The provision of a time-critical elective surgical service during the COVID-19 Crisis: a UK experience.

INTRODUCTION: With the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic. MATERIALS AND METHODS: A protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 'clean' site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff. RESULTS: A total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive. CONCLUSION: This study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.

Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

Electrophysiology-based stratification of pancreatic tumorigenicity by label-free single-cell impedance cytometry.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer lacking specific biomarkers that can be correlated to disease onset, promotion and progression. To assess whether tumor cell electrophysiology may serve as a marker for PDAC tumorigenicity, we use multi-frequency impedance cytometry at high throughput (∼350 cells/s) to measure the electrical phenotype of single PDAC tumor cells from xenografts, which are derived from primary pancreatic tumors versus those from liver metastases of different patients. A novel phase contrast metric based on variations in the high and low frequency impedance phase responses that is related to electrophysiology of the cell interior is found to be systematically altered as a function of tumorigenicity. PDAC cells of higher tumorigenicity exhibited lowered interior conductivity and enhanced permittivity, which is validated by the dielectrophoresis on the respective cell types. Using genetic analysis, we suggest the role of dysregulated Na+ transport and removal of Ca2+ ions from the cytoplasm on key oncogenic KRAS-driven processes that may be responsible for lowering of the interior cell conductivity. We envision that impedance cytometry can serve as a tool to quantify phenotypic heterogeneity for rapidly stratifying tumorigenicity. It can also aid in protocols for dielectrophoretic isolation of cells with a particular phenotype for prognostic studies on patient survival and to tailor therapy selection to specific patients.

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Action observation for sensorimotor learning in surgery.

BACKGROUND: Acquiring new motor skills to learn complex movements and master the use of a diverse range of instruments is fundamental for developing expertise in surgery. Although aspects of skill development occur through trial and error, watching the performance of another individual (action observation) is an increasingly important adjunct for the acquisition of these complex skills before performing a procedure. The aim of this review was to examine the evidence in support of the use of action observation in surgery. METHODS: A narrative review of observational learning for surgical motor skills was undertaken. Searches of PubMed and PsycINFO databases were performed using the terms 'observational learning' OR 'action observation' AND 'motor learning' OR 'skill learning'. RESULTS: Factors such as the structure of physical practice, the skill level of the demonstrator and the use of feedback were all found to be important moderators of the effectiveness of observational learning. In particular, observation of both expert and novice performance, cueing attention to key features of the task, and watching the eye movements of expert surgeons were all found to enhance the effectiveness of observation. It was unclear, however, whether repeated observations were beneficial for skill learning. The evidence suggests that these methods can be employed to enhance surgical training curricula. CONCLUSION: Observational learning is an effective method for learning surgical skills. An improved understanding of observational learning may further inform the refinement and use of these methods in contemporary surgical training curricula.

Analysis of Parasitic Protozoa at the Single-cell Level using Microfluidic Impedance Cytometry.

At present, there are few technologies which enable the detection, identification and viability analysis of protozoan pathogens including Cryptosporidium and/or Giardia at the single (oo)cyst level. We report the use of Microfluidic Impedance Cytometry (MIC) to characterise the AC electrical (impedance) properties of single parasites and demonstrate rapid discrimination based on viability and species. Specifically, MIC was used to identify live and inactive C. parvum oocysts with over 90% certainty, whilst also detecting damaged and/or excysted oocysts. Furthermore, discrimination of Cryptosporidium parvum, Cryptosporidium muris and Giardia lamblia, with over 92% certainty was achieved. Enumeration and identification of (oo)cysts can be achieved in a few minutes, which offers a reduction in identification time and labour demands when compared to existing detection methods.

When should resuscitation at birth cease?

It is rare for newborn infants to require prolonged resuscitation at birth. While there are detailed national and international guidelines on when and how to provide resuscitation to newborns, there is little existing guidance on when newborn resuscitation should be stopped. In this paper we review current guidance surrounding adult, paediatric and neonatal resuscitation as well as recent evidence of outcome for newborn infants requiring prolonged resuscitation. We discuss the ethical principles that can potentially guide decisions surrounding resuscitation and post-resuscitation care. We also propose a structured approach to stopping resuscitation.

Intestinal drug transporter expression and the impact of grapefruit juice in humans.

The goals of this study were to assess the extent of human intestinal drug transporter expression, determine the subcellular localization of the drug uptake transporter OATP1A2, and then to assess the effect of grapefruit juice consumption on OATP1A2 expression relative to cytochrome P450 3A4 and MDR1. Expression of drug uptake and efflux transporters was assessed using human duodenal biopsy samples. Fexofenadine uptake by different transporters was measured in a transporter-transfected cell line. We investigated the influence of grapefruit juice on pharmacokinetics of orally administered fexofenadine. The effect of grapefruit juice on the expression of intestinal transporters was determined using real-time polymerase chain reaction and Western blot analysis. In the duodenum of healthy volunteers, an array of CYP enzymes as well as uptake and efflux transporters was expressed. Importantly, uptake transporters thought to be liver-specific, such as OATP1B1 and 1B3, as well as OATP2B1 and 1A2 were expressed in the intestine. However, among OATP transporters, only OATP1A2 was capable of fexofenadine uptake when assessed in vitro. OATP1A2 colocalized with MDR1 to the brush border domain of enterocytes. Consumption of grapefruit juice concomitantly or 2 h before fexofenadine administration was associated with reduced oral fexofenadine plasma exposure, whereas intestinal expression of either OATP1A2 or MDR1 remained unaffected. In conclusion, an array of drug uptake and efflux transporters are expressed in the human intestine. OATP1A2 is likely the key intestinal uptake transporter for fexofenadine absorption whose inhibition results in the grapefruit juice effect. Although short-term grapefruit juice ingestion was associated with reduced fexofenadine availability, OATP1A2 or MDR1 expression was unaffected.

Screening for colorectal cancer: the cost to find an advanced adenoma.

OBJECTIVE: Cancer Care Ontario has recommended a program to screen for colorectal cancer using fecal occult blood testing (FOBT). Patients who test positive on FOBT will require further investigation. We examined the cost of finding an advanced adenoma in these patients using four different strategies. METHODS: Using decision analysis software (DATA 3.5, TreeAge Software, Boston, MA), we considered four strategies for evaluating patients referred for a positive FOBT: 1) flexible sigmoidoscopy to the splenic flexure, 2) flexible sigmoidoscopy with air contrast barium enema (ACBE), 3) virtual colonoscopy, and 4) colonoscopy. If an adenoma was found in any of the first three methods, colonoscopy and polypectomy were performed. An advanced adenoma was defined as a villous adenoma, tubular adenoma > or = 10 mm, high grade dysplasia, or cancer. Values for probabilities, test characteristics and costs ($CDN) were estimated from a MEDLINE literature review, local costs, and OHIP fee codes. Patients with adenomas identified as well as direct medical costs from a third party payer perspective were calculated. RESULTS: Assuming a probability of adenoma of 16.9%, the cost for each strategy (compared to no investigation) was as follows: flexible sigmoidoscopy to the splenic flexure, $226; flexible sigmoidoscopy with ACBE, $424; virtual colonoscopy, $597; and colonoscopy, $387. The cost to clear a patient of adenoma(s) was $1,930, $2,840, $3,681, and $2,290, respectively. Despite being most cost-effective, the sigmoidoscopy strategy was predicted to detect 69% of cases of advanced adenomas. The radiological strategies would be less expensive if ACBE cost less than $115 or virtual colonoscopy cost less than $291. The colonoscopy strategy was more cost-effective if the probability of an adenoma was > or = 33.5%. When the incremental costs were considered to investigate 1000 patients, virtual colonoscopy and sigmoidoscopy with ACBE were both more costly then colonoscopy, and neither detected as many cases of advanced adenomas. CONCLUSION: Improved access to colonoscopy seems to be the preferred approach to deal with increased referrals.

Attitudes of surgical trainees towards transplantation surgery as a career.

At present there are a number of unfilled consultant posts in transplantation surgery in the United Kingdom, particularly within the field of kidney transplantation. Unless the current shortfall is addressed, it seems highly probable that the number of unfilled consultant posts will continue to increase. This survey aimed to highlight the reasons underlying trainees' reluctance to enter the field of transplantation surgery and to assess how the specialty might be changed to attract new trainees. Questionnaires were sent to 102 surgical trainees requesting details on age, sex, training grade, research interests and chosen specialty. They were asked to consider nine specified reasons commonly thought to influence a trainee's decision on whether or not he/she would enter their chosen specialty and to grade each of these according to their relative importance in the context of considering a career in transplantation. The survey then suggested five changes in training/structure, and the trainees were again asked to grade the relative importance of each with regard to whether it would attract them towards transplantation surgery. Replies were received from 61 trainees (60%). Trainees were deterred from transplantation surgery because of the on-call commitment, unpredictable workload, lack of exposure and a lack of information on the specialty. A reduced on-call commitment, increased income, increased exposure, improved training structure and increased information would all serve to attract new trainees to the specialty. To attract new trainees to transplantation surgery, there must be exposure to the specialty at an earlier stage in training, and a proactive stance must be adopted in providing information for the trainees. In addition, there needs to be ongoing commitment to improvements in training structure. The issues of increased income and an acceptable on-call commitment must be addressed.