Immunohistochemical expression of hyaluronic acid in the normal prostate, benign prostate hyperplasia and prostate carcinoma

Hyaluronic acid (HA), a component of the extracellular matrix, is present in various tissues and tissue fluids. HA regulates cell adhesion and migration and it has been implicated in the progression of prostate cancer (PCa) as a molecule associated with the biological potential of PCa. The concentration of HA is elevated in several cancers, including bladder, colon, breast and Wilms’ tumor. In this study, we compared the immunohistochemical expression of HA in the normal prostate, benign prostate hyperplasia (BPH) and prostate carcinoma. HA was immunohistochemically detected in 22 prostate tissues (6 histologically normal, 10 with BPH and 6 with PCa). Formalin fixed, paraffin-embedded sections were stained using an ABC method with biotinylated HA binding protein (B-HABP). Negative controls included sections incubated without B-HABP as well as sections incubated with Streptomyces hyaluronidase. In normal and BPH prostate glands staining was localized predominantly in the gland surrounding stroma, as well as in the fibrovascular core of the papillary projections of the glands. In prostate carcinoma samples the amount of HA in the stroma was markedly increased and staining was not localized around glandular structures but was diffuse throughout the stroma. There was a sharp diminution at the interface between tumor stroma and non-tumoral connective tissue. HA appears to be a supplementary tumor-associated marker. Insight gained in the mechanisms of increased production and hyaluronidase digestion of HA may eventually lead to new targets for pharmacological intervention in the treatment of PCa

Current status of surgical treatment for pectus excavatum deformity

Pectus excavatum is the commonest anterior chest wall deformity which is the result of overgrowth and elon­gation of costal cartilages that push the normal sternum in. The deformity has serious pshychologic impact and limits the exercise tolerance of the patient, because of displacement of the heart within the left hemithorax. Repair of pectus excavatum is performed by the classical Ravich technique or the minimally invasive Nuss repair. The Ravich operation consists of resection of the deformed cartilages, bending the sternum in its normal position and maintenance of the sternum in the correct position by using a metal bar or a strong synthetic mesh. The Nuss procedure involves the thoracoscopic placement of a pre-formed curved metal bar behind the sternum which rises the sternum to the desired position. The selection of the technique depends on the age of the patient and the degree and symmetry of the deformity. The Nuss technique is suitable for children between 5 and 15 years old who have flexible chest wall and symmetric deformities, while the Ravich procedure is indicated in young adults and asymmetric forms. Indeed, the Nuss technique still undergoes modifications to become safer and simpler and further it needs expertise and special equipment

Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding, cytotoxicity, antiinflammatory and anti-coagulant effects towards platelet activating factor

The complex fac-[Re(CO)3(phendione)Cl] (1) (where phendione = 1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV–visible, FTIR, and NMR techniques. The DNA binding properties of 1 are investigated by UV-spectrophotometric (melting curves), covalent binding assay, CV (cyclic voltammetry), circular dichroism (CD) and viscosity measurements. Experimental data indicate that 1 fits into the major groove without disrupting the helical structure of the B-DNA in contrast to the free phendione which intercalates within the base pairs of DNA. Upon irradiation, complex 1promotes the cleavage of plasmid pBR322 DNA from supercoiled form I to nicked form II via a proton coupled electron transfer mechanism. This comes as a result of experimental data in anaerobic/aerobic conditions and in the presence of DMSO. The biological activities of 1 and its precursors [Re(CO)5Cl] and phendione are tested towards a series of cancerous cell lines as glioblastoma (T98G), prostate cancer (PC3) and breast cancer (MCF-7) as well as platelet activating factor (PAF)-aggregation. Moreover, all the aforementioned compounds are tested for their ability to modulate PAF-basic metabolic enzyme activities in preparations of rabbit leukolytes. The in vitro experiments indicate that phendione has a better antitumor effect than cisplatin whereas [Re(CO)5Cl] is a better PAF inhibitor than both the phendione ligand and 1. Moreover, for the first time it is indicated that [Re(CO)5Cl], with a IC50 of 17 nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC50 of 30 and 20 nM, respectively, whereas 1 affects PAF-catabolism

TELIOS: A Tool for the Automatic Generation of Logic Programming Machines

Abstract In this paper the tool TELIOS is presented, for the automatic generation of a hardware machine, corresponding to a given logic program. The machine is implemented using an FPGA, where a corresponding inference machine, in application specific hardware, is created on the FPGA, based on a BNF parser, to carry out the inference mechanism. The unification mechanism is based on actions embedded between the non-terminal symbols and implemented using special modules on the FPGA

ROB-MEN: a tool to assess risk of bias due to missing evidence in network meta-analysis

Background Selective outcome reporting and publication bias threaten the validity of systematic reviews and meta-analyses and can affect clinical decision-making. A rigorous method to evaluate the impact of this bias on the results of network meta-analyses of interventions is lacking. We present a tool to assess the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN). Methods ROB-MEN first evaluates the risk of bias due to missing evidence for each of the possible pairwise comparison that can be made between the interventions in the network. This step considers possible bias due to the presence of studies with unavailable results (within-study assessment of bias) and the potential for unpublished studies (across-study assessment of bias). The second step combines the judgements about the risk of bias due to missing evidence in pairwise comparisons with (i) the contribution of direct comparisons to the network meta-analysis estimates, (ii) possible small-study effects evaluated by network meta-regression, and (iii) any bias from unobserved comparisons. Then, a level of “low risk”, “some concerns”, or “high risk” for the bias due to missing evidence is assigned to each estimate, which is our tool’s final output. Results We describe the methodology of ROB-MEN step-by-step using an illustrative example from a published NMA of non-diagnostic modalities for the detection of coronary artery disease in patients with low risk acute coronary syndrome. We also report a full application of the tool on a larger and more complex published network of 18 drugs from head-to-head studies for the acute treatment of adults with major depressive disorder. Conclusions ROB-MEN is the first tool for evaluating the risk of bias due to missing evidence in network meta-analysis and applies to networks of all sizes and geometry. The use of ROB-MEN is facilitated by an R Shiny web application that produces the Pairwise Comparisons and ROB-MEN Table and is incorporated in the reporting bias domain of the CINeMA framework and software

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700