A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4+ and CD8+ T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765).

Multi-level tuberculosis of the spine identified by 18 F-FDG-PET/CT and concomitant urogenital tuberculosis: a case report from the spinal TB X cohort.

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and typically infects the lungs. However, extrapulmonary forms of TB can be found in approximately 20% of cases. It is suggested, that up to 10% of extrapulmonary TB affects the musculoskeletal system, in which spinal elements (spinal tuberculosis, STB) are involved in approximately 50% of the cases. STB is a debilitating disease with nonspecific symptoms and diagnosis is often delayed for months to years. In our Spinal TB X Cohort, we aim to describe the clinical phenotype of STB using whole-body 18 F-fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) and to identify a specific gene expression profile for the different stages of dissemination on PET/CT. Here we report on the first patient recruited into our cohort who underwent PET/CT before treatment initiation, at 6-months and at 12-months - time of TB treatment completion. CASE PRESENTATION: A 27-year-old immunocompetent male presented with severe thoracolumbar back pain for 9 months with severe antalgic gait and night sweats. Magnetic resonance imaging (MRI) of the whole spine revealed multilevel spinal disease (T5/6, T11/12, L3/4) in keeping with STB. After informed consent and recruitment into the Spinal TB X Cohort, the patient underwent PET/CT as per protocol, which revealed isolated multilevel STB (T4-7, T11/12, L3/4) with no concomitant lung or urogenital lesion. However, sputum and urine were Xpert MTB/RIF Ultra positive and Mtb was cultured from the urine sample. CT-guided biopsy of the T11/12 lesion confirmed drug-sensitive Mtb on Xpert MTB/RIF Ultra and the patient was started on TB treatment according to local guidelines for 12 months. The 6-month follow-up PET/CT revealed new and existing spinal lesions with increased FDG-uptake despite significant improvement of clinical features and laboratory markers. After 9 months of treatment, the patient developed an acute urethral stricture, most likely due to urogenital TB, and a suprapubic catheter was inserted. The 12-month PET/CT showed significantly decreased PET/CT values of all lesions, however, significant persistent spinal inflammation was present at the end of TB treatment. Clinically, the patient was considered cured by the TB control program and currently awaits urethroplasty. CONCLUSIONS: In our case, PET/CT emerged as a valuable imaging modality for the initial assessment, surpassing MRI by revealing more comprehensive extensive disease. Subsequent PET/CT scans at 6-month uncovered new lesions and increased inflammation in existing ones, while by the end of TB treatment, all lesions exhibited improvement. However, the interpretation of FDG avidity remains ambiguous, whether it correlates with active infection and viable Mtb. or fibro- and osteoblast activity indicative of the healing process. Additionally, the absence of extraspinal TB lesions on PET/CT despite positive microbiology from sputum and urine maybe explained by paucibacillary, subclinical infection of extraspinal organs. The Spinal TB X Cohort endeavours to shed light on whole-body imaging patterns at diagnosis, their evolution midway through TB treatment, and upon treatment completion. Ultimately, this study aims to advance our understanding of the biology of this complex disease.

A kinesin-3 recruitment complex facilitates axonal sorting of enveloped alpha herpesvirus capsids.

Axonal sorting, the controlled passage of specific cargoes from the cell soma into the axon compartment, is critical for establishing and maintaining the polarity of mature neurons. To delineate axonal sorting events, we took advantage of two neuroinvasive alpha-herpesviruses. Human herpes simplex virus 1 (HSV-1) and pseudorabies virus of swine (PRV; suid herpesvirus 1) have evolved as robust cargo of axonal sorting and transport mechanisms. For efficient axonal sorting and subsequent egress from axons and presynaptic termini, progeny capsids depend on three viral membrane proteins (Us7 (gI), Us8 (gE), and Us9), which engage axon-directed kinesin motors. We present evidence that Us7-9 of the veterinary pathogen pseudorabies virus (PRV) form a tripartite complex to recruit Kif1a, a kinesin-3 motor. Based on multi-channel super-resolution and live TIRF microscopy, complex formation and motor recruitment occurs at the trans-Golgi network. Subsequently, progeny virus particles enter axons as enveloped capsids in a transport vesicle. Artificial recruitment of Kif1a using a drug-inducible heterodimerization system was sufficient to rescue axonal sorting and anterograde spread of PRV mutants devoid of Us7-9. Importantly, biophysical evidence suggests that Us9 is able to increase the velocity of Kif1a, a previously undescribed phenomenon. In addition to elucidating mechanisms governing axonal sorting, our results provide further insight into the composition of neuronal transport systems used by alpha-herpesviruses, which will be critical for both inhibiting the spread of infection and the safety of herpesvirus-based oncolytic therapies.

Potential of digitalization within physiotherapy: a comparative survey.

BACKGROUND: Due to the global digitalization, implementation of digital elements into daily work can support physiotherapists' work but may also pose some challenges. Only little is known about physiotherapists' attitude towards digitalization. This study primarily aimed to analyze physiotherapists' attitude towards digitalization and to what extend digital tools have been implemented into their daily work. In second analysis, participants' characteristics such as age, working place, gender and mode of survey participation were assessed. METHODS: A 12-main-item survey amongst voluntary course participants of one physiotherapeutic training center was conducted via paper-based as well as online questionnaires between July 2018 and June 2019 including questions on participants' general as well as particular attitude towards digitalization, the use of (mobile) applications and possible advantages and disadvantages of the ongoing digital transformation. Sub-analysis was performed for age (≤40 years versus > 40 years), gender, mode of participation (paper vs. online) and working place (practice vs. hospital). RESULTS: Overall, 488 physiotherapists participated in the survey. In comparison of the age groups, younger participants had more concerns about data security (p = 0.042) and insufficient financial remuneration (p < 0.001). Younger participants stated higher satisfaction with data literacy than their counterparts (p = 0.0001). Physiotherapists working in the outpatient sector, rather than in hospitals, expected digitalization to increase more in relevance (p < 0.001). The online respondents (OG) indicated that they had more knowledge about key aspects of the current legal situation regarding digitalization than participants completing the paper-based survey (p = 0.002). 50.4% of the considered digitalization as useful for their job. CONCLUSIONS: The majority of participants saw high potential for digitalization in the physiotherapy sector. Younger physiotherapists seem to be more concerned about data security and insufficient financial remuneration. Physiotherapists in the outpatient sector seem to see more potential in digital transformations. General concerns like missing reimbursement, lack of data security or knowledge on legal frameworks should be addressed in the future. Further studies should focus on identifying specific digital tools which can support physiotherapists.

Age-Dependent Patient and Trauma Characteristics and Hospital Resource Requirements-Can Improvement Be Made? An Analysis from the German Trauma Registry.

Background and objectives: The burden of geriatric trauma patients continues to rise in Western society. Injury patterns and outcomes differ from those seen in younger adults. Getting a better understanding of these differences helps medical staff to provide a better care for the elderly. The aim of this study was to determine epidemiological differences between geriatric trauma patients and their younger counterparts. To do so, we used data of polytraumatized patients from the TraumaRegister DGU®. Materials and Methods: All adult patients that were admitted between 1 January 2013 and 31 December 2017 were included from the TraumaRegister DGU®. Patients aged 55 and above were defined as the elderly patient group. Patients aged 18-54 were included as control group. Patient and trauma characteristics, as well as treatment and outcome were compared between groups. Results: A total of 114,169 severely injured trauma patients were included, of whom 55,404 were considered as elderly patients and 58,765 younger patients were selected for group 2. Older patients were more likely to be admitted to a Level II or III trauma center. Older age was associated with a higher occurrence of low energy trauma and isolated traumatic brain injury. More restricted utilization of CT-imaging at admission was observed in older patients. While the mean Injury Severity Score (ISS) throughout the age groups stayed consistent, mortality rates increased with age: the overall mortality in young trauma patients was 7.0%, and a mortality rate of 40.2% was found in patients >90 years of age. Conclusions: This study shows that geriatric trauma patients are more frequently injured due to low energy trauma, and more often diagnosed with isolated craniocerebral injuries than younger patients. Furthermore, utilization of diagnostic tools as well as outcome differ between both groups. Given the aging society in Western Europe, upcoming studies should focus on the right application of resources and optimizing trauma care for the geriatric trauma patient.

Role of kinesins in directed adenovirus transport and cytoplasmic exploration.

Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B. The Kif5B RNAi phenotype was rescued by expression of RNAi-resistant Kif5A, B, or C, and Kif4A. Kif5B RNAi also inhibited a novel form of microtubule-based "assisted-diffusion" behavior which was apparent between 30 and 60 min p.i. We found the major capsid protein penton base (PB) to recruit kinesin-1, distinct from the hexon role we previously identified for cytoplasmic dynein binding. We propose that adenovirus uses independently recruited kinesin and dynein for directed transport and for a more random microtubule-based assisted diffusion behavior to fully explore the cytoplasm before docking at the nucleus, a mechanism of potential importance for physiological cargoes as well.

Would patients undergo postoperative follow-up by using a smartphone application?

BACKGROUND: eHealth applications have been proposed as an alternative to monitor patients in frequent intervals or over long distances. The aim of this study was to assess whether patients would accept an application on their smartphone to be monitored by their physicians. METHODS: During September 2017 and December 2017 a survey amongst smartphone users was conducted via paper and web-based questionnaires. RESULTS: More than half of the 962 participants (54%) were older than 55 years of age. The majority of the participants (68.7%) would accept a follow-up by a smartphone application obtaining personal healthcare data. 72.6% of all patients older than 55 years of age would use the application. The most prevalent reason against installing the application was data protection. Patients being currently treated in an orthopaedic practice and pedestrians were more eager to accept a follow-up by a mobile app than participants from social media. CONCLUSION: The majority of participants would accept a mobile application, collecting personal health-related data for postoperative follow-up, and saw a direct benefit for the patient in such an application.

[Digitalization in orthopedics and trauma surgery: current status of clinical and practical aspects 2020]. / Digitalisierung in Orthopädie und Unfallchirurgie: Stand 2020 in Klinik und Praxis.

This article deals with the current state mid-2020 in the clinical and practical aspects from the perspective of orthopedics and trauma surgery. The risks, difficulties, potentials and options are discussed in detail. The following topics are specifically debated: infrastructure of telematics, apps and mobile health, online video consultation, electronic medical records and data protection. The advantages and disadvantages and the current state of each topic in the special case of orthopedics and trauma surgery are discussed. Additionally, seven meaningful examples from the field of digital applications are named. A survey of members of the Professional Association of Orthopedic and Trauma Surgeons (BVOU) is described and analyzed. In a concluding perspective the current hurdles and future topics that need clarification are addressed.

[Computer-assisted decision-making for trauma patients]. / Computerassistierte Entscheidungsfindung beim Traumapatienten.

BACKGROUND: In the management of trauma patients in the resuscitation room many time-pressured and critical decisions must continuously be made in complex situations. Even experienced teams frequently make errors in this context. Computer-assisted decision-making systems can predict critical situations based on patient data continuously acquired online. Based on the calculated predictions these systems can suggest the next steps in managing the patient. This review summarizes the current literature on computer-assisted decision-making in the management of trauma patients. OBJECTIVE: A literature review summarizing existing concepts and applications of computer-assisted decision-making support for the management of trauma patients. METHODS: Narrative review article based on an analysis of literature in the German and English languages from the last 10 years. RESULTS: There exist numerous computer-assisted decision-making systems in the field of trauma care. Several studies could show that computer-assisted decision-making can improve the outcome in the preclinical setting, the resuscitation room and in the intensive care unit. For further validation and implementation of these systems, information technological barriers have to be overcome, existing systems need to be adapted to current data protection regulations and large multicenter studies are necessary. CONCLUSION: Computer-assisted decision-making can help to improve the management of trauma patients; however, before a ubiquitous implementation a number of technological and legislative barriers have to be overcome.

Functional Carboxy-Terminal Fluorescent Protein Fusion to Pseudorabies Virus Small Capsid Protein VP26.

Fluorescent protein fusions to herpesvirus capsids have proven to be a valuable method to study virus particle transport in living cells. Fluorescent protein fusions to the amino terminus of small capsid protein VP26 are the most widely used method to visualize pseudorabies virus (PRV) and herpes simplex virus (HSV) particles in living cells. However, these fusion proteins do not incorporate to full occupancy and have modest effects on virus replication and pathogenesis. Recent cryoelectron microscopy studies have revealed that herpesvirus small capsid proteins bind to capsids via their amino terminus, whereas the carboxy terminus is unstructured and therefore may better tolerate fluorescent protein fusions. Here, we describe a new recombinant PRV expressing a carboxy-terminal VP26-mCherry fusion. Compared to previously characterized viruses expressing amino-terminal fusions, this virus expresses more VP26 fusion protein in infected cells and incorporates more VP26 fusion protein into virus particles, and individual virus particles exhibit brighter red fluorescence. We performed single-particle tracking of fluorescent virus particles in primary neurons to measure anterograde and retrograde axonal transport, demonstrating the usefulness of this novel VP26-mCherry fusion for the study of viral intracellular transport.IMPORTANCE Alphaherpesviruses are among the very few viruses that are adapted to invade the mammalian nervous system. Intracellular transport of virus particles in neurons is important, as this process underlies both mild peripheral nervous system infection and severe spread to the central nervous system. VP26, the small capsid protein of HSV and PRV, was one of the first herpesvirus proteins to be fused to a fluorescent protein. Since then, these capsid-tagged virus mutants have become a powerful tool to visualize and track individual virus particles. Improved capsid tags will facilitate fluorescence microscopy studies of virus particle intracellular transport, as a brighter particle will improve localization accuracy of individual particles and allow for shorter exposure times, reducing phototoxicity and improving the time resolution of particle tracking in live cells.

Subcutaneous internal anterior fixation of pelvis fractures-which configuration of the InFix is clinically optimal?-a retrospective study.

INTRODUCTION: Subcutaneous internal fixation (InFix) has become a valid alternative for anterior fixation of pelvic ring injuries. Complications associated with this technique are lateral femoral cutaneous nerve (LFCN) irritation and anterior thigh pain due to prominent implants. The aim of this study was to identify a configuration of the InFix that causes the least adverse side effects. METHODS: Nineteen patients (6 females, mean age 61 years) with 38 hemipelves were included. Rod-to-bone distance and symphysis-rod distance were measured on AP- and outlet- radiographs. These distances were analyzed in relation to the primary outcomes: early removal of the InFix, post-operative complications and damage of the LFCN. RESULTS: Regarding rod-to-bone distance, a distance of 20 to 25 mm causes less complications, LFCN damage and no early removals of the InFix. Symphysis-to-rod distance analysis showed the best results regarding LFCN damage and other complications when the rod had a distance of less than 40 mm to the symphysis. A distance more than 40 mm was associated with fewer early removal of the InFix. CONCLUSIONS: Planned optimized configuration of the InFix with a rod-to-bone distance between 20 and 25 mm may reduce postoperative complications. Regarding LFCN damage, the rod-to-symphysis distance should not be more than 40 mm.

Dual-Color Herpesvirus Capsids Discriminate Inoculum from Progeny and Reveal Axonal Transport Dynamics.

Alphaherpesviruses such as herpes simplex virus and pseudorabies virus (PRV) are neuroinvasive double-stranded DNA (dsDNA) viruses that establish lifelong latency in peripheral nervous system (PNS) neurons of their native hosts. Following reactivation, infection can spread back to the initial mucosal site of infection or, in rare cases, to the central nervous system, with usually serious outcomes. During entry and egress, viral capsids depend on microtubule-based molecular motors for efficient and fast transport. In axons of PNS neurons, cytoplasmic dynein provides force for retrograde movements toward the soma, and kinesins move cargo in the opposite, anterograde direction. The dynamic properties of virus particles in cells can be imaged by fluorescent protein fusions to the small capsid protein VP26, which are incorporated into capsids. However, single-color fluorescent protein tags fail to distinguish the virus inoculum from progeny. Therefore, we established a dual-color system by growing a recombinant PRV expressing a red fluorescent VP26 fusion (PRV180) on a stable cell line expressing a green VP26 fusion (PK15-mNG-VP26). The resulting dual-color virus preparation (PRV180G) contains capsids tagged with both red and green fluorescent proteins, and 97% of particles contain detectable levels of mNeonGreen (mNG)-tagged VP26. After replication in neuronal cells, all PRV180G progeny exclusively contain monomeric red fluorescent protein (mRFP)-VP26-tagged capsids. We used PRV180G for an analysis of axonal capsid transport dynamics in PNS neurons. Fast dual-color total internal reflection fluorescence (TIRF) microscopy, single-particle tracking, and motility analyses reveal robust, bidirectional capsid motility mediated by cytoplasmic dynein and kinesin during entry, whereas egressing progeny particles are transported exclusively by kinesins. IMPORTANCE Alphaherpesviruses are neuroinvasive viruses that infect the peripheral nervous system (PNS) of infected hosts as an integral part of their life cycle. Establishment of a quiescent or latent infection in PNS neurons is a hallmark of most alphaherpesviruses. Spread of infection to the central nervous system is surprisingly rare in natural hosts but can be fatal. Pseudorabies virus (PRV) is a broad-host-range swine alphaherpesvirus that enters neuronal cells and utilizes intracellular transport processes to establish infection and to spread between cells. By using a virus preparation with fluorescent viral capsids that change color depending on the stage of the infectious cycle, we find that during entry, axons of PNS neurons support robust, bidirectional capsid motility, similar to cellular cargo, toward the cell body. In contrast, progeny particles appear to be transported unidirectionally by kinesin motors toward distal egress sites.

Conformational changes in the adenovirus hexon subunit responsible for regulating cytoplasmic dynein recruitment.

UNLABELLED: Virus capsids provide genome protection from environmental challenges but are also poised to execute a program of compositional and conformational changes to facilitate virion entry and infection. The most abundant adenovirus serotype 5 (AdV5) capsid protein, hexon, directly recruits the motor protein cytoplasmic dynein following virion entry. Dynein recruitment is crucial for capsid transport to the nucleus and requires the transient exposure of AdV5 hexon to low pH, presumably mimicking passage through the endosomal compartment. These results suggest a pH-dependent capsid modification during early infection. The changes to hexon structure controlling this behavior have not been explored. We report that hexon remains trimeric at low pH but undergoes more subtle conformational changes. These changes are indicated by increased sensitivities to SDS-mediated dissociation and dispase proteolysis. Both effects are reversed at neutral pH, as is dynein binding by low-pH-treated hexon. Dispase cleavage, which we find maps to a specific site within hypervariable region 1 (HVR1) of AdV5 hexon, has no apparent effect on virion entry but completely inhibits its transport to the nucleus. In addition, an AdV5 mutant containing HVR1 of AdV48 is unable to bind dynein and is strongly inhibited in the postentry transport step. These results reveal that conformational changes involving hexon HVR1 are the basis for a novel viral mechanism controlling capsid transport to the nucleus. IMPORTANCE: The adenovirus serotype 5 (AdV5) capsid protein hexon recruits the molecular motor protein cytoplasmic dynein in a pH-dependent manner, a function critical for efficient transport toward the nucleus and AdV5 infectivity. In this work, we describe how low-pH exposure induces reversible structural changes in AdV5 hexon and how these changes affect dynein binding. In addition, we identified a pH-sensitive dispase cleavage site in hexon HVR1, which depends on the same structural changes and furthermore regulates dynein recruitment and capsid redistribution in infected cells. These data provide the first evidence relating long-known but subtle pH-dependent structural changes in hexon to a more recently established essential but poorly understood role in virus transport. These results have broad implications for understanding virus infectivity in general, and our ability to block the recruitment mechanism has potential therapeutic implications as well.

Tuberculous Spondylodiscitis with Psoas Abscess Descending into the Anterior Femoral Compartment Identified Using 2-deoxy-2-[18F]fluoroglucose Positron Emission Tomography Computed Tomography.

A 24-year-old immunocompetent woman underwent whole-body 18F-FDG PET/CT for the evaluation of MRI-suspicious tuberculous spinal lesions. The PET/CT results showed no pathological uptake in either lung, and there were no pathological changes on CT. There was increased uptake in the right psoas muscle, extending continuously down anterior to the right hip joint, posterior to and around the trochanteric region of the right femur, and into the right thigh, with an SUVmaxbw of 17.0. Subsequently, the patient underwent CT-guided biopsy as per protocol, which revealed drug-sensitive Mycobacterium tuberculosis, and the patient was started on standard tuberculosis treatment for 12 months.

Professional Social Media Use Among Orthopedic and Trauma Surgeons in Germany: Cross-Sectional Questionnaire-Based Study.

BACKGROUND: Social media (SM) has been recognized as a professional communication tool in the field of orthopedic and trauma surgery that can enhance communication with patients and peers, and increase the visibility of research and offered services. The specific purposes of professional SM use and the benefits and concerns among orthopedic and trauma surgeons, however, remain unexplored. OBJECTIVE: This study aims to demonstrate the specific uses of different SM platforms among orthopedic and trauma surgeons in Germany as well as the advantages and concerns. METHODS: A web-based questionnaire was developed on the use of SM in a professional context by considering the current literature and the authors' topics of interest. The final questionnaire consisted of 33 questions and was distributed among German orthopedic and trauma surgeons via the mail distributor of the Berufsverband für Orthopädie und Unfallchirurgie (Professional Association of Orthopaedic Surgeons in Germany). The study was conducted between June and July 2022. A subgroup analysis was performed for sex (male vs female), age (<60 years vs ≥60 years), and type of workplace (practice vs hospital). RESULTS: A total of 208 participants answered the questionnaire (male: n=166, 79.8%; younger than 60 years: n=146, 70.2%). In total, all of the participants stated that they use SM for professional purposes. In contrast, the stated specific uses of SM were low. Overall, the most used platforms were employment-oriented SM, messenger apps, and Facebook. Instagram emerged as a popular choice among female participants and participants working in hospital settings. The highest specific use of SM was for professional networking, followed by receiving and sharing health-related information. The lowest specific use was for education and the acquisition of patients. Conventional websites occupied a dominating position, exceeding the use of SM across all specific uses. The key benefit of SM was professional networking. Under 50% of the participants stated that SM could be used to enhance communication with their patients, keep up-to-date, or increase their professional visibility. In total, 65.5% (112/171) of participants stated that SM use was time-consuming, 43.9% (76/173) stated that they lacked application knowledge, and 45.1% (78/173) stated that they did not know what content to post. Additionally, 52.9% (91/172) mentioned medicolegal concerns. CONCLUSIONS: Overall, SM did not seem to be used actively in the professional context among orthopedic and trauma surgeons in Germany. The stated advantages were low, while the stated concerns were high. Adequate education and information material are needed to elucidate the possible professional applications of SM and to address legal concerns.

Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by 18FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort study).

BACKGROUND: Tuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB (EPTB) has received little attention. Diagnosis of EPTB remains challenging due to the invasive procedures required for sample collection. Spinal TB (STB) accounts for 10% of EPTB and often leads to lifelong debilitating disease due to devastating spinal deformation and compression of neural structures. Little is known about the extent of disease, although both isolated STB and a disseminated form of STB have been described. In our Spinal TB X cohort study, we aim to describe the clinical phenotype of STB using whole-body 18FDG-PET/CT, identify a specific gene expression profile for different stages of dissemination and compare findings to previously described gene expression signatures for latent and active pulmonary TB. METHODS: A single-centre, prospective cohort study will be established to describe the distributional pattern of STB detected by whole-body 18FDG-PET/CT and gene expression profile of patients with suspected STB on magnetic resonance imaging (MRI) at point of diagnosis, six months, and 12 months. Blood biobanking will be performed at these time points. Specimens for microbiology will be obtained from sputum/urine, from easily accessible sites of disease (e.g., lymph nodes, abscess) identified in the first 18FDG-PET/CT, from CT-guided biopsy and/or surgery. Clinical parameters and functional scores will be collected at every physical visit. Data will be entered into RedCap® database; data cleaning, validation and analysis will be performed by the study team. The University of Cape Town Ethics Committee approved the protocol (243/2022). DISCUSSION: The Spinal TB X cohort study is the first prospective cohort study using whole-body 18FDG-PET/CT scans in patients with microbiologically confirmed spinal tuberculosis. Dual imaging techniques of the spine using 18FDG-PET/CT and magnetic resonance imaging as well as tissue diagnosis (microbiology and histopathology) will allow us to develop a virtual biopsy model. If successful, a distinct gene-expression profile will aid in blood-based diagnosis (point of care testing) as well as treatment monitoring and would lead to earlier diagnosis of this devastating disease. TRIAL REGISTRATION: The study has been registered on ClinicalTrials.gov (NCT05610098).

Perspectives of Patients With Orthopedic Trauma on Fully Automated Digital Physical Activity Measurement at Home: Cross-sectional Survey Study.

BACKGROUND: The automated digital surveillance of physical activity at home after surgical procedures could facilitate the monitoring of postoperative follow-up, reduce costs, and enhance patients' satisfaction. Data on the willingness of patients with orthopedic trauma to undergo automated home surveillance postoperatively are lacking. OBJECTIVE: The aims of this study were to assess whether patients with orthopedic trauma would be generally willing to use the proposed automated digital home surveillance system and determine what advantages and disadvantages the system could bring with it. METHODS: Between June 2021 and October 2021, a survey among outpatients with orthopedic trauma who were treated at a European level 1 trauma center was conducted. The only inclusion criterion was an age of at least 16 years. The paper questionnaire first described the possibility of fully automated movement and motion detection (via cameras or sensors) at home without any action required from the patient. The questionnaire then asked for the participants' demographics and presented 6 specific questions on the study topic. RESULTS: In total, we included 201 patients whose mean age was 46.9 (SD 18.6) years. Most of the assessed patients (124/201, 61.7%) were male. Almost half of the patients (83/201, 41.3%) were aged between 30 and 55 years. The most stated occupation was a nine-to-five job (62/199, 30.8%). The majority of the participants (120/201, 59.7%) could imagine using the proposed measurement system, with no significant differences among the genders. An insignificant higher number of younger patients stated that they would use the automated surveillance system. No significant difference was seen among different occupations (P=.41). Significantly more young patients were using smartphones (P=.004) or electronic devices with a camera (P=.008). Less than half of the surveyed patients (95/201, 47.3%) stated that they were using tracking apps. The most stated advantages were fewer physician visits (110/201, 54.7%) and less effort (102/201, 50.7%), whereas the most prevalent disadvantage was the missing physician-patient contact (144/201, 71.6%). Significantly more patients with a part-time job or a nine-to-five job stated that data analysis contributes to medical progress (P=.047). CONCLUSIONS: Most of the assessed participants (120/201, 59.7%) stated that they would use the automated digital measurement system to observe their postoperative follow-up and recovery. The proposed system could be used to reduce costs and ease hospital capacity issues. In order to successfully implement such systems, patients' concerns must be addressed, and further studies on the feasibility of these systems are needed.

Fractures of the Lower Extremity after E-Bike, Bicycle, and Motorcycle Accidents: A Retrospective Cohort Study of 624 Patients.

Electric bicycles (e-bikes) have gained enormous popularity in recent years, and as a result, they have successively become more involved in traffic accidents. The aim of the present study was to assess differences in severity and localization of injuries to the lower extremities after accidents with e-bikes, conventional bicycles, and motorcycles. A retrospective cohort-analysis of patients who sustained traumatic accidents with two-wheeled vehicles transferred to a level 1 trauma center in Switzerland was performed. We assessed patient demographics, injury pattern, and trauma severity (ISS), with a subgroup analysis of outcomes stratified by vehicle. In total, 624 patients (71% male) with injuries to the lower extremities after bicycle (n = 279), electric bike (n = 19), and motorcycle (n = 326) accident were included. The mean age of all assessed patients was 42.4 years (SD 15.8), with a significantly higher age in the e-bike cohort (p = 0.0001). High-velocity injuries were found significantly more often in the motorcycle and e-bike group. The motorcycle group had a significantly higher mean ISS (17.6) than the other groups (p = 0.0001). E-bike accidents produce a different injury profile to the lower extremities compared to motorcycle or bicycle accidents. Higher age, higher velocity, and different protective equipment seem to have an impact on these fracture patterns.

Digitalization in orthopaedics: a narrative review.

Advances in technology and digital tools like the Internet of Things (IoT), artificial intelligence (AI), and sensors are shaping the field of orthopaedic surgery on all levels, from patient care to research and facilitation of logistic processes. Especially the COVID-19 pandemic, with the associated contact restrictions was an accelerator for the development and introduction of telemedical applications and digital alternatives to classical in-person patient care. Digital applications already used in orthopaedic surgery include telemedical support, online video consultations, monitoring of patients using wearables, smart devices, surgical navigation, robotic-assisted surgery, and applications of artificial intelligence in forms of medical image processing, three-dimensional (3D)-modelling, and simulations. In addition to that immersive technologies like virtual, augmented, and mixed reality are increasingly used in training but also rehabilitative and surgical settings. Digital advances can therefore increase the accessibility, efficiency and capabilities of orthopaedic services and facilitate more data-driven, personalized patient care, strengthening the self-responsibility of patients and supporting interdisciplinary healthcare providers to offer for the optimal care for their patients.

Pre-hospital and Hospital Trauma Care during the Covid-19 Lockdown - Experience in a Metropolitan European Level 1 Trauma Centre.

BACKGROUND: Trauma case load is said to have declined during the Covid-19 pandemic, especially during the national lockdowns. Due to the altered frequency and changes in daily life, pre-hospital care (altered personal protective measurements) as well as mechanisms of trauma and initial trauma treatment may have changed. The purpose of this study was to assess differences in pre-hospital as well as initial treatment of trauma victims and trauma mechanisms during a national lockdown compared to the year before. MATERIAL AND METHODS: Pre-hospital as well as clinical data from all trauma patients admitted to our metropolitan level 1 trauma center resuscitation room during the hard lockdown in Switzerland (March 17 to April 26, 2020) and the same time period in 2019 were analyzed retrospectively. RESULTS: In total, we assessed 91 patients (51 lockdown cohort, 40 control cohort) with a mean age of 50.7 years. Significantly more trauma was sustained in the household environment during the lockdown (p = 0.015). Pre-hospital treatment remained similar between the two assessed groups. No difference was found in length of stay or mortality. In severely injured patients (ISS > 15), we found significantly fewer motor vehicle accidents (p = 0.018) and fewer horizontal decelerations (p = 0.006), but insignificantly more falls (p = 0.092) in the lockdown cohort. None of the patients in the lockdown cohort had a positive PCR test for Covid-19 on admission. CONCLUSION: Trauma systems seem not to have changed during hard lockdowns in terms of pre-hospital treatment. Fewer severely injured patients due to motor vehicle accidents and horizontal decelerations, but more household-related injuries were seen in the lockdown cohort than in the control cohort. A qualitative analysis of treatment during the hard lockdown is needed to gain further insights into the effect of the pandemic on trauma care.