Intensive hands-on microsurgery course provides a solid foundation for performing clinical microvascular surgery.

PURPOSE: Microvascular surgery requires highly specialized and individualized training; most surgical residency training programs are not equipped with microsurgery teaching expertise and/or facilities. The aim of this manuscript was to describe the methodology and clinical effectiveness of an international microsurgery course, currently taught year-round in eight countries. METHODS: In the 5-day microsurgery course trainees perform arterial and venous end-to-end, end-to-side, one-way-up, and continuous suture anastomoses and vein graft techniques in live animals, supported by video demonstrations and hands-on guidance by a full-time instructor. To assess and monitor each trainee's progress, the course's effectiveness is evaluated using "in-course" evaluations, and participant satisfaction and clinical relevance are assessed using a "post-course" survey. RESULTS: Between 2007 and 2017, more than 600 trainees participated in the microsurgery course. "In-course" evaluations of patency rates revealed 80.3% (arterial) and 39% (venous) performed in end-to-end, 82.7% in end-to-side, 72.6% in continuous suture, and 89.5% (arterial) and 62.5% (venous) one-way-up anastomoses, and 58.1% in vein graft technique. "Post-course" survey results indicated that participants considered the most important components of the microcourse to be "practicing on live animals", followed by "the presence of a full-time instructor". In addition, almost all respondents indicated that they were more confident performing clinical microsurgery cases after completing the course. CONCLUSIONS: Microvascular surgery requires highly specialized and individualized training to achieve the competences required to perform and master the delicate fine motor skills necessary to successfully handle and anastomose very small and delicate microvascular structures. The ever-expanding clinical applications of microvascular procedures has led to an increased demand for training opportunities. By teaching time-tested basic motor skills that form the foundation of microsurgical technique this international microsurgery-teaching course is helping to meet this demand.

Randomized Mechlorethamine/Chlormethine Induced Dermatitis Assessment Study (MIDAS) Establishes Benefit of Topical Triamcinolone 0.1% Ointment Cotreatment in Mycosis Fungoides.

INTRODUCTION: Treatment of early-stage mycosis fungoides (MF) requires safe, skin-directed therapies. Medication side effects can lead to underutilization of effective therapies. The objective of this study was to assess the use of topical triamcinolone 0.1% ointment as a means of reducing contact dermatitis associated with topical mechlorethamine/chlormethine gel for the treatment of MF. METHODS: This prospective, randomized, open-label study evaluated 28 adults with mycosis fungoides who were eligible for treatment with topical mechlorethamine/chlormethine gel from December 17, 2017 to December 23, 2020. Patients were treated for 4 months with clinical follow-up through 12 months. Patients had half of their lesions also treated with topical triamcinolone 0.1% ointment (while the other half were treated with mechlorethamine/chlormethine alone). The study was self-controlled with separate lesions in the same patient receiving each treatment arm. Treatment arms were determined by the flip of a coin. RESULTS: Twenty-eight patients enrolled (17 men (61%) and 11 women (39%)). Demographics included 25 White, 2 African Americans, and 1 Asian patient. Twenty-five completed the 12-month follow-up. Triamcinolone 0.1% ointment led to increased tolerability of mechlorethamine/chlormethine gel but did not change the efficacy of mechlorethamine/chlormethine. There was a statistically significant 50% decrease in dermatitis (SCORD score) at month 2 in the triamcinolone-treated arm. CONCLUSIONS: Topical triamcinolone ointment is a helpful adjuvant therapy when treating patients with topical mechlorethamine/chlormethine gel. It diminishes inflammation and does not reduce efficacy. The peak incidence of dermatitis in the study occurred in the second and third months. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03380026.

Levels of Evidence in Plastic and Reconstructive Surgery Research: Have We Improved Over the Past 10 Years?

Levels of evidence (LOE) aid in the critical appraisal of evidence by ranking studies based on limitation of its design. Analyzing LOE provides insight into application of evidence-based medicine. The aim of this study is to determine if the quality of evidence in plastic surgery research has improved over the past 10 years. Systematic review of research published in Plastics and Reconstructive Surgery journal over the years, 10-year period (2008, 2013, 2018), was performed. LOE for each article was determined using the American Society of Plastic Surgeons (ASPS) guidelines. Each level was calculated as percentage of publications per year and compared yearly and between different topics. Eight hundred eighty-four studies were included in the final analysis. The LOE of the research improved over the study period. Level 4 evidence was the most frequent published (50.6%, 447/884), with a decline from 63.2% in 2008 to 41.3% in 2018. Level 1 evidence improved each year and accounted for 2.1% of all research in 2018. Aesthetic surgery was the most frequent published topic with upper limb research demonstrating an 18.5% increase in high-quality evidence over the study period. Increased awareness of evidence-based medicine has improved the quality of plastic surgery research over the past decade. It is vital this continues to provide gold standard patient care.

The Distribution of Road Salt in Private Drinking Water Wells in a Southeastern New York Suburban Township.

We used a GIS analysis of sodium and chloride concentrations in private water wells in a southeastern New York township to describe the pattern of distribution of road salt in aquifers tapped for drinking water. The primary source of road salt was sodium chloride, and sodium and chloride concentrations were significantly correlated ( = 0.80, < 0.01). Chloride concentrations in wells increased as the percentage of impervious surface cover (ISC) within a 250-m radius around wells increased ( = 0.87, < 0.01) and declined with increasing distance to the nearest road ( = 0.76, < 0.01). Wells that were located lower in elevation than the nearest road had higher concentrations of chloride than wells that were higher than the nearest road, but this occurred only when the nearest road was >30 m from the wells ( < 0.01). Chloride concentrations were not affected by well depth or adjacent road type (major or minor roads). Surface geology and hydrologic soil class had significant effects ( < 0.01) on chloride concentrations in wells, with porous surface geology types and well-drained soils having higher concentrations; these effects may be confounded by the fact that ISC was more likely to occur on these permeable surface geology and soil types. Hot and cold spot analysis revealed substantial unevenness in chloride concentrations. Results for sodium were similar to those for chloride. Overall, these results indicate that road salt contamination of groundwater is unevenly distributed and is affected by landscape factors that can be used to guide well testing and best management practices of deicing salt distribution.

Non-progressing cancer patients have persistent B cell responses expressing shared antibody paratopes that target public tumor antigens.

There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility.

ASCOT: Autologous Bone Marrow Stem Cell Use for Osteoarthritis of the Thumb-First Carpometacarpal Joint.

BACKGROUND: The first carpometacarpal joint (CMCJ) in the hand is a commonly affected joint by osteoarthritis. It causes significant thumb base pain, limiting functional capacity. Microfracturing and application of autologous stem cells has been performed on large joints such as the knee but has never been evaluated for use in the smaller joints in the hand. Our aim was to determine the potential benefit of microfracturing and autologous bone marrow stem cells for treatment of osteoarthritis of the first CMCJ in the hand. METHODS: All inclusion criteria were satisfied. Preoperative assessment by the surgeon, physiotherapist, and occupational therapist was performed. The first CMCJ was microfractured and the Bone Marrow Stem Cells were applied directly. Postoperatively, the patients were followed up for 1 year. RESULTS: Fifteen patients met inclusion criteria; however, 2 patients were excluded due to postoperative cellulitis and diagnosis of De Quervain's tenosynovitis. The mean scores of the 13-patient preoperative and 1 year follow-up assessments are visual analog score at rest of 3.23-1.69 (P = 0.0292), visual analog score on activity of 7.92-4.23 (P = 0.0019), range of motion 45.77o-55.15o (P = 0.0195), thumb opposition score 7.62-9.23 (P = 0.0154), Disability of the Arm, Shoulder and Hand score of 51.67-23.08 (P = 0.0065). Strength improved insignificantly from 4.7 kg preoperatively to 5.53 kg at 12 months (P = 0.1257). All patients had a positive Grind test preoperatively and a negative test after 12 months. CONCLUSIONS: This innovative pilot study is a new approach to osteoarthritis of the thumb.

The E. coli molecular phenotype under different growth conditions.

Modern systems biology requires extensive, carefully curated measurements of cellular components in response to different environmental conditions. While high-throughput methods have made transcriptomics and proteomics datasets widely accessible and relatively economical to generate, systematic measurements of both mRNA and protein abundances under a wide range of different conditions are still relatively rare. Here we present a detailed, genome-wide transcriptomics and proteomics dataset of E. coli grown under 34 different conditions. Additionally, we provide measurements of doubling times and in-vivo metabolic fluxes through the central carbon metabolism. We manipulate concentrations of sodium and magnesium in the growth media, and we consider four different carbon sources glucose, gluconate, lactate, and glycerol. Moreover, samples are taken both in exponential and stationary phase, and we include two extensive time-courses, with multiple samples taken between 3 hours and 2 weeks. We find that exponential-phase samples systematically differ from stationary-phase samples, in particular at the level of mRNA. Regulatory responses to different carbon sources or salt stresses are more moderate, but we find numerous differentially expressed genes for growth on gluconate and under salt and magnesium stress. Our data set provides a rich resource for future computational modeling of E. coli gene regulation, transcription, and translation.

Aesthetic surgery training in a changing healthcare environment.

Aesthetic surgery is a rapidly evolving sub-speciality, both technologically and conceptually. It is therefore critical that plastic surgery training coincides with this rapid evolution. Recent fiscal limitations in public health provision and trainee working-time legislation may impact the delivery of high quality aesthetic surgery training. There is an urgent need to address the delivery of aesthetic training in current training paradigms in Ireland and we propose a number of strategies to obliterate the learning curve.

Bayesian second law of thermodynamics.

We derive a generalization of the second law of thermodynamics that uses Bayesian updates to explicitly incorporate the effects of a measurement of a system at some point in its evolution. By allowing an experimenter's knowledge to be updated by the measurement process, this formulation resolves a tension between the fact that the entropy of a statistical system can sometimes fluctuate downward and the information-theoretic idea that knowledge of a stochastically evolving system degrades over time. The Bayesian second law can be written as ΔH(ρ_{m},ρ)+〈Q〉_{F|m}≥0, where ΔH(ρ_{m},ρ) is the change in the cross entropy between the original phase-space probability distribution ρ and the measurement-updated distribution ρ_{m} and 〈Q〉_{F|m} is the expectation value of a generalized heat flow out of the system. We also derive refined versions of the second law that bound the entropy increase from below by a non-negative number, as well as Bayesian versions of integral fluctuation theorems. We demonstrate the formalism using simple analytical and numerical examples.

Trends in the Level of Evidence in Clinical Hand Surgery Research.

BACKGROUND: The application of evidence-based medicine (EBM) to the practice of hand surgery has been limited. Production of high-quality research is an integral component of EBM. With considerable improvements in the quality evidence in both orthopedic and plastic and reconstructive surgery, it is imperative that hand surgery research emulates this trend. METHODS: A systematic review was performed on all hand surgery articles published in 6 journals over a 20-year period. The journals included Plastic and Reconstruction Surgery, Journal of Plastic, Reconstructive and Aesthetic Surgery, Journal of Hand Surgery-European Volume, Journal of Hand Surgery-American Volume, Journal of Bone & Joint Surgery, and the Bone & Joint Journal. The level of evidence of each article was determined using the Oxford level of evidence. The quality of methodology of randomized controlled trials (RCTs) was assessed using Jadad scale. Statistical analysis involved chi-squares and Student t test (P < .05). RESULTS: A total of 972 original hand surgery research articles were reviewed. There was a significant increase in the average level of evidence of articles published between1993 and 2013. High-quality evidence only accounted for 11.2% of evidence published, with a significant increase over the study period (P = 0.001). Quantitative evaluation of the 26 published RCTs, using Jadad scale, revealed a progressive improvement in study design from 0.3 in 1993 to 3.33 in 2013. CONCLUSIONS: Hand surgery research has mirrored trends seen in other surgical specialties, with a significant increase in quality of evidence over time. Yet, high-quality evidence still remains infrequent.

Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining.

The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138(+) antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported.

Controlled Measurement and Comparative Analysis of Cellular Components in E. coli Reveals Broad Regulatory Changes in Response to Glucose Starvation.

How do bacteria regulate their cellular physiology in response to starvation? Here, we present a detailed characterization of Escherichia coli growth and starvation over a time-course lasting two weeks. We have measured multiple cellular components, including RNA and proteins at deep genomic coverage, as well as lipid modifications and flux through central metabolism. Our study focuses on the physiological response of E. coli in stationary phase as a result of being starved for glucose, not on the genetic adaptation of E. coli to utilize alternative nutrients. In our analysis, we have taken advantage of the temporal correlations within and among RNA and protein abundances to identify systematic trends in gene regulation. Specifically, we have developed a general computational strategy for classifying expression-profile time courses into distinct categories in an unbiased manner. We have also developed, from dynamic models of gene expression, a framework to characterize protein degradation patterns based on the observed temporal relationships between mRNA and protein abundances. By comparing and contrasting our transcriptomic and proteomic data, we have identified several broad physiological trends in the E. coli starvation response. Strikingly, mRNAs are widely down-regulated in response to glucose starvation, presumably as a strategy for reducing new protein synthesis. By contrast, protein abundances display more varied responses. The abundances of many proteins involved in energy-intensive processes mirror the corresponding mRNA profiles while proteins involved in nutrient metabolism remain abundant even though their corresponding mRNAs are down-regulated.

Levels of Evidence in the Plastic Surgery Literature: A Citation Analysis of the Top 50 'Classic' Papers.

BACKGROUND: The plastic surgery literature is vast, consisting of a plethora of diverse articles written by a myriad of illustrious authors. Despite this considerable archive of published material, it remains nebulous as to which precise papers have had the greatest impact on our specialty. The aim of this study was to identify the most cited papers in the plastic surgery literature and perform a citation analysis paying particular attention to the evidence levels of the clinical studies. METHODS: We identified the 50 most cited papers published in the 20 highest impact plastic surgery journals through the Web of Science. The articles were ranked in order of number of citations acquired and level of evidence assessed. RESULTS: The top 50 cited papers were published in six different journals between the years 1957 and 2007. Forty-two of the papers in the top 50 were considered as level IV or V evidence. No level I or II evidence was present in the top 50 list. The average level of evidence of the top 50 papers was 4.28. CONCLUSIONS: In the plastic surgery literature, no positive correlation exists between a high number of citations and a high level of evidence. Anatomical reconstructive challenges tend to be the main focus of plastic surgery rather than pathologic diseases and consequently, papers with lower levels of evidence are relatively more valuable in plastic surgery than many other specialties.

Fat grafting: a citation analysis of the seminal articles.

BACKGROUND: There has been substantial rise in the volume of published works on fat transfer in the medical literature in the past 25 years, and this is indicative of its growing popularity. However, many unanswered questions remain, and there is no consensus as to the optimum technique. Consequently, the scientific and clinical research on fat grafting continues to increase rapidly. The purpose of our study was to perform a bibliometric analysis of the most-cited articles in fat transfer. METHODS: Through the Web of Science, all articles relating to fat grafting were identified in the plastic and reconstructive literature. The 100 most-cited articles were identified and analyzed individually. RESULTS: Total citations ranged from 35 to 363 and the most-cited paper by Sidney Coleman was published in Plastic and Reconstructive Surgery. The United States produced 46% of the most-cited papers, and the University of California was the most prolific institution. Twenty-one articles focused on lipofilling to the face while 14 articles looked at fat grafting to the breast. CONCLUSIONS: The scientific relevance of a published work is reflected in the number of citations from peers that it receives. Therefore, the 100 most-cited papers in fat grafting have been the most influential articles on this field, and they are likely to be the ones that are remembered most.

International importance of robust breast device registries.

BACKGROUND: Breast implants are high-risk devices that have been at the epicenter of much debate and controversy. In light of the Poly Implant Prothèse crisis, data registries among 11 national societies around the world are cooperatively calling for the urgent need to establish robust national clinical quality registries based on international best practice within a framework of international collaboration. METHODS: A survey was conducted on the historic and current status of national breast device registries. Eleven countries participated in the study, illustrating different data collection systems and registries around the world. Data collection was designed to illustrate the capabilities of current national registries, with particular focus on capture rate and outcome reporting mechanisms. RESULTS: A study of national breast implant registries revealed that less than half of the participating countries had operational registries and that none of these had adequately high data capture to enable reliable outcome analysis. The study revealed that the two most common problems that discouraged participation are the complexity of data sets and the opt-in consent model. CONCLUSIONS: Recent implant crises have highlighted the need for robust registries. This article argues the importance of securing at least 90 percent data capture, which is achievable through the opt-out consent model. Since adopting this model, the Australian Breast Device Registry has increased data capture from 4 percent to over 97 percent. Simultaneously, it is important to foster international collaboration from the outset to avoid duplication of efforts and enable the development of effective international early warning systems.

Galactose metabolic genes in yeast respond to a ratio of galactose and glucose.

Natural environments are filled with multiple, often competing, signals. In contrast, biological systems are often studied in "well-controlled" environments where only a single input is varied, potentially missing important interactions between signals. Catabolite repression of galactose by glucose is one of the best-studied eukaryotic signal integration systems. In this system, it is believed that galactose metabolic (GAL) genes are induced only when glucose levels drop below a threshold. In contrast, we show that GAL gene induction occurs at a constant external galactose:glucose ratio across a wide range of sugar concentrations. We systematically perturbed the components of the canonical galactose/glucose signaling pathways and found that these components do not account for ratio sensing. Instead we provide evidence that ratio sensing occurs upstream of the canonical signaling pathway and results from the competitive binding of the two sugars to hexose transporters. We show that a mutant that behaves as the classical model expects (i.e., cannot use galactose above a glucose threshold) has a fitness disadvantage compared with wild type. A number of common biological signaling motifs can give rise to ratio sensing, typically through negative interactions between opposing signaling molecules. We therefore suspect that this previously unidentified nutrient sensing paradigm may be common and overlooked in biology.

An Analysis of the "Classic" Papers in Aesthetic Surgery.

INTRODUCTION: Over the past 50 years, there has been a significant increase in published articles in the medical literature. The aesthetic surgery literature is vast, consisting of a plethora of diverse articles written by a myriad of illustrious authors. Despite this considerable archive of published material, it remains nebulous as to which precise papers have had the greatest impact on our specialty. The aim of our study was to identify and analyse the characteristics of the top 50 papers in the field of aesthetic surgery in the published literature. METHODS: The 50 most cited papers were identified in several surgical journals through the Web of Science. The articles were ranked in order of the number of citations received. These classic 50 papers were analysed for article type, their journal distribution, level of evidence as well as geographic and institutional origin. RESULTS: Six journals contributed to the top 50 papers in aesthetic surgery with Plastic and Reconstructive Surgery contributing the most with 31 papers.

How to Recover a Qubit That Has Fallen into a Black Hole.

We demonstrate an algorithm for the retrieval of a qubit, encoded in spin angular momentum, that has been dropped into a no-firewall black hole. Retrieval is achieved analogously to quantum teleportation by collecting Hawking radiation and performing measurements on the black hole. Importantly, these methods require only the ability to perform measurements from outside the event horizon.