. To examine the usefulness of the Vitek, API, and ATB systems in identifying two gemella species. METHODS: All alpha haemolytic streptococci other than Streptococcus pneumoniae isolated from blood cultures during a six year period were identified by conventional biochemical methods, the Vitek system, and the API system. 16S rRNA gene sequencing was performed on all isolates identified by both kits as gemella with >or= 95% confidence or by either kit as any bacterial species with < 95% confidence. The ATB expression system was used to identify the two isolates that were defined as gemella species by 16S rRNA gene sequencing. RESULTS: Of the 302 alpha haemolytic streptococci other than S pneumoniae isolated, one was identified as Gemella morbillorum, and another as Gemella haemolysans by 16S rRNA gene sequencing. The patient with monomicrobial G morbillorum bacteraemia was a 66 year old man with community acquired infective endocarditis with septic thromboemboli. The patient with G haemolysans bacteraemia was a 41 year old woman with hospital acquired polymicrobial bacteraemia during the neutropenic period of an autologous bone marrow transplant for non-Hodgkin's lymphoma, the first case of its kind in the English literature. The API and ATB expression systems only identified the second strain as G haemolysans at 94% and 99% confidence, respectively, whereas the Vitek system identified none of the two strains correctly at > 70% confidence. CONCLUSIONS: Gemella bacteraemia is uncommon. 16S rRNA gene sequencing is the method of choice for identification of gemella and gemella-like isolates.

Emergence of cotrimoxazole- and quinolone-resistant Campylobacter infections in bone marrow transplant recipients.

Clinical and microbiological data were collected prospectively from 704 patients who underwent bone marrow transplantation (BMT) during an 11-year period (1991-2001), and the first two cases of Campylobacter infection occurring in BMT recipients in the pre-engraftment period were identified. The two cases occurred on days 2 and 3 post-BMT, respectively. Both patients had Campylobacter jejuni enteritis, and one case was complicated by bacteraemia. In both cases the presenting symptoms were indistinguishable from hospital-acquired pre-engraftment diarrhoea, which is commonly caused by Clostridium difficile. Both of the Campylobacter jejuni isolates were resistant to cotrimoxazole and ciprofloxacin. Both patients responded to intravenous meropenem and subsequently had uneventful marrow engraftment.

Imaging of non-small-cell lung cancer with indium-111 pentetreotide.

PURPOSE: Lung cancer is the leading cause of cancer deaths in the United States. Non-small-cell lung cancer (NSCLC) accounts for 75% to 85% of lung cancers. CT has been the standard anatomic study for localizing and staging NSCLC, although it is associated only with moderate accuracy. In-111 pentetreotide, a radiolabeled somatostatin analog largely used in the scintigraphic localization of neuroendocrine tumors, has been shown incidentally to identify NSCLC lesions. This observation is important in the workup for metastatic disease for neuroendocrine tumors, because presumed metastatic lesions may actually be second primary tumors of NSCLC. In-111 may also serve as a potentially useful adjunct to CT in the anatomic evaluation of NSCLC. The purpose of this study was to determine the likelihood of detecting and localizing NSCLC using In-111 pentetreotide scintigraphy. MATERIALS AND METHODS: Ten patients with known or possible NSCLC were examined using In-111 pentetreotide. Scans were compared with the patients' previously performed chest radiographs and CT scans. RESULTS: In-111 pentetreotide imaging correctly identified sites of tumor involvement as detected by chest CT and surgery in all 10 patients with NSCLC. CONCLUSION: This study demonstrates the uptake of In-111 pentetreotide by NSCLC. This important observation should be considered in the workup for metastatic disease of neuroendocrine tumors with In-111 pentetreotide, because NSCLC can be a source of false-positive findings. In-111 pentetreotide imaging may also serve as a potentially useful adjunct to CT for identifying obscured or equivocal lesions and as an aid in localizing tissue for biopsy.

Ameloblastic carcinoma of the jaws. A report of two cases.

Two cases of ameloblastic carcinoma of the jaws are reported. Histopathologically, the lesions showed cytologic features of malignancy in addition to classical ameloblastoma patterns and were therefore documented as examples of ameloblastic carcinoma. The negative cytokeratin expression by the malignant cells on histochemical analysis is notably different from that normally observed in classical ameloblastomas.

Prospective randomized study of thrice weekly six-month and nine-month chemotherapy for cervical tuberculous lymphadenopathy.

The aim of this study is to compare the efficacy of a thrice weekly 6-month regimen, 4S3H3R3Z3/2H3R3 (which consists of an initial 4 months of streptomycin (S), isoniazid (H), rifampicin (R), and pyrazinamide (Z) followed by 2 months of isoniazid and rifampicin), with a thrice weekly 9-month regimen, 4S3H3R3Z3/5H3R3 (which consists of an initial 4 months of streptomycin, isoniazid, rifampicin, and pyrazinamide followed by 5 months of isoniazid and rifampicin), in the treatment of cervical tuberculous lymphadenopathy. A total of 113 patients were recruited between August 1987 and December 1993. Twenty-two patients were excluded from the analysis because of defaulting treatment or modification of regimen. Ninety-one patients were included in the analysis. Forty-three patients were given the 6-month regimen, and 48 patients were given the 9-month regimen. Two (5%) patients of the 6-month regimen and one (2%) patient of the 9-month regimen had primary failure after completion of treatment (relative risk, 2.23; 95% confidence interval, 0.21 to 23.76). Of the 88 patients who had initial clinical remission after completion of treatment, the 5-year actuarial remission rates were 89% for the 6-month regimen and 90% for the 9-month regimen (Wilcoxon, p = 0.44). There were no significant differences of both primary failure rate and 5-year actuarial remission rate of the two regimens. The 6-month regimen is recommended as the initial treatment of tuberculous lymphadenopathy.

Cord compression due to extramedullary hemopoiesis in a patient with thalassemia.

STUDY DESIGN: This is a case report of a patient with thalassemia who had acute spinal cord compression at the T3 to T8 level and presented for treatment. METHODS: Magnetic resonance imaging and surgical decompression and transfusion therapy was chosen as the preferred treatment modality. RESULTS: Neurologic recovery was satisfactory from the immediate postoperative period, and full recovery was observed 2 months after surgery. CONCLUSION: Clinical awareness is important for early diagnosis. Documentation with an imaging technique, such as magnetic resonance imaging, is mandatory. Optimal treatment is tailor-made and depends on the clinical situation and the expertise available.