IMPROVER (Involving Men with Prostate Cancer in Engaged Research): Assessing Patient Experience With Testing, Diagnosis, And Surveillance.

BACKGROUND: Our understanding of patient experiences with prostate cancer testing for diagnosis and surveillance is limited. The aim of this study was to collaborate with patients and clinicians to understand their lived experience and unmet needs around the early detection, diagnosis and monitoring (active surveillance) of prostate cancer. METHODS: Two focus groups were held with patients (n = 20) and healthcare professionals (n = 16), to identify the main challenges in prostate cancer detection, diagnosis, and monitoring. This information formed the basis of an online questionnaire for broader dissemination. RESULTS: A total of 1138 analyzable responses were obtained from people tested for prostate cancer (69% tested positive) in Europe and the US. Only 29 healthcare professionals completed the survey. Almost one-third of people reported knowing very little/nothing about prostate cancer prior to testing. Prior disease awareness was significantly higher in those who tested negative (P < .0001). Most respondents (n = 857; 75%) felt informed about the steps involved in testing. Receiving written information was a key factor; 91% of those who felt uninformed were not given any written information. Overall, most people felt "satisfied" with the typical prostate cancer tests: PSA, DRE, mpMRI, and biopsy. However, dissatisfaction for prostate biopsy (12%) was almost double that of other tests (P < .0001). Most patients understood why each test was done, and felt that their results and next steps were clearly explained to them; though PSA scored lowest in all of these fields. Apart from PSA, test satisfaction was lower when used repeatedly for surveillance, compared to once-off detection/diagnosis. CONCLUSIONS: Greater public awareness and education around prostate cancer, as well as clear and accessible written information for patients at the beginning of their cancer journey is needed. Further research is needed into alternative, less invasive tests, particularly when used repeatedly in the surveillance population.

Unveiling the epigenomic mechanisms of acquired platinum-resistance in high-grade serous ovarian cancer.

Resistance to platinum-based chemotherapy is the major cause of death from high-grade serous ovarian cancer (HGSOC). We hypothesise that detection of specific DNA methylation changes may predict platinum resistance in HGSOC. Using a publicly available "discovery" dataset we examined epigenomic and transcriptomic alterations between primary platinum-sensitive (n = 32) and recurrent acquired drug resistant HGSOC (n = 28) and identified several genes involved in immune and chemoresistance-related pathways. Validation via high-resolution melt analysis of these findings, in cell lines and HGSOC tumours, demonstrated the most consistent changes were observed in three of the genes: APOBEC3A, NKAPL and PDCD1. Plasma samples from an independent HGSOC cohort (n = 17) were analysed using droplet digital PCR. Hypermethylation of NKAPL was detected in 46% and hypomethylation of APOBEC3A in 69% of plasma samples taken from women with relapsed HGSOC (n = 13), with no alterations identified in disease-free patients (n = 4). Following these results, and using a CRISPR-Cas9 approach, we were also able to demonstrate that in vitro NKAPL promoter demethylation increased platinum sensitivity by 15%. Overall, this study demonstrates the importance of aberrant methylation, especially of the NKAPL gene, in acquired platinum resistance in HGSOC.

Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study.

BACKGROUND: The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). METHODS: Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a -30-day composite clinical outcome (RRT - or death). RESULTS: A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, p = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, p = 0.139). CONCLUSION: A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.

Antibacterial mesh: a novel technique involving naturally occurring cellular proteins.

BACKGROUND: Naturally occurring antimicrobial peptides are possibly the "next frontier" in infection prevention. Binding them to mesh could reduce the rate of mesh infections. This study identifies an antimicrobial agent capable of significant antibacterial activity when bound to mesh. METHODS: Lysozyme, human beta defensin (HBD-3), human cathelicidin (LL-37), and lysostaphin were adsorbed to polypropylene mesh at various concentrations. Treated meshes were placed in a suspension of 1 × 10(6) Staphylococcus aureus. Antibacterial action was monitored by turbidimetric assay, fluorescent imaging, and a colony counting method. RESULTS: A very high rate of lysis of S aureus cells was observed in the lysostaphin-treated group as measured by optical density; none survived as seen on colony count assays. Optical density for mesh coated with lysozyme, HBD-3, and LL-37 did not differ from untreated controls, with 100% survival rates by colony counts. CONCLUSION: Lysostaphin had superior antibacterial activity following adsorption to mesh.

Perceptions of student-observers in the operating room.

BACKGROUND: Student observation of surgical procedures is standard practice performed at the discretion of the attending surgeon and the participating medical facility. The goal of our study was to evaluate patient, physician, and operating room (OR) staff opinions concerning student observation of surgical procedures at different levels of academic training. MATERIALS AND METHODS: Following Institutional Review Board approval, patients undergoing elective surgery were consented to participate in the survey. An anonymous online survey was sent to attending surgeons and OR staff. RESULTS: The majority of patients (97), physicians (91), and OR staff (71) believe that OR observational experience is important to medical student training. Patients (92%) and OR staff (97%) more so than physicians (72%) rated OR observational experience as important for nursing student education (P < 0.001). Comparatively, all groups believe this experience is less important for college and high school students (P < 0.01). When asked if patients should be informed preoperatively of student-observer presence during procedures, more patients and OR staff replied affirmatively compared with physicians (P < 0.001). Similarly, patients and OR staff more frequently believed that informed consent for OR student-observers was necessary (P < 0.0001). CONCLUSION: All groups acknowledged the educational value of student observational experience, although significant disparity was noted relative to academic level and the group responding. Additionally, opinions of the OR staff were more closely aligned with those of patients. Further assessment of the role of informed consent for student-observer OR presence and potential implications is needed.

The addition of lysostaphin dramatically improves survival, protects porcine biomesh from infection, and improves graft tensile shear strength.

BACKGROUND: Lysostaphin (LS), a naturally occurring Staphylococcal endopeptidase, has the ability to penetrate biofilm, and has been identified as a potential antimicrobial to prevent mesh infection. The goals of this study were to determine if LS adhered to porcine mesh (PM) can impact host survival, reduce the risk of long-term PM infection, and to analyze lysostaphin bound PM (LS-PM) mesh-fascial interface in an infected field. METHODS: Abdominal onlay PMs measuring 3×3 cm were implanted in select groups of rats (n=75). Group assignments were based on bacterial inoculum and presence of LS on mesh. Explantation occurred at 60 d. Bacterial growth and mesh-fascial interface tensile strength were analyzed. Standard statistical analysis was performed. RESULTS: Only one out of 30 rats with bacterial inoculum not treated with LS survived. All 30 LS treated rats survived and had normal appearing mesh, including 20 rats with a bacterial inoculum (10(6) and 10(8) CFU). Mean tensile strength for controls and LS and no inoculum samples was 3.47±0.86 N versus 5.0±1.0 N (P=0.008). LS groups inoculated with 10(6) and 10(8) CFU exhibited mean tensile strengths of 4.9±1.5 N and 6.7±1.6 N, respectively (P=0.019 and P<0.001 compared with controls). CONCLUSION: Rats inoculated with S. aureus and not treated with LS had a mortality of 97%. By comparison, LS treated animals completely cleared S. aureus when challenged with bacterial concentrations of 1×10(6) and 1×10(8) with maintenance of mesh integrity at 60 d. These findings strongly suggest the clinical use of LS-treated porcine mesh in contaminated fields may translate into more durable hernia repair.

Poor resident-attending intraoperative communication may compromise patient safety.

BACKGROUND: Prior research suggests that hierarchy in medicine may impact communication and patient safety. This study examined the factors that influence surgical trainees in expressing their opinion in the operating room and the consequences this might have on patient safety. METHODS: An anonymous survey of general surgery, gynecology, and orthopedic surgery residents and attendings was conducted at a teaching institution in 2010. Separate surveys were used for attendings and for trainees consisting of 26 and 27 questions, respectively, with 17 questions in common. The surveys assessed whether the surgical hierarchy interfered with the residents voicing concerns about patient safety. Survey data was compiled, and χ2, Fisher exact tests, and the Wilcoxon rank sum test were used depending on the normality of the data. RESULTS: Thirty-eight trainees and 23 attendings participated in the survey; 74%-78% of trainees and attendings recalled an incident where the trainee spoke up and prevented an adverse event. While all attendings reported that they encourage residents to question their intraoperative decision making, only 55% of residents agreed (P<0.01). Residents indicated that they were more likely to voice their opinion with some attendings than with others based on their personality. Both groups agreed that the hierarchical structure of general surgical residency is necessary. CONCLUSION: Our findings indicate that resident attending intraoperative communication can prevent adverse patient events. Trainees often feel impaired in voicing their concerns to their attendings. Strategies that improve resident attending communication intraoperatively are needed as they are likely to enhance patient safety.