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In this issue, Walter et al. report the results of two clinical trials of a new therapeutic vaccine, IMA901, for the treatment of renal cell carcinoma (RCC). IMA901 consists of ten tumor-associated peptides identified as naturally presented T cell epitopes in RCC, and the authors show longer overall survival in subjects with immune responses to multiple vaccine peptides and identify serum and cellular biomarkers that may help predict overall survival in future studies of the vaccine. IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02 + subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3) + regulatory T (T reg ) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T reg cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.

Saatkamp, A., Cochrane, A., Commander, L., Guja, L., Jimenez-Alfaro, B., Larson, J., Nicotra, A., Poschlod, P., Silveira, F.A.O., Cross, A., Dalziell, E.L., Dickie, J., Erickson, T.E., Fidelis, A., Fuchs, A., Golos, P.J., Hope, M., Lewandrowski, W., Merritt, D.J., Miller, B.P., Miller, R., Offord, C.A., Ooi, M.K.J., Satyanti, A., Sommerville, K.D., Tangney, R., Tomlinson, S., Turner, S., Walck, J.L.

Background The rapid adoption of digital skin imaging applications has increased the utilization of smartphone‐acquired images in dermatology. While this has enormous potential for scaling the assessment of concerning skin lesions, the insufficient quality of many consumer/patient‐taken images can undermine clinical accuracy and potentially harm patients due to lack of diagnostic interpretability. We aim to characterize the current state of digital skin imaging applications and comprehensively assess how image acquisition features address image quality. Materials and methods Publicly discoverable mobile, web, and desktop‐based skin imaging applications, identified through keyword searches in mobile app stores, Google Search queries, previous teledermatology studies, and expert recommendations were independently assessed by three reviewers. Applications were categorized by primary audience (consumer‐facing, nonhospital‐based practice, or enterprise/health system), function (education, store‐and‐forward teledermatology, live‐interactive teledermatology, electronic medical record adjunct/clinical imaging storage, or clinical triage), in‐app connection to a healthcare provider (yes or no), and user type (patient, provider, or both). Results Just over half (57%) of 191 included skin imaging applications had at least one of 14 image acquisition technique features. Those that were consumer‐facing, intended for educational use, and designed for both patient and physician users had significantly greater feature richness (p < 0.05). The most common feature was the inclusion of text‐based imaging tips, followed by the requirement to submit multiple images and body area matching. Conclusion Very few skin imaging applications included more than one image acquisition technique feature. Feature richness varied significantly by audience, function, and user categories. Users of digital dermatology tools should consider which applications have standardized features that improve image quality.

Background Despite the increasing ubiquity and accessibility of teledermatology applications, few studies have comprehensively surveyed their features and technical standards. Importantly, features implemented after the point of capture are often intended to augment image utilization, while technical standards affect interoperability with existing healthcare systems. We aim to comprehensively survey image utilization features and technical characteristics found within publicly discoverable digital skin imaging applications. Materials and Methods Applications were identified and categorized as described in Part I. Included applications were then further assessed by three independent reviewers for post‐imaging content, tools, and functionality. Publicly available information was used to determine the presence or absence of relevant technology standards and/or data characteristics. Results A total of 20 post‐image acquisition features were identified across three general categories: (1) metadata attachment, (2) functional tools (i.e., those that utilized images or in‐app content to perform a user‐directed function), and (3) image processing. Over 80% of all applications implemented metadata features, with nearly half having metadata features only. Individual feature occurred and feature richness varied significantly by primary audience (p < 0.0001) and function (p < 0.0001). On average, each application included under three features. Less than half of all applications requested consent for user‐uploaded photos and fewer than 10% provided clear data use and privacy policies. Conclusion Post‐imaging functionality in skin imaging applications varies significantly by primary audience and intended function, though nearly all applications implemented metadata labeling. Technical standards are often not implemented or reported consistently. Gaps in the provision of clear consent, data privacy, and data use policies should be urgently addressed.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work–life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Objective The aim of the study is to evaluate healthcare practitioners’ views on and satisfaction with (i) digital image acquisition and storage and (ii) store-and-forward teledermoscopy services for the diagnosis of skin cancer in their clinical practice. Methods An online survey was conducted among 59 healthcare practitioners (GPs (n=17), dermatologists (n=22), dermatology registrars (n=18), a dermatology research fellow (n=1) and a plastic surgeon (n=1)) to assess usability of digital image acquisition and storage for when the imaging process is conducted by the healthcare practitioners themselves, or by their patients. The study identifies the enablers and barriers of this emerging mode of medical practice. A thematic analysis was used to extract key themes from open-ended responses, which involved identifying themes and patterns within and across participants. Results Thirty-four healthcare practitioners (58%) had previously used a mobile dermatoscope within their practice. Participants most appreciated its use in their practice for lesion monitoring (59%) and record keeping (39%). Challenges reported were the increased time to support the additional workload (45%), technical issues (33%) and cost of equipment (27%). Practitioners were unsure (36%) or did not advocate teledermoscopy for direct-to-consumer use (41%). Only 23% supported the use of direct-to-consumer teledermoscopy. Conclusion While most practitioners are receptive to mobile teledermoscopy, there was less support for patient-initiated use, whereby the patient controls the imaging process. As technology improves rapidly it is important to evaluate practitioners’ acceptance and satisfaction of evolving telehealth services, moving forward with models of practice where healthcare practitioners and other healthcare providers will feel comfortable engaging in telehealth services.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient’s pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Purpose The rapid spread of SARS-CoV-2, the virus that is responsible for causing COVID-19, has presented the medical community with another example of when convalescent plasma (CP) is still used today. The ability to standardize CP at the onset of a pandemic is unlikely to exist in a reliable and uniformly reproducible way. We hypothesized that CP of unknown strength given in a serial manner will promote health and reduce mortality in those inflicted with COVID-19. Methods Participants were given up to 8 CP-units depending on their condition upon entry into the study and their response. Results 102 out of 117 participants were given CP. The earlier a participant received CP corelated with survival (p = 0.0004). The number of CP-units given, throughout all the clinical severities, was not significant with outcomes, p = 0.3947. A higher number of CP-units given to the severe/critical participants (without biological immunosuppressants or restrictive lung disease) did correlate with survival p = 0.0116 (2.8 vs. 2 units). Lower platelets on admission corelated with mortality. Platelet levels increase correlated with CP infusions p < 0.0001. Conclusion This study supports the serial use of CP of unknown strength based on clinical response for those infected with COVID-19. The use of 3–4 units of CP was found to be statistically significant for survival for severe and critical participants without restrictive lung disease and chronic biological immunosuppression. Increased platelet levels after CP infusions supports that CP is promoting overall health regardless of outcomes.

As a relatively nascent discipline, conservation physiology has struggled to deliver science that is relevant to decision-makers or directly useful to practitioners. A growing body of literature has revealed that co-produced research is more likely to generate knowledge that is not only relevant, but that is also embraced and actionable. Co-production broadly involves conducting research collaboratively, inclusively, and in a respectful and engaged manner—spanning all stages from identifying research needs to study design, data collection, interpretation and application. This approach aims to create actionable science and deliver meaningful benefits to all partners involved. Knowledge can be co-produced with practitioners/managers working for regulators or stewardship bodies, Indigenous communities and governments, industry (e.g. fishers, foresters, farmers) and other relevant actors. Using diverse case studies spanning issues, taxa and regions from around the globe, we explore examples of co-produced research related to conservation physiology. In doing so, we highlight benefits and challenges while also identifying lessons for others considering such an approach. Although co-production cannot guarantee the ultimate success of a project, for applied research (such as what conservation physiology purports to deliver), embracing co-production is increasingly regarded as the single-most important approach for generating actionable science to inform conservation. In that sense, the conservation physiology community would be more impactful and relevant if it became commonplace to embrace co-production as demonstrated by the case studies presented here. LAY SUMMARY This article aims to highlight successful applications of co-production within the realm of conservation physiology. Relying on the diverse experiences of co-authors, we also offer guidance to those embracing co-production in their conservation physiology projects.

Imaging is increasingly being used in dermatology for documentation, diagnosis, and management of cutaneous disease. The lack of standards for dermatologic imaging is an impediment to clinical uptake. Standardization can occur in image acquisition, terminology, interoperability, and metadata. This paper presents the International Skin Imaging Collaboration position on standardization of metadata for dermatologic imaging. Metadata is essential to ensure that dermatologic images are properly managed and interpreted. There are two standards-based approaches to recording and storing metadata in dermatologic imaging. The first uses standard consumer image file formats, and the second is the file format and metadata model developed for the Digital Imaging and Communication in Medicine (DICOM) standard. DICOM would appear to provide an advantage over using consumer image file formats for metadata as it includes all the patient, study, and technical metadata necessary to use images clinically. Whereas, consumer image file formats only include technical metadata and need to be used in conjunction with another actor—for example, an electronic medical record—to supply the patient and study metadata. The use of DICOM may have some ancillary benefits in dermatologic imaging including leveraging DICOM network and workflow services, interoperability of images and metadata, leveraging existing enterprise imaging infrastructure, greater patient safety, and better compliance to legislative requirements for image retention.