Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart.

Adding a cationic helper lipid to a lipid nanoparticle (LNP) can increase lung delivery and decrease liver delivery. However, it remains unclear whether charge-dependent tropism is universal or, alternatively, whether it depends on the component that is charged. Here, we report evidence that cationic cholesterol-dependent tropism can differ from cationic helper lipid-dependent tropism. By testing how 196 LNPs delivered mRNA to 22 cell types, we found that charged cholesterols led to a different lung:liver delivery ratio than charged helper lipids. We also found that combining cationic cholesterol with a cationic helper lipid led to mRNA delivery in the heart as well as several lung cell types, including stem cell-like populations. These data highlight the utility of exploring charge-dependent LNP tropism.

The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. RESULTS: No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. CONCLUSION: These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.

Optimization of Gradient-Echo Echo-Planar Imaging for T2* Contrast in the Brain at 0.5 T.

Gradient-recalled echo (GRE) echo-planar imaging (EPI) is an efficient MRI pulse sequence that is commonly used for several enticing applications, including functional MRI (fMRI), susceptibility-weighted imaging (SWI), and proton resonance frequency (PRF) thermometry. These applications are typically not performed in the mid-field (<1 T) as longer T2* and lower polarization present significant challenges. However, recent developments of mid-field scanners equipped with high-performance gradient sets offer the possibility to re-evaluate the feasibility of these applications. The paper introduces a metric "T2* contrast efficiency" for this evaluation, which minimizes dead time in the EPI sequence while maximizing T2* contrast so that the temporal and pseudo signal-to-noise ratios (SNRs) can be attained, which could be used to quantify experimental parameters for future fMRI experiments in the mid-field. To guide the optimization, T2* measurements of the cortical gray matter are conducted, focusing on specific regions of interest (ROIs). Temporal and pseudo SNR are calculated with the measured time-series EPI data to observe the echo times at which the maximum T2* contrast efficiency is achieved. T2* for a specific cortical ROI is reported at 0.5 T. The results suggest the optimized echo time for the EPI protocols is shorter than the effective T2* of that region. The effective reduction of dead time prior to the echo train is feasible with an optimized EPI protocol, which will increase the overall scan efficiency for several EPI-based applications at 0.5 T.

Penile Prosthesis Placement by a Dedicated Transgender Surgery Unit: A Retrospective Analysis of Complications.

BACKGROUND: Penile prostheses may be used as a component of genital gender affirmation surgery for the purpose of achieving penile rigidity after phalloplasty, and transgender individuals experience higher complication rates than cisgender individuals. AIM: To observe complications with transmasculine penile prosthesis surgery over time and across surgical conditions. METHODS: Retrospective chart review of all transmasculine patients with phalloplasty undergoing penile prosthesis placement between 4/14/2017 and 2/11/2020 (80 patients). OUTCOMES: Independent variables include implant type, previous genital surgeries, and simultaneous genital surgeries. Dependent variables include prosthesis infection and mechanical complication (device malfunction, dislodgement, erosion). RESULTS: There was an overall complication requiring surgery rate of 36% and infection rate of 20% (15/67 for inflatable prostheses and 1/13 for semirigid), with 14% (11/80) experiencing infection requiring removal. Differences in infection rates appeared insignificant across categories of previous surgery or with simultaneous surgery, but we did notice a markedly lower rate for semirigid prostheses compared to inflatable. There was a significant relationship between infection and case number, with the probability of infection decreasing over time. Device loss at 9 months was 21% overall. Preoperative conditions of the neophallus such as prior stricture correction and perioperative factors such as simultaneous clean and clean-contaminated procedures seemed to pose no additional increase in complication rates. CLINICAL IMPLICATIONS: Type and number of prior and simultaneous non-prosthetic surgeries should not be considered as a risk factor for penile prosthesis after phalloplasty for transmasculine patients, even those that are clean-contaminated STRENGTHS & LIMITATIONS: Our cohort size is large compared to currently available studies, although not large enough to generate sufficient power for group comparisons. We have reported every genital surgical step between phalloplasty and penile prosthesis placement and recorded complications with subsequent devices after failure. Patient-reported outcomes were not collected. CONCLUSION: We demonstrate that preoperative conditions of the neophallus, such as prior stricture correction, and perioperative factors, such as simultaneous clean and clean-contaminated procedures, seem to pose no additional increase in complication rates. Our data suggest that surgical experience may further decrease complications over time. B. L. Briles, R. Y. Middleton, K. E. Celtik, et al. Penile Prosthesis Placement by a Dedicated Transgender Surgery Unit: A Retrospective Analysis of Complications. J Sex Med 2022;19:641-649.

Free-breathing liver fat and R2∗ quantification using motion-corrected averaging based on a nonlocal means algorithm.

PURPOSE: To propose a motion-robust chemical shift-encoded (CSE) method with high signal-to-noise (SNR) for accurate quantification of liver proton density fat fraction (PDFF) and R2∗ . METHODS: A free-breathing multi-repetition 2D CSE acquisition with motion-corrected averaging using nonlocal means (NLM) was proposed. PDFF and R2∗ quantified with 2D CSE-NLM were compared to two alternative 2D techniques: direct averaging and single acquisition (2D 1ave) in a digital phantom. Further, 2D NLM was compared in patients to 3D techniques (standard breath-hold, free-breathing and navigated), and the alternative 2D techniques. A reader study and quantitative analysis (Bland-Altman, correlation analysis, paired Student's t-test) were performed to evaluate the image quality and assess PDFF and R2∗ measurements in regions of interest. RESULTS: In simulations, 2D NLM resulted in lower standard deviations (STDs) of PDFF (2.7%) and R2∗ (8.2  s-1 ) compared to direct averaging (PDFF: 3.1%, R2∗ : 13.6  s-1 ) and 2D 1ave (PDFF: 8.7%, R2∗ : 33.2  s-1 ). In patients, 2D NLM resulted in fewer motion artifacts than 3D free-breathing and 3D navigated, less signal loss than 2D direct averaging, and higher SNR than 2D 1ave. Quantitatively, the STDs of PDFF and R2∗ of 2D NLM were comparable to those of 2D direct averaging (p>0.05). 2D NLM reduced bias, particularly in R2∗ (-5.73 to -0.36  s-1 ) that arises in direct averaging (-3.96 to 11.22  s-1 ) in the presence of motion. CONCLUSIONS: 2D CSE-NLM enables accurate mapping of PDFF and R2∗ in the liver during free-breathing.

Vaginoplasty tips and tricks.

Vaginoplasty is a commonly performed surgery for the transfeminine patient. In this review, we discuss how to achieve satisfactory surgical outcomes, and highlight solutions to common complications involved with the surgery, including: wound separation, vaginal stenosis, hematoma, and rectovaginal fistula. Pre-operative evaluation and standard technique are outlined. Goal outcomes regarding aesthetics, creation of a neocavity, urethral management, labial appearance, vaginal packing and clitoral sizing are all described. Peritoneal vaginoplasty technique and visceral interposition technique are detailed as alternatives to the penile inversion technique in case they are needed to be used. Post-operative patient satisfaction, patient care plans, and solutions to common complications are reviewed.

The Critical Nature of Addressing Burnout Prevention: Results From the Critical Care Societies Collaborative's National Summit and Survey on Prevention and Management of Burnout in the ICU.

OBJECTIVES: To summarize the results of expert discussions and recommendations from a National Summit and survey on the promoting wellness and preventing and managing burnout in the ICU. DATA SOURCES: Literature review; Critical Care Societies Collaborative (CCSC) Statement on Burnout Syndrome in Critical Care Healthcare Professionals: A Call for Action; CCSC's National Summit on Prevention and Management of Burnout in the ICU; and a descriptive survey on strategies for addressing burnout using Research Electronic Data Capture (REDCap) (project-redcap.org). DATA SYNTHESIS: Building on the CCSC call for action to address burnout among critical care professionals, the CCSC sponsored the National Summit on Prevention and Management of Burnout in the ICU with 55 invited experts in various fields including psychology, sociology, integrative medicine, psychiatry, suicide prevention, bereavement support, ethics, palliative care, meditation, mindfulness-based stress reduction, among others. Attendees joined breakout groups, to identify factors influencing burnout in ICU professionals and the value of organizational and individual interventions. As a follow-up to the Summit, a descriptive survey assessing strategies for addressing burnout was sent via email or newsletter blast with responses received from 680 CCSC members, including physicians, nurses, pharmacists, therapists, and others. CONCLUSIONS: The Summit attendees identified the importance of raising awareness among critical care clinicians and key stakeholders, advocating for workplace changes to promote healthy work environments, and promoting research to further explore practical strategies to address, mitigate, and prevent burnout. Critical care clinicians reported that a number of initiatives are being implemented both at their hospitals and at the unit level to build resilience and address burnout prevention. However, other respondents reported that no measures were being used within their organizations, and that colleagues were experiencing burnout. Dissemination and application of resiliency building measures and strategies to address burnout in critical care clinicians are needed.

Workforce, Workload, and Burnout in Critical Care Organizations: Survey Results and Research Agenda.

OBJECTIVES: This report provides analyses and perspective of a survey of critical care workforce, workload, and burnout among the intensivists and advanced practice providers of established U.S. and Canadian critical care organizations and provides a research agenda. DESIGN: A 97-item electronic survey questionnaire was distributed to the leaders of 27 qualifying organizations. SETTING: United States and Canada. PARTICIPANTS: Leaders of critical care organizations in the United States and Canada. INTERVENTIONS: None. DATA SYNTHESIS AND MAIN RESULTS: We received 23 responses (85%). The critical care organization survey recorded substantial variability of most organizational aspects that were not restricted by the critical care organization definition or regulatory mandates. The most common physician staffing model was a combination of full-time and part-time intensivists. Approximately 80% of critical care organizations had dedicated advanced practice providers that staffed some or all their ICUs. Full-time intensivists worked a median of 168 days (range 42-192 d) in the ICU (168 shifts = 24 7-d wk). The median shift duration was 12 hours (range, 7-14 hr), and the median number of consecutive shifts allowed was 7 hours (range 7-14 hr). More than half of critical care organizations reported having burnout prevention programs targeted to ICU physicians, advanced practice providers, and nurses. CONCLUSIONS: The variability of current approaches suggests that systematic comparative analyses could identify best organizational practices. The research agenda for the study of critical care organizations should include studies that provide insights regarding the effects of the integrative structure of critical care organizations on outcomes at the levels of our patients, our workforce, our work practices, and sustainability.

Prospective comparison of longitudinal change in hepatic proton density fat fraction (PDFF) estimated by magnitude-based MRI (MRI-M) and complex-based MRI (MRI-C).

PURPOSE: To compare longitudinal hepatic proton density fat fraction (PDFF) changes estimated by magnitude- vs. complex-based chemical-shift-encoded MRI during a weight loss surgery (WLS) program in severely obese adults with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: This was a secondary analysis of a prospective dual-center longitudinal study of 54 adults (44 women; mean age 52 years; range 27-70 years) with obesity, biopsy-proven NAFLD, and baseline PDFF ≥ 5%, enrolled in a WLS program. PDFF was estimated by confounder-corrected chemical-shift-encoded MRI using magnitude (MRI-M)- and complex (MRI-C)-based techniques at baseline (visit 1), after a 2- to 4-week very low-calorie diet (visit 2), and at 1, 3, and 6 months (visits 3 to 5) after surgery. At each visit, PDFF values estimated by MRI-M and MRI-C were compared by a paired t test. Rates of PDFF change estimated by MRI-M and MRI-C for visits 1 to 3, and for visits 3 to 5 were assessed by Bland-Altman analysis and intraclass correlation coefficients (ICCs). RESULTS: MRI-M PDFF estimates were lower by 0.5-0.7% compared with those of MRI-C at all visits (p < 0.001). There was high agreement and no difference between PDFF change rates estimated by MRI-M vs. MRI-C for visits 1 to 3 (ICC 0.983, 95% CI 0.971, 0.99; bias = - 0.13%, p = 0.22), or visits 3 to 5 (ICC 0.956, 95% CI 0.919-0.977%; bias = 0.03%, p = 0.36). CONCLUSION: Although MRI-M underestimates PDFF compared with MRI-C cross-sectionally, this bias is consistent and MRI-M and MRI-C agree in estimating the rate of hepatic PDFF change longitudinally. KEY POINTS: • MRI-M demonstrates a significant but small and consistent bias (0.5-0.7%; p < 0.001) towards underestimation of PDFF compared with MRI-C at 3 T. • Rates of PDFF change estimated by MRI-M and MRI-C agree closely (ICC 0.96-0.98) in adults with severe obesity and biopsy- proven NAFLD enrolled in a weight loss surgery program. • Our findings support the use of either MRI technique (MRI-M or MRI-C) for clinical care or by individual sites or for multi-center trials that include PDFF change as an endpoint. However, since there is a bias in their measurements, the same technique should be used in any given patient for longitudinal follow-up.

Feasibility of perioperative volatile organic compound breath testing for prediction of paralytic ileus following laparoscopic colorectal resection.

BACKGROUND: Despite implementation of enhanced recovery after surgery (ERAS) and laparoscopic techniques, postoperative ileus (POI) remains frequent after colorectal surgery, impacting the patient, their recovery and health-care resources. Presently there are no tests that reliably predict or enable early POI diagnosis. Volatile organic compounds (VC) are products of human and microbiota cellular metabolism and we hypothesised that a detectable alteration occurs in POI. METHOD: This was a prospective observational study of patients undergoing laparoscopic colorectal resection within an established ERAS programme. Standardized end-expiratory breath sampling was performed on the morning of surgery and on the first three postoperative mornings. The concentrations of VCs commonly found in intestinal gas were analysed using selected ion flow tube mass spectrometry and GastroCH4 ECK®. Feasibility data, bowel preparation, postoperative oral intake, POI and 30-day morbidity were recorded. RESULTS: Of the 75 potentially eligible patients, 58 (77%) agreed to participate. Per-protocol breath sampling was successfully completed in 94%. There were no analytical failures. Baseline and postoperative concentrations of VCs were broadly comparable and were not altered by bowel preparation or postoperative oral intake. POI developed in 14 (29%) patients. Preoperative ammonia concentration was higher in patients who developed POI [830 parts per billion (ppb) vs 510 ppb, P = 0.027]. There was an increase in the concentration of acetic acid detected on day 2 in patients who developed POI (99 ppb vs 171 ppb, P = 0.021). CONCLUSION: Repeated VC breath sampling and analysis is feasible in the perioperative setting. An elevated ammonia concentration on the morning of surgery may be a potential predictor of POI.

Monitoring Fatty Liver Disease with MRI Following Bariatric Surgery: A Prospective, Dual-Center Study.

Purpose To longitudinally monitor liver fat before and after bariatric surgery by using quantitative chemical shift-encoded (CSE) MRI and to compare with changes in body mass index (BMI), weight, and waist circumference (WC). Materials and Methods For this prospective study, which was approved by the internal review board, a total of 126 participants with obesity who were undergoing evaluation for bariatric surgery with preoperative very low calorie diet (VLCD) were recruited from June 27, 2010, through May 5, 2015. Written informed consent was obtained from all participants. Participants underwent CSE MRI measuring liver proton density fat fraction (PDFF) before VLCD (2-3 weeks before surgery), after VLCD (1-3 days before surgery), and 1, 3, and 6-10 months following surgery. Linear regression was used to estimate rates of change of PDFF (ΔPDFF) and body anthropometrics. Initial PDFF (PDFF0), initial anthropometrics, and anthropometric rates of change were evaluated as predictors of ΔPDFF. Mixed-effects regression was used to estimate time to normalization of PDFF. Results Fifty participants (mean age, 51.0 years; age range, 27-70 years), including 43 women (mean age, 50.8 years; age range, 27-70 years) and seven men (mean age, 51.7 years; age range, 36-62 years), with mean PDFF0 ± standard deviation of 18.1% ± 8.6 and mean BMI0 of 44.9 kg/m2 ± 6.5 completed the study. By 6-10 months following surgery, mean PDFF decreased to 4.9% ± 3.4 and mean BMI decreased to 34.5 kg/m2 ± 5.4. Mean estimated time to PDFF normalization was 22.5 weeks ± 11.5. PDFF0 was the only strong predictor for both ΔPDFF and time to PDFF normalization. No body anthropometric correlated with either outcome. Conclusion Average liver proton density fat fraction (PDFF) decreased to normal (< 5%) by 6-10 months following surgery, with mean time to normalization of approximately 5 months. Initial PDFF was a strong predictor of both rate of change of PDFF and time to normalization. Body anthropometrics did not predict either outcome. Online supplemental material is available for this article. © RSNA, 2018.

Choosing Wisely in Critical Care: Results of a National Survey From the Critical Care Societies Collaborative.

OBJECTIVES: Over-utilization of tests, treatments, and procedures is common for hospitalized patients in ICU settings. American Board of Internal Medicine Foundation's Choosing Wisely campaign tasked professional societies to identify sources of overuse in specialty care practice. The purpose of this study was to assess how critical care clinicians were implementing the Critical Care Societies Collaborative Choosing Wisely recommendations in clinical practice. DESIGN: Descriptive survey methodology with use of Research Electronic Data Capture (https://projectredcap.org/) sent via email newsletter blast or to individual emails of the 150,000 total members of the organizations. SETTING: National survey. SUBJECTS: ICU physicians, nurses, advanced practice providers including nurse practitioners and physician assistants, and pharmacist members of four national critical care societies in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A six-question survey assessed what Choosing Wisely recommendations had been implemented in ICU settings and if the impact was assessed. A total of 2,520 responses were received from clinicians: nurses (61%; n = 1538), physicians (25.9%; n = 647), advanced practice providers (10.5%; n = 263), and pharmacists (2.1%; n = 52), reflecting a 1.6% response rate of the total membership of 150,000 clinicians. Overall, 1,273 respondents (50.6%) reported they were familiar with the Choosing Wisely campaign. Respondents reported that Choosing Wisely recommendations had been integrated in a number of ways including being implemented in clinical care (n = 817; 72.9%), through development of a specific clinical protocol or institutional guideline (n = 736; 65.7%), through development of electronic medical record orders (n = 626; 55.8%), or with integration of longitudinal tracking using an electronic dashboard (n = 213; 19.0%). Some respondents identified that a specific quality improvement initiative was developed related to the Choosing Wisely recommendations (n = 468; 41.7%), or that a research initiative had been conducted (n = 156; 13.9%). CONCLUSIONS: The results provide information on the application of the Choosing Wisely recommendations to clinical practice from a small sample of critical care clinicians. However, as only half of the respondents report implementation, additional strategies are needed to promote the Choosing Wisely recommendations to make impactful change to improve care in ICU settings.

Supply Chain Delays in Antimicrobial Administration After the Initial Clinician Order and Mortality in Patients With Sepsis.

OBJECTIVES: There is mounting evidence that delays in appropriate antimicrobial administration are responsible for preventable deaths in patients with sepsis. Herein, we examine the association between potentially modifiable antimicrobial administration delays, measured by the time from the first order to the first administration (antimicrobial lead time), and death among people who present with new onset of sepsis. DESIGN: Observational cohort and case-control study. SETTING: The emergency department of an academic, tertiary referral center during a 3.5-year period. PATIENTS: Adult patients with new onset of sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 4,429 consecutive patients who presented to the emergency department with a new diagnosis of sepsis. We defined 0-1 hour as the gold standard antimicrobial lead time for comparison. Fifty percent of patients had an antimicrobial lead time of more than 1.3 hours. For an antimicrobial lead time of 1-2 hours, the adjusted odds ratio of death at 28 days was 1.28 (95% CI, 1.07-1.54; p = 0.007); for an antimicrobial lead time of 2-3 hours was 1.07 (95% CI, 0.85-1.36; p = 0.6); for an antimicrobial lead time of 3-6 hours was 1.57 (95% CI, 1.26-1.95; p < 0.001); for an antimicrobial lead time of 6-12 hours was 1.36 (95% CI, 0.99-1.86; p = 0.06); and for an antimicrobial lead time of more than 12 hours was 1.85 (95% CI, 1.29-2.65; p = 0.001). CONCLUSIONS: Delays in the first antimicrobial execution, after the initial clinician assessment and first antimicrobial order, are frequent and detrimental. Biases inherent to the retrospective nature of the study apply. Known biologic mechanisms support these findings, which also demonstrate a dose-response effect. In contrast to the elusive nature of sepsis onset and sepsis onset recognition, antimicrobial lead time is an objective, measurable, and modifiable process.

The Surgical Techniques and Outcomes of Secondary Phalloplasty After Metoidioplasty in Transgender Men: An International, Multi-Center Case Series.

INTRODUCTION: Some transgender men express the wish to undergo genital gender-affirming surgery. Metoidioplasty and phalloplasty are procedures that are performed to construct a neophallus. Genital gender-affirming surgery contributes to physical well-being, but dissatisfaction with the surgical results may occur. Disadvantages of metoidioplasty are the relatively small neophallus, the inability to have penetrative sex, and often difficulty with voiding while standing. Therefore, some transgender men opt to undergo a secondary phalloplasty after metoidioplasty. Literature on secondary phalloplasty is scarce. AIM: Explore the reasons for secondary phalloplasty, describe the surgical techniques, and report on the clinical outcomes. METHODS: Transgender men who underwent secondary phalloplasty after metoidioplasty were retrospectively identified in 8 gender surgery clinics (Amsterdam, Belgrade, Bordeaux, Austin, Ghent, Helsinki, Miami, and Montreal). Preoperative consultation, patient motivation for secondary phalloplasty, surgical technique, perioperative characteristics, complications, and clinical outcomes were recorded. MAIN OUTCOME MEASURE: The main outcome measures were surgical techniques, patient motivation, and outcomes of secondary phalloplasty after metoidioplasty in transgender men. RESULTS: Eighty-three patients were identified. The median follow-up was 7.5 years (range 0.8-39). Indicated reasons to undergo secondary phalloplasty were to have a larger phallus (n = 32; 38.6%), to be able to have penetrative sexual intercourse (n = 25; 30.1%), have had metoidioplasty performed as a first step toward phalloplasty (n = 17; 20.5%), and to void while standing (n = 15; 18.1%). Each center had preferential techniques for phalloplasty. A wide variety of surgical techniques were used to perform secondary phalloplasty. Intraoperative complications (revision of microvascular anastomosis) occurred in 3 patients (5.5%) undergoing free flap phalloplasty. Total flap failure occurred in 1 patient (1.2%). Urethral fistulas occurred in 23 patients (30.3%) and strictures in 27 patients (35.6%). CLINICAL IMPLICATIONS: A secondary phalloplasty is a suitable option for patients who previously underwent metoidioplasty. STRENGTHS & LIMITATIONS: This is the first study to report on secondary phalloplasty in collaboration with 8 specialized gender clinics. The main limitation was the retrospective design. CONCLUSION: In high-volume centers specialized in gender affirming surgery, a secondary phalloplasty in transgender men can be performed after metoidioplasty with complication rates similar to primary phalloplasty. Al-Tamimi M, Pigot GL, van der Sluis WB, et al. The Surgical Techniques and Outcomes of Secondary Phalloplasty After Metoidioplasty in Transgender Men: An International, Multi-Center Case Series. J Sex Med 2019;16:1849-1859.

2D versus 3D laparoscopic total mesorectal excision: a developmental multicentre randomised controlled trial.

AIMS: The role of laparoscopy in rectal cancer has been questioned. 3D laparoscopic systems are suggested to aid optimal surgical performance but have not been evaluated in advanced procedures. We hypothesised that stereoscopic imaging could improve the performance of laparoscopic total mesorectal excision (TME). METHODS: A multicentre developmental randomised controlled trial comparing 2D and 3D laparoscopic TME was performed (ISRCTN59485808). Trial surgeons were colorectal consultants that had completed their TME proficiency curve and underwent stereoscopic visual testing. Patients requiring elective laparoscopic TME with curative intent were centrally randomised (1:1) to 2D or 3D using Karl Storz IMAGE1 S D3-Link™ and 10-mm TIPCAM®1S 3D passive polarising laparoscopic systems. Outcomes were enacted adverse events as assessed by the observational clinical human reliability analysis technique, intraoperative data, 30-day patient outcomes, histopathological specimen assessment and surgeon cognitive load. RESULTS: 88 patients were included. There were no differences in patient or tumour demographics, surgeon stereopsis, case difficulty, cognitive load, operative time, blood loss or conversion between the trial arms. 1377 intraoperative adverse events were identified (median 18 per case, IQR 14-21, range 2-49) with no differences seen between the 2D and 3D arms (18 (95% CI 17-21) vs. 17 (95% CI 16-19), p = 0.437). 3D laparoscopy had non-significantly higher mesorectal fascial plane resections (94 vs. 77%, p = 0.059; OR 0.23 (95% CI 0.05-1.16)) but equal lymph node yield and circumferential margin distance and involvement. 30-day morbidity, anastomotic leak, re-operation, length of stay and readmission rates were equal between the 2D and 3D arms. CONCLUSION: Feasibility of performing multicentre 3D laparoscopic multicentre trials of specialist performed complex procedures is shown. 3D imaging did not alter the number of intraoperative adverse events; however, a potential improvement in mesorectal specimen quality was observed and should form the focus of future 3D laparoscopic TME trials.

Charles Darwin, Richard Owen, and Natural Selection: A Question of Priority.

No single author presented Darwin with a more difficult question about his priority in discovering natural selection than the British comparative anatomist and paleontologist Richard Owen. Owen was arguably the most influential biologist in Great Britain in Darwin's time. Darwin wanted his approbation for what he believed to be his own theory of natural selection. Unfortunately for Darwin, when Owen first commented in publication about Darwin's theory of descent he was openly hostile (Edinb. Rev. vol. 111, Article VIII, 1860, pp. 487-533, anonymous). Darwin was taken off-guard. In private meetings and correspondence prior to 1860 Owen had been nothing but polite and friendly, even helping Darwin in cataloguing and analyzing Darwin's zoological specimens from the Beagle voyage. Every early indication predicted a life-long friendship and collaboration. But that was not to be. Owen followed his slashing review with a mounting campaign in the 1860s to denounce and discredit both Darwin and his small but ascendant circle of friends and supporters. But that was not enough for Owen. Starting in 1866, perhaps by now realizing Darwin had landed the big fish, Owen launched a new campaign, to claim the discovery of "Darwin's theory" for himself. Darwin naturally fought back, mainly in the "Historical Sketch" that he prefaced to Origin starting in 1861. But when we peel back the layers of personal animus and escalating vituperation we discover in fact their quarrel was generated more by mutual misunderstanding than scientific disagreement. The battle ended only when Darwin finally penetrated to the crux of the matter and put an end to the rivalry in 1872, in the final version of the Sketch.

Noise properties of proton density fat fraction estimated using chemical shift-encoded MRI.

PURPOSE: The purpose of this work is to characterize the noise distribution of proton density fat fraction (PDFF) measured using chemical shift-encoded MRI, and to provide alternative strategies to reduce bias in PDFF estimation. THEORY: We derived the probability density function for PDFF estimated using chemical shift-encoded MRI, and found it to exhibit an asymmetric noise distribution that contributes to signal-to-noise-ratio dependent bias. METHODS: To study PDFF noise bias, we performed (at 1.5 T) numerical simulations, phantom acquisitions, and a retrospective in vivo experiment. In each experiment, we compared the performance of three statistics (mean, median, and maximum likelihood estimator) in estimating the PDFF in a region of interest. RESULTS: We demonstrated the presence of the asymmetric noise distribution in simulations, phantoms, and in vivo. In each experiment we demonstrated that both the median and proposed maximum likelihood estimator statistics outperformed the mean statistic in mitigating noise-related bias for low signal-to-noise-ratio acquisitions. CONCLUSIONS: Characterization of the noise distribution of PDFF estimated using chemical shift-encoded MRI enabled new strategies based on median and maximum likelihood estimator statistics to mitigate noise-related bias for accurate PDFF measurement from a region of interest. Such strategies are important for quantitative chemical shift-encoded MRI applications that typically operate in low signal-to-noise-ratio regimes. Magn Reson Med 80:685-695, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Fully phase-encoded MRI near metallic implants using ultrashort echo times and broadband excitation.

PURPOSE: To develop a fully phase-encoded MRI method for distortion-free imaging near metallic implants, in clinically feasible acquisition times. THEORY AND METHODS: An accelerated 3D fully phase-encoded acquisition with broadband excitation and ultrashort echo times is presented, which uses a broadband radiofrequency pulse to excite the entire off-resonance induced by the metallic implant. Furthermore, fully phase-encoded imaging is used to prevent distortions caused by frequency encoding, and to obtain ultrashort echo times for rapidly decaying signal. RESULTS: Phantom and in vivo acquisitions were used to describe the relationship among excitation bandwidth, signal loss near metallic implants, and T1 weighting. Shorter radiofrequency pulses captured signal closer to the implant by improving spectral coverage and allowing shorter echo times, whereas longer pulses improved T1 weighting through larger maximum attainable flip angles. Comparisons of fully phase-encoded acquisition with broadband excitation and ultrashort echo times to T1 -weighted multi-acquisition with variable resonance image combination selective were performed in phantoms and subjects with metallic knee and hip prostheses. These acquisitions had similar contrast and acquisition efficiency. CONCLUSIONS: Accelerated fully phase-encoded acquisitions with ultrashort echo times and broadband excitation can generate distortion free images near metallic implants in clinically feasible acquisition times. Magn Reson Med 79:2156-2163, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Outcomes of Single Stage Phalloplasty by Pedicled Anterolateral Thigh Flap versus Radial Forearm Free Flap in Gender Confirming Surgery.

PURPOSE: Phalloplasty is a critical step in female-to-male (transmale) gender confirming genital surgery. We examined outcomes between transmales who underwent phalloplasty with vaginectomy and full-length urethroplasty using the anterolateral thigh pedicled flap or the radial forearm free flap. MATERIALS AND METHODS: We performed a single center, retrospective study of patients who underwent phalloplasty with vaginectomy and full-length urethroplasty using an anterolateral thigh pedicled flap or a radial forearm free flap from April 2013 to July 2016. All patients had at least 6 months of followup. Urethral and nonurethral complications were recorded. Complication rates were assessed using the OR of the anterolateral thigh pedicled flap and the radial forearm free flap groups. RESULTS: Of the 213 patients 149 and 64 underwent radial forearm free flap and anterolateral thigh pedicled flap phalloplasty, respectively. Patients with a radial forearm free flap had a significantly higher body mass index than those with an anterolateral thigh pedicled flap. The overall urethral complication rate for radial forearm free flap and anterolateral thigh pedicled flap phalloplasty was 31.5% and 32.8%, and the rate of partial or total neophallus loss was 3.4% and 7.8%, respectively. Patients in the pedicled flap cohort experienced significantly greater odds of urethral fistula (OR 2.50, p = 0.024), nonurethral complications (OR 2.38, p = 0.027) and phallus wound dehiscence (OR 5.03, p = 0.026). CONCLUSIONS: Anterolateral thigh pedicled flap phalloplasty was associated with overall greater odds of urethral and other complications at 6 months of followup. Our findings can help guide surgical decision making when selecting a flap for phalloplasty.

Time from colorectal cancer diagnosis to laparoscopic curative surgery-is there a safe window for prehabilitation?

BACKGROUND: There is a growing interest in the adoption of formal prehabilitation programmes prior to elective surgery but regulatory targets mandate prompt treatment following cancer diagnosis. We aimed to investigate if time from diagnosis to surgery is linked to short- and long-term outcomes. METHODS: An exploratory analysis was performed utilising a dedicated, prospectively populated database. Inclusion criteria were biopsy-proven colorectal adenocarcinoma undergoing elective laparoscopic surgery with curative intent. Demographics, date of diagnosis and surgery was captured with patients dichotomised using 4-, 8- and 12-week time points. All patients were followed in a standardised pathway for 5 years. Overall survival was assessed with the Kaplan-Meier log-rank method. RESULTS: Six hundred sixty-eight consecutive patients met inclusion criteria. Mean time from diagnosis to surgery was 53 days (95% CI 48.3-57.8). Identified risk factors for longer time to surgery were males (OR 1.92 [1.2-3.1], p = 0.008), age ≤ 65 (OR 1.9 [1.2-3], p = 0.01), higher ASA scores (p = 0.01) stoma formation (OR 6.9 [4.1-11], p < 0.001) and neoadjuvant treatment (OR 5.06 [3.1-8.3], p < 0.001). There was no association between time to surgery and BMI (p = 0.36), conversion (16.3%, p = 0.5), length of stay (p = 0.33) and readmission or reoperation (p = 0.3). No differences in five-year survival were seen in those operated within 4, 8 and 12 weeks (p = 0.397, p = 0.962 and p = 0.611, respectively). Multivariate analysis showed time from diagnosis to surgery was not associated with five-year overall survival (HR 0.99, p = 0.52). CONCLUSION: Time from colorectal cancer diagnosis to curative laparoscopic surgery did not impact on overall survival. This finding may allow preoperative pathway alteration without compromising safety.