Current Treatment Options: Uterine Sarcoma.

OPINION STATEMENT: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.

Using Porous Liquids to Perform Liquid-Liquid Separations.

Porous liquids (PLs) are a new type of fluid sorbent investigated mainly for the separation of gas mixtures. Here, we explore their application to the separation of miscible liquids, using MEG/water (MEG=monoethylene glycol) and EtOH/water as proof-of-principle. Recovery of used MEG is industrially important but its extraction into conventional solvents from water is difficult. PLs ZIF-8@PDMS (PL1, PDMS=polydimethylsilicone) or ZIF-8@sesame oil (PL2) each consisting of 25 wt % of the hydrophobic microporous material ZIF-8 dispersed in PDMS or sesame oil respectively, were formulated and found to be exceedingly physically stable to sedimentation. A 5 nm PEEK membrane was used to provide a permeable barrier between the PL and the alcohol/water phase. MEG was selectively extracted through the membrane from approximately 50 : 50 wt % MEG/water mixtures into the PL phase and this procedure could be applied repeatedly. It was effective for MEG/water mixtures as dilute as 3 : 97 wt %. The PL could also be regenerated (80 °C at 0.01 bar) and re-used, suggesting its potential for continuous, cyclic extraction. Furthermore, PL3 (silicalite-1@PDMS) was effective in selective alcohol extraction from beverages. It shows potential for lowering the alcohol concentration in gin or wine due to its excellent chemical stability and nontoxicity. Overall, we show that the enhanced adsorption properties of PLs due the presence of empty pores, which provides unusually high gas solubilities, also makes them, in principle, applicable to liquid-liquid separations.

Adverse Reactions Associated with Intravenous Immunoglobulin Administration in the Treatment of Neurological Disorders: A Systematic Review.

Intravenous immunoglobulin (IVIg), which is used to treat multiple neurological conditions, may be associated with serious adverse reactions. The individual neurological disease characteristics associated with adverse reactions, along with strategies to prevent and treat adverse reactions, are uncertain. A systematic review was conducted of the databases PubMed, Embase, and Cochrane Library to summarise studies that report adverse reactions of IVIg therapy in patients with neurological disease. There were 65 studies included in the review. The reported rates of adverse reactions vary widely, but the best evidence suggests rates between 25 and 34% per patient. Common adverse reactions include headache and laboratory abnormalities. Less common but serious adverse reactions included thromboembolic complications and anaphylaxis. Overall, there is a lack of high-quality comparative data to definitively determine if any specific neurological indications are associated with a higher risk of adverse reactions. However, individual neurological disease characteristics possibly associated with an increased likelihood of adverse reactions include limited mobility (as in certain neuromuscular conditions), paraproteinaemia (as in certain peripheral neuropathies), and cardiomyopathy (as in certain myopathies). There is limited evidence to support the effectiveness of prevention and treatment strategies, which may include modification to dose, reduced infusion rate, and premedication. Further studies regarding methods to prevent and treat IVIg-ARs in neurology patients are required.

The Role of Augmented Reality in Surgical Training: A Systematic Review.

This review aims to provide an update on the role of augmented reality (AR) in surgical training and investigate whether the use of AR improves performance measures compared to traditional approaches in surgical trainees.PUBMED, EMBASE, Google Scholar, Cochrane Library, British Library and Science Direct were searched following PRIMSA guidelines. All English language original studies pertaining to AR in surgical training were eligible for inclusion. Qualitative analysis was performed and results were categorised according to simulator models, subsequently being evaluated using Messick's framework for validity and McGaghie's translational outcomes for simulation-based learning.Of the 1132 results retrieved, 45 were included in the study. 29 platforms were identified, with the highest 'level of effectiveness' recorded as 3. In terms of validity parameters, 10 AR models received a strong 'content validity' score of 2.15 models had a 'response processes' score ≥ 1. 'Internal structure' and 'consequences' were largely not discussed. 'Relations to other variables' was the best assessed criterion, with 9 platforms achieving a high score of 2. Overall, the Microsoft HoloLens received the highest level of recommendation for both validity and level of effectiveness.Augmented reality in surgical education is feasible and effective as an adjunct to traditional training. The Microsoft HoloLens has shown the most promising results across all parameters and produced improved performance measures in surgical trainees. In terms of the other simulator models, further research is required with stronger study designs, in order to validate the use of AR in surgical training.

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study.

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research.

Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis).

Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied genome-wide association study, comparative population genomics and biological experiments to show that the 2,809-bp-long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3' truncated and containing only 5' UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5' UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.

The changing state of porous materials.

Porous materials contain regions of empty space into which guest molecules can be selectively adsorbed and sometimes chemically transformed. This has made them useful in both industrial and domestic applications, ranging from gas separation, energy storage and ion exchange to heterogeneous catalysis and green chemistry. Porous materials are often ordered (crystalline) solids. Order-or uniformity-is frequently held to be advantageous, or even pivotal, to our ability to engineer useful properties in a rational way. Here we highlight the growing evidence that topological disorder can be useful in creating alternative properties in porous materials. In particular, we highlight here several concepts for the creation of novel porous liquids, rationalize routes to porous glasses and provide perspectives on applications for porous liquids and glasses.

Towards MOFs' mass market adoption: MOF Technologies' efficient and versatile one-step extrusion of shaped MOFs directly from raw materials.

Metal Organic Frameworks (MOFs) offer unparalleled physical and sorption properties due to their chemical tunability and unmatched porosity. MOFs are consequently envisaged to play a key role in commercial gas storage and separation applications. However, it is essential to tackle their current market entry barriers, if mainstream adoption is to be realised. MOF Technologies is a pioneer in MOF commercialisation and has developed innovative solutions with unprecedented efficiency to bring these materials to market. A continuous, versatile and sustainable one-step production method of MOFs in shaped form is demonstrated for the first time. Its advantages for large-scale production and mass customisation are exemplified and validated with performance evaluation under realistic operating conditions.

Liquids with permanent porosity.

Porous solids such as zeolites and metal-organic frameworks are useful in molecular separation and in catalysis, but their solid nature can impose limitations. For example, liquid solvents, rather than porous solids, are the most mature technology for post-combustion capture of carbon dioxide because liquid circulation systems are more easily retrofitted to existing plants. Solid porous adsorbents offer major benefits, such as lower energy penalties in adsorption-desorption cycles, but they are difficult to implement in conventional flow processes. Materials that combine the properties of fluidity and permanent porosity could therefore offer technological advantages, but permanent porosity is not associated with conventional liquids. Here we report free-flowing liquids whose bulk properties are determined by their permanent porosity. To achieve this, we designed cage molecules that provide a well-defined pore space and that are highly soluble in solvents whose molecules are too large to enter the pores. The concentration of unoccupied cages can thus be around 500 times greater than in other molecular solutions that contain cavities, resulting in a marked change in bulk properties, such as an eightfold increase in the solubility of methane gas. Our results provide the basis for development of a new class of functional porous materials for chemical processes, and we present a one-step, multigram scale-up route for highly soluble 'scrambled' porous cages prepared from a mixture of commercially available reagents. The unifying design principle for these materials is the avoidance of functional groups that can penetrate into the molecular cage cavities.

Treatment of vulvar and vaginal dysplasia: plasma energy ablation versus carbon dioxide laser ablation.

OBJECTIVE: Plasma energy ablation vaporizes tissues similar to carbon dioxide laser ablation, but is not hindered by the unique hazards and regulation of laser technology. We aimed to evaluate the complication rate and effectiveness of plasma versus laser ablation in the treatment of vulvovaginal high-grade squamous intra-epithelial lesions (HSIL). METHODS: We performed a retrospective cohort study of women treated with plasma or carbon dioxide laser ablation for histologically proven HSIL of the vulva or vagina from January 2014 to October 2019 at a single institution. Demographic factors, surgical characteristics, and complications were compared by ablation type using Fisher's exact tests. Recurrence-free survival was evaluated by ablation type using Kaplan-Meier curves, weighted log-rank tests, and Cox proportional hazards ratio estimates. RESULTS: Forty-two women were included; 50% underwent plasma and 50% underwent carbon dioxide laser ablation. Demographic factors were similar between the groups. 50% (n=21) were immunosuppressed, 45.2% (n=19) had prior vulvovaginal HSIL treatment, and 35.7% (n=15) were current smokers. Most women (n=25, 59.5%) were treated for vulvar HSIL, 38.1% (n=16) for vaginal HSIL. Complication rates did not differ by treatment: 9.5% (n=2) for laser ablation versus 4.8% (n=1) for plasma ablation (p=1.0). Over a median follow-up time of 29.3 months (IQR 11.0-45.0 months), recurrence rates were similar: 28.6% in the laser ablation group versus 33.3% in the plasma ablation group (weighted log rank p=0.43; 24-month HR 0.54, 95% CI 0.15 to 2.01). CONCLUSION: Plasma energy ablation of vulvovaginal HSIL has similar complication rates and recurrence risk to carbon dioxide laser ablation. This technique could be considered as an alternative treatment modality for vulvovaginal HSIL and warrants further investigation.

Does the external remote controller's reading correspond to the actual lengthening in magnetic-controlled growing rods?

PURPOSE: Magnetic-controlled growing rods (MCGRs) are now routinely used in many centres to treat early-onset scoliosis (EOS). MCGR lengthening is done non-invasively by the external remote controller (ERC). Our experience suggests that there may be a discrepancy between the reported rod lengthening on the ERC and the actual rod lengthening. The aim of this study was to investigate this discrepancy. METHODS: This was a prospective series. Eleven patients who were already undergoing treatment for EOS using MCGRs were included in this study. RESULTS: One hundred and ninety-two sets of ultrasound readings were obtained (96 episodes of rod lengthening on dual-rod constructs) and compared to their ERC readings. Only 15/192 (7.8%) readings were accurate; 27 readings (14.9%) were false positive; and 8 readings (4.2%) were an underestimation while 142 readings (74.0%) were an overestimation by the ERC. Average over-reporting by the ERC was 5.31 times of the actual/ultrasound reading. When comparing interval radiographs with lengthening obtained on ultrasound, there was a discrepancy with an average overestimation of 1.35 times with ultrasound in our series. There was a significant difference between ERC and USS (p = 0.01) and ERC and XR (p = 0.001). However, there was no significant difference between USS and XR (p > 0.99). CONCLUSION: The reading on the ERC does not equate to the actual rod lengthening. The authors would recommend that clinicians using the MCGR for the treatment of early-onset scoliosis include pre- and post-extension imaging (radiographs or ultrasound) to confirm extension lengths at each outpatient extension. In centres with ultrasound facilities, we would suggest that patients should have ultrasound to monitor each lengthening after distraction but also 6-month radiographs. These slides can be retrieved under Electronic Supplementary Material.

Iterative approach to journal club.

To identify, evaluate and refine a journal club (JC) format that increases faculty and resident engagement. An initial needs assessment followed by a trial of three JC formats: traditional single presenter, debate style and facilitated small group discussion was piloted over 6 months. Anonymous feedback was collected. The facilitated small group format was chosen. Narrative and quantitative feedback were collected from residents and faculty at 6-month intervals for the next 24 months. Changes to the format were made using feedback. Fourteen residents (n=20, 70%) and 10 faculty (n=20, 50%) completed baseline surveys. We initially observed low resident (8/14, 57%) interest in JCs. Additionally, 9/14 (64%) of residents and 1/15 (7%) of faculty reported low confidence presenting articles publicly. After implementation of the new JC format, resident reported enjoyment, on a scale of 1-5, improved from 3.6 to 4.4 (p<0.01). We observed improvement in resident confidence in the ability to critique a paper (2.7 to 4.1, p<0.01) and in confidence speaking in front of both peers (3.8 to 4.6, p<0.01) and faculty (3.0 to 3.8, p=0.04). Faculty confidence with literature critique decreased (from 4.2 to 3.8), but enjoyment remained stable (4.3 to 4.2). A facilitated small group JC format was preferred in our programme. We observed measurable improvements in both resident interest and confidence, as well as sustained faculty interest in JCs. We fostered an environment of inquiry and identified areas of continued professional development.

Greener Dye Synthesis: Continuous, Solvent-Free Synthesis of Commodity Perylene Diimides by Twin-Screw Extrusion.

A continuous, scalable, and solvent-free method for the synthesis of various naphthalic imides and perylene diimides (PDIs) using twin-screw extrusion (TSE) is reported. Using TSE, naphthalic imides were obtained quantitatively without the need for excess amine reactant or product purification. With good functional-group tolerance, alkyl and benzyl amine derived PDIs (incl. commercial dyes) were obtained in 50-99 % yield. Use of K2 CO3 , enabled synthesis of more difficult aniline-derived PDIs. Furthermore, an automated continuous TSE process for Pigments Black 31 and 32 is demonstrated, with a throughput rate of about 1500 g day-1 , corresponding to a space time yield of about 30×103  kg m-3  day-1 , which is 1-2 orders of magnitude greater than for solvent-based batch methods. These methods provide substantial waste reductions and improved efficiency compared to conventional solvent-based methods.

Phenomenological Inferences on the Kinetics of a Mechanically Activated Knoevenagel Condensation: Understanding the "Snowball" Kinetic Effect in Ball Milling.

We focus on understanding the kinetics of a mechanically activated Knoevenagel condensation conducted in a ball mill, that is characterized by sigmoidal kinetics and the formation of a rubber-like cohesive intermediate state coating the milling ball. The previously described experimental findings are explained using a phenomenological kinetic model. It is assumed that reactants transform into products already at the very first collision of the ball with the wall of the jar. The portion of reactants that are transformed into products during each oscillation is taken to be a fraction of the amount of material that is trapped between the ball and the wall of the jar. This quantity is greater when the reaction mixture transforms from its initial powder form to the rubber-like cohesive coating on the ball. Further, the amount of reactants processed in each collision varies proportionally with the total area of the layer coating the ball. The total area of this coating layer is predicted to vary with the third power of time, thus accounting for the observed dramatic increase of the reaction rate. Supporting experiments, performed using a polyvinyl acetate adhesive as a nonreactive but cohesive material, confirm that the coating around the ball grows with the third power of time.

Bilateral breast reconstruction with deep inferior epigastric perforator flaps in slim patients.

BACKGROUND: Slim women are not always considered candidates for bilateral autologous breast reconstruction. The study aims to assess the volume considerations and complications of deep inferior epigastric perforator (DIEP) flap in bilateral breast reconstruction among slim patients. METHODS: All patients undergoing bilateral DIEP breast reconstruction at the Royal Marsden Hospital, London, September 2007-March 2015, were reviewed. Flap weight was compared to mastectomy weight (weight ratio) and complications were recorded. Subgroup analyses according to Body Mass Index (BMI) were performed. RESULTS: One-hundred seventy patients (340 flaps) were included. There were 42 in the slim-group (BMI <25) (84 flaps), 70 in the traditional (BMI = 25.0-29.9) (140 flaps), and 58 in the obese (BMI >30) (116 flaps). There were no significant differences in reconstruction weight ratio between the slim and the traditional groups (1.04 ± 0.31 versus 0.95 ± 0.38, p = .267). When comparing the slim to obese group the ratio was lower for the obese group, inferring that a larger reconstruction was performed (p = .016). Complications was less frequent in the slim group compared to the traditional and the obese groups (31% compared to 50% and to 53% (p = .060 and p = .021, respectively). Donor-site specific complications did not differ between groups (29% 26% and 29%; p = .823 and .830, respectively). CONCLUSION: The DIEP flaps may be a safe option for bilateral breast reconstruction among patients with BMI <25 without sacrifice in volume or increase in donor-site complications; low BMI does not in itself contraindicate bilateral DIEP breast reconstruction.