Factors associated with pathological up-staging in MRI cT3a prostate cancer - a retrospective study from a high-volume centre.

INTRODUCTION: Multiparametric MRI (mpMRI) parameters of pT3a prostate cancer have not been examined in large cohort studies. Therefore, we aimed to identify factors associated with up-staging of mpMRI cT3a in post-operative histopathological confirmation. METHODS: Retrospective analysis of a prospectively maintained database of a single UK cancer centre. Only cT3a cases who underwent robotic-assisted radical prostatectomy (RARP) were included (N = 383). MRI and specimen histopathology was reviewed independently by expert uro-radiologists and uro-histopathologists, respectively. Factors included age, BMI, prostate-specific antigen (PSA) level, biopsy international society of urological pathology (ISUP) grade, Prostate Imaging Reporting & Data System (PI-RADS®) score, tumour size, tumour coverage of gland (%), gland weight and surgical margins were analysed as predictors of pT3a prostate cancer. RESULTS: N = 383. Mean age 66 years (58-71), mean BMI 27.1 kg/m2 (25.0-30.0). 314 (82.0%) cases down- unchanged or down-staged, and 69 (18.0%) cases upstaged. PSA level (P = 0.002), PI-RADS score (P < 0.001) and ISUP grade (P < 0.001) are positively associated with upstage categories. ISUP grade ≥3 (OR 5.45, CI 1.88, 9.29, P < 0.002), PI-RADS score ≥4 (OR 3.92, CI 1.88-9.29, P < 0.001) and tumour coverage (OR 1.06, CI 1.05-1.08, P < 0.001) significantly positively associated with upstaging disease, with concurrent decreased probability of downstaging (OR 0.55, 0.14, 0.44, respectively, P < 0.05). Tumour coverage was positively correlated with increasing positive surgical margins (P < 0.05). Capsular contact > 15 mm was very unlikely to be upstaged (OR 0.36, CI 0.21-0.62, P < 0.001), aligning with published results past the widely accepted significant level for extracapsular disease on MRI. CONCLUSION: The study has identified PSA level, ISUP, PI-RADS score, tumour volume and percentage coverage are key predictive factors in cT3a upstaging. This study uniquely shows tumour coverage percentage as a predictor of cT3a upstaging on mpMRI. ISUP is the strongest predictor, followed by PI-RADS score and tumour coverage of gland. Multi-institutional studies are needed to confirm our findings.

"The Warmth of His Continuing Interest": Henry K. Beecher, the Bioethics Revolution, and Pharmaceutical Industry Funding of Academic Medical Science in Cold War America.

This paper examines anesthesiologist Henry K. Beecher's funding relationship with pharmaceutical manufacturer Edward Mallinckrodt, Jr. Beecher is a familiar figure to both medical ethicists and historians of medicine for his role in the bioethics revolution of the 1960s and 1970s. In particular, his 1966 article "Ethics and Clinical Research" is widely considered a turning point in the post-World War II debate about informed consent. We argue that Beecher's scientific interests should be understood in the context of his funding relationship with Mallinckrodt and that this relationship shaped the direction of his work in important ways. We also argue that Beecher's views on research ethics reflected his assumption that collaboration with industry was a normal part of how academic science is conducted. In the conclusion of the paper we suggest that Beecher's failure to consider his relationship with Mallinckrodt as worthy of ethical deliberation has important lessons for academic researchers who collaborate with industry today.

Global assessment of marine and freshwater recreational fish reveals mismatch in climate change vulnerability and conservation effort.

Recreational fisheries contribute substantially to the sociocultural and economic well-being of coastal and riparian regions worldwide, but climate change threatens their sustainability. Fishery managers require information on how climate change will impact key recreational species; however, the absence of a global assessment hinders both directed and widespread conservation efforts. In this study, we present the first global climate change vulnerability assessment of recreationally targeted fish species from marine and freshwater environments (including diadromous fishes). We use climate change projections and data on species' physiological and ecological traits to quantify and map global climate vulnerability and analyze these patterns alongside the indices of socioeconomic value and conservation effort to determine where efforts are sufficient and where they might fall short. We found that over 20% of recreationally targeted fishes are vulnerable to climate change under a high emission scenario. Overall, marine fishes had the highest number of vulnerable species, concentrated in regions with sensitive habitat types (e.g., coral reefs). However, freshwater fishes had higher proportions of species at risk from climate change, with concentrations in northern Europe, Australia, and southern Africa. Mismatches in conservation effort and vulnerability were found within all regions and life-history groups. A key pattern was that current conservation effort focused primarily on marine fishes of high socioeconomic value rather than on the freshwater and diadromous fishes that were predicted to be proportionately more vulnerable. While several marine regions were notably lacking in protection (e.g., Caribbean Sea, Banda Sea), only 19% of vulnerable marine species were without conservation effort. By contrast, 72% of freshwater fishes and 33% of diadromous fishes had no measures in place, despite their high vulnerability and cultural value. The spatial and taxonomic analyses presented here provide guidance for the future conservation and management of recreational fisheries as climate change progresses.

The Impact of Total Body Prehabilitation on Post-Operative Outcomes After Major Abdominal Surgery: A Systematic Review.

BACKGROUND: Despite advances in perioperative care, post-operative clinical and functional outcomes after major abdominal surgery can be suboptimal. Prehabilitation programmes attempt to optimise a patient's preoperative condition to improve outcomes. Total body prehabilitation includes structured exercise, nutritional optimisation, psychological support and cessation of negative health behaviours. This systematic review aims to report on the current literature regarding the impact of total body prehabilitation prior to major abdominal surgery. METHODS: Relevant studies published between January 2000 and July 2017 were identified using MEDLINE, EMBASE, AMED, CINAHL, PsychINFO, PubMed, and the Cochrane Database. All studies published in a peer-reviewed journal, assessing post-operative clinical and functional outcomes, following a prehabilitation programme prior to major abdominal surgery were included. Studies with less than ten patients, or a prehabilitation programme lasting less than 7 days were excluded. RESULTS: Sixteen studies were included, incorporating 2591 patients, with 1255 undergoing a prehabilitation programme. The studies were very heterogeneous, with multiple surgical sub-specialties, prehabilitation techniques, and outcomes assessed. Post-operative complication rate was reduced in six gastrointestinal studies utilising either preoperative exercise, nutritional supplementation in malnourished patients or smoking cessation. Improved functional outcomes were observed following a multimodal prehabilitation programme. Compliance was variably measured across the studies (range 16-100%). CONCLUSIONS: There is substantial heterogeneity in the prehabilitation programmes used prior to major abdominal surgery. A multimodal approach is likely to have better impact on functional outcomes compared to single modality; however, there is insufficient data either to identify the optimum programme, or to recommend routine clinical implementation.

Use of a 23-hour emergency department observation unit for the management of patients with toxic exposures.

BACKGROUND: A significant proportion of patients with toxic exposures presenting to the ED require admission. However, most will improve within 24 hours, and so could potentially be managed in a short-stay observation unit. We describe the management and outcomes of these patients in a 23-hour ED observation unit (EDOU). METHODS: A retrospective chart review of all patients with toxic exposures admitted to the EDOU in Singapore between 1 April 2013 and 31 March 2015 was performed. Patient demographics, exposure patterns, clinical presentation and interventions received were abstracted. The poisoning severity score (PSS) was retrospectively determined. Outcomes were length of stay and disposition. RESULTS: A total of 286 patients were analysed, of which 78.0% had intentional self-poisoning, 12.2% had bites/stings and 9.8% had unintentional or occupational toxic exposures. Analgesics (29.4%), sedatives (12.3%) and antidepressants (6.8%) were the most common drugs encountered. The majority of patients had a mild (68.9%) or moderate (15.4%) PSS, but 4.2% were graded as severe. Most patients with deliberate self-poisoning were reviewed by psychiatry (88.8%) and social services (74.9%). Most patients (92.0%) were medically cleared during their stay in EDOU, including all 12 with a severe PSS. Of these, 200 (69.9%) were discharged and 63 (22.0%) were transferred directly to a psychiatric unit. The median length of stay in the EDOU was 18 hours (IQR 13-23). CONCLUSION: Most patients admitted to the EDOU were successfully managed and medically cleared within 23 hours, including those with a severe PSS. The EDOU appears to be a suitable alternative to inpatient admission for selected patients.

Medical Narrative and the Rhetoric of Identification: The Many Faces of Anna White Dildane.

When Anna White Dildane, a prostitute and heroin addict, was committed to the Laboratory of Social Hygiene (LSH) in 1917, she was treated by a staff that anticipated the methods of the biopsychosocial model later developed by Engel. That is to say, the staff members believed that Anna's rehabilitation was contingent on a scientific diagnosis of the physical, mental, and social factors that underlay her condition. However, using Anna and the LSH as a case study, we draw from Latour to show the limitations of this "modern" method of diagnosis and treatment that persists today. Using Burke, we advocate for a pragmatic orientation focused on creating rhetorically oriented narratives whose aim is to help patients make judgments about their health and future, namely, by bringing about the experience of "form" capable of constituting new types of identification. Effective medical rhetoric thus adopts a method of persuasion that begins with the narrative and self-understanding of the patient, links aspects of that narrative with the technical expertise of physicians and other health care providers, and crafts a new, more specialized narrative attentive to the desires and constraints of a patient's form of identification that is ultimately the seat of judgment.

Pharmaceutical patenting and the transformation of American medical ethics.

The attitudes of physicians and drug manufacturers in the US toward patenting pharmaceuticals changed dramatically from the mid-nineteenth century to the mid-twentieth. Formerly, physicians and reputable manufacturers argued that pharmaceutical patents prioritized profit over the advancement of medical science. Reputable manufactures refused to patent their goods and most physicians shunned patented products. However, moving into the early twentieth century, physicians and drug manufacturers grew increasingly comfortable with the idea of pharmaceutical patents. In 1912, for example, the American Medical Association dropped the prohibition on physicians holding medical patents. Shifts in wider patenting cultures therefore transformed the ethical sensibilities of physicians.

Big pharma and the problem of disease inflation.

Over the course of the past decade, critics have increasingly called attention to the corrosive influence of the pharmaceutical industry on both biomedical research and the practice of medicine. Critics describe the industry's use of ghostwriting and other unethical techniques to expand their markets as evidence that medical science is all-too-frequently subordinated to the goals of corporate profit. While we do not dispute this perspective, we argue that it is imperative to also recognize that the goals of medical science and industry profit are now tightly wed to one another. As a result, medical science now operates to expand disease definitions, lower diagnostic thresholds, and otherwise advance the goals of corporate profit through the redefinition and expansion of what it means to be ill. We suggest that this process has led to a variety of ethical problems that are not fully captured by current critiques of ghostwriting and other troubling practices by the pharmaceutical industry. In our conclusion, we call for physicians, ethicists, and other concerned observers to embrace a more fundamental critique of the relationship between biomedical science and corporate profit.

The testing of Sanocrysin: science, profit, and innovation in clinical trial design, 1926-31.

This article provides a detailed analysis of the origins and significance of the 1926 clinical trial of Sanocrysin, a gold compound thought at the time to be useful in the treatment of tuberculosis. This experiment is generally considered to be the first clinical trial in the United States that used a formal system of randomization to divide research subjects into treatment and nontreatment groups; it was probably also the first clinical trial in the United States to use placebo shams in a nontreatment control group to overcome the problem of what researchers at the time called "psychic influence." As such, it was an extremely important moment in the history of clinical trial design. Yet, as I argue, the Sanocrysin experiment also needs to be understood in terms of both the regulatory environment at the time and the commercial interests of Parke, Davis & Company, the pharmaceutical manufacturer that was intent on introducing the drug. Although some historians argue that therapeutic reformers in the twentieth century used experimental science to rein in the commercial forces of the market, this article suggests that, at least in this case, the promotion of rigorous clinical science and the pursuit of corporate profit were deeply intertwined.

Relationship of pharyngeal water content and jugular volume with severity of obstructive sleep apnea in renal failure.

BACKGROUND: In patients with end-stage renal disease (ESRD), fluid overload may contribute to their high prevalence of obstructive sleep apnea (OSA) by increasing the amount of fluid displaced from the legs into the neck overnight, and possibly compressing the upper airway (UA). Indeed, in ESRD patients, the amount of overnight rostral fluid displacement from the legs is related to the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index, AHI). We, therefore, hypothesized that in ESRD patients, the greater the UA-mucosal water content (UA-MWC) and internal jugular vein volume (IJVVol), the higher the AHI. METHODS: We studied 20 patients with ESRD on thrice weekly hemodialysis who had undergone diagnostic polysomnography (age 41.0 ± 12.3 years, with a body mass index (BMI) of 25.8 ± 6.3 kg/m(2) and an AHI of 20.2 ± 26.8). The leg fluid volume (LFV) was measured by bioelectric impedance. The IJVVol and MWC were measured by UA magnetic resonance imaging (MRI). RESULTS: The only significant independent correlates of the AHI were IJVVol (r = 0.801, P < 0.0001) and UA-MWC (r = 0.720, P = 0.0005) which together explained 72% of its variability. CONCLUSIONS: These data suggest that fluid overload via increased IJVVol, and UA-MWC, contributes to the pathogenesis of OSA in patients with ESRD. These findings help us to explain the high prevalence of OSA in ESRD patients, and attenuation of OSA in association with nocturnal dialysis. They also suggest the need for randomized trials to determine whether more aggressive fluid removal in ESRD patients will alleviate OSA.

The utility of the ChatGPT artificial intelligence tool for patient education and enquiry in robotic radical prostatectomy.

OBJECTIVES: To assess the ChatGPT (Open AI) artificial intelligence platform's utility and accuracy as a patient education tool in robotic-assisted radical prostatectomy. MATERIALS AND METHODS: The ChatGPT 3.5 interface ( https://chat.openai.com/chat ) was interrogated and asked the 14 questions related to the frequency of complications of robotic-assisted radical prostatectomy as listed on British Association of Urological Surgeons (BAUS) patient information leaflet "Robotic-Assisted Laparoscopic Radical Prostatectomy)" published July 2021. The AI's responses to each question were tabulated, and compared alongside the official figures quoted from the BAUS information leaflet. A global assessment of the AI's response was also made for accuracy and relevance to patients. RESULTS: Of the 14 questions asked, 11/14 (78.6%) of ChatGPT's quoted figures were considered concordant and comparable to those quoted by the BAUS patient information leaflet. 13/14 (92.9%) of ChatGPT's responses were globally assessed to contain accurate information, appropriate, and pertinent to a patient's potential enquiry. CONCLUSION: ChatGPT is a powerful tool and is able to generate accurate and helpful information for patients seeking information regarding urological procedures and their potential complications. It is not, however, infallible, and urologists should remain vigilant in their patient interactions to any potential misinformation a patient may have gathered from it in their personal research prior to surgery.

Catalytic coupling of CO2 with epoxide over supported and unsupported amines.

Catalytic coupling of carbon dioxide with epoxide to cyclic carbonate is an important reaction that has recently been receiving renewed interest. This route allows the use of carbon dioxide as a greener chemical feedstock, which challenges the current practices for the synthesis of cyclic carbonates and derivatives. The present study is mainly concerned with catalytic coupling reaction between CO(2) and propylene oxide using organic amine as catalyst. The structural aspects of amines and the effects of their immobilization on solid surfaces on reaction kinetics are particularly studied. It is found that 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) amine maintains high catalytic activity both with and without solid support, but other primary amines, such as p-phenylenediamine give much reduced activity when placed on a solid surface. It is attributed to the absence of surface hydrogen in the supported TBD, prohibiting the catalyst sites from CO(2) poisoning. The coupling of other epoxides, including epichlorohydrin and styrene oxide over the solid supported amine, is also briefly carried out. Reaction mechanisms are proposed to explain the experimental observations.

Clinical trials and the origins of pharmaceutical fraud: Parke, Davis & Company, virtue epistemology, and the history of the fundamental antagonism.

This paper describes one possible origin point for fraudulent behavior within the American pharmaceutical industry. We argue that during the late nineteenth century therapeutic reformers sought to promote both laboratory science and increasingly systematized forms of clinical experiment as a new basis for therapeutic knowledge. This process was intertwined with a transformation in the ethical framework in which medical science took place, one in which monopoly status was replaced by clinical utility as the primary arbiter of pharmaceutical legitimacy. This new framework fundamentally altered the set of epistemic virtues-a phrase we draw from the philosophical field of virtue epistemology-considered necessary to conduct reliable scientific inquiry regarding drugs. In doing so, it also made possible new forms of fraud in which newly emergent epistemic virtues were violated. To make this argument, we focus on the efforts of Francis E. Stewart and George S. Davis of Parke, Davis & Company. Therapeutic reformers within the pharmaceutical industry, such as Stewart and Davis, were an important part of the broader normative and epistemic transformation we describe in that they sought to promote laboratory science and systematized clinical trials toward the twin goals of improving pharmaceutical science and promoting their own commercial interests. Yet, as we suggest, Parke, Davis & Company also serves as an example of a company that violated the very norms that Stewart and Davis helped introduce. We thus seek to describe one possible origin point for the widespread fraudulent practices that now characterize the pharmaceutical industry. We also seek to describe an origin point for why we conceptualize such practices as fraudulent in the first place.

Metastatic neuroendocrine tumor masquerading as liver abscesses.

Fever and deranged transaminases with liver mass(es) on imaging mandates further evaluation of the mass(es) and should be followed radiologically and clinically. In the absence of a definitive diagnosis, repeat biopsy should be done.

Massive inguinoscrotal herniation of the bladder: challenges in non-operative management.

Massive inguinoscrotal hernias containing the bladder are rare but can present with significant complications such as obstructive uropathy and urinary sepsis. A comorbid 71-year-old gentleman presented with an enlarging inguinoscrotal mass and an acute kidney injury (AKI). Imaging revealed a large inguinoscrotal hernia containing the bladder, and bilateral hydronephrosis. Renal function improved on urethral catheterization. Admitted under general surgery originally, the patient declined any surgical intervention and had his catheter removed as an outpatient, without urological follow up. He represented 6 months later with urinary sepsis and a new AKI. Repeat imaging revealed a progression of the bilateral hydronephrosis. Subsequently admitted under urology, bilateral nephrostomies as well as a catheter were inserted. Once stable, he was discharged with both as part of his long-term management. Non-operative management of this condition may occasionally be necessary, and so requires effective multidisciplinary decision making. Real-world organizational and geographical factors contributed to the challenges in this case.

A thing patented is a thing divulged: Francis E. Stewart, George S. Davis, and the legitimization of intellectual property rights in pharmaceutical manufacturing, 1879-1911.

This article examines the efforts of pharmacist and physician Francis E. Stewart to legitimize the commercial introduction of new drugs by reinterpreting the ethical status of patent rights in pharmaceutical manufacturing. I argue that patents had long been understood by the orthodox medical community as an unethical form of medical monopoly and that, as a result, drug companies that marketed their goods primarily to physicians in the years immediately following the Civil War had little room to develop or introduce new products. In collaboration with George S. Davis and the pharmaceutical manufacturing firm Parke, Davis, & Company, Stewart worked to redefine patents as an ethical means of encouraging scientific and commercial innovation. In doing so, he sought to reconcile medical science and commerce so that they were mutually beneficial to one another. However, I also suggest that his efforts had an ironic effect in that they helped legitimatize a form of patent protection that Stewart himself came to believe to be unethical in nature.