Comparing spatial distributions of ALA-PpIX and indocyanine green in a whole pig brain glioma model using 3D fluorescence cryotomography.

Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.

Measuring Peri-Anastomotic Pressure to Identify Patients at High-Risk for Dialysis Associated Steal Syndrome.

OBJECTIVE: Dialysis Access-associated Steal Syndrome (DASS) is one of the most serious complications of hemoaccess surgery. Treatment algorithms involve significant morbidity; a tool to reliably identify patients at risk who could benefit from interventions at time of operation would be useful. We present a strategy of using peri-anastomotic pressure (PAP) measurement to identify patients who may be at high risk of developing DASS. METHODS: Patients who underwent dialysis access creation between January 1, 2018 and September 30, 2022 at our institution were reviewed. Beginning October 2019, we developed a strategy of measuring systolic pressure at the arterial anastomosis intra-operatively. A ratio of this value compared to the systemic systolic pressure was calculated. In patients believed to be high-risk for developing DASS based on clinical findings, selective banding of the access was performed intra-operatively to augment distal perfusion. RESULTS: Of 857 total patients, 36 (4.2%) developed clinically significant DASS, defined as requiring operative treatment, either intraoperatively or during follow-up (mean, 76 days; range, 0-602 days). DASS was more common for femoral-based accesses (6/12, 46.2%) compared to upper extremity accesses (30/840, 3.6%, p < 0.001). No patients who underwent radiocephalic arteriovenous fistula (AVF) or infraclavicular axillary arteriovenous graft construction developed DASS. There was no difference in DASS for upper extremity AVFs (20/576, 3.47%) vs. AV grafts (10/264, 3.79%, p = 0.82). 216 patients had PAP measured intra-operatively. Fourteen (6.5%) of these 216 patients developed DASS requiring intervention in follow-up. The mean PAP ratio of these 14 patients was 0.395 vs. 0.557 for the 202 patients who did not [CI 0.07-0.25, p = 0.001]. Seventeen patients who had low PAP ratio with poor distal perfusion underwent intra-operative banding, which improved mean PAP ratios from a mean of 0.33 to 0.58. Despite banding, 3 of these 17 (17.6%) patients in this high-risk subgroup went on to develop DASS postoperatively. The calculated mean PAP ratio in patients who either developed DASS post-operatively or underwent prophylactic banding intra-operatively was 0.37, which was significantly lower than the mean ratio of 0.57 in the control group (p = 0.001). CONCLUSIONS: Low PAP ratios (less than 0.50) identified patients at elevated risk for DASS, but prophylactic banding did not always prevent the occurrence of DASS in select patients. Because steal is a dynamic phenomenon, intraoperative conditions are not always going to reflect later adaptation. Nonetheless, PAP measurement may identify a subgroup warranting procedural modification or closer postoperative physiologic monitoring.

Comparing fluorescent contrast agents for fluorescence guided surgery using 3-D cryo-imaging.

Fluorescence cryo-imaging is a high-resolution optical imaging technique that produces 3-D whole-body biodistributions of fluorescent molecules within an animal specimen. To accomplish this, animal specimens are administered a fluorescent molecule or reporter and are frozen to be autonomously sectioned and imaged at a temperature of -20°C or below. Thus, to apply this technique effectively, administered fluorescent molecules should be relatively invariant to low temperature conditions for cryo-imaging and ideally the fluorescence intensity should be stable and consistent in both physiological and cryo-imaging conditions. Herein, we assessed the mean fluorescence intensity of 11 fluorescent contrast agents as they are frozen in a tissue-simulating phantom experiment and show an example of a tested fluorescent contrast agent in a cryo-imaged whole pig brain. Most fluorescent contrast agents were stable within ~25% except for FITC and PEGylated FITC derivatives, which showed a dramatic decrease in fluorescence intensity when frozen.

Heart failure diagnostic accuracy, intraoperative fluid management, and postoperative acute kidney injury: a single-centre prospective observational study.

BACKGROUND: The accurate diagnosis of heart failure (HF) before major noncardiac surgery is frequently challenging. The impact of diagnostic accuracy for HF on intraoperative practice patterns and clinical outcomes remains unknown. METHODS: We performed an observational study of adult patients undergoing major noncardiac surgery at an academic hospital from 2015 to 2019. A preoperative clinical diagnosis of HF was defined by keywords in the preoperative assessment or a diagnosis code. Medical records of patients with and without HF clinical diagnoses were reviewed by a multispecialty panel of physician experts to develop an adjudicated HF reference standard. The exposure of interest was an adjudicated diagnosis of heart failure. The primary outcome was volume of intraoperative fluid administered. The secondary outcome was postoperative acute kidney injury (AKI). RESULTS: From 40 659 surgeries, a stratified subsample of 1018 patients were reviewed by a physician panel. Among patients with adjudicated diagnoses of HF, those without a clinical diagnosis (false negatives) more commonly had preserved left ventricular ejection fractions and fewer comorbidities. Compared with false negatives, an accurate diagnosis of HF (true positives) was associated with 470 ml (95% confidence interval: 120-830; P=0.009) lower intraoperative fluid administration and lower risk of AKI (adjusted odds ratio:0.39, 95% confidence interval 0.18-0.89). For patients without adjudicated diagnoses of HF, non-HF was not associated with differences in either fluids administered or AKI. CONCLUSIONS: An accurate preoperative diagnosis of heart failure before noncardiac surgery is associated with reduced intraoperative fluid administration and less acute kidney injury. Targeted efforts to improve preoperative diagnostic accuracy for heart failure may improve perioperative outcomes.

The Schroth Method for Pediatric Scoliosis: A Systematic and Critical Analysis Review.

BACKGROUND: The Schroth method is the most commonly used patient scoliosis-specific exercise paradigm for treating pediatric scoliosis. The aim of this study is to systematically and critically examine the evidence for the Schroth method for pediatric scoliosis. METHODS: PubMed, MEDLINE, CINAHL, and Web of Science were searched through April 5, 2024, for articles examining the Schroth method for pediatric scoliosis (<18 years old). Thirteen review questions were created spanning the study aim. Each included article was independently assessed for the level of evidence (I-IV). Research questions were given a grade of recommendation (A, B, C, and I [insufficient]). RESULTS: A total of 29 articles (41.4% Level I, 31.0% Level II, 13.8% Level II, and 13.8% Level IV) met inclusion criteria out of 845 initially retrieved, describing 1,555 patients with scoliosis aged 4 to 18 years. There was grade A evidence that the Schroth method is most commonly used for adolescent idiopathic scoliosis (AIS), can improve the angle of trunk rotation, and is safe; grade B evidence for improvement in posture; and grade I evidence for improvement in Cobb angle, cosmetic deformity, quality of life, ideal treatment parameters, economic value, utility in delaying/preventing surgery, effectiveness in relation to patient characteristics (e.g., skeletal maturity or curve size), and comparative effectiveness to other conservative interventions. CONCLUSION: While there is good evidence that the Schroth method is commonly and safely used in AIS and can minimally improve the angle of trunk rotation and fair evidence of improvement in posture, there is insufficient evidence regarding multiple important clinical and economic outcomes, such as comparative effectiveness to other conservative interventions and improvement of Cobb angle. Although clinicians may consider the Schroth method as 1 option of several conservative strategies, clinical benefit may be limited, and further high-quality research is needed to evaluate its performance in areas of insufficient evidence.

Impact of NSD1 Alternative Transcripts in Actin Filament Formation and Cellular Division Pathways in Fibroblasts.

Germline variants in the NSD1 gene are responsible for Sotos syndrome, while somatic variants promote neoplastic cell transformation. Our previous studies revealed three alternative RNA isoforms of NSD1 present in fibroblast cell lines (FBs): the canonical full transcript and 2 alternative transcripts, termed AT2 (NSD1 Δ5Δ7) and AT3 (NSD1 Δ19-23 at the 5' end). The precise molecular pathways affected by each specific isoform of NSD1 are uncharacterized to date. To elucidate the role of these isoforms, their expression was suppressed by siRNA knockdown in FBs and protein expression and transcriptome data was explored. We demonstrate that one gene target of NSD1 isoform AT2 is ARP3 actin-related protein 3 homolog B (ACTR3B). We show that loss of both canonical NSD1 and AT2 isoforms impaired the ability of fibroblasts to regulate the actin cytoskeleton, and we observed that this caused selective loss of stress fibers. Our findings provide novel insights into NSD1 function by distinguishing isoform function and demonstrating an essential role of NSD1 in regulating the actin cytoskeleton and stress fiber formation in fibroblasts.

Jewish Americans' identity salience and effects on attitudes toward diversity.

Although Jewish people in the US are often racialized (i.e., perceived by others) as White, Jewish Americans vary in the extent to which they consider themselves White, and in how strongly they identify with being Jewish. Based on prior findings that identifying with a White ethnic subgroup (e.g., Irish, Italian) can reduce prejudice toward racial and ethnic minorities, we predicted that strongly identified Jewish Americans would exhibit less intergroup bias than weakly identified Jewish Americans. For the present research, we recruited participants whose religious affiliation was Jewish but who self-identified as racially White. In a preregistered correlational study, Jewish identification was associated with lower bias, whereas White identification was associated with greater bias, toward Whites relative to racial/ethnic minorities. The relationship between Jewish identification and intergroup bias was accounted for by high Jewish identifiers' perceptions that they could personally contribute to diversity in groups and organizations. Across three meta-analyzed experiments, participants whose religious minority (Jewish) identity was made salient exhibited less intergroup bias than did control participants, and in one preregistered experiment, perceived personal contributions to diversity mediated the effect of condition on intergroup bias. Implications for the forms of ethnic identity that predict more versus less intergroup bias in an increasingly multicultural society are discussed.

Implementation and Evaluation of an Academic Development Rotation for Surgery Residents.

OBJECTIVE: To describe the design, implementation, and evaluation of a two-week rotation intended to enhance junior surgical residents' preparation for their dedicated professional development time (PDT) and academic careers. DESIGN: As part of a multifaceted effort to promote residents' academic development, we designed a two-week, nonclinical "Academic Development Block" (ADB) rotation for postgraduate year (PGY)-2 and -3 residents. During this rotation, residents meet with clinical, research, and peer mentors and work on academic activities, with relevant deliverables specific to each class year. We analyzed feedback from postrotation surveys and interviews, which were inductively coded and thematically analyzed, and data on resident grant applications and earnings before and after implementation. SETTING: The general surgery residency program at a major urban, university-affiliated academic medical center. ADBs were first implemented in 2021. PARTICIPANTS: A total of 39 PGY-2 and PGY-3 residents rotated through the program with 51 ADBs over the first two years of implementation. RESULTS: Surveys indicated overwhelmingly positive perceptions on the value of ADBs, including the amount of structure and resources available. Free-response and interview themes indicated appreciation for time to meet with mentors, develop ideas, and complete academic work. Residents believed the ADB rotation accelerated their transition into PDT and was a marker of institutional commitment. Areas for improvement pertained to the timing of ADBs and pairing of mentors. Both cohorts who participated in at least 1 ADB had higher proportions of residents who successfully applied for grants and a greater amount of total funding awarded compared to all 4 of the most recent cohorts prior to implementation. CONCLUSIONS: A short academic development rotation protected from clinical responsibilities is a well-regarded intervention to help residents refine their career goals and prepare for their PDT. Similar initiatives may be of interest to residency programs seeking to foster their residents' academic career development.

Segmental range-of-motion by vertebral level in fused and unfused patients with adolescent idiopathic scoliosis: a systematic review of the literature.

PURPOSE: This study aims to understand global and segmental spinal ROM in surgical and nonsurgical AIS patients. METHODS: This systematic review examined segmental vertebral ROM in AIS patients using PubMed, SPORTDiscus, MEDLINE, and Web of Science until October 8th, 2023. Inclusion criteria were articles on segmental motion in AIS patients, both operative and non-operative, under 18 years old. RESULTS: Seventeen articles met eligibility criteria from 2511 initially retrieved. All patients (n = 996) had AIS (549 non-operative; 447 were operative), with a frequency-weighted mean age of 15.1 ± 1.6 years and a baseline Cobb angle of 51.4 ± 13.3 degrees. Studies showed heterogenous segmental flexibility in the unfused spine, with the apical curve and upper thoracic segments being more rigid and lower segments more flexible at -5 disk segments from the apex. Most studies showed a predictable loss of motion in fused spinal regions postoperatively and a variable loss of global motion depending on the LIV and number of fused segments. A 7° global loss of total trunk flexion per level was observed with increasingly caudal LIV, starting at L1. Anterior vertebral body tethering (AVBT) preserved motion post-surgery but reduced coronal plane motion. AVBT saw less motion loss compared to posterior spinal fusion (PSF) but had higher revision and complication rates. CONCLUSION: Preservation of spinal segments correlated with improved motion postoperatively. Increasing caudal LIV in PSF showed sagittal flexion loss. AVBT preserved more sagittal ROM than PSF but increased coronal motion loss, complications, and revision rates, with the largest benefit at LIV L4. Data on segmental motion are limited and further research on postoperative segmental ROM is required.

Evidence of an excitatory purinergic innervation in mouse corpus cavernosum smooth muscle.

BACKGROUND: Evidence suggests that the corpus cavernosum smooth muscle (CCSM) cells of several species, including humans, express purinergic P2X receptors, but it is not known if the corpus cavernosum has an excitatory purinergic innervation. AIM: In this study we aimed to determine if the mouse CCSM has a functional purinergic innervation. METHODS: Mouse CCSM myocytes were enzymatically isolated and studied using the perforated patch configuration of the patch clamp technique. Isometric tension was measured in whole cavernosum tissue subjected to electrical field stimulation (EFS) to evoke nerve-mediated responses. OUTCOMES: The mouse CCSM myocytes expressed P2X1 receptors, and adenosine triphosphate (ATP) evoked inward currents in these cells. In addition, P2X1-mediated contractions were recorded in whole tissue in response to EFS. RESULTS: In cells held under a voltage clamp at -60 mV, ATP (1 µm) evoked large inward currents (mean approximately 900 pA). This current rapidly declined but was repeatable at 8-minute intervals. α,ß-methylene ATP (10 µM), an agonist of P2X1 and P2X3 receptors, caused a similar current that also rapidly declined. Desensitization to α,ß-methylene ATP negated the effect of ATP, but the ATP effect was restored 8 minutes after washout of α,ß-methylene ATP. The effect of ATP was reversibly blocked by NF449 (1 µm), a selective antagonist of P2X1 receptors. In isometric tension experiments electrical field stimulation (EFS) at 0.5-8 Hz evoked frequency-dependent contractions in the presence of l-nitro arginine (l-NO-Arg) (100 µm). When phentolamine (3 µm) and atropine (1 µm) were applied, there remained a nonadrenergic, noncholinergic component of the response to EFS, consisting mainly of a transient contraction. This was significantly reduced by NF449 (1 µm). Finally, in immunocytochemistry experiments, isolated CCSM myocytes stained positively when exposed to an antibody raised against P2X1 receptors. CLINICAL IMPLICATIONS: Previous studies have shown that P2X1 receptors in CCSM are upregulated in diabetes. These findings, taken together with the functional evidence presented here, indicate that P2X1 receptors may provide an alternative therapeutic target for treatment of erectile dysfunction in patients with diabetes, which is known to be relatively resistant to treatment with phosphodiesterase 5 inhibitors. STRENGTHS AND LIMITATIONS: Strengths of this study are the use of a combination of functional experiments (patch clamp) and immunocytochemical analyses to show expression of P2X1 receptors on CCSM myocytes while also performing functional experiments to show that stimulation these receptors results in contraction of CCSM. A limitation of this study was the use of animal rather than human tissue. CONCLUSION: This investigation provides evidence that mouse corpus cavernosum smooth muscle cells express P2X1 receptors and that these receptors are involved in mediating part of the contractile response to nerve stimulation evoked by EFS.

Persistent pain after total temporomandibular joint replacement surgery: clinical characteristics, comorbidities, and risk factors.

Chronic post-surgical pain (CPSP) after temporomandibular joint (TMJ) surgery is an under-recognized problem. The aim of this study was to document the characteristics of CPSP and identify patient risk factors and comorbidities associated with the development of CPSP after total TMJ replacement (TJR). This was a retrospective cohort study of patients who underwent TJR between 2000 and 2018 at Massachusetts General Hospital, Boston, USA. The primary outcome was the presence of CPSP and use of pain medications after TJR. The secondary outcome was the risk factors associated with the development of CPSP. A total 88 patients were included (79 females, 9 males). The mean follow-up was 4.2 years. Overall, 68 (77.3%) had CPSP and 20 (22.7%) had no CPSP. Of those with CPSP, 32.4% had severe pain and 45.6% continued to take pain medications. Of the 27 patients with data available on the characteristics of the pain, the majority had myofascial pain, while some developed neuropathic pain. A significant difference was noted between the CPSP and non-CPSP groups in terms of preoperative pain, smoking behavior, and use of opioids, non-steroidal anti-inflammatory drugs, muscle relaxants, and neuropathic pain medications.

Differentiating Between Knee Septic Arthritis and Lyme Arthritis in Children: A Clinical Prediction Algorithm for a Geographically Diverse Population.

BACKGROUND: Knee septic arthritis (SA) and Lyme arthritis (LA) often have similar presentations but bacterial SA necessitates urgent surgery. Predictive factors for differentiating SA and other infectious/inflammatory conditions have been published. Our purpose was to test these algorithms using a retrospective multicenter musculoskeletal infection database. METHODS: Patients ≤18 years old with isolated knee SA or LA were identified. Diagnostic criteria for SA were synovial WBC count >50,000 cells/mm3, imaging with fluid aspiration suggestive of SA, or joint aspirate/tissue sample cultured positive for bacteria. Diagnostic criteria for LA was positive Lyme titer. Demographics, weightbearing status, admission vitals, and laboratory tests were collected. Predictive factors from Baldwin criteria for differentiating knee SA and LA, and Kocher criteria for differentiating hip SA and transient synovitis were tested. RESULTS: One hundred fifty-five patients (119 SA and 36 LA) were analyzed. Patients with SA were younger (2.2 vs. 8.0 y), more nonweightbearing (74% vs. 33%), had a higher pulse (127 vs. 106), and higher WBC (12.4 vs. 10.2) (all P<0.001).Baldwin criteria (pain with joint motion, history of fever, CRP >40 mg/L, age <2 y) were tested. Pain with motion was not collected in our database. Of the remaining factors, the probability of SA was 63% with 0 and 92% with 3 factors (AUC 0.64). Kocher criteria (nonweightbearing, temperature >101.3°F, WBC >12.0, ESR >40) and CRP >20 mg/L were also tested. The probability of SA was 41% with 0 and 96% with all factors (AUC 0.69).Using our cohort data, regression analysis with backward stepwise elimination determined that age <4 years, nonweightbearing, admission WBC >13.0, platelets <325, and ESR >70 were predictive factors for SA. The probability of SA with 0 factors was 16%, 1 factor 52%, 2 factors 86%, 3 factors 97%, and 4 factors 100% (AUC 0.86). CONCLUSIONS: Our model identified age <4 years, nonweightbearing, admission WBC >13.0, platelets <325, and ESR >70 as independent predictive factors for knee SA. The more factors present, the higher the likelihood of having SA versus LA. LEVEL OF EVIDENCE: Diagnostic level III.

The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF): Rationale and design.

AIMS: Benefits of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved and mildly reduced ejection fraction (HFpEF/HFmrEF) have not been established. Conventional randomized controlled trials are complex and expensive. The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF) is a unique pragmatic registry-based randomized controlled trial. METHODS: SPIRRIT-HFpEF is a multicentre, prospective, randomized, open-label, blinded endpoint trial conducted on platforms in the Swedish Heart Failure Registry (SwedeHF) and the United States (US) Trial Innovation Network. Patients with HFpEF/HFmrEF are randomized 1:1 to spironolactone (or eplerenone) in addition to usual care, versus usual care alone. The primary outcome is total number of cardiovascular deaths and hospitalizations for heart failure. Outcomes are collected from Swedish administrative complete coverage registries and a US call centre and subsequently adjudicated. Simple eligibility criteria were based on data available in SwedeHF: heart failure as outpatient or at discharge from hospital, left ventricular ejection fraction ≥40%, N-terminal pro-B-type natriuretic peptide >300 ng/L (in sinus rhythm) or >750 ng/L (in atrial fibrillation), with pre-specified adjustment for elevated body mass index, and chronic loop diuretic use. Power and sample size assessments were based on an event-driven design allowing enrolment over approximately 6 years, and application of hazard ratios from the TOPCAT trial, Americas subset. The final sample size is expected to be approximately 2400 patients. CONCLUSION: SPIRRIT-HFpEF will be informative on the effectiveness of generic MRAs in HFpEF and HFmrEF, and on the feasibility of conducting pragmatic and registry-based trials in heart failure and other chronic conditions.

Changing the focus: Facilitating engagement in physical activity for people living with mild dementia in a local community-Protocol for a pre-post mixed methods feasibility study.

This study aims to address and improve the low physical activity levels among people with mild dementia by implementing a novel shared decision-making and motivational support program, named "Changing the Focus". It will utilise a pre-post mixed methods approach, aiming to recruit 60 community living older people with mild dementia and their care-partners. The shared decision-making process will involve the person living with dementia, their care-partner, and a research therapist, using a purpose-designed discussion tool including factors such as preferred physical activities, health status, local opportunities and program accessibility. This process aims to identify personalised local physical activity opportunities. Participants will be supported with the help of a research therapist to engage in targeted community-based physical activities for 12-months, to progress towards the recommended physical activity guidelines of 150 minutes per week. The intervention provided by the research therapist will include three home visits (baseline, 6- and 12-months) and seven motivational support phone calls (within the first six months). Research therapists may provide additional home visits and support calls as needed. Primary outcomes include program participation (participants living with dementia continuing with the program after 12-months), total physical activity time per week (measured using the Active Australia Survey at baseline, 6- and 12- months) and program acceptability (assessed through semi-structured interviews with participants, care-partners, referrers, and physical activity providers). Secondary outcomes include physical performance, mental health, wellbeing measures, and impact on care-partners (evaluated through physical tests or validated scales at baseline, 6- and 12-months). Other implementation aspects include reach, maintenance, safety (falls, other adverse events) and an economic evaluation. Results will inform feasibility, potential benefits, and challenges associated with this innovative shared decision-making and supported physical activity program for people living with mild dementia. Findings will guide future large-scale studies and contribute to enhancing physical activity opportunities for this population.

Unraveling the Long-term Natural History of Branch Duct Intraductal Papillary Mucinous Neoplasm: Beyond 10 years.

OBJECTIVE: To describe the long-term natural history of Branch duct intraductal papillary mucinous neoplasm (BD-IPMN). BACKGROUND: The BD-IPMN is a known precursor of pancreatic cancer, yet its long-term natural history is largely unknown. METHODS: We retrospectively reviewed patients with BD-IPMN who were followed at the Massachusetts General Hospital for at least ten years without surgical intervention. Patient and cyst characteristics, development of worrisome features (WF), need for surgery, and malignancy were recorded. The risk of pancreatic cancer in this cohort was compared with the general population by determining the Standardized Incidence Ratio (SIR). RESULTS: 316 patients with BD-IPMN who were followed for at least ten years without intervention were identified. The median age was 63 years, and the median follow-up was 13.5 years (range 10 - 28.8 years). Median cyst size at diagnosis was 1.2 cm (IQR 0.8 - 1.7), was 1.8 cm (IQR 1.2-2.6) at ten years, and increased to 2.0 cm (IQR 1.3 - 3.0) by the end of surveillance. At the 10-year mark, 24% of patients had WF, and by the end of surveillance, an additional 20% had developed WF or high-risk stigmata. 8.2% of patients developed pancreatic malignancy (high-grade dysplasia or invasive cancer). The SIR for pancreatic cancer was 9.28 (95%CI of 5.82 - 14.06), with almost two-thirds of invasive cancers occurring within the pancreatic cyst. CONCLUSIONS: After ten years of surveillance for BD-IPMN without intervention, the disease continues to progress and one of every 12 patients will develop malignancy. The risk of pancreatic cancer appears to be nine times higher than in the comparable age-matched population.

Animal models of temporomandibular joint heterotopic ossification: a scoping review.

There are few animal models for heterotopic ossification of the temporomandibular joint (TMJ-HO). This scoping review provides an overview of current knowledge on the induction methods and specific conditions required to produce TMJ-HO in various animal models. Two independent reviewers selected papers from the PubMed, Web of Science, and Cochrane Library databases. The inclusion criteria were articles in English, in vivo studies, and a TMJ-HO induction method. Observational, in vitro, human studies, reviews, and book chapters were excluded. Twenty-four publications were included. HO was surgically, genetically, or chemically induced through single or combined defects in the condyle, articular disc, and temporal bone in animal models (sheep=9 studies, mouse=5, rat=4, rabbit=2, pig=2, goat=1, dog=1, monkey=1) specific for traumatic TMJ-HO (n=4), ankylosis (n=9), osteoarthritis (n=8), experimental disc perforation (n=1), status post-TMJ replacement (n=1), and status post bilateral sagittal split osteotomy (n=1). TMJ-HO remains challenging to study due to its multifactorial etiology and largely unknown pathogenesis, which varies between species. There is a need for more accurate, reproducible animal models that can be extrapolated to human TMJ-HO and a consolidated clinical classification system to allow for meaningful future research.

Enhancing Qualitative and Quantitative Data Linkages in Complex Mixed Methods Designs: Illustrations from a Multi-Phase Healthcare Delivery Study.

While mixed methods research is increasingly used to examine determinants of unwarranted variability in healthcare delivery and outcomes, novel integrative approaches are required to meet the needs of mixed methods healthcare delivery research. This article describes novel refining strategies that enhance the linkage between qualitative and quantitative dimensions of a mixed methods healthcare delivery research study. Leveraging our study experiences, this paper demonstrates several refining strategies: (1) using mediated allocation concealment to facilitate qualitative sampling; (2) informing qualitative inquiry through quantitative analytics; and (3) training and immersing multidisciplinary researchers in qualitative data collection and analysis. Developing and implementing strategies in mixed methods healthcare delivery research could advance methodological rigor and strengthen multidisciplinary collaboration.

Outcomes of the My Therapy self-management program in people admitted for rehabilitation: A stepped wedge cluster randomized clinical trial.

BACKGROUND: Self-management programs can increase the time spent on prescribed therapeutic exercises and activities in rehabilitation inpatients, which has been associated with better functional outcomes and shorter hospital stays. OBJECTIVES: To determine whether implementation of a self-management program ('My Therapy') improves functional independence relative to routine care in people admitted for physical rehabilitation. METHODS: This stepped wedge, cluster randomized trial was conducted over 54 weeks (9 periods of 6-week duration, April 2021 - April 2022) across 9 clusters (general rehabilitation wards) within 4 hospitals (Victoria, Australia). We included all adults (≥18 years) admitted for rehabilitation to participating wards. The intervention included routine care plus 'My Therapy', comprising a sub-set of exercises and activities from supervised sessions which could be performed safely, without supervision or assistance. The primary outcomes were the proportion of participants achieving a minimal clinically important difference (MCID) in the Functional Independence Measure, (FIM™) and change in total FIM™ score from admission to discharge. RESULTS: 2550 participants (62 % women) were recruited (control: n = 1458, intervention: n = 1092), with mean (SD) age 77 (13) years and 37 % orthopedic diagnosis. Under intervention conditions, participants reported a mean (SD) of 29 (21) minutes/day of self-directed therapy, compared to 4 (SD 14) minutes/day, under control conditions. There was no evidence of a difference between control and intervention conditions in the odds of achieving an MCID in FIM™ (adjusted odds ratio 0.93, 95 % CI 0.65 to 1.31), or in the change in FIM™ score (adjusted mean difference: -0.27 units, 95 % CI -2.67 to 2.13). CONCLUSIONS: My Therapy was delivered safely to a large, diverse sample of participants admitted for rehabilitation, with an increase in daily rehabilitation dosage. However, given the lack of difference in functional improvement with participation in My Therapy, self-management programs may need to be supplemented with other strategies to improve function in people admitted for rehabilitation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12621000313831), https://www.anzctr.org.au/.

Onward to Better Surgery - the Critical Need for Improved Ex Vivo Testing and Training Methods.

Guided surgery has demonstrated significant improvements in patient outcomes in some disease processes. Interest in this field has led to substantial growth in the technologies under investigation. Most likely no single technology will prove to be "best," and combinations of macro- and microscale guidance-using radiological imaging navigation, probes (activatable, perfusion, and molecular-targeted; large- and small-molecule), autofluorescence, tissue intrinsic optical properties, bioimpedance, and other characteristics-will offer patients and surgeons the greatest opportunity for high-success/low-morbidity medical interventions. Problems are arising, however, from the lack of valid testing formats; surgical training simulators suffer the same problems. Small animal models do not accurately recreate human anatomy, especially in terms of tissue volume. Large animal models are expensive and have difficulty replicating many pathological states, particularly when molecular specificity for individual cancers is required. Furthermore, the sheer number of technologies and the potential for synergistic combination leads to exponential growth of testing requirements that is unrealistic for in vivo testing. Therefore, critical need exists to expand the ex vivo/in vitro testing platforms available to investigators and, once validated, a need to increase the acceptance of these methods for funding and regulatory endpoints. Herein is a review of the available ex vivo/in vitro testing formats for guided surgery, a review of their advantages/disadvantages, and consideration for how our field may safely and more swiftly move forward through stronger adoption of these testing and validation methods.