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ZUSAMMENFASSUNGDas Merkelzellkarzinom ist ein aggressiver neuroendokriner Tumor, welcher durch schnelles Wachstum und frühzeitige Metastasierung charakterisiert ist. Das mediane Erkrankungsalter liegt zwischen 75–80 Jahren. Mit Zunahme des durchschnittlichen Bevölkerungsalters tritt der einstmals seltene Tumor immer häufiger auf. Neben den klassischen Therapiesäulen Chirurgie, Strahlentherapie und Chemotherapie spielt die Immunonkologie auch beim Merkelzellkarzinom eine zunehmend wichtige Rolle.

Return to international travel in the COVID-19 pandemic recovery period is expected to increase the number of patients with imported malaria in the United States (US). Malaria prevention in travelers and preparedness for timely diagnosis and appropriate treatment are key to minimize imported malaria morbidity and mortality. Intravenous artesunate (IVAS) is now available from commercial distributors in the US for the treatment of severe malaria. Hospitals and pharmacists should have a plan for malaria treatment, including stocking artemether-lumefantrine for uncomplicated malaria, and stocking or planning for rapid procurement of IVAS for the treatment of severe malaria.

Importance A same-day ophthalmic urgent care clinic can provide efficient eye care, a rich educational environment, and can improve patient experience. Objective The aim of this study was to systematically evaluate volume, financial impact, care metrics, and the breadth of pathology of urgent new patient encounters based on their site of initial presentation. Design, Setting, and Participants A retrospective analysis was performed on consecutive urgent new patient evaluations in our same-day triage clinic at the Henkind Eye Institute at Montefiore Medical Center between February 2019 and January 2020. The cohort of patients who presented directly to this urgent care clinic were referred to as the “TRIAGE” group. Patients who initially presented to an emergency department (ED), and were subsequently referred to our triage clinic, are referred to as the “ED + TRIAGE” group. Main Outcomes and Measures Visits were evaluated on a variety of metrics, including diagnosis, duration, charge, cost, and revenue. Furthermore, return to the ED or inpatient admission was documented. Results Of 3,482 visits analyzed, 2,538 (72.9%) were in the “TRIAGE” group. Common presenting diagnoses were ocular surface disease (n = 486, 19.1%), trauma (n = 342, 13.5%; most commonly surface abrasion n = 195, 7.7%), and infectious conjunctivitis (n = 304, 12.0%). Patients in the “TRIAGE” group, on average, were seen 184.6% faster (158.2 vs. 450.2 minutes) than patients in the “ED + TRIAGE” group (p Conclusions and Relevance A same-day ophthalmology triage clinic provides efficient care, while providing a rich learning environment for residents. Less wait time with direct access to subspecialist care can help improve quality, outcome, and satisfaction metrics.

The Pajarito fault system is a complex zone of deformation and a seismically active region nestled within the Rio Grande rift in north-central New Mexico. Numerous laterally discontinuous faults and associated folds and fractures interact in a manner that has important implications for seismic hazards and risk mitigation. Previous efforts have established a foundation for the location of lineaments and structures in the Pajarito fault system; however, ensuring the completeness of the current lineament mapping is required for identifying areas for field validation, evaluating the potential for future seismic activity, and better understanding fault interaction. Assistance with this fault-mapping task via automated or semiautomated techniques as applied to lidar data over a large area of interest is highly desirable. A proof-of-concept processing flow which transforms lidar point-cloud data into a raster of surficial fault candidates is described and illustrated herein. These initial results hold great promise toward achieving our ultimate goal.

Proximal interphalangeal joint flexion contracture is a frequent condition in hand therapy. Clinicians most frequently apply orthosis management for conservative treatment. Orthoses should apply forces for long periods of time following the total end range time (TERT) concept. These forces necessarily transmit through the skin; however, skin has physiological limitations determined by blood flow. Using three fresh frozen human cadavers, this study quantified and compared forces, skin contact surfaces and pressure of two finger orthoses, an elastic tension digital neoprene orthosis (ETDNO) and an LMB 501 orthosis. The study also investigated the effects of a new method of orthosis construction (serial ETDNO orthoses) that customizes forces to a specific finger position. We evaluated forces and contact surfaces for multiple ETDNO models tailored to the cadaver fingers in multiple PIP flexion positions. The results showed that the LMB 501 orthosis applied pressures beyond the recommended limits if applied for more than eight hours a day. This fact was the cause of time limited LMB orthosis application. This results also show that, at 30° of PIPJ flexion, straight ETDNOs created a mean pressure approaching the end of the recommended pressure limits. If the therapist modified the ETDNO design, the skin pressure decreased and reduced the risk of skin damage. With the results of this study, we concluded that for PIPJ flexion contracture, the upper limit of force application is 200 g (1.96 N). Forces beyond this amount would likely cause skin irritation and possibly skin injuries. This would cause a reduction in the daily TERT and limit outcomes.

For animals undergoing rehabilitation it is vital to monitor welfare in a way that is feasible, practical, and limits stress to the animal. The industry gold standard is to assess welfare under the Five Domains model, including nutrition, environment, physical health, and behaviour as the first four physical domains and mental domain as the fifth. Feasibility and effectiveness of these domains for assessing welfare of sea turtles undergoing rehabilitation were reviewed and it was determined that the mental state can be best assessed through behavioural changes. A scoping review of the literature was conducted using Scopus and Web of Science to investigate use of environmental enrichment devices (EEDs) as a measure of welfare in sea turtles. Behavioural assessments using EEDs were found to be well-documented; however, most EED studies pertained largely to livestock or zoo animals. Furthermore, studies rarely concentrated on reptiles, and specifically sea turtles. Results also showed that certain welfare assessment methods may be less appropriate for short-term captivity experienced during rehabilitation. Additionally, the hospital environment limits the ability to address some of the domains (ie biosecurity, feasibility, safety of turtle, etc, might be compromised). This review shows that only three of the nine environmental enrichment strategies described in the literature suit the specific requirements of sea turtles in rehabilitation: feeding, tactile, and structural. It is documented that turtles display behaviours that would benefit from EEDs and, therefore, more specific studies are needed to ensure the best welfare outcomes for sea turtles undergoing rehabilitation.

Zusammenfassung Hintergrund Das kutane Plattenepithelkarzinom (PEK) ist nach dem Basalzellkarzinom der zweithäufigste bösartige Hauttumor. In Deutschland wurden 2014 über 50.000 PEK-Neuerkrankungen dokumentiert. Mit Zunahme der durchschnittlichen Lebenserwartung und Komorbiditäten treten mittlerweile auch gehäuft lokal fortgeschrittene Tumore mit Metastasierung auf. Methode Selektive Literaturrecherche in PubMed und unter Berücksichtigung der deutschen S3-Leitlinien „Aktinische Keratosen und Plattenepithelkarzinom der Haut“ und „Prävention von Hautkrebs“. Ergebnisse Beim PEK ist der Goldstandard die vollständige Exzision des Primärtumors mittels histopathologischer Kontrolle der Schnittränder. Eine Radiotherapie kann eingesetzt werden, wenn eine vollständige Exzision nicht erreicht werden kann bzw. Inoperabilität besteht. Im Falle eines metastasierten (mPEK) oder lokal fortgeschrittenen (laPEK) PEK, welches nicht kurativ operiert oder bestrahlt werden kann, werden systemische medikamentöse Therapien eingesetzt. Mit der Zulassung des PD1-Antikörpers Cemiplimab steht seit 2019 in der EU eine neue systemische Therapie zur Behandlung des fortgeschrittenen PEK zur Verfügung. Nach bis zu 3 Jahren Follow-up sprechen noch 46% der Patienten mit mPEK und laPEK auf Cemiplimab an, der Medianwert für das Gesamtüberleben und die Ansprechdauer ist in beiden Gruppe noch nicht erreicht. Weitere Antikörper gegen PD1 oder PDL1, Kombinationstherapien sowie die Immuntherapie mit onkolytischen Viren ermöglichen zahlreiche Therapieoptionen und sind aktuell Gegenstand der Forschung. Schlussfolgerung Mit der Zunahme von fortgeschrittenen Stadien des PEK nimmt die Wichtigkeit des interdisziplinären Tumorboards für den Therapieentscheid immer mehr zu. Die Weiterentwicklung bestehender therapeutischer Konzepte, die Identifikation von gut wirksamen Kombinationstherapien sowie die Entwicklung weiterer verträglicher zielgerichteter Systemtherapien ist eine entscheidende dermatoonkologische Herausforderung der nächsten Jahre.

ZusammenfassungDas Merkelzellkarzinom ist ein aggressiver neuroendokriner Tumor, welcher durch schnelles Wachstum und frühzeitige Metastasierung charakterisiert ist. Das mediane Erkrankungsalter liegt zwischen 75–80 Jahren. Mit Zunahme des durchschnittlichen Bevölkerungsalters tritt der einstmals seltene Tumor immer häufiger auf. Neben den klassischen Therapiesäulen Chirurgie, Strahlentherapie und Chemotherapie spielt die Immunonkologie auch beim Merkelzellkarzinom eine zunehmend wichtige Rolle.

We investigate offline dynamic optimization (ODO) and multi-layer control schemes to optimally operate the epoxidation of oleic acid. The process involves a two-phase reaction mixture with highly exothermic reactions wherein the reactor temperature needs to be controlled to guarantee safe operation. Optimal operating conditions are computed using ODO and the control scheme is responsible to enforce such conditions. We compare a conventional control scheme, which uses PI controllers, against two multi-layer control schemes: (i) using nonlinear model predictive control (NMPC) and (ii) using dynamic real-time optimization (DRTO) together with NMPC. With ODO and NMPC we achieve a reduction in process time greater than 75%, compared to a standard process, while still maintaining safe operating conditions. With DRTO and NMPC, the same reduction in process time is obtained, however with a maximum violation of the temperature constraint by 12%. This may be due to model-plant mismatch and large computational time required for the optimization.

OBJECTIVE To investigate the therapeutic effects of topical equine amniotic membrane (eAM) suspension following corneal wounding in a controlled experimental setting. PROCEDURES Equine amniotic membrane was collected, gamma irradiated, homogenized for topical suspension preparation, and cryopreserved. Corneoscleral rims harvested from fresh rabbit globes were wounded via keratectomy and were maintained in an air-liquid interface ex vivo corneal culture model. Treatment groups included topical gamma irradiated eAM suspension (n = 20) and a control group (n = 20). Re-epithelialization of the wound was assessed with daily photographic evaluation of area of fluorescein uptake (mm2 ). Corneal wound haze after a 21-day period was assessed by photographic analysis of haze area (mm2 ) and pixel intensity (0-255). Histologic processing of corneal tissue was performed, and protein identification of eAM suspension using Liquid chromatography-mass spectrometry (LC-MS). RESULTS The average day of complete corneal re-epithelialization in controls (5.5 ± 1.1) and topically treated (5.5 ± 0.6) corneas, and rates of reduction in area of fluorescein uptake over time did not significantly differ (p = .44). The corneal wound haze was significantly reduced in mean area by approximately 52% and intensity by 57% in corneas treated with topical eAM suspension (p

Background Combination of immune checkpoint inhibitors and mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) has been proposed to enhance the durability of anti-tumour responses induced by MAPKi. Here, we present phase I safety results from an open-label, phase I/II study of pembrolizumab (PEM), encorafenib (ENC) and binimetinib (BIN) triplet therapy in advanced, B-Raf proto-oncogene serine/threonine kinase (BRAF)V600–mutated melanoma (IMMU-TARGET, NCT02902042 ). Methods The dose finding phase I part used a 3 + 3 design, starting with the approved doses of PEM (200 mg every three weeks), ENC (450 mg once daily [QD]) and BIN (45 mg twice daily [BID]) as dose level (DL) 0. Reduction of the ENC and BIN doses (300 mg QD and 30 mg BID at DL-1 and 200 mg QD and 30 mg BID at DL-2) was preplanned in case of ≥2 dose-limiting toxicities (DLTs). Primary objectives were to estimate the recommended phase II dose of the triplet combination, DLT and safety. As per the sponsor's decision, the study was terminated after the phase I part, as the clinical efficacy of the combination is currently being investigated in a pivotal, placebo-controlled (PEM mono), double-blinded phase III trial (STARBOARD, NCT04657991 ). Results Fifteen patients were enrolled. DLTs of DL0 were creatine phosphokinase (CPK) elevation plus cytokine release syndrome (n = 1) and gamma glutamyl transferase (GGT) increase (n = 1). No DLT was observed in further 3 + 3 patients at DL-1. One (isolated GGT elevations) DLT of DL0 was questionable, as the patient had further episodes of isolated GGT elevations after treatment discontinuation. Hence, further 6 patients were enrolled at DL0: here, no DLT occurred. In total, 13 of 15 patients (87%) experienced a treatment-related adverse event (TRAE) and 8 patients (53%), a grade ≥III TRAE; there were no TRAE-related deaths. Increases in aspartate aminotransferases, GGT (6/15 patients) and CPK elevations (4/15) were the most common grade III–IV TRAE. In median, patients received triplet therapy for 24 weeks (interquartile range [IQR], 12–45). Of the 14 patients evaluable for efficacy, the overall response rate was 64% (95% confidence interval [CI], 35–87). At a median follow-up of 25 months (IQR, 9–28), progression-free survival at 12 months was 41% (95% CI, 13–68). Conclusions Triplet therapy with PEM, ENC and BIN as used in the study was feasible and safe and led to clinically meaningful disease control.

(1) Background: Pyoderma gangrenosum (PG) is often situated on the lower legs, and the differentiation from conventional leg ulcers (LU) is a challenging task due to the lack of clear clinical diagnostic criteria. Because of the different therapy concepts, misdiagnosis or delayed diagnosis bears a great risk for patients. (2) Objective: to develop a deep convolutional neural network (CNN) capable of analysing wound photographs to facilitate the PG diagnosis for health professionals. (3) Methods: A CNN was trained with 422 expert-selected pictures of PG and LU. In a man vs. machine contest, 33 pictures of PG and 36 pictures of LU were presented for diagnosis to 18 dermatologists at two maximum care hospitals and to the CNN. The results were statistically evaluated in terms of sensitivity, specificity and accuracy for the CNN and for dermatologists with different experience levels. (4) Results: The CNN achieved a sensitivity of 97% (95% confidence interval (CI) 84.2–99.9%) and outperformed dermatologists, with a sensitivity of 72.7% (CI 54.4–86.7%) significantly (p < 0.03). However, dermatologists achieved a slightly higher specificity (88.9% vs. 83.3%). (5) Conclusions: For the first time, a deep neural network was demonstrated to be capable of diagnosing PG, solely on the basis of photographs, and with a greater sensitivity compared to that of dermatologists.

The immunogenicity risk of therapeutic protein aggregates has been extensively investigated over the past decades. While it is established that not all aggregates are equally immunogenic, the specific aggregate characteristics, which are most likely to induce an immune response, remain ambiguous. The aim of this study was to perform comprehensive in vitro and in vivo immunogenicity assessment of human insulin aggregates varying in size, structure and chemical modifications, while keeping other morphological characteristics constant. We found that flexible aggregates with highly altered secondary structure were most immunogenic in all setups, while compact aggregates with native-like structure were found to be immunogenic primarily in vivo. Moreover, sub-visible (1–100 µm) aggregates were found to be more immunogenic than sub-micron (0.1–1 µm) aggregates, while chemical modifications (deamidation, ethylation and covalent dimers) were not found to have any measurable impact on immunogenicity. The findings highlight the importance of utilizing aggregates varying in few characteristics for assessment of immunogenicity risk of specific morphological features and may provide a workflow for reliable particle analysis in biotherapeutics.

BACKGROUND Falls are the leading cause of fatal injury, and the most common cause of nonfatal trauma, among older adults. However, patient perspectives on preferences for obtaining fall education are not well reported. OBJECTIVE To identify components of successful fall prevention education. DESIGN Prospective qualitative study. SETTING Tertiary care center; institutional. PARTICIPANTS Adults aged 65 years or older with a history of falls who received services from inpatient trauma or outpatient geriatric services. INTERVENTIONS One-hour face-to-face semistructured interview. MAIN OUTCOME MEASURE Semistructured interviews sought to determine participants' history of fall education and perceived strengths and weaknesses of various formats of fall education. RESULTS Nearly all participants (9/10) indicated they had not received fall prevention education of any kind. Many participants (6/10) reported that, despite not receiving any formal education about falls, they had either given or received information about falls from other older adults in their communities. Participants indicated that framing fall education as a part of healthy aging would be more desirable and mentioned involving participants' families as part of the education. The majority of participants (7/10) suggested fall education be delivered through in-person discussion with providers, and most (9/10) indicated this would provide a personalized approach with opportunity for questions. Participants specified fall education should consist of both environmental modifications (5/10) and awareness of one's surroundings (4/10). CONCLUSIONS Despite histories of falls, nearly all participants reported they had not received formal fall education. However, many indicated they received fall information informally through their communities. Participants agreed successful fall prevention education would be delivered in an empowering way by a trusted member of the care team.

Insomnia is an adverse cancer outcome impacting mood, pain, quality of life, and mortality in cancer patients. Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for diverse psychophysiological disorders, including pain and insomnia. Primarily studied in breast cancer, there is limited research on CBT within gynecology oncology. This study examined CBT effects on subjective and behavioral sleep outcomes: Sleep Efficiency (SE), Sleep Quality (SQ), Total Wake Time (TWT), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO). Thirty-five women with insomnia status/post-surgery for gynecologic cancer were randomized to CBT for insomnia and pain (CBTi.p., N=18) or Psychoeducation (N=17). Sleep was assessed via sleep diaries and wrist-worn actigraphy at baseline (T1), post-intervention (T2), and two-month follow-up (T3). Intent-to-treat analyses utilizing mixed linear modeling examined longitudinal group differences on sleep controlling for age and advanced cancer. All participants demonstrated improved (1) subjective SE (0.5, p

To assess the proportion of indeterminate QuantiFERON-TB Gold Plus (QFT-Plus) results in patients admitted for severe coronavirus disease 2019 (COVID-19) pneumonia and evaluate the factors associated with indeterminate QFT-Plus results.Data on COVID-19 admissions at Mayo Clinic in Florida were extracted between October 13, 2020, and September 20, 2021, and data from a prepandemic cohort were extracted between October 13, 2018, and September 20, 2019. A secondary analysis of the COVID-19 cohort was performed using gradient boosting modeling to generate variable importance and SHapley Additive exPlanations plots.Our findings demonstrated more indeterminate QFT-Plus test results in patients hospitalized for severe COVID-19 infection than in patients without COVID-19 (139 of 495, 28.1%). The factors associated with indeterminate QFT-Plus test results included elevated levels of C-reactive protein, ferritin, lactate dehydrogenase and interleukin-6 and included lower levels of leukocyte, lymphocyte, and platelet counts.The patients with severe COVID-19 had a higher likelihood of indeterminate QFT-Plus results, which were associated with elevated levels of inflammatory markers consistent with severe infection. Interferon-gamma release assay screening tests are likely confounded by COVID-19 infection itself, limiting the screening ability for latent tuberculosis infection reactivation. Indeterminate QFT-Plus results may also require follow-up QFT-Plus testing after patient recovery from COVID-19, increasing the cost and complexity of medical decision making and management. Additional risk assessments may be needed in this patient population for screening for latent tuberculosis infection in patients with severe COVID-19.

Over the past decade, advancements in collection platforms such as unoccupied aerial systems (UAS), survey-grade GNSS, sensor packages, processing software, and spatial analytical tools have facilitated change detection analyses at an unprecedented resolution over broader spatial and temporal extents and in environments where such investigations present challenges. These technological improvements, coupled with the accessibility and versatility of UAS technology, have pushed the boundaries of spatial and temporal scales in geomorphic change detection. As a result, the cm-scale analysis of topographic signatures can detect and quantify surface anomalies during geomorphic evolution. This review focuses on the use of UAS photogrammetry for fine spatial (cm) and temporal (hours to days) scale geomorphic analyses, and it highlights analytical approaches to detect and quantify surface processes that were previously elusive. The review provides insight into topographic change characterization with precise spatial validations applied to landscape processes in various fields, such as the cryosphere and geosphere, as well as anthropogenic earth processes and national security applications. This work sheds light on previously unexplored aspects of both natural and human-engineered environments, demonstrating the potential of UAS observations in change detection. Our discussion examines the emerging horizons of UAS-based change detection, including machine learning and LIDAR systems. In addition, our meta-analysis of spatial and temporal UAS-based observations highlights the new fine-scale niche of UAS-photogrammetry. This scale advancement sets a new frontier in change detection, offering exciting possibilities for the future of land surface analysis and environmental monitoring in the field of Earth Science.

Focusing on fingers with proximal interphalangeal joint flexion contractures, this study seeks to determine whether significant differences exist between the joint passive range of motion PROM improvement when receiving higher doses of daily total end range time (TERT) compared to those that receive lower doses. The study randomized a parallel group of fifty-seven fingers in fifty patients with concealed allocation and assessor blinding. Divided into two groups receiving different doses of daily total end range time with an elastic tension digital neoprene orthosis, they also participated in an identical exercise program. Patients reported orthosis wear time, and the researchers performed goniometric measurements at every session during the three-week period. The primary outcome related the time patients wore the orthosis to the degrees of improvement in PROM extension. Compared to group B (daily TERT of twelve hours), group A (TERT, twenty+ hours) showed a statistically significant greater improvement in PROM after three weeks of treatment. Group A improved by a mean of 29° compared to group B’s mean of 19° improvement. This study provides evidence that a higher dose of daily TERT can generate better results in the treatment of the proximal interphalangeal joint flexion contractures.

ZusammenfassungDie Nachfrage nach Studienplätzen der Humanmedizin übersteigt seit vielen Jahren deutlich das Angebot der staatlichen Medizinfakultäten in Deutschland. Durch den zunehmenden Ärztemangel steigt auf der anderen Seite der Bedarf an ausgebildeten Medizinerinnen und Medizinern. Um diese Lücke zu schließen, wurden in den letzten Jahren zahlreiche Möglichkeiten neu eröffnet, in Deutschland Humanmedizin zu studieren. Neben Neugründungen von Fakultäten sind insbesondere Kooperationen von Kliniken mit europäischen Universitäten und Privatuniversitäten zu nennen. Dieser Beitrag gibt eine Übersicht über die Optionen und Rahmenbedingungen.

ZusammenfassungIm Zuge der Neugründung medizinischer Fakultäten in Deutschland muss auch die dermatologische Forschung und Lehre aufgebaut werden. Diese großen Zusatzaufgaben neben der Krankenversorgung stellen eine Herausforderung für die Klinikleitungen dar. In diesem Übersichtsbeitrag beschreiben exemplarisch Chefärztinnen und Chefärzte neuer Universitätshautkliniken und dermatologischer Fachabteilungen die Auswirkungen, die die Umwandlung in eine Universitätsklinik auf die Forschung und Lehre sowie den klinischen Alltag mit sich gebracht hat.

Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Introduction Indocyanine green (ICG) angiography is a novel technology that has been predictive of postoperative wound complications. It is unknown whether this technology can successfully predict complications after sarcoma resection. In this study, we aimed to evaluate the sensitivity and specificity of ICG angiography in predicting postoperative wound complications after soft-tissue sarcoma resection. Methods A prospective cohort study of 23 patients was performed beginning October 2017 at our institution. Patients who underwent soft-tissue sarcoma resection were included. After tumor resection and wound closure, evaluation of tissue perfusion in skin edges was performed with ICG angiography. Wound complications were recorded in the postoperative follow-up. Results Eight patients developed postoperative wound complications. Six patients were predicted to have wound complications on the final ICG scans. The accuracy of ICG angiography was dependent on the anatomic location, with improved accuracy in the lower extremity. ICG angiography had a sensitivity of 50%, a specificity and a positive predictive value of 100%, and a negative predictive value of 70% for wound complications after soft-tissue sarcoma resections located in the lower extremity. Conclusion ICG angiography has a high predictive value in the lower extremity for postoperative wound complications. Level of evidence Level III, Diagnostic.

This paper describes the guidelines for writing effective manuscript that complies with general scientific writing style and in particular with those that are incorporated by the editors and reviewers of the Global Clinical Engineering Journal (www.GlobalCE.org) when they evaluate submission of manuscripts. Readers of this paper will gain understandings of the manuscript preferred writing format and of the submission’s individual sections. Examples are provided for each of individual sections that further explain their purpose and contrast of their various styles. When the guidance provided in this paper is incorporated into a new submission, it is expected to elevate the quality of the writing as well as the desire of young clinical engineers to publish about their work and the interest of the scientific community to read it.

This compendium is a follow-up to the 2018 American Diabetes Association compendium Diagnosis and Management of Diabetic Foot Complications. Whereas the first compendium offered a broad general overview of diabetic foot conditions, this second volume presents a detailed discussion of the prevention and treatment of diabetic foot infections (DFIs), a major contributor to high amputation rates among people with diabetes. The treatise begins from the viewpoint of basic science, describing the impact of infection on the healing process of experimental wounds. There follow overviews of biofilm development in chronic diabetic foot ulcers (DFUs), the microbiology of DFIs, and the crucial role of debridement in ensuring positive outcomes of DFI treatment. Next, the authors provide a practical guide to the diagnosis and clinical management of DFIs. Current controversies regarding the treatment of osteomyelitis are addressed, including the relative value of antibiotics versus surgery and the use of intravenous versus oral antibiotics. The compendium closes with a look at new topical treatments and the role of emerging technologies in infection control.This publication has been supported by unrestricted educational grants to the American Diabetes Association from Healogics, Inc., and Organogenesis, Inc.The opinions expressed are those of the authors and do not necessarily reflect those of Healogics, Inc., Organogenesis, Inc., or the American Diabetes Association. The content was developed by the authors and does not represent the policy or position of the American Diabetes Association, any of its boards or committees, or any of its journals or their editors or editorial boards.

Computers & chemical engineering 164, 107899 (2022). doi:10.1016/j.compchemeng.2022.107899, Published by Elsevier Science, Amsterdam [u.a.]

Background: Minority and older adult patients remain underrepresented in cancer clinical trials (CCTs). The current study sought to examine sociodemographic inequities in CCT interest, eligibility, enrollment, decline motivation, and attrition across two psychosocial CCTs for gynecologic, gastrointestinal, and thoracic cancers. Methods: Patients were approached for recruitment to one of two interventions: (1) a randomized control trial (RCT) examining effects of a cognitive-behavioral intervention targeting sleep, pain, mood, cytokines, and cortisol following surgery, or (2) a yoga intervention to determine its feasibility, acceptability, and effects on mitigating distress. Prospective RCT participants were queried about interest and screened for eligibility. All eligible patients across trials were offered enrollment. Patients who declined yoga intervention enrollment provided reasons for decline. Sociodemographic predictors of enrollment decisions and attrition were explored. Results: No sociodemographic differences in RCT interest were observed, and older patients were more likely to be ineligible. Eligible Hispanic patients across trials were significantly more likely to enroll than non-Hispanic patients. Sociodemographic factors predicted differences in decline motivation. In one trial, individuals originating from more urban areas were more likely to prematurely discontinue participation. Discussion: These results corroborate evidence of no significant differences in CCT interest across minority groups, with older adults less likely to fulfill eligibility criteria. While absolute Hispanic enrollment was modest, Hispanic patients were more likely to enroll relative to non-Hispanic patients. Additional sociodemographic trends were noted in decline motivation and geographical prediction of attrition. Further investigation is necessary to better understand inequities, barriers, and best recruitment practices for representative CCTs.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs. Eighty percent or better concurrence among the panellists was considered a consensus. A large number of critical questions were discussed and agreed upon. Important takeaways included that wound care needs to be simplified to a point that it can be delivered by the patient or the patient's family. Another one was that telemonitoring, which has proved very useful during the COVID-19 pandemic, can help reduce the frequency of interventions by a visiting nurse or a wound care center. Defining patient expectations is critical to designing a successful treatment. Patient outcomes might include wound specific outcomes such as time to heal, wound size reduction, as well as improvement in quality of life. For those patients with expectations of healing, an aggressive approach to achieve that goal is recommended. When healing is not an expectation, such as in patients receiving palliative wound care, outcomes might include pain reduction, exudate management, odour management and/or other quality of life benefits to wound care.

The Jemez Mountains salamander (

Combination of immune checkpoint inhibitors and mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) has been proposed to enhance the durability of anti-tumour responses induced by MAPKi. Here, we present phase I safety results from an open-label, phase I/II study of pembrolizumab (PEM), encorafenib (ENC) and binimetinib (BIN) triplet therapy in advanced, B-Raf proto-oncogene serine/threonine kinase (BRAF)The dose finding phase I part used a 3 + 3 design, starting with the approved doses of PEM (200 mg every three weeks), ENC (450 mg once daily [QD]) and BIN (45 mg twice daily [BID]) as dose level (DL) 0. Reduction of the ENC and BIN doses (300 mg QD and 30 mg BID at DL-1 and 200 mg QD and 30 mg BID at DL-2) was preplanned in case of ≥2 dose-limiting toxicities (DLTs). Primary objectives were to estimate the recommended phase II dose of the triplet combination, DLT and safety. As per the sponsor's decision, the study was terminated after the phase I part, as the clinical efficacy of the combination is currently being investigated in a pivotal, placebo-controlled (PEM mono), double-blinded phase III trial (STARBOARD,NCT04657991).Fifteen patients were enrolled. DLTs of DL0 were creatine phosphokinase (CPK) elevation plus cytokine release syndrome (n = 1) and gamma glutamyl transferase (GGT) increase (n = 1). No DLT was observed in further 3 + 3 patients at DL-1. One (isolated GGT elevations) DLT of DL0 was questionable, as the patient had further episodes of isolated GGT elevations after treatment discontinuation. Hence, further 6 patients were enrolled at DL0: here, no DLT occurred. In total, 13 of 15 patients (87%) experienced a treatment-related adverse event (TRAE) and 8 patients (53%), a grade ≥III TRAE; there were no TRAE-related deaths. Increases in aspartate aminotransferases, GGT (6/15 patients) and CPK elevations (4/15) were the most common grade III-IV TRAE. In median, patients received triplet therapy for 24 weeks (interquartile range [IQR], 12-45). Of the 14 patients evaluable for efficacy, the overall response rate was 64% (95% confidence interval [CI], 35-87). At a median follow-up of 25 months (IQR, 9-28), progression-free survival at 12 months was 41% (95% CI, 13-68).Triplet therapy with PEM, ENC and BIN as used in the study was feasible and safe and led to clinically meaningful disease control.