Monofluorophos-Metal Complexes: Ripe for Future Discoveries in Homogeneous Catalysis.

The discovery that cyclic (ArO)2PF can support Rh-catalysts for hydroformylation with significant advantages in tuning regioselectivity transformed the study of metal complexes of monofluorophos ligands from one of primarily academic interest to one with potentially important applications in catalysis. In this review, the syntheses of monofluorophosphites, (RO)2PF, and monofluorophosphines, R2PF, are discussed and the factors that control the kinetic stability of these ligands to hydrolysis and disproportionation are set out. A survey of the coordination chemistry of these two classes of monofluorophos ligands with d-block metals is presented, emphasising the bonding of the fluorophos to d-block metals, predominantly in low oxidation states. The application of monofluorophos ligands in homogeneous catalysis (especially hydroformylation and hydrocyanation) is discussed, and it is argued that there is great potential for monofluorophos complexes in future catalytic applications.

Mechanical mapping of the prostate in vivo using Dynamic Instrumented Palpation; towards an in vivo strategy for cancer assessment.

A calibrated palpation sensor has been developed for making instrumented Digital Rectal Examinations (iDREs) with a view to assessing patients for prostate cancer. The instrument measures the dynamic stiffness of the palpable surface of the prostate, and has been trialled on 12 patients in vivo. The patients had been diagnosed with prostate cancer and were scheduled for radical prostatectomy. As far as possible, patients with asymmetric disease were chosen so as to give a variation in gland condition over the palpable surface. The device works by applying an oscillating pressure (force) to a flexible probe whose displacement into the tissue is also measured in order to yield a dynamic stiffness, the static stiffness being incidentally measured at the mean oscillatory force. The device was deployed mounted on the index finger of a urologist and measurements taken at 12-16 positions on each patient using light and firm pressure and palpation frequencies of 1 or 5 Hz. In parallel, conventional DRE assessments were made by a consultant urologist for cancer. After in vivo measurement, the glands were removed and examined histologically with each palpation point being classified as cancerous (C) or not (NC). The work has established the first measurements of static modulus of living prostate tissue to be: 26.8 (13.3) kPa for tissue affected by prostate cancer (C classification), and 24.8 kPa (11.9) for tissue unaffected by cancer (NC classification), values quoted as median (interquartile range). The dynamic properties were characterised by: dynamic modulus, 5.15 kPa (4.86) for the C classification and 4.61 kPa (3.08) for the NC classification and the time lag between force and displacement at 5 Hz palpation frequency, 0.0175 s (0.0078) for the C classification and 0.0186 s (0.0397) for the NC classification, values again quoted as median (interquartile range). With the limited set of features that could be generated, an Artificial Neural Network (ANN) classification yielded a sensitivity of 97%, negative predictive value of 86%, positive predictive value of 67% and accuracy of 70% but with relatively poor specificity (30%). Besides extending the feature set, there are a number of changes in probe design, probing strategy and in mechanics analysis, which are expected to improve the diagnostic capabilities of the method.

Protocol for the TRANSLATE prospective, multicentre, randomised clinical trial of prostate biopsy technique.

OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.

Locating and sizing tumor nodules in human prostate using instrumented probing - computational framework and experimental validation.

Detection of tumor nodules is key to early cancer diagnosis. This study investigates the potential of using the mechanical data, acquired from probing the prostate for detecting the existence, and, more importantly, characterizing the size and depth, from the posterior surface, of the prostate cancer (PCa) nodules. A computational approach is developed to quantify the uncertainty of nodule detectability and is based on identifying stiffness anomalies in the profiles of point force measurements across transverse sections of the prostate. The capability of the proposed method was assessed firstly using a 'training' dataset of in silico models including PCa nodules with random size, depth and location, followed by a clinical feasibility study, involving experimental data from 13 ex vivo prostates from patients who had undergone radical prostatatectomy. Promising levels of sensitivity and specificity were obtained for detecting the PCa nodules in a total of 44 prostate sections. This study has shown that the proposed methods could be a useful complementary tool to exisiting diagnostic methods of PCa. The future study will involve implementing the proposed measurement and detection strategies in vivo, with the help of a miniturized medical device.

Associations Between Self-Reported Behavioral and Learning Concerns and DMD Isoforms in Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder resulting from loss of dystrophin. In addition to its role in muscle, isoforms of dystrophin are expressed in different cell types of the brain, and DMD has been linked to language delays, behavioral abnormalities and learning disabilities. OBJECTIVE: To determine whether disruption of specific DMD isoforms, age, corticosteroid use, ambulation status, or country are associated with behavioral and/or learning concerns in DMD. METHODS: De-identified data were collected from the Duchenne Registry from 2007-2019. Females, patients with BMD, and those without genetic testing reports were excluded from the cohort. For the genetic analysis, patients were divided into four subgroups based on the location of their mutation and the predicted isoforms affected. Bivariate analysis was conducted using chi-square for categorical variables. Two multivariate logistic regressions were used to assess independent associations with behavioral and learning concerns, respectively, and to estimate the effect size of each variable. RESULTS: DMD mutations disrupting expression of Dp140 and Dp71 were associated with a higher likelihood of reported behavioral and learning concerns. Corticosteroid use, categorical age, and country were other factors associated with behavior and learning concerns. CONCLUSION: This data adds to our current understanding of DMD isoforms, their mutational consequence and impact on behavior and learning.

Tetanus: A Rare Complication of Black Tar Heroin Use.

Tetanus is associated with high morbidity and mortality, although this is rarely encountered in high-income countries. We present a case of tetanus in an unvaccinated patient secondary to black tar heroin use that highlights the importance of considering tetanus in appropriate clinical contexts, harm reduction interventions, and universal tetanus vaccination campaigns.

Major adverse cardiac events after emergency department evaluation of chest pain patients with advanced testing: Systematic review and meta-analysis.

OBJECTIVES: Our primary objective was to describe the risk of major adverse cardiac events (MACE) at 1, 6, and 12 months after a negative coronary computed tomography angiogram (cCTA), electrocardiogram (ECG) stress test, stress echocardiography, and myocardial perfusion scintigraphy (MPS) in low- to intermediate-risk patients. METHODS: Initially, 952 articles were identified for screening, 81 met criteria for full-text review, and once risk of bias was assessed, 33 articles were included in this meta-analysis. We utilized a random-effects model to assess pooled MACE event proportion for patients undergoing evaluation of acute coronary syndrome (ACS) when risk stratified to a low- to intermediate-risk category after undergoing standard testing. Heterogeneity analysis was performed using Cochrane's Q-test and I2 statistic. RESULTS: Twenty-one studies evaluated follow-up at 1 month with cCTA having a 0.09% (95% confidence interval [CI] = 0.03% to 0.26%) pooled MACE compared to 0.23% (95% CI = 0.01% to 5.8%) of the exercise stress testing (p = 1). MPS and cCTA had an overall event rate of 0.15% (95% CI = 0.06% to 0.41%) at 6 months (I2  = 0%). At 12 months, a subgroup analysis found a pooled cCTA MACE of 0.16% (95% CI = 0.04% to 0.65%) compared to 1.68% (95% CI = 0.01% to 2.6%) for stress echocardiography with low within-group heterogeneity (I2  = 0%). Subgroup analysis of cCTA with no disease versus nonobstructive disease (<50% stenosis) did not find statistical difference in the MACE at both 1 month (0.17% [95% CI = 0.04% to 0.67%] vs. 0.06% [95% CI = 0.01% to 0.34%]) and 12 months (0.44% [95% CI = 0.09% to 2.2% vs. 0.54% [95% CI = 0.19% to 1.5%]). CONCLUSIONS: Patients presenting with chest pain who have a coronary CTA showing < 50% stenosis, negative ECG stress test, stress echocardiography, or stress myocardial perfusion scan in the past 12 months can be discharged without any further risk stratification if their ECG and troponin are reassuring given low MACE.

Seeing Red: Blood Sample Hemolysis Is Associated with Prolonged Emergency Department Throughput.

INTRODUCTION: Hemolyzed emergency department (ED) blood specimens impose substantial burdens on various aspects of delivering care. The ED has the highest incidence of hemolysis among hospital departments. This study assessed the association and potential impact of hemolyzed blood samples on patient throughput time using ED length of stay (LOS) as the primary outcome measure. METHODS: This study was a secondary analysis of data collected during a performance improvement project aimed at reducing the incidence of hemolysis in ED blood specimens. The electronic medical record was queried for potassium orders and results and for key patient throughput time points. Throughput times were stratified according to hemolysis, ED disposition (admitted vs discharged), and Emergency Services Index (ESI) triage categorization. Two-tailed t tests were used to compare throughput times for patients with and without hemolysis. RESULTS: Potassium values were reported for 11 228 patient visits. The mean ED LOS was 287 minutes for patients with nonhemolyzed samples and 349 minutes for patients who had hemolyzed samples, a mean delay of 62 minutes. The mean throughput time for discharged patients was 92 minutes shorter in the group without hemolysis (337 vs 429 minutes). The mean throughput time for admitted patients was 28 minutes shorter in the group without hemolysis (264 vs 292 minutes). The increased LOS for patients with a hemolyzed blood sample was independent of the most commonly encountered ESI levels. CONCLUSION: Hemolysis of blood samples obtained in the ED is associated with prolonged patient throughput via delays in patient disposition, independent of various markers of acuity, such as the patients' ultimate disposition or triage categorization.

Identification of tumor nodule in soft tissue: An inverse finite-element framework based on mechanical characterization.

Identification and characterization of nodules in soft tissue, including their size, shape, and location, provide a basis for tumor identification. This study proposes an inverse finite-element (FE) based computational framework, for characterizing the size of examined tissue sample and detecting the presence of embedded tumor nodules using instrumented palpation, without a priori anatomical knowledge. The inverse analysis was applied to a model system, the human prostate, and was based on the reaction forces which can be obtained by trans-rectal mechanical probing and those from an equivalent FE model, which was optimized iteratively, by minimizing an error function between the two cases, toward the target solution. The tumor nodule can be identified through its influence on the stress state of the prostate. The effectiveness of the proposed method was further verified using a realistic prostate model reconstructed from magnetic resonance (MR) images. The results show the proposed framework to be capable of characterizing the key geometrical indices of the prostate and identifying the presence of cancerous nodules. Therefore, it has potential, when combined with instrumented palpation, for primary diagnosis of prostate cancer, and, potentially, solid tumors in other types of soft tissue.

An intervention based on the Electronic Medical Record to improve smoking cessation guidance in an urban tertiary care center emergency department.

INTRODUCTION: Smoking remains a major public health issue and a leading cause of death and disability in the United States. The objective of this study was to determine the effect of a simple intervention on smoking guidance, based on the electronic medical record (EMR), including providing discharge instructions and/or cessation counseling to emergency department (ED) patients who smoke. METHODS: This was an interventional before-and-after study in an ED with 70000 visits per year. A pre-intervention and post-intervention chart review was performed on a random sample of ED visits occurring in 2014 and 2016, identifying smokers and the frequency with which smokers received discharge instructions and/or cessation counseling. In the fall of 2015, our EMR was programmed to deploy smoking cessation discharge instructions automatically. RESULTS: In all, 28.7% (172/600; 95% CI: 25.2-32.4%) reported current smoking in the pre-intervention ED population and 27.6% (166/600; 95% CI: 24.2-31.4%) reported smoking in the post-intervention population. Smoking cessation guidance was provided to a total of 3.5% of self-reported smokers in the pre-intervention group (6/172; 95% CI: 1.4-7.6%); 1.2% (2/172; 95% CI: 0.3-4.1%) were informed of smoking cessation resources as part of their printed ED discharge instructions and 2.3% (4/172; 95% CI: 0.9-5.8%) received smoking cessation counseling by the ED provider. There was a statistically significant increase in the proportion of patients receiving any smoking cessation guidance after the intervention. All patients (166/166; 95% CI: 97-100% in this period received ED discharge instructions and a list of smoking cessation resources and 3.6% of smokers (6/166; 95% CI: 1.7-7.7%) received smoking cessation counseling by the ED provider. CONCLUSIONS: Automated deployment of smoking cessation discharge instructions in the EMR improves smoking cessation discharge instructions, and also has a positive impact on improving rates of in-person counseling by ED providers.

Impact of Interventions to Change CBC and Differential Ordering Patterns in the Emergency Department.

Objectives: A CBC with leukocyte differential (CBC-DIFF) is a frequently ordered emergency department (ED) test. The DIFF component often does not add to clinical decision making. Our objective was to evaluate the impact of a performance improvement project on CBC ordering. Methods: ED orders for CBC-DIFF were identified through the laboratory information system. Two interventions were evaluated: an educational intervention regarding CBC-DIFF uses and a reprioritization of ED CBC-DIFF and CBC in the electronic medical record (EMR) orders. Pearson χ2 tests were used to assess for differences in the proportions. Results: There was no difference in the proportion of CBC tests performed after the education intervention (175/6,192, 2.8% [95% CI, 2.39%-3.21%] vs 219/6,270, 3.5% [95% CI, 3.05%-3.95%]). There was a significant increase in CBC samples ordered following the EMR intervention (604/6,044, 9.1% [95% CI, 8.37%-9.83%]; P < .01). Conclusions: Reprioritizing EMR laboratory orders can reduce overutilization of CBC-DIFF testing.

A novel method for rapid and quantitative mechanical assessment of soft tissue for diagnostic purposes: A computational study.

Biological tissues often experience drastic changes in their microstructure due to their pathophysiological conditions. Such microstructural changes could result in variations in mechanical properties, which can be used in diagnosing or monitoring a wide range of diseases, most notably cancer. This paves the avenue for non-invasive diagnosis by instrumented palpation although challenges remain in quantitatively assessing the amount of diseased tissue by means of mechanical characterization. This paper presents a framework for tissue diagnosis using a quantitative and efficient estimation of the fractions of cancerous and non-cancerous tissue without a priori knowledge of tissue microstructure. First, the sample is tested in a creep or stress relaxation experiment, and the behavior is characterized using a single term Prony series. A rule of mixtures, which relates tumor fraction to the apparent mechanical properties, is then obtained by minimizing the difference between strain energy of a heterogeneous system and an equivalent homogeneous one. Finally, the percentage of each tissue constituent is predicted by comparing the observed relaxation time with that calculated from the rule of mixtures. The proposed methodology is assessed using models reconstructed from histological samples and magnetic resonance imaging of prostate. Results show that estimation of cancerous tissue fraction can be obtained with a maximum error of 12% when samples of different sizes, geometries, and tumor fractions are presented. The proposed framework has the potential to be applied to a wide range of diseases such as rectal polyps, cirrhosis, or breast and prostate cancer whose current primary diagnosis remains qualitative.

Quantitative mechanical assessment of the whole prostate gland ex vivo using dynamic instrumented palpation.

An instrumented palpation sensor, designed for measuring the dynamic modulus of tissue in vivo, has been developed and trialled on ex vivo whole prostate glands. The sensor consists of a flexible membrane sensor/actuator with an embedded strain gauge and is actuated using a dynamically varying airflow at frequencies of 1 and 5 Hz. The device was calibrated using an indentation stiffness measurement rig and gelatine samples with a range of static modulus similar to that reported in the literature for prostate tissue. The glands were removed from patients with diagnosed prostate cancer scheduled for radical prostatectomy, and the stiffness was measured within 30 min of surgical removal. Each prostate was later examined histologically in a column immediately below each indentation point and graded into one of the four groups; normal, benign prostatic hyperplasia, cancerous and mixed cancer and benign prostatic hyperplasia. In total, 11 prostates were assessed using multiple point probing, and the complex modulus at 1 and 5 Hz was calculated on a point-by-point basis. The device yielded values of quasi-static modulus of 15 ± 0.5 kPa and dynamic modulus of 20 ± 0.5 kPa for whole prostates, and a sensitivity of up to 80% with slightly lower specificity was achieved on diagnosis of prostate cancer using a combination of mechanical measures. This assessment did not take into account some obvious factors such as edge effects, overlap and clinical significance of the cancer, all of which would improve performance. The device, as currently configured, is immediately deployable in vivo. A number of improvements are also identified which could improve the sensitivity and specificity in future embodiments of the probe.

Histology-based homogenization analysis of soft tissue: application to prostate cancer.

It is well known that the changes in tissue microstructure associated with certain pathophysiological conditions can influence its mechanical properties. Quantitatively relating the tissue microstructure to the macroscopic mechanical properties could lead to significant improvements in clinical diagnosis, especially when the mechanical properties of the tissue are used as diagnostic indices such as in digital rectal examination and elastography. In this study, a novel method of imposing periodic boundary conditions in non-periodic finite-element meshes is presented. This method is used to develop quantitative relationships between tissue microstructure and its apparent mechanical properties for benign and malignant tissue at various length scales. Finally, the inter-patient variation in the tissue properties is also investigated. Results show significant changes in the statistical distribution of the mechanical properties at different length scales. More importantly the loss of the normal differentiation of glandular structure of cancerous tissue has been demonstrated to lead to changes in mechanical properties and anisotropy. The proposed methodology is not limited to a particular tissue or material and the example used could help better understand how changes in the tissue microstructure caused by pathological conditions influence the mechanical properties, ultimately leading to more sensitive and accurate diagnostic technologies.

Primary SWL Is an Efficient and Cost-Effective Treatment for Lower Pole Renal Stones Between 10 and 20 mm in Size: A Large Single Center Study.

INTRODUCTION: To assess the clinical features, outcomes, complications, and cost-effectiveness of shockwave lithotripsy (SWL), flexible ureterorenoscopy (FURS), and percutaneous nephrolithotomy (PCNL) in the treatment of lower pole (LP) stones (10-20 mm) in a large tertiary referral center. PATIENTS AND METHODS: Consecutive patients treated for solitary LP stones (10-20 mm) between 2008 and 2013 were identified from a prospective database. SWL was used as primary treatment in all cases (following a stone multidisciplinary team assessment), with FURS and PCNL reserved for SWL contraindications, failure, or patient choice. "Success" was defined as stone free and/or clinically insignificant stone fragments (≤3 mm) at 1 and 3 months follow-up. Effect of anatomy on SWL success was determined from using CT images and regression analysis. Average cost per treatment modality (including additional second-line treatments) was calculated for each group using the National Health Service England 2014/15 National Tariff Healthcare Resource Group codes. RESULTS: Two hundred twenty-five patients were included (mean age 54.9; median stone size 12 mm). One hundred ninety-eight (88%), 21 (9.3%), and 6 (2.7%) patients underwent SWL, FURS, and PCNL as primary treatments, respectively, for median stone sizes of 12, 12, and 20 mm. Overall success rates were 82.8%, 76.1%, and 66.7%, respectively (p < 0.05). Sixty-three percent of patients undergoing primary SWL were effectively treated after one session. Anatomical analysis determined infundibulopelvic angle and infundibular length to be significantly different in patients effectively treated with SWL (p = 0.04). The average cost per treatment modality was also significantly lower for SWL (£750) than for FURS (£1261) or PCNL (£2658) (p < 0.01). CONCLUSION: SWL is both an efficacious and cost-effective primary treatment for patients with solitary LP stones (10-20 mm). The majority of patients can be effectively treated with primary SWL in a dedicated stone center, with the benefits of a short length of stay, low complication, and auxiliary treatment rates. The referral of such patients to high-volume lithotripsy centers with demonstrable outcomes should be given due consideration.

Striated Muscle in Radical Prostatectomy Specimens: A Marker of Apical Dissection Quality and an Independent Predictor of Urinary Continence after Endoscopic Extraperitoneal Radical Prostatectomy.

INTRODUCTION: The study aimed to determine if the presence and amount of striated muscle on the apical sections of the cruciate sections of laparoscopic radical prostatectomy (LRP) specimens predict early and long-term urinary continence outcomes. PATIENTS AND METHODS: We conducted a retrospective review of our prospectively collected single surgeon LRP database. We identified patients based on their continence outcomes (continent (0 pads) or incontinent at 12 months), with an approximate even spread early continent and incontinent patients). An uropathologist separate from the urology team was blinded to outcome and assessed each patients' apical cruciate sections (H&E stained) for the presence, percentage and maximal diameter of muscle and extraprostatic tissue on these sections. Specifically 2 scoring systems were used: (1) semi-quantitative estimation of percentage of muscle on the apical cruciate sections (low <5% and high >5%) and (2) percentage of total extraprostatic tissue on cruciate section (low <10% and high >10%). Logistic regression and classification and regression tree analyses were performed to identify the predictors of urinary incontinence (UI). RESULTS: In total 80 patients were analyzed, 38 were continent and 42 were incontinent at 12 months follow-up. The percentage of extraprostatic tissue/muscle being an independent predictor of being wet at 12 months (p = 0.002) on multivariate regression along with age (p = 0.04). Using percentage of extraprostatic tissue in cruciate section (high >10%) to predict UI at 12 months, it yielded 71% sensitivity, 82% specificity, 81% PPV, 72% NPV and 76% accuracy. CONCLUSION: The use of simple additional reporting of muscle and extraprostatic tissue on the apical sections of RP specimens can help to better predict the likelihood of continence return.

Acetabular fractures in skeletally immature rugby players.

Since the introduction of professionalism to the sport of rugby union, an increasing rate of injury has been noted in the playing population. In addition, overall participation numbers have increased globally, with more amateurs and young people involved in the sport. Acetabular fractures are generally seen after violent trauma and can be associated with poor long-term outcomes. We have previously described two acetabular fractures in young patients (16 and 24 years of age) sustained during rugby matches. We present a case series of four closed, isolated acetabular fractures in three skeletally immature male patients (13-16 years of age), two of which required open reduction and internal fixation. Three of these fractures occurred in conjunction with hip dislocations. All injuries were sustained while engaged in playing rugby union, two during seasonal match play and one during a training drill.