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Most patients with epithelial ovarian cancer (EOC) experience drug-resistant disease recurrence. Identification of new treatments is a high priority, and preclinical studies in mouse models of EOC may expedite this goal. We previously developed methods for magnetic resonance imaging (MRI) for tumor detection and quantification in a transgenic mouse model of EOC. The goal of this study was to determine whether three-dimensional (3D) fluorescence molecular tomography (FMT) and fluorescent molecular imaging probes could be effectively used for in vivo detection of ovarian tumors and response to therapy. Ovarian tumor-bearing TgMISIIR-TAg mice injected with fluorescent probes were subjected to MRI and FMT. Tumor-specific probe retention was identified in vivo by alignment of the 3D data sets, confirmed by ex vivo fluorescent imaging and correlated with histopathologic findings. Mice were treated with standard chemotherapy, and changes in fluorescent probe binding were detected by MRI and FMT. Ovarian tumors were detected using probes specific for cathepsin proteases, matrix metalloproteinases (MMPs), and integrin αvβ3. Cathepsin and integrin αvβ3 probe activation and retention correlated strongly with tumor volume. MMP probe activation was readily detected in tumors but correlated less strongly with tumor volume. Tumor regression associated with response to therapy was detected and quantified by serial MRI and FMT. These results demonstrate the feasibility and sensitivity of FMT for detection and quantification of tumor-associated biologic targets in ovarian tumors and support the translational utility of molecular imaging to assess functional response to therapy in mouse models of EOC.

A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumorigenesis. The goal of this study was to assess the feasibility of using a newly developed near-infrared bioactivatable probe (MMPSense 680) that reports the activity of a broad array of MMP isoforms to detect early colorectal adenomas. Adenomatous polyposis coli (Apc)+/Min-FCCC mice that spontaneously develop multiple colorectal adenomas were injected with MMPSense 680, and the colons were imaged in an IVIS Spectrum system ex vivo. Image analyses were correlated with histopathologic findings for all regions of interest (ROIs). The biochemical basis of fluorescent signal was investigated by immunohistochemical staining of MMP-7 and -9. A strong correlation (Kendall = 0.80) was observed between a positive signal and the presence of pathologically confirmed colonic adenomas; 92.9% of the 350 ROIs evaluated were classified correctly. The correlation between two independent observers was 0.87. MMP-7 expression was localized to epithelial cells of adenomas and microadenomas, whereas staining of MMP-9 was found in infiltrating polymorphonuclear leukocytes within the adenomas. MMPSense 680 identifies colorectal adenomas, both polypoid and nonpolypoid, in Apc+/Min-FCCC mice with high specificity. Use of this fluorescent probe in combination with colonoscopy could aid in preventing colorectal neoplasias by providing new opportunities for early detection and therapeutic intervention.

Objectives: (1) Improve resident skills in delivering difficult news (DDN) by educating pediatrics residents using a communication framework with validity evidence, the m-SPIKES framework. (2) Determine whether small group practice with peer role-play or Rapid Cycle Deliberate Practice (RCDP) simulation is a more effective practice modality for improving DDN., Methods: IRB-exempt single-institution pilot randomized controlled trial involving twenty-eight pediatrics residents. Residents attended an educational intervention that consisted of a large-group didactic session to learn the m-SPIKES framework followed by randomization into either peer role-play or RCDP groups for small group practice. The residents completed pre- and post-surveys regarding self-efficacy in DDN using a Likert scale and were evaluated for fundamental communication skills and mastery of m-SPIKES by trained faculty during a simulation with a standardized patient before and after the educational intervention. Data was analyzed using bivariate inferential statistical analysis with t-tests., Results: After the educational intervention, residents in both cohorts were found to have significantly increased self-efficacy in DDN, fundamental communication skills, and overall mastery of the use of m-SPIKES (p=<0.001). The two cohorts had similar improvements in self-efficacy (p=0.223) and fundamental communication skills (p=0.306), however the peer role play showed a significant improvement in mastery of m-SPIKES when compared to the RCDP group (p=0.046)., Conclusions: While this educational intervention demonstrated a significant improvement in DDN skills for all residents in both the peer role-play and RCDP groups, more studies are needed to determine whether the use of RCDP is advantageous in communication education., Competing Interests: Declaration of Competing Interest None, (Copyright © 2025. Published by Elsevier Inc.)

Combined distal interphalangeal joint (DIP) arthrodesis with proximal interphalangeal joint (PIP) arthroplasty or arthrodesis presents unique challenges. Although less common than isolated surgery for the DIP and PIP joints, with an aging population, combined DIP and PIP procedures are an increasingly encountered occurrence. Anatomical and morphological studies have provided length and width measurement standards for the middle and distal phalanges, allowing for planning to assess the compatibility of strategies. Besides reviewing anatomical studies to provide length and width guidelines for hardware placement, we will also discuss optimal hardware combinations for combined surgical intervention in the DIP and PIP joints. Conflict may exist between hardware used for the DIP arthrodesis and implants used for the PIP arthroplasty. As an example, if K-wires are used for DIP arthrodesis, any intervention in the PIP joint will be compatible. However, if headless screws are used for DIP arthrodesis, these should ideally not reach proximal to the midpoint of the middle phalanx. Other techniques, such as single or multiple oblique screws, and tension bands are compatible with PIP arthroplasty. Hence, options for management of the PIP joint are dependent on the technique used for DIP arthrodesis., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2025 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: The branching pattern of the deep motor branch of the ulnar nerve (DBUN) in the hand is complex. The anatomy of the motor branch innervating the fourth lumbrical (4L), where paralysis results in a claw hand deformity after ulnar nerve injury, is not well defined. This cadaver study focused on mapping and defining anatomical landmarks in relation to the motor branch to the 4L., Methods: Ten fresh-frozen cadaver hands were dissected. The DBUN was exposed and followed distally, identifying all motor branches, until the branch to the 4L was seen. The small finger flexor tendons were reflected distally to enable visualization of the entire 4L motor branch and its distal entry point. The origin of the 4L motor branch was mapped in relation to fixed anatomical landmarks in the hand., Results: A consistent motor branch to the 4L and third palmar interosseous (3PI) muscles was seen originating from the DBUN in all specimens. The mean number of motor branches innervating the hypothenar muscles proximal to the 4L/3PI motor branch was 2.1 (range 1 to 5). The mean distance from the origin of the DBUN to the 4L/3PI motor branch was 2.9 cm (range 2.5 to 4.2 cm). The mean length of the 4L/3PI branch was 3.1 cm (range 2.3 to 4.5 cm). In seven specimens, the 4L/3PI branch demonstrated an intramuscular course through the 3PI before terminating in the 4L. In three specimens the 4L/ 3PI branch ran on the volar surface of the 3PI before terminating in the 4L., Conclusions: A consistent 4L/3PI motor branch was mapped and characterized in all specimens., Clinical Relevance: These findings provide a guide for intraoperative localization of the 4L/3PI motor branch and also may provide further evidence to explain findings seen after distal nerve transfers to treat ulnar nerve injury., Competing Interests: Conflicts of Interest This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. All authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: Artificial Intelligence (AI) has the potential to transform medical imaging and radiotherapy; both fields where radiographers' use of AI tools is increasing. This study aimed to explore the views of those professionals who are now using AI tools., Methods: A small-scale exploratory research process was employed, where qualitative data was obtained from five UK-based participants; all professionals working in medical imaging and radiotherapy who use AI in clinical practice. Five semi-structured interviews were conducted online. Verbatim transcription was performed using an open-source automatic speech recognition model. Conceptual content analysis was performed to analyse the data and identify common themes., Results: Participants spoke about the possibility of AI deskilling staff and changing their roles, they discussed issues around data protection and data sharing strategies, the important role of effective leadership of AI teams, and the seamless integration into workflows. Participants thought that the benefits of adopting AI were smoother clinical workflows, support for the workforce in decision-making, and enhanced patient safety/care. They also highlighted the need for tailored AI education/training, multidisciplinary teamwork and support., Conclusion: Participants who are now using AI tools felt that clinical staff should be empowered to support AI implementation by adopting new and clearly defined roles and responsibilities. They suggest that attention to patient care and safety is a key to successful AI adoption. Despite the increasing adoption of AI, participants in the UK described a gap in knowledge with professionals still needing clear guidance, education and training regarding AI in preparation for more widespread adoption., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: This review aimed to 1) identify existing rural strengths in the literature that proposed a relationship to mental health, 2) classify strengths into a socioecological framework, and 3) identify which strengths make a conceptual link to improved mental health., Methods: Literature was systematically reviewed using online databases (PubMed, PsycInfo, CINAHL, and Scopus). Applicable original research studies that met the inclusion criteria, published (1990-2022) from Australia, Canada, and the United States were thematically analysed., Results: Sixty-one articles from Australia (n=28, 46%), Canada (n=8, 13%), and the United States (n=25, 41%) identified mental health-strengths relationships (e.g. social networks, nature). Twenty-seven studies proposed conceptual links to improved mental health and identified potential 'mechanisms' to harness strengths (e.g. identification, referral)., Conclusions: Despite an entrenched rural deficit discourse, many strengths of rural communities were identified in the literature that, using an adapted socioecological framework to categorise, may be harnessed to improve the mental health of communities across the socioecological continuum., Implications for Public Health: Understanding existing strengths that are embedded in rural communities can inform future mental health policy and commissioning models in a way that is relevant and sustainable for communities, while recognising rural agency., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Pain after brachial plexus injury (BPI) can be severely debilitating and is poorly understood. We hypothesized that pain interference (PI) ("the extent to which pain hinders engagement in life") would be predicted by depression, anxiety, severity of pain symptoms, and poorer preoperative muscle function., Methods: Among patients in a prospective multicenter BPI cohort study, 37 completed Patient-Reported Outcomes Measurement Information System (PROMIS) PI questionnaires before and 1 year after surgery. At both times, participants completed anxiety and depression questionnaires and BPI-specific measures of pain symptoms, physical limitations, and emotional recovery. Surgeon-graded muscle testing, injury severity, age at the time of injury, body mass index, and time from injury to surgery were included. We performed a bivariate analysis of predictors for preoperative and 1-year PROMIS PI followed by multivariable regression modeling using stepwise selection and Bayesian Information Criterion to select covariates., Results: Before surgery, the mean PROMIS PI score was 60.8 ± 11.0, with moderate correlations between PROMIS PI and depression, as well as between PROMIS PI and functional limitations. At 1 year after surgery, the mean PROMIS PI score was 59.7 ± 9.5. There was no difference in preoperative and 1-year PROMIS PI. There were strong correlations between PROMIS PI and pain symptoms, functional limitations, and emotional aspects of recovery at the 1-year follow-up that remained significant in multivariable regression. There were no notable associations between muscle testing and PI., Conclusions: Pain interference remained substantial and elevated in BPI patients 1 year after surgery. We noted strong associations between PI and pain symptoms, functional limitations, and emotional aspects of recovery. These findings demonstrate the persistence of pain as a feature throughout life after BPI and that its treatment should be considered a priority alongside efforts to improve extremity function., Type of Study/level of Evidence: Prognosis IV., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: Free functional gracilis transfer (FFGT) is a useful option for reconstruction of elbow flexion following brachial plexus injury presenting late or with poor outcomes from previous nerve surgery. In this systematic review and meta-analysis, we aimed to investigate variables associated with superior outcomes. The efficacy of single versus double FFGT, where the first FFGT is performed to restore elbow flexion, and the choice of donor nerve for neurotization were evaluated., Methods: A meta-analysis was conducted, including studies that provided postoperative Medical Research Council (MRC) grade for elbow flexion, Disabilities of the Arm, Shoulder, and Hand and visual analog scale scores, quantitative elbow flexion strength, and range of motion. A random effects meta-regression analysis was performed to identify factors associated with improved outcomes., Results: Thirty-seven studies, with 1,607 patients, were analyzed. Single FFGT was reported in 34 studies (n = 1,398), and double FFGT was reported in 10 studies (n = 209). The mean follow-up duration was 37.3 ± 21.1 months. Following single FFGT, 75.4% and 48.9% achieved MRC grades ≥3 and ≥4, respectively. Following double FFGT, 100% achieved an MRC grade ≥3 and 62.7% ≥4. The likelihood of achieving M3 and M4 was significantly greater for double FFGT. Overall, FFGT innervated by the spinal accessory nerve had significantly better recovery of MRC grade ≥3. When comparing only single and double FFGT innervated by spinal accessory nerve, there was no significant difference in recovery of elbow flexion. The meta-regression analysis showed a significant negative correlation between the patient's age and the probability of achieving an MRC grade of ≥3 and 4., Conclusions: In the overall analysis encompassing all innervating nerves, double FFGT was superior to single FFGT. Subgroup analysis of single and double FFGT innervated by the spinal accessory nerve showed no significant difference. Increasing age was a significant risk factor for poorer outcomes., Type of Study/level of Evidence: Therapeutic IV., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

In response to the current disparity in risk assessment values for PFOA from different agencies and countries, an international effort facilitated by the Alliance for Risk Assessment (ARA) was recently undertaken to characterize the range of scientifically supportable safe dose estimates. In this assessment (Burgoon et al., 2023), an evaluation of the evidence regarding the potential modes of action (MOA) for PFOA toxicity was performed first, so that it could be used to inform subsequent decisions regarding potential critical effects and studies. This review describes the evidence considered in the MOA evaluations that were performed as part of the ARA effort. The overall conclusions of this evaluation are that the available mechanistic data do not support any conclusion that reported epidemiological associations of blood concentrations of PFOA as low as 10 ng/mL with various health effects should be considered causal. It is more likely that the reported associations may instead reflect reverse causality/pharmacokinetic confounding. These conclusions are consistent with the opinions of the World Health Organization (WHO, 2022)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The surgical management of adult traumatic brachial plexus injuries (BPI) is challenging, with no consensus on optimal strategies. This study aimed to gather preferred reconstructive strategies from BPI surgeons for actual cases from a multicenter cohort to identify areas of agreement., Methods: Four case files (history, physical examination, and imaging and electrodiagnostic testing results) were distributed to eight self-designated Level IV expert BPI surgeons in the United States. Each surgeon independently reviewed the cases and provided a preferred reconstructive plan via free text response., Results: For a pan-plexus case after blunt trauma (67 years old; 3 months from injury): three surgeons recommended nerve grafting upper trunk roots to distal targets. There was disagreement in shoulder reconstruction: one suggested early shoulder fusion, two preferred cranial nerve XI to suprascapular nerve (SSN) transfer, and two anticipated future salvage shoulder fusion. For elbow reconstruction, six surgeons preferred intercostal nerve to musculocutaneous nerve transfer. For an upper trunk injury from a motorcycle accident (33 years old; 6 months from injury), only one surgeon recommended nerve grafting, six preferred XI to SSN transfer, all recommended triceps-to-axillary transfer, and all but one favored a double fascicular transfer., Conclusions: There is inconsistency in the use of nerve grafting for BPI patients, especially in pan-plexus injuries where options are limited. Variability exists in shoulder reconstruction and stability management, with some advocating early glenohumeral arthrodesis. Although single fascicular and triceps-to-axillary transfers are consistently favored, there is no consensus for restoring shoulder and elbow function when intraplexal transfers are unavailable., Clinical Relevance: This study highlights substantial variability in surgical approaches to BPI among experts, underscoring the need for standardized treatment protocols. Understanding these diverse strategies can inform clinical decision making and help develop more uniform guidelines to improve patient outcomes., Competing Interests: Conflicts of Interest Author C.J.D. received grant funding from the American Foundation for Surgery of the Hand (clinical research grant) and National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases) - R01 AR079139-01 to support this work. No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: The International Association for the Study of Lung Cancer developed a global multicenter database to propose evidence-based revisions for the ninth edition of the TNM classification of pleural mesothelioma (PM). This study analyzes the M category to validate eighth edition M category recommendations., Methods: Cases were submitted electronically or by transfer of existing institutional databases for patients with histologically or cytologically confirmed PM. The presence and number of metastases (single versus multiple) in each of eight organ systems were reported for patients with M1 disease at diagnosis. Overall survival (OS) was calculated by the Kaplan-Meier method. Differences in OS were assessed by log-rank test., Results: Of 7338 submitted cases, 3598 were eligible and 3221 had sufficient data for clinical staging; 228 cases (7%) were M1. Median overall estimated survival was inferior for M1 compared with M0 patients: 10.5 months versus 21.5 months, respectively (p < 0.0001); estimated 1-year survival was 46% versus 71%, respectively. OS differences between M categories were preserved within histologic subgroups. Among 158 patients with organ-specific documentation of M1 disease, there was no statistically significant difference in OS between those with intrathoracic versus more distant metastatic disease (14.4 mo versus 10.9 mo, p = 0.64). No significant survival difference was detected between patients with metastatic disease in a single-organ system versus multiple-organ systems (12.6 mo versus 8.8 mo, p = 0.45)., Conclusions: This evidence-based analysis of the M category for PM conforms with the eighth edition M descriptors. No changes are proposed in the ninth edition of the mesothelioma M category., Competing Interests: Disclosure Dr. Kindler’s work is supported in part by the University of Chicago Cancer Center Support Grant P30 CA014599. Dr. Rusch’s work is supported in part by MSK Cancer Center Support Grant P30 CA008748. Dr. Nowak acknowledges support from the National Health and Medical Research Council, Australia, APP2008104 and APP1197652. No tobacco industry support has been received for the conduct of this research. None of the investigators involved have received tobacco industry support. Dr. Kindler has relationships with Amgen (consultant), Opna Bio LLC (consultant), and Enlivex Therapeutics (consultant). Dr. Pass has relationships with Roche (steering committee and speakers bureau) and AstraZeneca (advisory board). Dr. Ripley receives institutional clinical trial funding from AstraZeneca and Merck (speakers bureau). Dr. Rusch receives institutional clinical trial funding from Genentech; receives meeting preparation and travel reimbursement from NIH/NCI Thoracic Malignancy Steering Committee; and serves as unpaid member, DSMC Committee, MARS II trial (Cancer Research UK). The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Diagnosis of neurogenic thoracic outlet syndrome (nTOS) remains a challenge. The role of electrodiagnostic studies (EDX) in the workup of nTOS remains controversial. The aim of this study was to report the EDX findings in a cohort of patients who underwent surgery for nTOS and also analyze patient-related and intraoperative factors associated with positive EDX findings supportive of nTOS diagnosis., Methods: Baseline characteristics of patients, including age, sex, duration of symptoms, type of nTOS, and pattern of brachial plexus involvement, were gathered and analyzed. All patients received a preoperative EDX evaluation and were divided into two groups based on positive or negative EDX results for comparison., Results: A total of 30 consecutive patients were included in this study comprising 11 (36.7%) men and 19 (63.3%) women, with a mean age of 44.6 ± 17.6 years. Twenty-two (73.3%) patients had type 1 nTOS with muscle weakness and atrophy, followed by 7 (23.4%) patients with type 3, and 1 (3.3%) patient with type 2 nTOS. In terms of nTOS pattern, 26 (86.7%) patients had lower plexus pattern of involvement (C8-T1), followed by 17 (56.7%) with upper-middle plexus pattern (C6-C7), and 13 (43.3%) with upper plexus pattern (C5-dorsal scapular nerve (DSN)). When comparing the characteristics of patients with positive and negative EDX findings suggestive of nTOS, only older age and type 1 nTOS (P < 0.05) were significantly associated with positive EDX findings., Conclusions: Currently, EDX assessment may not be the best modality for diagnosis of nTOS. Interindividual variation in findings reported by different clinicians performing the EDX remains a significant limiting factor. Older patients and those with more severe nTOS (type 1) are more likely to have positive results with EDX., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Pleural mesothelioma (PM) is a cancer with a usually dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centers around the world., Methods: This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥5 years from surgery) treated within a multimodality therapy approach, including macroscopic complete resection. Overall survival was calculated with Kaplan-Meier analysis, and patients were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis., Results: There were 276 long-term survivors (166 men [63%]), with a median age of 59 years (range 21-83 years) at the time of diagnosis. The histology was epithelioid for 246 patients and nonepithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients had died, 104 were alive, and 10 were lost to follow-up. Pathologic tumor stages were: pT1 (n = 50), pT2 (n = 63), pT3 (n = 90), or pT4 (n = 16) and pN0 (n = 150), pN1 (n = 20), and pN2 (n = 39). The matched control data set included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, we found moderate evidence that a low white blood cell count before surgery was more often observed in long-term survivors., Conclusions: The data show that long-term survival in PM is possible in a subgroup of surgically treated patients. Histologic subtype and white blood cell count seem to be prognosticators for longer survival., Competing Interests: Disclosures Isabelle Opitz reports a relationship with Roche that includes: funding grants and speaking and lecture fees; with AstraZeneca that includes: consulting or advisory and speaking and lecture fees; with Bristol-Myers Squibb Co that includes: consulting or advisory; with MSD that includes: consulting or advisory; with Medtronic that includes: funding grants; and with Intuitive that includes: consulting or advisory. Hasan Batirel reports a relationship with Johnson and Johnson that includes: consulting or advisory, paid expert testimony, and speaking and lecture fees; with Medtronic that includes: speaking and lecture fees; and with AstraZeneca that includes: speaking and lecture fees. Harvey Pass reports a relationship with Jones and Bartlett Publishing that includes book royalties. Andrea Wolf reports a relationship with Asbestos Disease Awareness Organization that includes: board membership. Marc de Perrot reports a relationship with Roche that includes: consulting or advisory, and with AstraZeneca that includes: consulting or advisory and speaking and lecture fees. Marc de Perrot reports a relationship with BMS that includes: consulting or advisory; with Merck that includes: consulting or advisory and speaking and lecture fees; and with Bayer that includes: speaking and lecture fees. Mir Alireza Hoda reports a relationship with Medtronic that includes: speaking and lecture fees; with MSD that includes: consulting or advisory and speaking and lecture fees; with BMS that includes: consulting or advisory and speaking and lecture fees; with AstraZeneca that includes: consulting or advisory and speaking and lecture fees; and with the Austrian Society of Surgical Oncology (ACO-ASSO) that includes: board membership. Seiki Hasegawa reports a relationship with the Department of Thoracic Oncology, Hyogo Medical University that includes: speaking and lecture fees. Raphael Bueno reports a relationship with Verastem that includes: funding grants. Raphael Bueno reports a relationship with Genentech that includes: funding grants and travel reimbursement; with Roche that includes: funding grants and travel reimbursement; with Myriad Genetics that includes: funding grants; with Novartis that includes: funding grants; with Siemens that includes: funding grants; with Gritstone that includes: funding grants; with Epizyme that includes: funding grants; with MedGenome that includes: funding grants; with Merck that includes: funding grants; with Bicycle Therapeutics that includes: funding grants; with Bayer that includes: funding grants; with Intuitive Surgical that includes: funding grants; with Northpond that includes: funding grants; with Regeneron that includes: consulting or advisory; with University of Miami Miller School of Medicine that includes: speaking and lecture fees; with Shanghai International Forum on the Standard Treatments of Thoracic Tumors that includes: speaking and lecture fees; with Thornton Law Firm LLP that includes: paid expert testimony; with Blankingship & Keith that includes: paid expert testimony; with Public Health Advocacy Institute that includes: paid expert testimony; with Dolan, Dobrinsky, Rosenblum, Bluestein that includes: paid expert testimony; with Kelley and Uustal that includes: paid expert testimony; with Foster & Eldridge LLP that includes: paid expert testimony; with Adler, Cohen, Harvey, Wakeman, Guekguezian LLP that includes: paid expert testimony; with Navigation Sciences that includes: equity or stocks; and with Covidien and Medtronic that includes: consulting or advisory. Raphael Bueno has patent licensed to Raphael Bueno. The other authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The objective of this study was to determine regional variation in need for mental health care for Aboriginal and Torres Strait Islander adults (18+ years)., Methods: Three Australian Indigenous health surveys were analysed, and prevalence rates of high/very high psychological distress (as per the Kessler-5 tool) by the Index of Relative Socio-economic Disadvantage were computed and combined via meta-analysis. These estimates were applied to census population data to estimate regional needs and summed to geographic planning regions. Final estimates were assessed for face validity by comparing with other existing estimates of mental health need., Results: The Index of Relative Socioeconomic Disadvantage had a dose-response relationship with high/very high psychological distress, whereby the more disadvantaged an area, the greater the levels of reported distress. This methodology resulted in varying levels of need within South East Queensland., Conclusions: The approach was found to have good face validity and provides a data-driven method to determine relative levels of need., Implications for Public Health: To ensure equity of mental health service provision, planners should account for variation in levels of need within a catchment. This method may be used throughout Australia to determine regional variation in need for care where other data are lacking to ensure evidence-based investment planning decisions at the local level., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: There are many myths regarding Alzheimer's disease (AD) that have been circulated on the internet, each exhibiting varying degrees of accuracy, inaccuracy, and misinformation. Large language models, such as ChatGPT, may be a valuable tool to help assess these myths for veracity and inaccuracy; however, they can induce misinformation as well., Objective: This study assesses ChatGPT's ability to identify and address AD myths with reliable information., Methods: We conducted a cross-sectional study of attending geriatric medicine clinicians' evaluation of ChatGPT (GPT 4.0) responses to 16 selected AD myths. We prompted ChatGPT to express its opinion on each myth and implemented a survey using REDCap to determine the degree to which clinicians agreed with the accuracy of each of ChatGPT's explanations. We also collected their explanations of any disagreements with ChatGPT's responses. We used a 5-category Likert-type scale with a score ranging from -2 to 2 to quantify clinicians' agreement in each aspect of the evaluation., Results: The clinicians (n = 10) were generally satisfied with ChatGPT's explanations. Among the 16 myths, the clinicians were generally satisfied with these explanations, with [mean (SD) score of 1.1(±0.3)]. Most clinicians selected "Agree" or "Strongly Agree" for each statement. Some statements obtained a small number of "Disagree" responses. There were no "Strongly Disagree" responses., Conclusion: Most surveyed health care professionals acknowledged the potential value of ChatGPT in mitigating AD misinformation; however, the need for more refined and detailed explanations of the disease's mechanisms and treatments was highlighted., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The choice of midurethral sling type may impact efficacy and complications in women undergoing transvaginal native tissue repair of pelvic organ prolapse., Objective: The primary aim was to determine if the single-incision sling is noninferior to retropubic sling for the management of stress urinary incontinence among patients undergoing reconstructive or obliterative native tissue vaginal repair. The secondary aims were to compare adverse events and surgeon ease of use with sling assignment., Study Design: A multicenter, noninferiority, randomized trial of women with ≥ stage II pelvic organ prolapse and objectively confirmed stress urinary incontinence undergoing reconstructive or obliterative vaginal repair was performed. Women were randomized to concomitant single-incision (Altis sling, Coloplast Minneapolis, MN) with suprapubic sham incisions or retropubic slings. The primary dichotomous outcome was abnormal lower urinary tract function within 12 months postsurgery, defined as bothersome stress urinary incontinence symptoms (>1 Pelvic Floor Distress Inventory question no. 17); retreatment for stress urinary incontinence or treatment for urinary retention. Secondary outcomes were adverse events, Patient Global Impression of Improvement of bladder function, and surgeon ease of use (1, worst; 10, best). All subjects completed validated questionnaires and underwent a Pelvic Organ Prolapse Quantification, cough stress test, and postvoid residual preoperatively, at 6 weeks and 12 months postoperatively. Assuming a subjective cure rate for retropubic of 82%, 80% power, and 1-sided 5% significance level, we estimated that 127 patients in each arm were needed to declare noninferiority of the single-incision sling if the upper bound of the 95% confidence interval for the between-group difference per protocol in abnormal bladder function was <12%. Assuming a 10% loss to follow-up, the total enrollment goal was 280., Results: Between December 2018 and January 2023, 280 subjects were enrolled across 7 sites, and 255 were randomized: 126 were for single-incision, and 129 were for retropubic sling. There were no preoperative or operative characteristic differences between groups. Overall, 81% had reconstructive, and 19% had obliterative native tissue repairs. The primary outcome, abnormal lower urinary tract function at 12 months, occurred in 29 (25%) of single-incision vs 24 (20%) of the retropubic sling group (risk difference, 0.04472 [95% confidence interval, -0.03 to 0.1133]; P=.001 for noninferiority). Bothersome stress urinary incontinence occurred in 20% vs 17% (P=.27) and was retreated in 4% vs 2% (P=.44) of single-incision vs retropubic groups, respectively. Adverse events were reported in 24 (16%) of single-incision vs 14 (9%) of the retropubic group (95% confidence interval, 0.95-3.29; P=.70) and included de novo or worsening urgency incontinence symptoms, urinary tract infection, mesh exposure, need for prolonged catheter drainage, and de novo pain, without differences between groups. Patient Global Impression of Improvement (very satisfied and satisfied) was 71% vs 67% (P=.43), and median surgeon ease of sling use was 8 (7-10) vs 9 (8-10), P=.03 in single-incision vs retropubic, respectively., Conclusion: For women undergoing vaginal repair, single-incision was noninferior to retropubic sling for stress urinary incontinence symptoms, and complications, including treatment for urinary retention, did not differ., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Although proximal row carpectomy (PRC) has increasingly been shown to have superior features to four-corner fusion (4CF), individual surgeons may remain convinced of the superiority of one procedure based on personal experience and individual biases. Hence, we sought to perform an updated meta-analysis with some of the largest studies to date to compare outcomes and complications between these procedures in the treatment of scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists., Methods: A systematic review and meta-analysis was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Embase, Web of Science, and Cochrane were queried for articles on PRC and 4CF performed for scapholunate advanced collapse and scaphoid nonunion advanced collapse wrist. Primary outcomes included wrist range of motion; grip strength; outcome measures, including Disabilities of Arm, Shoulder, and Hand and Quick Disabilities of Arm, Shoulder, and Hand scores, Patient-Rated Wrist and Hand Evaluation, and visual analog scale pain scores; and surgical complications., Results: Sixty-one studies reported on 3,174 wrists, of which 54% were treated with PRC and 46% were treated with 4CF. The weighted mean follow-up was 61 months (range, 12-216 months). Meta-analysis comparing PRC and 4CF demonstrated that PRC had significantly greater postoperative extension; ulnar deviation; postoperative improvement in extension, flexion, ulnar deviation; and visual analog scale score. No comparisons showed significant differences in grip strength. The percentage of wrists requiring arthrodesis was 5.2% for PRC and 11% for 4CF. There was an 8.9% (57/640 wrists) 4CF nonunion rate and 2.2% (17/789) hardware removal rate after 4CF., Conclusions: In the treatment of scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists, PRC results in better outcomes and a lower complication rate compared to 4CF., Type of Study/level of Evidence: Therapeutic IV., Competing Interests: Conflicts of Interest K.A.H. is a paid consultant for LinkBio Corp. T.W.W. is a consultant for and receives royalties from Exactech, Inc. No benefits in any form have been received or will be received by the other authors related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: Venous thromboembolism (VTE) events are a preventable complication for patients undergoing surgery for breast cancer. However, there is a lack of consistency in the existing literature regarding the potential risk factors affecting these individuals., Methods: This study aimed to investigate the potential risk factors associated with an increased risk of VTE following surgery for breast cancer. Data on patient characteristics such as age, body mass index (BMI), existing comorbidities, smoking history, surgical interventions, duration of hospitalization, and post-operative complications were recorded and analyzed., Results: Thirty-one studies investigating the incidence of VTE following surgical interventions for breast cancer were included. This study included 22,155 female patients with a mean age of 50.8 ± 2.9 years. The weighted mean length of surgery and hospital stay were 382.1 ± 170.0 min and 4.5 ± 2.7 days, respectively. The patients were followed-up for a weighted mean duration of 13.8 ± 21.2 months. The total incidence of VTE events was 2.2% (n = 489). Meta-analysis showed that patients with post-operative VTE had a significantly higher mean age and BMI, as well as longer mean length of surgery (P < 0.05). Comparing the techniques of autologous breast reconstruction showed that the risk of post-operative VTE is significantly higher with deep inferior epigastric perforator (DIEP) flaps, compared with the transverse rectus abdominus myocutaneous and latissimus dorsi myocutaneous flaps (P < 0.05). Compared with delayed reconstruction, immediate reconstruction was associated with a significantly higher incidence of VTE (P < 0.05). Smoking history, length of hospital stay, and Caprini score did not correlate with increased incidence of post-operative VTE., Conclusion: The incidence rate of VTE events in patients receiving surgical treatment for breast cancer is 2.2%. Risk factors for developing post-operative VTE in this patient population were found to be older age, increased BMI, extended length of surgical procedures, and DIEP flap reconstruction., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The need for a stronger evidence-base in paramedicine has precipitated a rapid development of prehospital research agendas. Paramedics are increasingly involved in research, leading to changes in their role. Yet, the integration of research responsibilities has proven to be challenging, resulting in varying attitudes and levels of engagement., Objective: This systematic review aimed to explore paramedics' views and experiences of research as researchers during training and within practice., Methods: A systematic search was performed across six databases. Qualitative empirical peer-reviewed articles that discussed paramedic perspectives on engaging with research activity were included. Of 10,594 articles identified initially, 11 were included in the final synthesis after quality appraisal. Data were extracted and subjected to narrative synthesis., Results: The following four themes were identified: motivation to engage, moral dilemmas, structural issues within the profession, and reflections on trial involvement. Attitudes toward research, understanding of related concepts, and the drive for patient benefit were interwoven core issues., Conclusions: Research was highly valued when links to patient benefit were obvious, however, this review highlights some cultural resistance to research, particularly regarding informed consent and changes to standard practice. Paramedic research methods training should provide structured opportunities to explore concerns and emphasize the role of research in developing a high-quality evidence base to underpin safe practice. Currently, there is inadequate organizational support for paramedics to engage effectively in research activity, with minimal allocations of time, training, and remuneration. Without properly integrating research activity into the paramedic role, their capacity to engage with research activity is limited., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background & Objectives: Blunt cerebrovascular injury (BCVI) includes carotid and/or vertebral artery injury following trauma, and conveys an increased stroke risk. We conducted a systematic review and meta-analysis to provide a comprehensive summary of prognostic factors associated with risk of stroke following BCVI., Methods: We searched the EMBASE and MEDLINE databases from January 1946 to June 2023. We identified studies reporting associations between patient or injury factors and risk of stroke following BCVI. We performed meta-analyses of odds ratios (ORs) using the random effects method and assessed individual study risk of bias using the QUIPS tool. We separately pooled adjusted and unadjusted analyses, highlighting the estimate with the higher certainty., Results: We included 26 cohort studies, involving 20,458 patients with blunt trauma. The overall incidence of stroke following BCVI was 7.7 %. Studies were predominantly retrospective cohorts from North America and included both carotid and vertebral artery injuries. Diagnosis of BCVI was most commonly confirmed with CT angiography. We demonstrated with moderate to high certainty that factors associated with increased risk of stroke included carotid artery injury (as compared to vertebral artery injury, unadjusted odds ratio [uOR] 1.94, 95 % CI 1.62 to 2.32), Grade III Injury (as compared to grade I or II) (uOR 2.45, 95 % CI 1.88 to 3.20), Grade IV injury (uOR 3.09, 95 % CI 2.20 to 4.35), polyarterial injury (uOR 3.11 (95 % CI 2.05 to 4.72), occurrence of hypotension at the time of hospital admission (adjusted odds ratio [aOR] 1.32, 95 % CI 0.87 to 2.03) and higher total body injury severity (aOR 5.91, 95 % CI 1.90 to 18.39)., Conclusion: Local anatomical injury pattern, overall burden of injury and flow dynamics contribute to BCVI-related stroke risk. These findings provide the foundational evidence base for risk stratification to support clinical decision making and further research., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Controversy exists regarding the best option for revision surgery in refractory cubital tunnel syndrome (CuTS). The purpose of this systematic review was to evaluate the effectiveness of revision surgery and determine the optimal surgical approach for patients requiring revision surgery for CuTS., Methods: A literature search was conducted. Characteristics of the included studies were summarized descriptively. The risk ratio between patient-reported preoperative and postoperative outcomes relating to pain, motor, and sensory deficits was calculated. A meta-regression analysis was performed to evaluate the postoperative symptom improvements based on the type of secondary surgery. Random-effects meta-analysis and descriptive statistics were used when appropriate., Results: A total of 471 patients were evaluated in 20 studies. In total, 254 (53.9%) male and 217 (46.1%) female patients, with an average age of 49.2 ± 14.1 years, were included in this study. Pain was the most common symptom (n = 346, 81.6%), followed by sensory and motor dysfunction in 342 (80.6%) and 223 (52.6%) patients, respectively. Meta-analysis comparing preoperative and postoperative symptoms between patients who had submuscular transposition (SMT), subcutaneous transposition (SCT), and neurolysis showed that a significant subgroup difference exists between the types of revision surgery in sensory and motor improvements. Meta-regression showed that SMT was associated with better outcomes compared with SCT in motor and sensory improvements., Conclusions: Revision surgery for CuTS can be useful for addressing recurrent and persistent symptoms. Compared with neurolysis and SCT, SMT seems to be the superior option for revision surgery, demonstrating substantial improvement in all symptom domains., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Most N-Nitrosamine compounds are found to be genotoxic in several animal species. Some are classified as probable or possible human carcinogens and very low acceptable daily intake has been established such as 96 ng/day for N-nitrosodimethylamine (NDMA) and 26.5 ng/N-nitrosodiethylamine (NDEA). The pharmaceutical industry has considered all processing areas for potential formation or contamination of N-nitrosamine. One risk is the potential contamination of nitrosamine during drug product blister packaging using lidding foils containing nitrocellulose, and different approaches have been used by pharmaceutical companies to evaluate and mitigate this risk. Herein we share a perspective from IQ Consortium N-nitrosamine Working Group on some of the approaches and corresponding results. From these assessments, it was concluded that the risk of nitrosamine contamination during blister packaging is negligible. The approaches shared in this perspective can be incorporated into risk assessment for nitrosamine contamination during drug product packaging at other pharmaceutical companies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Evaluate ear health and hearing among urban Aboriginal children and quantify relationships with child, family and social factors., Methods: Baseline questionnaire and ear health examinations from 1430 children with diagnoses (0.5-18 years) attending Aboriginal Health Services enrolled in SEARCH. Ear health outcomes were Otitis Media (OM), and hearing loss (three-frequency average hearing loss >20dB) diagnosed using pneumatic otoscopy, tympanometry, and audiometry., Results: Half the children 0.5-3 years had OM (51.5%, 136/264). One third 0.5-18 years (30.4%; 435/1430) had OM, including 1.8% (26/1430) with perforation (0.8% chronic suppurative OM, 0.6% dry perforation and 0.4% acute OM with perforation). One quarter 0.5-18 years (25.7%; 279/1087) had hearing loss; 12.4% unilateral, 13.2% bilateral (70.6% with bilateral loss had concurrent OM). OM was associated with: younger age (0.5-<3 years versus 6-18 years) age-sex-site; adjusted prevalence ratio (aPR)=2.64, 95%, 2.18-3.19); attending childcare/preschool (aPR=1.24, 95%CI, 1.04-1.49); foster care (aPR=1.40, 95%CI, 1.10-1.79); previous ear infection/s (aPR=1.68, 95%CI, 1.42-1.98); and ≥2 people/bedroom (aPR=1.66, 95%CI, 1.24-2.21). Hearing impairment was associated with younger age (0.5-<6 years vs. ≥6 years aPR=1.89, 95%CI, 1.40-2.55) and previous ear infection (aPR=1.87, 95%CI, 1.31-2.68)., Conclusions: Half the urban Aboriginal children in this cohort had OM and two-thirds with hearing impairment had OM., Implications for Public Health: Findings highlight importance of early detection and support for ear health, particularly in pre-school-aged children with risk factors., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Duplex ultrasound allows accurate preoperative flap planning through mapping of perforator location and anatomy. In the hand and upper extremity, where thickness of the subcutaneous fat is less compared with other areas of the body, color Doppler ultrasound is particularly sensitive for analyzing the location and characteristics of perforators. In this study, we will first review evidence on use of ultrasound in flap planning. Second, we will provide a technical guide on ultrasound settings for preoperative flap planning. Finally, we will discuss case examples that show the use of ultrasound for accurate perforator mapping to facilitate rapid flap harvest. Color Doppler ultrasound is inexpensive and readily available to be incorporated into the armamentarium of the hand surgeon for preoperative flap planning., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: It remains unclear whether first rib resection (FRR), performed via a supraclavicular (SCFRR) or transaxillary (TAFRR) approach, is necessary for patients with neurogenic thoracic outlet syndrome (nTOS). In a systematic review and meta-analysis, we performed a direct comparison of patient-reported functional outcomes following different surgical approaches for nTOS., Methods: The authors searched PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, Google Scholar, and the gray literature. Data were extracted based on the procedure type. Well-validated patient-reported outcome measures were analyzed in separate time intervals. Random-effects meta-analysis and descriptive statistics were used where appropriate., Results: Twenty-two articles were included, with 11 discussing SCFRR (812 patients), 6 discussing TAFRR (478 patients), and 5 discussing rib-sparing scalenectomy (RSS; 720 patients). The mean difference between preoperative and postoperative Disabilities of the Arm, Shoulder and Hand score was significantly different comparing RSS (43.0), TAFRR (26.8), and SCFRR (21.8). The mean difference between preoperative and postoperative visual analog scale scores was significantly higher for TAFRR (5.3) compared to SCFRR (3.0). Derkash scores were significantly worse for TAFRR compared to RSS or SCFRR. RSS had a success rate of 97.4% based on Derkash score, followed by SCFRR and TAFRR at 93.2% and 87.9%, respectively. RSS had a lower complication rate compared to SCFRR and TAFRR. There was a difference in complication rates: 8.7%, 14.5%, and 3.6% for SCFRR, TAFRR, and RSS, respectively., Conclusions: Mean differences in Disabilities of the Arm, Shoulder and Hand scores and Derkash scores were significantly better for RSS. Higher complication rates were reported after FRR. Our findings suggest that RSS is an effective option for the treatment of nTOS., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Thin skin flaps have gained popularity for extremity reconstruction. However, the use of the profunda artery perforator (PAP) flap has not been explored as much. With its concealed donor site on the medial thigh and bulk, the PAP has become popular for reconstruction in the breast, head, and neck. The thickness of the subfascial PAP flap is decreased through elevation on the thin or superthin plane, making it more suitable for extremity reconstruction., Methods: A consecutive series of 28 patients with 29 flaps who received a thin or superthin single perforator PAP flap for upper or lower extremity reconstruction was reviewed. Our technique for preoperative localization of the dominant perforator using computed tomography angiography (CTA) and color duplex ultrasonography (CDU) is described., Results: Flap success rate was 93.1%. Mean flap artery diameter, vein diameter, area, and thickness were 1.7 + 0.4 mm, 2.2 + 0.4 mm, 157.3 + 52.1 cm 2 , and 0.7 + 0.2 cm, respectively. Skin thickness at the suprafascial bifurcation point of a dominant "T" perforator measured on preoperative CTA correlated with actual intraoperative flap thickness. Patient body mass index did not correlate with flap thickness., Conclusions: The thin and superthin PAP flap has multiple favorable characteristics, making it suitable for extremity reconstruction, and it has become the workhorse skin flap in our institution. Conventional low-frequency CDU together with CTA can be used effectively to map the dominant perforator preoperatively, allowing accurate flap design and rapid flap harvest., Level of Evidence: Therapeutic Level IV., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: This study examined (1) the utility of a clinical system to record acoustic change complex (ACC, an event-related potential recorded by electroencephalography) for assessing speech discrimination in infants, and (2) the relationship between ACC and functional performance in real life., Methods: Participants included 115 infants (43 normal-hearing, 72 hearing-impaired), aged 3-12 months. ACCs were recorded using [szs], [uiu], and a spectral rippled noise high-pass filtered at 2 kHz as stimuli. Assessments were conducted at age 3-6 months and at 7-12 months. Functional performance was evaluated using a parent-report questionnaire, and correlations with ACC were examined., Results: The rates of onset and ACC responses of normal-hearing infants were not significantly different from those of aided infants with mild or moderate hearing loss but were significantly higher than those with severe loss. On average, response rates measured at 3-6 months were not significantly different from those at 7-12 months. Higher rates of ACC responses were significantly associated with better functional performance., Conclusions: ACCs demonstrated auditory capacity for discrimination in infants by 3-6 months. This capacity was positively related to real-life functional performance., Significance: ACCs can be used to evaluate the effectiveness of amplification and monitor development in aided hearing-impaired infants., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The most recent version of the octamethylcyclotetrasiloxane (D 4 ) physiologically based pharmacokinetic (model) was developed using the available kinetic studies in male and female F344 rats. Additional data, which had not been included in the D 4 model development, allowed for a more detailed assessment of the loss of D 4 following long-term exposure in both SD and F344 rats. This new data demonstrated a deficiency in the published PBPK model predictions of terminal concentrations of D 4 in plasma and fat 14 days after the end of exposures for 28-days, 6 h/day, where the model predictions were an order of magnitude lower than the data. To capture this time-point without altering the end-of-exposure peak concentrations in blood and fat required conversion of the one-way (liver to fat) mobile lipoprotein pool (MLP) into a bi-directional pool between liver and fat. Simulation of the D 4 pharmacokinetics in the SD rat, as opposed to the F344 rat, also required a reduction of both fold induction of liver metabolism (KMAX: 5- to 2-fold) and maximal rate of metabolism (VMAXC: 5.0-1.54 mg/kg 0.75 ). The revised MLP description was extended to the human D 4 model using a parallelogram approach between rat and human MLP parameters to establish the parameters for the current model in the absence of similar long-term clearance data in the human. The revised human D 4 model provided good fits to the human inhalation and dermal exposure studies while not appreciably altering cross-species dose metrics based on the free concentration of D 4 in blood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Mental disorders can affect workforce participation via a range of mechanisms. In this study, we aimed to estimate the association between different types of mental disorders and working years lost, defined as the number of years not actively working or enrolled in an educational programme., Methods: In this population-based cohort study, we included all people aged 18-65 years (mean 38·0 [SD 13·9]) in the Danish Civil Registration System from Jan 1, 1995 to Dec 31, 2016. Information on mental disorders was obtained from the Danish Psychiatric Central Research Register and information on labour market characteristics was obtained from administrative registers. Follow-up started at age 18 years, immigration to Denmark, or on Jan 1, 1995, whichever came later; and it ended at age 65 years, death, emigration from Denmark, disability pension, voluntary early retirement, or Dec 31, 2016 (whichever came earlier). As the main outcome, we estimated working years lost for those diagnosed with any mental disorder and 24 types of mental disorders, as well as for the general population of same age and sex. We decomposed total working years lost into periods of unemployment or sick leave, disability pension, voluntary early retirement, or death. Data on ethnicity were not available through administrative registers., Findings: A total of 5 163 321 individuals, 2 642 383 men and 2 520 938 women, were followed up for 65·4 million person-years. Overall, 488 775 (9·47%) individuals were diagnosed with a mental disorder. On average, individuals with mental disorders lost an additional 10·52 (95% CI 10·48-10·57) years of working life compared with the general Danish population. Receiving a disability pension (7·54 [7·49-7·59] years) and longer periods of unemployment (2·24 [2·21-2·27] years) accounted for most of this difference., Interpretation: Our findings foreground the substantial impact of mental disorders on workforce participation. There is a need to invest in programmes that reduce the burden of working years lost and assist people with mental disorders in returning to the workforce., Funding: Lundbeck Foundation and Danish National Research Foundation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The Steering Committee of the Alliance for Risk Assessment (ARA) opened a call for scientists interested in resolving what appeared to be a conundrum in estimating of the half-life of perfluorooctanoate (PFOA) in humans. An Advisory Committee was formed from nominations received and a subsequent invitation led to the development of three small independent working groups to review appropriate information and attempt a resolution. Initial findings were shared among these groups and a conclusion developed from the ensuing discussions. Many human observational studies have estimated the PFOA half-life. Most of these studies note the likely occurrence of unmonitored PFOA exposures, which could inflate values of the estimated PFOA half-life. Also, few of these studies estimated the half-life of PFOA isomers, the branched chains of which likely have shorter half-lives. This could deflate values of the estimated linear PFOA half-life. Fortunately, several studies informed both of these potential problems. The majority opinion of this international collaboration is that the studies striking the best balance in addressing some of these uncertainties indicate the likely central tendency of the human PFOA half-life is less than 2 years. The single best value appears to be the geometric mean (GM) of 1.3 years (Zhang et al., 2013, Table 3), based on a GM = 1.7 years in young females (n = 20) and GM = 1.2 years in males of all ages and older females (n = 66). However, a combined median value from Zhang et al. (2013) of 1.8 years also adds value to this range of central tendency. While the Collaboration found this study to be the least encumbered with unmonitored PFOA exposures and branched isomers, more studies of similar design would be valuable. Also valuable would be clarification around background exposures in other existing studies in case adjustments to half-life estimates are attempted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Traditional subfascial harvest of the profunda artery perforator (PAP) flap results in a thick flap, which routinely requires secondary thinning. The aim of this study was to characterize the suprafascial perforator anatomy of PAPs on preoperative computed tomography angiography (CTA) and correlate radiological findings with our clinical experience in extremity reconstruction., Methods: Suprafascial PAP anatomy was reviewed in CTAs in 159 thighs. Findings on CTA were correlated with intraoperative findings in a cohort of patients who had a PAP flap for extremity reconstruction., Results: Two main perforator patterns, a "T" (superficial bifurcation) and "Y" (deeper bifurcation) were identified. The ratio between the total skin thickness and the distance from the skin to the perforator bifurcation point and the total skin thickness was higher in the "T" perforator pattern. A dominant "T" perforator (n = 97) was more common than "Y" (n = 62). A dominant "T" perforator was more common in women and with higher body mass index (BMI). In the clinical study, we found a positive correlation between the skin thickness of the bifurcation point of a dominant "T" perforator and the thickness of the superficial fascia where a thin PAP flap is elevated., Conclusions: A dominant "T" perforator on preoperative CTA accurately predicts thickness of a PAP flap elevated at the level of the superficial fascia., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Nonsyndromic congenital mitten hand with thumb and index finger syndactyly is rare. Reconstruction of this condition is challenging, requiring repositioning of the thumb and creation of a wide and deep first webspace. The aim of this paper is to describe the characteristics of patients with this condition and also to describe our surgical technique., Methods: We describe our technique in 16 consecutive children utilizing complete mobilization of the first metacarpal and thumb as an island flap on the neurovascular bundle, with a rotational osteotomy to reposition the thumb in pronation. In addition, a dorsal M flap was used to reconstruct the first webspace. Patients in this series also had varying degrees of symbrachydactyly with hypoplastic or aplastic phalanges of the central digits., Results: There were 9 male and 7 female patients, with a mean age of 24.4 ± 22.4 months at the time of surgery. Mean follow-up was 19.1 ± 18.3 months. All reconstructions healed well. The mean thumb web distance in the affected hands was 4.2 cm (range 3.5 to 5). All reconstructed thumbs had a good opposition. Two children initially had mild hypertrophic scarring, which resolved with pressure gloves. No other complications were observed., Conclusion: One-stage reconstruction of the thumb and first webspace can be effectively achieved with our technique of complete mobilization of the thumb unit, rotational osteotomy, and a dorsal interdigitating M flap., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Healthcare related quality of life (QoL) is defined as the impact one's level of health and wellbeing has on a number of domains, including physical, mental, spiritual and social functions. Photodynamic therapy (PDT), a cancer treatment modality, is increasingly used to treat or palliate head and neck pathologies. Due to the complex nature of this area of the body, both the pathology and the treatment of it can severely affect the quality of life. Thus far, no questionnaire has been developed which focuses on quality-of-life post-PDT of head and neck pathologies., Patients and Methods: We have developed the University College London Quality of Life Questionnaire for Patients undergoing PDT in the Head and Neck, using meta-tetra(hydroxyphenyl)chlorin (mTHPC) as the photosensitiser. This was modified from the University of Washington quality of life (UW-QOL) questionnaire. Thirty-eight patients who received mTHPC-PDT for various head and neck pathologies completed the questionnaire, with a mean follow-up of 56 days., Results: All patients reported improved QoL following mTHPC-PDT. The main problem that was reported was post-PDT pain, which is a common side effect. Visual symptoms, breathing, speaking and swallowing problems improved significantly in the 4th week following treatment and significant improvement in activities of daily living, social life, mood and anxiety were reported in the subsequent weeks., Conclusions: mTHPC-PDT confers improvement in QoL score in selected head and neck cancer patients with figures comparable to other treatment modalities. This exploratory study demonstrated patterns of QoL outcome. Further work needs to be done for survey validation and inclusion of a larger cohort which will allow optimal sub-group analysis and help guide further interventions., (Copyright © 2022. Published by Elsevier B.V.)

Background: We report our findings from an anatomical study on harvest of a vascularized scapular bone graft from a supine position. A clinical case is presented to illustrate the operative approach., Methods: Twenty cadaveric hemibody specimens were dissected in the supine position. Outcomes of interest included the characterization of anatomical variants and measurements of pedicle length. Specific measurements included distance from the origin of the subscapular artery (at the axillary artery) to the branch point of the angular artery from the thoracodorsal artery or serratus branch and the length of the angular branch proper., Results: There are five reported anatomic variations regarding the origin of the angular branch of the thoracodorsal artery. In our cadaveric cohort only four known types were seen, and an entirely new variant was encountered. Six cadaveric dissections exhibited a type 3 configuration, six were type 1, four were type 2, three were type 4, and one was a previously unreported variant we termed a type 6, with multiple angular artery branches originating from the posterior branch of the thoracodorsal. The mean distance between the origin of the subscapular artery and the takeoff of the angular branch was 6.3 ± 2.0 cm. The mean length of the angular branch was 3.7 ± 1.4 cm., Conclusions: Supine positioning for harvest of a vascularized bone graft obviates the need for an intraoperative position change and allows reconstruction of bone defects in the hand and upper extremity within a single surgical field., Competing Interests: Declaration of Competing Interest None of the authors or any member of his or her immediate family has funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An important advantage of computed tomography coronary angiography (CCTA) is its ability to visualize the presence and severity of atherosclerotic plaque, rather than just assessing coronary artery stenoses. Until recently, assessment of plaque subtypes on CCTA relied on visual assessment of the extent of calcified/non-calcified plaque, or visually identifying high-risk plaque characteristics. Recent software developments facilitate the quantitative assessment of plaque volume or burden on CCTA, and the identification of subtypes of plaque based on their attenuation density. These techniques have shown promise in single and multicenter studies, demonstrating that the amount and type of plaque are associated with subsequent cardiac events. However, there are a number of limitations to the application of these techniques, including the limitations imposed by the spatial resolution of current CT scanners, challenges from variations between reconstruction algorithms, and the additional time to perform these assessments. At present, these are a valuable research technique, but not yet part of routine clinical practice. Future advances that improve CT resolution, standardize acquisition techniques and reconstruction algorithms and automate image analysis will improve the clinical utility of these techniques. This review will discuss the technical aspects of quantitative plaque analysis and present pro and con arguments for the routine use of quantitative plaque analysis on CCTA., Competing Interests: Declaration of competing interest JPE Equity and Consultant, Cleerly Healthcare Inc. The other authors have no conflicts of interest., (Copyright © 2021 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Hemodynamic effects on the retrograde visceral reconstruction (RVR) for thoracoabdominal aortic aneurysms treatment by anastomotic angle remains unclear. This study aims to qualitatively and quantitatively investigate the effects of different anastomotic angles on hemodynamics and patency., Methods: Three RVR models with 45°, 60° and 90° anastomotic angles were reconstructed respectively by manipulating apostoperative patient-specific model. The manipulated models of the RVRs were numerically simulated and analyzed in terms of hemodynamics including theinstant and cumulative patency, flow pattern and indicators based on wall shear stress (WSS)., Results: Although a smaller anastomotic angle may decrease the patency rate of common iliac arteries, it can improve the visceral perfusion during a cardiac cycle. More importantly, RVR with the smallest anastomotic angle experienced a minimal low time-averaged wall shear stress, high oscillatory shear index and relative residence time in the anastomosis region, whereas the largest anastomotic angle can introduce more unfavorable WSS in the graft trunk. Furthermore, a spiral flow pattern was observed in the proximal graft trunk of all three models, where no high-risk shear distribution was detected in this region., Conclusion: A smaller anastomotic angle may have more benefits of hemodynamic environment in RVR, especially the WSS distribution and flow pattern in the graft trunk. We may also suggest that additional stents or an extended cuff for the graft can be used to induce spiral flow intentionally, which can further improve local hemodynamic environment and long-term prognosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Top dose selection for repeated dose animal studies has generally focused on identification of apical endpoints, use of the limit dose, or determination of a maximum tolerated dose (MTD). The intent is to optimize the ability of toxicity tests performed in a small number of animals to detect effects for hazard identification. An alternative approach, the kinetically derived maximum dose (KMD), has been proposed as a mechanism to integrate toxicokinetic (TK) data into the dose selection process. The approach refers to the dose above which the systemic exposures depart from being proportional to external doses. This non-linear external-internal dose relationship arises from saturation or limitation of TK process(es), such as absorption or metabolism. The importance of TK information is widely acknowledged when assessing human health risks arising from exposures to environmental chemicals, as TK determines the amount of chemical at potential sites of toxicological responses. However, there have been differing opinions and interpretations within the scientific and regulatory communities related to the validity and application of the KMD concept. A multi-stakeholder working group, led by the Health and Environmental Sciences Institute (HESI), was formed to provide an opportunity for impacted stakeholders to address commonly raised scientific and technical issues related to this topic and, more specifically, a weight of evidence approach is recommended to inform design and dose selection for repeated dose animal studies. Commonly raised challenges related to the use of TK data for dose selection are discussed, recommendations are provided, and illustrative case examples are provided to address these challenges or refute misconceptions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)