Gothenburg Breast reconstruction (GoBreast) II protocol: a Swedish partially randomised patient preference, superiority trial comparing autologous and implant-based breast reconstruction.

INTRODUCTION: Although breast reconstruction is an integral part of breast cancer treatment, there is little high-quality evidence to indicate which method is the most effective. Randomised controlled trials (RCTs) are generally thought to provide the most solid scientific evidence, but there are significant barriers to conducting RCTs in breast reconstruction, making both recruitment and achieving unbiased and generalisable results a challenge. The objective of this study is to compare implant-based and autologous breast reconstruction in non-irradiated patients. Moreover, the study aims to improve the evidence for trial decision-making in breast reconstruction. METHODS AND ANALYSIS: The study design partially randomised patient preference trial might be a way to overcome the aforementioned challenges. In the present study, patients who consent to randomisation will be randomised to implant-based and autologous breast reconstruction, whereas patients with strong preferences will be able to choose the method. The study is designed as a superiority trial based on the patient-reported questionnaire BREAST-Q and 124 participants will be randomised. In the preference cohort, patients will be included until 62 participants have selected the least popular alternative. Follow-up will be 60 months. Embedded qualitative studies and within-trial economic evaluation will be performed. The primary outcome is patient-reported breast-specific quality of life/satisfaction, and the secondary outcomes are complications, factors affecting satisfaction and cost-effectiveness. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority (2023-04754-01). Results will be published in peer-reviewed scientific journals and presented at peer-reviewed scientific meetings. TRIAL REGISTRATION NUMBER: NCT06195865.

A systematic review of randomised controlled trials in breast reconstruction.

BACKGROUND: For preference sensitive treatments, such as breast reconstructions, there are barriers to conducting randomised controlled trials (RCTs). The primary aims of this systematic review were to investigate what type of research questions are explored by RCTs in breast reconstruction, where have they been performed and where have they been published, and to thematise the research questions and thus create an overview of the state of the research field. METHODS: Randomised controlled trials investigating any aspect of breast reconstructions were included. The PubMed database was searched with a pre-defined search string. Inclusion and data abstraction was performed in a pre-defined standardised fashion. For the purpose of this study, we defined key issues as comparison of categories of breast reconstruction and comparison of immediate and delayed breast reconstruction, when the thematisation was done. RESULTS: A total of 419 abstracts were retrieved from the search. Of the 419, 310 were excluded as they were not RCTs concerning some aspect of breast reconstruction, which left us with 110 abstracts to be included in the study. The research questions of the included studies could more or less be divided into seven different themes inclusive of 2 key issues: Other issues - comparison of different categories of breast reconstruction, comparison of immediate and delayed breast reconstruction, surgical details within a category of breast reconstruction, surgical details valid for several categories of breast reconstruction, donor site management, anaesthetics, and non-surgical details. Only five studies compared key issues, and they all illustrate the challenges with RCTs in breast reconstruction. CONCLUSIONS: A total of 110 publications based on RCTs in breast reconstruction have been published. Seven themes of research questions could be identified. Only five studies have explored the key issues. Better scientific evidence is needed for the key issues in breast reconstruction, for example by implementing a new study design in the field.

Thermally controlled microfluidic back pressure regulator.

By using the temperature dependence of viscosity, we introduce a novel type of microfluidic lab-on-a-chip back pressure regulator (BPR) that can be integrated into a micro-total-analysis-system. A BPR is an important component used to gain pressure control and maintain elevated pressures in e.g. chemical extractions, synthesis, and analyses. Such applications have been limited in microfluidics, since the back pressure regularly has been attained by passive restrictors or external large-scale BPRs. Herein, an active microfluidic BPR is presented, consisting of a glass chip with integrated thin-film heaters and thermal sensors. It has no moving parts but a fluid restrictor where the flow resistance is controlled by the change of viscosity with temperature. Performance was evaluated by regulating the upstream pressure of methanol or water using a PID controller. The developed BPR has the smallest reported dead volume of 3 nL and the thermal actuation has time constants of a few seconds. The pressure regulation were reproducible with a precision in the millibar range, limited by the pressure sensor. The time constant of the pressure changes was evaluated and its dependence of the total upstream volume and the compressibility of the liquids is introduced.

Microfluidic active pressure and flow stabiliser.

In microfluidics, a well-known challenge is to obtain reproducible results, often constrained by unstable pressures or flow rates. Today, there are existing stabilisers made for low-pressure microfluidics or high-pressure macrofluidics, often consisting of passive membranes, which cannot stabilise long-term fluctuations. In this work, a novel stabilisation method that is able to handle high pressures in microfluidics is presented. It is based on upstream flow capacitance and thermal control of the fluid's viscosity through a PID controlled restrictor-chip. The stabiliser consists of a high-pressure-resistant microfluidic glass chip with integrated thin films, used for resistive heating. Thereby, the stabiliser has no moving parts. The quality of the stabilisation was evaluated with an ISCO pump, an HPLC pump, and a Harvard pump. The stability was greatly improved for all three pumps, with the ISCO reaching the highest relative precision of 0.035% and the best accuracy of 8.0 ppm. Poor accuracy of a pump was compensated for in the control algorithm, as it otherwise reduced the capacity to stabilise longer times. As the dead volume of the stabiliser was only 16 nL, it can be integrated into micro-total-analysis- or other lab-on-a-chip-systems. By this work, a new approach to improve the control of microfluidic systems has been achieved.

Microfluidic Control Board for High-Pressure Flow, Composition, and Relative Permittivity.

Flow control is central to microfluidics and chromatography. With decreasing dimensions and high pressures, precise fluid flows are often needed. In this paper, a high-pressure flow control system is presented, allowing for the miniaturization of chromatographic systems and the increased performance of microfluidic setups by controlling flow, composition, and relative permittivity of two-component flows with CO2. The system consists of four chips: two flow actuator chips, one mixing chip, and one relative permittivity sensor. The actuator chips, throttling the flow, required no moving parts as they instead relied on internal heaters to change the fluid resistance. This allows for flow control using miniaturized fluid delivery systems containing only a single pump or pressure source. Mobile phase gradients between 49% and 74% methanol in CO2 were demonstrated. Depending on how the actuator chips were dimensioned, the position of this range could be set for different method-specific needs. With the microfluidic control board, both flow and composition could be controlled from constant pressure sources, drift could be removed, and variations in composition could be lowered by 84%, resulting in microflows of CO2 and methanol with a variation in the composition of ±0.30%.

Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with hematological malignancies.

Staphylococcus epidermidis is an important cause of bloodstream infections in patients with hematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for hematological malignancies at the University Hospital of Örebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing, staphylococcal chromosome cassette mec (SCCmec) typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson's Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). Ninety three percent (226/243) of the ST2 isolates displayed either SCCmec type III or IV. ST2 and 215 were isolated during the entire study period, and together these STs caused temporal peaks in the number of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271 isolates (95%), compared with 34/100 (34%) in other STs (p<0.001). In conclusion, in this long-term study of patients with hematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

Characterization of SCCmec elements in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures from neonates during three decades.

Staphylococcus epidermidis is a major cause of nosocomial infections in immunocompromised patients and the predominant pathogen in catheter-related infections and bloodstream infections. Approximately 70-80% of S. epidermidis carry the mecA gene encoding methicillin resistance. The mecA gene is located on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). The aim of this study was to characterize the SCCmec elements as well as the adjacent arginine catabolic mobile element (ACME) in 30 clinical blood isolates of mecA positive S. epidermidis obtained from neonates and collected over a period of three decades. The ccr and mec gene complexes were identified using PCR. The SCCmec elements were found among 29/30 isolates and 13 different combinations of ccr gene complexes and mec gene complexes were identified. Staphylococcus epidermidis regularly carried multiple copies of ccr gene complexes, but only one class of mec gene complex. Three isolates could be assigned the SCCmec type III (3A). The combinations of ccr gene complexes and the mec gene complexes differed among the three decades. The most frequent combination was class B mec in combination with ccr1 and ccr2. Staphylococcus epidermidis may constitute a large reservoir for SCCmec elements, and frequent exchange of mobile genetic elements between staphylococcal species may explain the emergence of new MRSA strains.