Neue klinische Aspekte und Phänotypisierung der Multiplen Symmetrischen Lipomatose

Am Universitätsklinikum Regensburg fiel uns bei der Behandlung von Patienten mit MSL auf, dass der Phänotyp nur selten nach den gängigen Klassifikationen adäquat beschrieben werden konnten. Zudem erwies sich die medizinische Literatur zur MSL als dürftig, da diese Erkrankung bislang, vermutlich aufgrund der geringen Inzidenz, selten im Fokus wissenschaftlicher Untersuchungen stand. Deshalb untersuchten wir in unserer Studie 45 Patienten, welche unter MSL leiden, um Daten aus der Anamnese, den Phänotyp, die Blutwerte und die Nebenerkrankungen der Patienten zu erheben. Ziel unserer Studie war, die Phänotypisierung anzupassen, neue wissenschaftliche Erkenntnisse zu gewinnen und Anregungen für weitergehende Untersuchungen zu erhalten. Zunächst wurden allgemeine Daten, wie Geschlechterverteilung, mittleres Alter, mittleres Gewicht, mittlere Körpergröße und der mittlere Body-Mass-Index über beide Geschlechter sowie geschlechterspezifisch berechnet und die Punkt-Prävalenz ermittelt. Dabei wurden die Daten von 19 Patienten prospektiv und von 26 Patienten retrospektiv erhoben. Anhand von Fotographien von insgesamt 33 Patienten wurde sodann die Klassifikation nach Donhauser auf ihre Anwendbarkeit getestet. Dafür wurden 11 Beobachter aufgefordert, die Patienten nach Donhauser zu klassifizieren. Dies gelang lediglich bei 45% der Patienten. Anschließend wurden die Beobachter gebeten für jeden Patienten anzugeben, welche Körperregionen von der MSL-üblichen Fettvermehrung betroffen sind. Dazu wurde der Körper in 12 Körperregionen eingeteilt, die von den Beobachtern jeweils auf Fettvermehrungen hin überprüft werden sollten. Aus diesen Daten ergaben sich 5 Fettverteilungsmuster, welche als Typ Ia, Ib, Ic, II und III definiert wurden. Diesen 5 Typen konnten 100% unserer Patienten zugeordnet werden. Beim Literaturstudium fällt auf, dass ein Großteil der Daten veraltet bzw. fehlinterpretiert und –zitiert ist. In dieser Arbeit wurden Daten anhand der deutschlandweit größten Kohorte (n=45) erhoben. Es konnte eine neue und zutreffende Klassifikation zur Phänotypisierung der MSL mit fünf Subtypen (Ia, Ib, Ic, II und III) aufgestellt werden. Diese konnte erfolgreich auf die 45 untersuchten Patienten angewandt werden. Wir konnten nachweisen, dass die Punkt-Prävalenz der MSL in der Oberpfalz bei 1:24.274 und das Verhältnis zwischen männlichen und weiblichen Patienten bei 1:2,5 liegt. Des Weiteren konnte festgestellt werden, dass Hypercholesterinämie und Hypothyreodismus gängige Nebenerkrankungen der MSL sind und die Blutwerte der betroffenen Patienten, bis auf eine Hypercholesterinämie und einzelne erhöhte TSH-Werte, normal sind. Ein Zusammenhang mit Alkoholkonsum konnte nicht nachgewiesen werden. Die Pathogenese der MSL bleibt nach wie vor unbekannt

Do not drop: Mechanical shock in vials causes cavitation, protein aggregation and particle formation

Industry experience suggests that g-forces sustained when vials containing protein formulations are accidentally dropped can cause aggregation and particle formation. To study this phenomenon, a shock tower was used to apply controlled g-forces to glass vials containing formulations of two monoclonal antibodies and recombinant human growth hormone (rhGH). High-speed video analysis showed cavitation bubbles forming within 30 μs and subsequently collapsing in the formulations. As a result of echoing shock waves, bubbles collapsed and reappeared periodically over a millisecond timecourse. Fluid mechanics simulations showed low-pressure regions within the fluid where cavitation would be favored. A hydroxyphenylfluorescein assay determined that cavitation produced hydroxyl radicals. When mechanical shock was applied to vials containing protein formulations, gelatinous particles appeared on the vial walls. Size exclusion chromatographic analysis of the formulations after shock did not detect changes in monomer or soluble aggregate concentrations. However, subvisible particle counts determined by microflow image analysis increased. The mass of protein attached to the vial walls increased with increasing drop height. Both protein in bulk solution and protein that became attached to the vial walls after shock were analyzed by mass spectrometry. rhGH recovered from the vial walls in some samples revealed oxidation of Met and/or Trp residues

Video Tutorial for Clinical Flap-Monitoring in Plastic Surgery

Free tissue transfer is a well-established technique in the field of plastic reconstructive surgery. Despite great progress being made in relation to technical issues and the anatomical understanding of free flap transfers, a loss rate of between 2% and 5% remains.1–5 The main reasons for free flap failure are vascular problems, such as vascular thrombosis (venous and arterial), arterial insufficiency, active bleeding or hematoma, and venous congestion.1–4 Many studies have demonstrated that the salvage rate for flaps is inversely related to the time between the onset of vascular compromise and surgical intervention.6,7 To guarantee an immediate reaction in case of perfusion problems in free flap surgery, a continuous and sufficient flap monitoring is indispensable. Although there are numerous techniques to assess flap vitality, clinical examination remains the gold standard.8 Besides this preferred method, a handheld and implantable Doppler, microdialysis, video-based application, real-time measurement of oxygen saturation, fluorescence angiography, spectroscopy, contrast-enhanced duplex, and activated clotting time have been proposed as alternative modalities for monitoring, though none of these has provided better results than clinical examination.9,10 The postoperative clinical examination and monitoring of flaps is frequently delegated to nurses and paramedics. Thus, there is often a high variation in skill level due to the lack of clinical experience needed to assess flap vitality.11 When asked, even young plastic surgeons often admit uncertainty when it comes to assessing postoperative flap vitality. To guarantee a high level of monitoring quality, constant training is indispensable. As mentioned above, perfusion compromise—being of arterial or venous origin—emerges rarely and is hard to include consistently within a training program. Therefore, educational material that clearly elucidates different qualities in vascular compromise in flaps is highly desirable

Therapist versus Machine—Immediate Effects of Manual versus Mechanical Lymphatic Drainage in Patients with Secondary Lymphedema

Background: Complex decongestive therapy (CDT) is the standard and basic therapy for lymphedema. The central component of CDT is manual lymphatic drainage (MLD). In addition to CDT, other measures such as intermittent pneumatic compression therapy (IPCT) (active compression machine therapy) are available. In this prospective research study, the objective and subjective effects of MLD and IPCT on lymphedema of the lower extremity were investigated and both therapies were directly compared. Furthermore, the patients’ body mass index (BMI) and stage of lymphedema were tested for their effect on the respective therapy. Methods: Patients participating in the study received both therapies (MLD and IPCT) on the same lymphedema-affected limb at an interval of two days. The objective volumetric therapy effect was measured by the digital volume measurement of the affected limb. The subjective effects of the therapies were measured using two specially designed questionnaires. Results: A total of 40 patients were included in the study. There was no significant difference in the volume differences between the interventions, BMI categories, lymphedema, or treatment order regarding the immediate and two-day effect. Conclusions: No significant difference was found in the subjective or objective therapy efficacy of the two methods. Intermittent pneumatic compression therapy is considered a comparable therapeutic procedure when properly indicated

A Novel Method of Outcome Assessment in Breast Reconstruction Surgery: Comparison of Autologous and Alloplastic Techniques Using Three-Dimensional Surface Imaging

Background Breast reconstruction is an important coping tool for patients undergoing a mastectomy. There are numerous surgical techniques in breast reconstruction surgery (BRS). Regardless of the technique used, creating a symmetric outcome is crucial for patients and plastic surgeons. Three-dimensional surface imaging enables surgeons and patients to assess the outcome's symmetry in BRS. To discriminate between autologous and alloplastic techniques, we analyzed both techniques using objective optical computerized symmetry analysis. Software was developed that enables clinicians to assess optical breast symmetry using three-dimensional surface imaging. Methods Twenty-seven patients who had undergone autologous (n = 12) or alloplastic (n = 15) BRS received three-dimensional surface imaging. Anthropomorphic data were collected digitally using semiautomatic measurements and automatic measurements. Automatic measurements were taken using the newly developed software. To quantify symmetry, a Symmetry Index is proposed. Results Statistical analysis revealed that there is no difference in the outcome symmetry between the two groups (t test for independent samples; p = 0.48, two-tailed). Conclusion This study's findings provide a foundation for qualitative symmetry assessment in BRS using automatized digital anthropometry. In the present trial, no difference in the outcomes' optical symmetry was detected between autologous and alloplastic approaches. Level of evidence Level IV.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

Do-It-Yourself Preoperative High-Resolution Ultrasound-Guided Flap Design of the Superficial Circumflex Iliac Artery Perforator Flap (SCIP)

The superficial circumflex iliac artery perforator (SCIP) flap is a well-documented, thin, free tissue flap with a minimal donor site morbidity, and has the potential to become the new method for resurfacing moderate-size skin defects. The aim of this study is to describe an easy, reliable, systematic, and standardized approach for preoperative SCIP flap design and perforator characterization, using color-coded duplex sonography (CCDS). A list of customized settings and a straightforward algorithm are presented, which are easily applied by an operator with minimal experience. Specific settings for SCIP flap perforator evaluation were investigated and tested on 12 patients. Deep and superficial superficial circumflex iliac artery (SCIA) branches, along with their corresponding perforators and cutaneous veins, were marked individually with a permanent marker and the anatomy was verified intraoperatively. From this, a simplified procedure for preoperative flap design of the SCIP flap was developed. Branches could be localized and evaluated in all patients. A preoperative structured procedure for ultrasonically guided flap design of the SCIP flap is described. A 100% correlation between the number and emergence points of the branches detected by preoperative CCDS mapping and the intraoperative anatomy was found

Enhancing Woodbury’s Urban Tree Canopy

Report completed by students enrolled in FNRM 4501/5501 - Urban Forest Management: Managing Greenspaces for People, taught by Dr. Eric North in Spring 2021.This project was completed as part of a partnership between the City of Woodbury, the Metropolitan Council, and the University of Minnesota’s Resilient Communities Project (http://www.rcp.umn.edu). The goal of this project was to provide recommendations on how the City can equitably increase its tree canopy coverage and update its approved tree species list. City of Woodbury project lead Kristin Seaman collaborated with students in Eric North’s course, FNRM 4501/5501 - Urban Forest Management: Managing Greenspaces for People, to assess Woodbury's current tree canopy, investigate how it could be equitably expanded in the future, and provide analysis and recommendations for the City to incorporate into their updated tree canopy plan. Final student reports and presentations are available. A videorecording of the students' final presentation is also available at https://vimeo.com/547699038.This project was supported by the Resilient Communities Project (RCP), a program at the University of Minnesota whose mission is to connect communities in Minnesota with U of MN faculty and students to advance community resilience through collaborative, course-based projects. RCP is a program of the Center for Urban and Regional Affairs (CURA). More information at http://www.rcp.umn.edu. Additional funding and support was provided by the Metropolitan Council of the Twin Cities

Single-molecule tracking reveals two low-mobility states for chromatin and transcriptional regulators within the nucleus

peer reviewedHow transcription factors (TFs) navigate the complex nuclear environment to assemble the transcriptional machinery at specific genomic loci remains elusive. Using single-molecule tracking, coupled with machine learning, we examined the mobility of multiple transcriptional regulators. We show that H2B and ten different transcriptional regulators display two distinct low-mobility states. Our results indicate that both states represent dynamic interactions with chromatin. Ligand activation results in a dramatic increase in the proportion of steroid receptors in the lowest mobility state. Mutational analysis revealed that only chromatin interactions in the lowest mobility state require an intact DNA-binding domain as well as oligomerization domains. Importantly, these states are not spatially separated as previously believed but in fact, individual H2B and TF molecules can dynamically switch between them. Together, our results identify two unique and distinct low-mobility states of transcriptional regulators that appear to represent common pathways for transcription activation in mammalian cells

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI