A Mesoporous Gold Sensor Unveils Phospho PD-L1 in Extracellular Vesicles as a Proxy for PD-L1 Expression in Lung Cancer Tissue.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy or fine needle aspiration that are currently used to identify patients most likely to respond to single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient tissue to generate a PD-L1 tissue proportion score (TPS) ≥ 50% using immunohistochemistry remains a challenge that potentially may be overcome by liquid biopsies. This study utilized a mesoporous gold sensor (MGS) assay to examine the phosphorylation status of PD-L1 in plasma extracellular vesicles (EV pPD-L1) and PD-L1 levels in plasma from NSCLC patient samples and their association with tumor PD-L1 TPS. The 3-dimensional mesoporous network of the electrodes provides a large surface area, high signal-to-noise ratio, and a superior electro-conductive framework, thereby significantly improving the detection sensitivity of PD-L1 nanosensing. Test (n = 20) (Pearson's r = 0.99) and validation (n = 45) (Pearson's r = 0.99) cohorts show that EV pPD-L1 status correlates linearly with the tumor PD-L1 TPS assessed by immunohistochemistry irrespective of the tumor stage, with 64% of patients overall showing detectable EV pPD-L1 levels in plasma. In contrast to the EV pPD-L1 results, plasma PD-L1 levels did not correlate with the tumor PD-L1 TPS score or EV pPD-L1 levels. These data demonstrate that EV pPD-L1 levels may be used to select patients for appropriate PD-1 and PD-L1 ICI therapy regimens in early, locally advanced, and advanced NSCLC and should be tested further in randomized controlled trials. Most importantly, the assay used has a less than 24h turnaround time, facilitating adoption of the test into the routine diagnostic evaluation of patients prior to therapy.

Biomechanical evaluation of double-stranded knot configurations in high-strength sutures and tapes.

PURPOSE: Recently, a new dynamic high-strength suture (DC) was introduced, also available in tape form (DT), featuring a salt-infused silicone core attracting water in a fluid environment to preserve tissue approximation. The aims of this study were to (1) assess the influence of securing throw number on knot security of two double-stranded knot configurations (Cow-hitch and Nice-knot) tied with either dynamic (DC and DT) or conventional (FW and ST) high-strength sutures and tapes, and (2) compare the ultimate force and knot slippage of the novel dynamic versus conventional sutures and tapes when used with their minimal number of needed securing throws. METHODS: Seven specimens of each FW, ST, DC and DT were considered for tying with Cow-hitch or Nice-knots. The base of these Cow-hitch and Nice-knots was secured with surgeons` knots using 1-3 alternating throws. Tensile tests were conducted under physiologic conditions to evaluate knot slippage, ultimate force at rupture, and minimum number of throws ensuring 100% knot security.  RESULTS:  For both Cow-hitch and Nice-knots, 100% security was achieved with 2 securing throws for DC, DT, ST, and with 3 securing throws for FW. With these minimum numbers of securing throws, ultimate force was significantly higher for Nice-knots versus Cow-hitch tied with DT (p = 0.001) and slippage was significantly less with Nice-knots versus Cow-hitch tied with DC (p = 0.019). CONCLUSIONS: The minimum number of securing throws required to achieve 100% security was 2 with DC, DT and ST for both Cow-hitch and Nice-knots configurations, in contrast to FW where 3 securing throws were needed. With these minimum numbers of securing throws, Nice-knots were associated with significantly higher ultimate forces when using DT and lower slippage with DC versus Cow-hitch knots.

Computer Hexapod-assisted Orthopaedic Surgery for the Correction of Multiplanar Deformities throughout the Lower Limb.

Introduction: Computerised hexapod-assisted orthopaedic surgery (CHAOS) is a method by which complex multiplanar, multilevel deformity can be corrected with a high degree of accuracy utilising minimally invasive techniques within a single operative event. This study's aim was to report the reliability, accuracy and magnitude of correction achieved, alongside patient-reported outcomes and risk factors for complications when using the CHAOS technique throughout the lower limb. Materials and methods: Retrospective review of medical records and radiographs for consecutive patients who underwent CHAOS for lower limb deformity correction at a tertiary centre between 2012 and 2020. Results: There were 70 cases in 56 patients, with the site of surgery being the femur in 48 cases, proximal tibia in 17 and distal tibia in 5 cases. Multiplanar correction was performed in 43 cases, and multilevel osteotomy was undertaken in 23 cases. Fixation was undertaken with intramedullary nailing (IMN) in 49 cases and locked plates in 21.The maximum corrections were 40° rotation, 20° coronal angulation, 51° sagittal angulation and 62-mm mechanical axis deviation (MAD). Deformity correction was mechanically satisfactory in all patients bar one who was undercorrected requiring revision. The mean patient global impression of change (PGIC) score was 6.2 out of 7.Overall complication rate was 12/70 (17%). Complications from femoral surgery included two nonunions, one case of undercorrection, one case of stiffness, one muscle hernia and one pulmonary embolism. Complications from tibial surgery were one compartment syndrome, one pseudoaneurysm of the anterior tibial artery requiring stenting, one transient neurapraxia of the common peroneal nerve, one locking plate fatigue failure, one seroma and one superficial wound infection. Conclusion: Computerised hexapod-assisted orthopaedic surgery can be used for accurate correction of complex multilevel and multiplanar deformities of both the femur and tibia. The risk profile appears to differ between femoral and tibial surgeries, and also to that of traditional circular frame correction. Patients remain highly satisfied with both the functional and symptomatic outcomes. How to cite this article: French JMR, Filer J, Hogan K, et al. Computer Hexapod-assisted Orthopaedic Surgery for the Correction of Multiplanar Deformities throughout the Lower Limb. Strategies Trauma Limb Reconstr 2024;19(1):9-14.

Delayed Abdominal Flap for Upper Extremity Soft Tissue Coverage.

Unlike other body parts, the upper extremity has critical structures close to the skin, making soft tissue injuries more complex. These injuries can result from various causes, including trauma and necrotizing soft tissue infections, necessitating reconstruction. Historically, pedicled flaps from the groin and abdomen were commonly used for upper extremity reconstruction, but they had limitations, such as the need for flap division and debulking, patient discomfort, and stiffness. Free flap reconstruction has become the preferred method, but it still faces challenges like patient and facility issues, the absence of recipient vessels after injury, and multi-surface wounds. This case report describes a 67-year-old patient with a severe necrotizing soft tissue infection in the right upper extremity. After multiple debridement procedures, the patient underwent hand amputation and soft tissue coverage using an abdominal wall-based flap. The objectives of achieving stable soft tissue coverage while preserving maximal length of the upper extremity were successfully achieved, and the patient expressed satisfaction with the outcomes. Inadequate management of upper extremity wounds can lead to amputation and psychological distress. The reconstructive ladder is used to approach upper extremity soft tissue defects, with free tissue transfer being the standard for larger defects. However, abdominal flaps still have indications when free tissue transfer is not feasible or contraindicated. It is imperative that plastic surgeons have these techniques in their armamentarium to provide a service to the ever more complex patient with an upper extremity wound.

Transport digitalisation: Navigating futures of hypercognitive disablement.

People living with cognitive impairments face new forms of disablement in the context of transport digitalisation, an issue recently catalysed by controversies regarding rail ticket office closures. Transport can dramatically impact the lives of people diagnosed with dementia, who often find their mobility suddenly and dramatically impaired. Unfortunately, sociological analysis of cognitive disability has traditionally been undermined by under-theorisation. One solution can be found in classic bioethical work on hypercognitivism-the veneration of cognitive acuity-and its disabling consequences. A hypercognitive approach can nurture an attentiveness to the specificities of digital disablement. Here, disability does not emerge from digitalisation inherently, but is instead intensified by the implementation of digitalisation in line with value commitments. A more robust sociology of cognitive disability could better represent the interests of people with cognitive impairments and resist the new forms of disability that current digitalisation risks spreading.

Lorlatinib After Alectinib-Induced Pneumonitis: A Case Report.

ALK gene rearrangements are detected in approximately 3% to 5% of NSCLC. ALK tyrosine kinase inhibitors, such as third-generation lorlatinib, have exhibited remarkable efficacy in ALK-rearranged NSCLC; however, they have been associated with a low incidence of treatment-limiting and potentially fatal drug-induced interstitial lung disease (ILD). There is concern that this may represent a class effect, a theory that is supported by a number of case reports. Because of clinical trial exclusion criteria, there are limited prospective data to guide decision-making after ALK tyrosine kinase inhibitors-induced ILD. A systematic review of the literature was conducted and only identified four reported cases of lorlatinib safety in this context. Here, we report the successful sequencing of lorlatinib in a patient who discontinued alectinib secondary to grade 3 drug-induced ILD.

Cognitivism ageing: The Alzheimer conundrum as switched ontology & the potential for a new materialist dementia.

Following recent regulatory approvals for anti-Alzheimer's monoclonal antibodies, this paper considers the contemporary role of cognitivism in defining the ontological commitments of dementia research, as well as movements away from cognitivism under the umbrella of 4E cognitive science. 4E cognitive theories, extending cognition into bodies, their environs, and active relations between the two, share potentially fruitful affinities with new materialisms which focus on the co-constitution of matter in intra-action. These semi-overlapping conceptual positions furnish some opportunity for an ontological alternative to longstanding cognitivist commitments, particularly to the isolated brain as a material catalyst for commercial interventions. After outlining mainstream cognitivism and its shortcomings, I explore 4E and new materialism as possibly transformative conceptual schemas for dementia research, a field for which cognitivist imaginings of cognitive decline in later life have profound and often regrettable ramifications. To realise this new materialist dementia, I sketch out a cognitive ontology based on Barad's agential realism. This facilitates a reassessment of the biggest conundrum in dementia research - the lack of neat correlation between (apparently material) neuropathology and (apparently immaterial) cognitive impairment - alongside the continued failure of efforts to develop effective interventions. It also gives social researchers working on cognitive decline in later life an opportunity to reappraise the nature of social science as a response to such phenomena. If cognition and cognitive ageing are reimagined as an emergent characteristic of intra-acting matter, then new materialist social science might be at least as conducive to salutogenic interventions as the neuropsychiatric technoscience that dominates the contemporary dementia research economy despite continual failures. I argue that a new materialist cognitive ontology could help us think beyond an ageing cognitivism and, by extension, beyond the Alzheimer conundrum.

A narrative review of supportive and end of life care considerations in advanced hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, and case numbers continue to rise in the United States. HCC carries a poor prognosis, and management requires a multidisciplinary approach. This narrative review aims to identify opportunities for further integration of palliative care (PC) in HCC care. Given the high symptom burden faced by patients with HCC, early PC consultation can be beneficial for patients. METHODS: A search of PubMed was conducted from inception of the database to March 1, 2023. The search was composed of keywords and controlled vocabulary terms for concepts related to palliative medicine and symptom management in the setting of HCC. KEY CONTENT AND FINDINGS: This narrative review finds that although PC has been integrated into HCC guidelines, partnerships between PC and hepatology are still nascent in clinical practice. Treatment-related barriers pose a challenge to timely integration of PC in the care of HCC patients; evaluation or listing for transplantation can be perceived as a barrier to PC consultation, and unpredictable clinical courses make prognostication challenging. Providers may hesitate to pursue PC referral due to a lack of consensus around the role of PC, and for those that are referred, timing of consultation remains an issue, especially for those who are potential liver transplant candidates. There are few studies of PC in HCC, limiting evidence-based recommendations that can be made regarding PC involvement in this patient population. CONCLUSIONS: While PC is not routinely integrated into HCC care, recent guideline recommendations and a growing number of studies may change this over time. Although further evidence is needed, PC and hepatology teams partnering together can explore ways to improve the care of this patient population. PC consultation early in HCC care could assist in management of symptom relief, psychosocial and spiritual support, and caregiver support. Effective communication will be required to set parameters for referral and clarify potential outcomes of consultation. Teams should be prepared for the challenges involved in a culture change and paradigm shift in clinical practice.

Knowledge Retention From Emergency Medicine Simulation-Based Learning Curriculum for Pre-clinical Medical Students.

Introduction Traditional medical school curricula rely on textbook-based learning during the first two years, often limiting students' clinical exposure. Simulation-based learning (SBL) provides an opportunity for students to gain clinical exposure and competency with common procedures as well as to gain knowledge related to common clinical topics. Retention of factual knowledge is a current topic of discussion as medical learners often have difficulty with long-term retention. The aim of this study was to assess if students would learn, retain, and enjoy emergency medicine (EM)-focused SBL. Materials and methods We developed an EM-focused SBL curriculum consisting of four main educational events: suturing, medical stabilization, mass casualty triage, and point-of-care ultrasound (POCUS). Participants were first- and second-year healthcare students enrolled in a traditional, preclinical curriculum, who completed pre- and post-event quizzes consisting of multiple-choice questions on topics covered during the SBL scenario. We compared pre- and post-event quiz scores using a one-way paired t-test. Quizzes were readministered up to 100 days after each SBL event to test knowledge retention, and scores were compared across time by repeated-measures analysis of variance (RMANOVA). Results For suture (n=22), mass casualty (n=20), and ultrasound simulations (n=17), post-event mean quiz scores increased significantly in comparison to mean quiz scores from before the event (p≤0.05). Medical stabilization simulation post-event scores were increased but did not reach statistical significance. Data collected at 45, 74, and 94 days following the suture lab as well as 29 and 49 days after the medical evacuation event, and 20 days after the mass casualty event showed no statistical decrease in quiz means suggesting retention of knowledge among learners. Subjective assessments of participant satisfaction demonstrated an enjoyment of the events. Discussion EM-focused SBL events offered enjoyable learning opportunities for students to effectively obtain and possibly retain clinical knowledge. Conclusion SBL has the potential to improve student retention of clinical knowledge during the preclinical years and, therefore, should be further explored and implemented as a core pillar of medical education as opposed to its current state as a learning adjunct.

Prompt Management of Airbag Burn Injuries Leads to Optimized Patient Outcomes: A Pilot Study.

BACKGROUND: Dual airbags are required to be installed and available for use in all motor vehicles since 1997. The National Highway Traffic Safety Administration reported that 50,457 lives were saved by airbags from 1987 to 2017; however, airbag deployment can cause injuries, including thermal and chemical burns, hyperpigmentation, and dysaesthesia. There is little information available in the literature regarding differences in outcomes between promptly visiting a plastic surgeon and waiting for treatment, especially as an injury may not be immediately apparent or patients may not know that airbag burn injuries may be delayed in presenting. METHODS: This is a retrospective cohort pilot study conducted among 14 patients who presented to a plastic surgeon between January 1, 2019 and June 30, 2022 owing to injuries from airbag deployment. An early visit was considered ≤30 days, and a late visit was >30 days. Other variables collected included age, sex, Fitzpatrick skin type, smoking status, comorbidities, type of injury, injury site, pain status, hyper/hypopigmentation, dysaesthesia, epithelialization, and improvements in pain, pigmentation, and dysaesthesia from treatment. RESULTS: The mean age was 36.0 years (standard deviation (SD) 17.9). The majority were female (85.7%), non-smokers (87.5%), and not diabetic (75.0%). Only six patients (42.9%) visited their doctor within one month of injury. Most patients experienced dysaesthesia (85.7%) and pain (71.4%). Thirteen of the 14 patients had hyperpigmentation or hyperemia, and one had hypopigmentation. Full or slight epithelialization was seen in 35.7%, and nine of the 14 patients had no epithelialization. Ongoing issues were a factor for 64.3% of these patients; 42.9% had ongoing issues with hyperpigmentation. A full recovery was seen in 28.6% of the patients. The patients who saw the plastic surgeon by day 30 or less (early) from the time of injury had a 66.7% improvement in pigmentation and 33.3% resolution in pain. Of those who went to the surgeon beyond 30 days (late), 25% had improvement in pigmentation and 37.5% had resolution of pain. Improvement in dysaesthesia occurred in both groups, but those who saw the plastic surgeon early had 33.3% resolution, while 37.5% of those who went late improved. Of those who went late to the surgeon, only 12.5% had epithelialization, while 66.7% of those who went within 30 days showed signs of (full or slight) epithelialization. CONCLUSION: Patients involved in motor vehicle collisions (MVCs) should be informed of the delayed fashion in which airbag burns can develop. An ostensibly mild burn may portend long-term consequences, especially if such injuries are not addressed in a prompt manner. Our study demonstrates how airbag burn injuries and their sequelae are best addressed with early care.

How frail is frail in oncology studies? A scoping review.

AIMS: The frailty index (FI) is one way in which frailty can be quantified. While it is measured as a continuous variable, various cut-off points have been used to categorise older adults as frail or non-frail, and these have largely been validated in the acute care or community settings for older adults without cancer. This review aimed to explore which FI categories have been applied to older adults with cancer and to determine why these categories were selected by study authors. METHODS: This scoping review searched Medline, EMBASE, Cochrane, CINAHL, and Web of Science databases for studies which measured and categorised an FI in adults with cancer. Of the 1994 screened, 41 were eligible for inclusion. Data including oncological setting, FI categories, and the references or rationale for categorisation were extracted and analysed. RESULTS: The FI score used to categorise participants as frail ranged from 0.06 to 0.35, with 0.35 being the most frequently used, followed by 0.25 and 0.20. The rationale for FI categories was provided in most studies but was not always relevant. Three of the included studies using an FI > 0.35 to define frailty were frequently referenced as the rationale for subsequent studies, however, the original rationale for this categorisation was unclear. Few studies sought to determine or validate optimum FI categorises in this population. CONCLUSION: There is significant variability in how studies have categorised the FI in older adults with cancer. An FI ≥ 0.35 to categorise frailty was used most frequently, however an FI in this range has often represented at least moderate to severe frailty in other highly-cited studies. These findings contrast with a scoping review of highly-cited studies categorising FI in older adults without cancer, where an FI ≥ 0.25 was most common. Maintaining the FI as a continuous variable is likely to be beneficial until further validation studies determine optimum FI categories in this population. Differences in how the FI has been categorised, and indeed how older adults have been labelled as 'frail', limits our ability to synthesise results and to understand the impact of frailty in cancer care.

Administration of immune checkpoint inhibitors at rural towns using the Teleoncology model of care-A North Queensland perspective.

OBJECTIVE: This study aimed at evaluating the safety of administering immune checkpoint inhibitors (ICIs) and monitoring for immune-related adverse events (irAEs) using the Teleoncology model of care. DESIGN: A retrospective cohort study comparing two patient groups. SETTING: The North Queensland Teleoncology Network (NQTN) operated by the Townsville (THHS) and Cairns Hospital Health Services (CHHS) with the Townsville Cancer Centre (TCC) acting as the control group setting. PARTICIPANTS: Patients who received ICI treatment via the NQTN between January 2015 and April 2019. Patients who received ICI at the TCC over the same time period were used for comparison. MAIN OUTCOME MEASURES: Rates of high-grade irAEs and irAE-related deaths. RESULTS: Fifty-two patients received a total of 822 cycles of ICIs via the Teleoncology model through NQTN. Over the same time period, 142 patients received a total of 1521 cycles at the TCC. There were no significant differences in all demographic characteristics between either group, including tumour profile and Indigenous status. There were no statistically significant differences between the rates of high-grade irAE across multiple body organ systems (p = 0.151) and rate of hospital admissions (13.5% (NQTN) vs 5.6% (TCC), p = 0.702). There were no irAE-related deaths in either group. CONCLUSIONS: The results suggest that with adequate governance and clinical resources, ICIs can be administered safely using Teleoncology models to rural and remote towns.

Regulating the disenfranchised: Reciprocity & resistance under the Mental Capacity Act.

This paper interrogates the legitimacy of formal ethical regulation regarding people with dementia under the Mental Capacity Act, 2005 in England and Wales. Under the Act, research among people diagnosed with dementia must be approved by Health Research Authority committees, irrespective of whether that research engages with health organisations or service users. As examples, I discuss two ethnographic dementia studies that do not engage with healthcare services, but which nonetheless require HRA approval. These instances raise questions regarding legitimacy and reciprocity in the governance of dementia. Through capacity legislation, the state exerts control over people with dementia, automatically delineating them as healthcare subjects because of their diagnoses. This diagnosis functions as a form of administrative medicalisation, rendering dementia a medical entity and those diagnosed with it the property of formal healthcare. However, many people with dementia in England and Wales do not receive related health or care services beyond diagnosis. This institutional imbalance of high governance and low support undermines the contractual citizenship of people with dementia, wherein state-citizen rights and responsibilities should be reciprocal. In response, I consider resistance to this system in ethnographic research. "Resistance" here is not necessarily deliberate, hostile, difficult or perceived, but rather encompasses micropolitical effects that are contrary to power or control, sometimes emerging from systems themselves rather than individual resistive actors. Resistance can be unintentional, through mundane failures to satisfy specific aspects of governance bureaucracies. It can also be deliberate, through refusals to comply with restrictions that seem cumbersome, inapplicable or unethical, potentially raising questions of malpractice and misconduct. I suggest that resistance is made more probable due to the expansion of governance bureaucracies. On the one hand, the potential for both unintentional and intentional transgression increases, while on the other hand, the capacity for those transgressions to be discovered and rectified decreases, because the maintenance of control over such a system requires vast resources. Behind this ethico-bureaucratic tumult, people with dementia themselves are largely invisible. People with dementia often have no interaction with committees that determine their research participation. This further renders ethical governance a particularly disenfranchising facet of the dementia research economy. The state stipulates that people with dementia must be treated differently because of their diagnoses, without consulting those people. In response, resistance to unethical governance could be intuitively deemed ethical per se, but I suggest that such a simplistic binary is somewhat misleading.

The art of friendliness: Organiser perspectives on curating dementia friendly cultural events.

Over recent decades, the arts have become a popular response to dementia. Amidst wider concerns with accessibility, widening participation and audience diversity, coupled with greater attention to creativity across dementia studies, many arts organisations are now offering dementia friendly initiatives. While dementia friendliness has been well-established for almost a decade, the meaning of friendliness remains vague. This paper reports results from a study of how stakeholders navigate this nebulousness when developing their own dementia friendly cultural events. To assess this, we interviewed stakeholders working for arts organisations in the northwest of England. We found that participants built up local informal networks of knowledge exchange, sharing experiences between stakeholders. The dementia friendliness that characterises this network centres on the crafting of vibes that enable people with dementia to 'unhide' themselves. Through this accommodating approach, dementia friendliness converges with stakeholder interests, becoming something of an art form in its own right, typified by active embodied experience, flexible and creative self-expression, and being in-the-moment.

Single-Stage Externalized Locked Plating for Treatment of Unstable Meta-Diaphyseal Tibial Fractures.

(1) Background: Unstable meta-diaphyseal tibial fractures represent a heterogeneous group of injuries. Recently, good clinical results have been reported when applying a technique of externalized locked plating in appropriate cases, highlighting its advantage in terms of less additional tissue injury compared with conventional methods of fracture fixation. The aims of this prospective clinical cohort study were, firstly, to investigate the biomechanical and clinical feasibility and, secondly, to evaluate the clinical and functional outcomes of single-stage externalized locked plating for treatment of unstable, proximal (intra- and extra-articular) and distal (extra-articular), meta-diaphyseal tibial fractures. (2) Methods: Patients, who matched the inclusion criteria of sustaining a high-energy unstable meta-diaphyseal tibial fracture, were identified prospectively for single-stage externalized locked plating at a single trauma hospital in the period from April 2013 to December 2022. (3) Results: Eighteen patients were included in the study. Average follow-up was 21.4 ± 12.3 months, with 94% of the fractures healing without complications. The healing time was 21.1 ± 4.6 weeks, being significantly shorter for patients with proximal extra- versus intra-articular meta-diaphyseal tibial fractures, p = 0.04. Good and excellent functional outcomes in terms of HSS and AOFAS scores, and knee and ankle joints range of motion were observed among all patients, with no registered implant breakage, deep infection, and non-union. (4) Conclusions: Single-stage externalized locked plating of unstable meta-diaphyseal tibial fractures provides adequate stability of fixation with promising clinical results and represents an attractive alternative to the conventional methods of external fixation when inclusion criteria and rehabilitation protocol are strictly followed. Further experimental studies and randomized multicentric clinical trials with larger series of patients are necessary to pave the way of its use in clinical practice.

Augmented screwdrivers can increase the performance of orthopaedic surgeons compared with use of normal screwdrivers.

Orthopaedic screws insertion can be trivialised as a simple procedure, however it is frequently performed poorly. Limited work exists defining how well surgeons insert screws or whether augmented screwdrivers can aid surgeons to reduce stripping rates and optimise tightness. We aimed to establish the performance of surgeons inserting screws and whether this be improved with screwdriver augmentation. 302 orthopaedic surgeons tightened 10 non-locking screws to what they determined to be optimum tightness into artificial bone sheets. The confidence in the screw purchase was given (1-10). A further 10 screws were tightened, using an augmented screwdriver that indicated when a predetermined optimum tightness was reached. The tightness for unstripped insertions under normal conditions and with the augmented screwdriver were 81% (95% CI 79-82%)(n = 1275) and 70% (95% CI 69-72%)(n = 2577) (p < 0.001). The stripping rates were 58% (95% CI 54-61%) and 15% (95% CI 12-17%) respectively (p < 0.001). The confidences when using the normal and augmented screwdrivers respectively were 7.2 and 7.1 in unstripped insertions and 6.2 and 6.5 in stripped insertions. Performance improved with an augmented screwdriver, both in reduced stripping rates and greater accuracy in detecting stripping. Augmenting screwdrivers to indicate optimum tightness offer potentially enormous clinical benefits by improving screw fixation.

Acquired Hemophilia A Secondary to an Immune Checkpoint Inhibitor: A Case Report.

We report a case of a patient with extensive-stage SCLC who developed acquired hemophilia A during maintenance atezolizumab therapy. The patient initially presented with asymptomatic anemia, a prolonged acquired prothrombin time, and factor VIII (FVIII) deficiency. Acquired FVIII autoantibodies were detected, confirming the diagnosis of acquired hemophilia. Atezolizumab was ceased and high-dose prednisolone was initiated. He subsequently developed an extensive spontaneous upper limb subcutaneous hematoma and shoulder hemarthrosis despite improving FVIII inhibitor titers on prednisolone. His acute bleeding was successfully treated with recombinant factor VII, and rituximab was added to prednisolone. Given the quiescent malignancy, 16 months of preceding treatment with atezolizumab, and improvement with immunosuppression, a diagnosis of immune checkpoint inhibitor-induced hemophilia A was made. Severe hematologic immune-related adverse events such as this case of acquired hemophilia have rarely been reported in the literature.

The impact of frailty on health outcomes in older adults with lung cancer: A systematic review.

BACKGROUND: Frailty is prevalent in older adults with lung cancer, however the impact of frailty in this population is not well understood. The aim of this review was to evaluate the outcomes that are measured in frail older adults with lung cancer, and to determine the associations between frailty and these outcomes. METHODS: A systematic online search of PubMed, EMBASE, and Cochrane databases was conducted to identify all English-language studies between January 2015 and May 2022 prospectively evaluating frailty and outcomes in older adults (median age > 65 years) with lung cancer. Studies were excluded if frailty was defined by a single domain assessment or not clearly defined. Quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Of 1891 studies screened, 16 met inclusion criteria. The median number of patients was 96 (range 26-494) and the mean age was 76.6 years. Eight different frailty assessments were used, and frailty definitions varied widely. The most frequently assessed outcomes were overall survival (n = 13,81%), treatment-related toxicity (n = 8,50%), hospitalisation (n = 5,31%), and treatment completion/discontinuation (n = 4,25%). Quality of life (n = 3,19%), function (n = 1,6%), frailty trajectory (n = 1,6%), and emergency visits (n = 1,6%) were infrequently assessed. Frailty had a strong and consistent association with mortality (Hazard Ratio range: 3.5-11.91). It was also associated with treatment-related toxicity and treatment selection. The remaining outcomes were not statistically significant. CONCLUSION: These data support frailty as an important predictor of mortality in older adults with lung cancer, however further research is warranted to determine the association between frailty and other meaningful endpoints for this vulnerable population.

Merging antimicrobial and visible emission properties within 1,3,4-trisubstituted-1,2,3-triazolium salts.

Bioactive molecules displaying visible wavelength emission can be useful for bioimaging, chemosensing and photodynamic therapy applications. Reported herein are 1,3,4-trisubsituted-1,2,3-triazolium salts displaying both antimicrobial and visible emission properties. Using a click chemistry approach, 2-fluorenyl, 1-naphthyl, 2-naphthyl, 2-anthracenyl and 1-pyrenyl units were incorporated at the N1 position, imparting visible emission properties to their triazolium bromide salts with Stokes shifts greater than 100 nm relative to the emission of their triazole precursors. The increasing size of such hydrophobic aryl units impacts minimum inhibitory concentration (MIC) values against Gram-positive bacteria, Gram-negative bacteria and yeast, and can be counterbalanced by hydrophobic substituent variation at other positions of the molecule in order to preserve bioactivity. Among the series of compounds studied are analogs displaying blue, green and yellow colored emission and MIC values as low as 0.4 µM (Gram-positive bacteria), 8 µM (Gram-negative bacteria) and 2 µM (yeast). XRD analysis validates the regioselective benzylation at the N3 position of the 1,2,3-triazole ring and the ability of such compounds to associate through dimeric intermolecular π-stacking interactions.