Localized Evaluation for Constructing Discrete Vector Fields.

Topological abstractions offer a method to summarize the behavior of vector fields, but computing them robustly can be challenging due to numerical precision issues. One alternative is to represent the vector field using a discrete approach, which constructs a collection of pairs of simplices in the input mesh that satisfies criteria introduced by Forman's discrete Morse theory. While numerous approaches exist to compute pairs in the restricted case of the gradient of a scalar field, state-of-the-art algorithms for the general case of vector fields require expensive optimization procedures. This paper introduces a fast, novel approach for pairing simplices of two-dimensional, triangulated vector fields that do not vary in time. The key insight of our approach is that we can employ a local evaluation, inspired by the approach used to construct a discrete gradient field, where every simplex in a mesh is considered by no more than one of its vertices. Specifically, we observe that for any edge in the input mesh, we can uniquely assign an outward direction of flow. We can further expand this consistent notion of outward flow at each vertex, which corresponds to the concept of a downhill flow in the case of scalar fields. Working with outward flow enables a linear-time algorithm that processes the (outward) neighborhoods of each vertex one-by-one, similar to the approach used for scalar fields. We couple our approach to constructing discrete vector fields with a method to extract, simplify, and visualize topological features. Empirical results on analytic and simulation data demonstrate drastic improvements in running time, produce features similar to the current state-of-the-art, and show the application of simplification to large, complex flows.

A Practical Solver for Scalar Data Topological Simplification.

This paper presents a practical approach for the optimization of topological simplification, a central pre-processing step for the analysis and visualization of scalar data. Given an input scalar field f and a set of "signal" persistence pairs to maintain, our approaches produces an output field g that is close to f and which optimizes (i) the cancellation of "non-signal" pairs, while (ii) preserving the "signal" pairs. In contrast to pre-existing simplification algorithms, our approach is not restricted to persistence pairs involving extrema and can thus address a larger class of topological features, in particular saddle pairs in three-dimensional scalar data. Our approach leverages recent generic persistence optimization frameworks and extends them with tailored accelerations specific to the problem of topological simplification. Extensive experiments report substantial accelerations over these frameworks, thereby making topological simplification optimization practical for real-life datasets. Our approach enables a direct visualization and analysis of the topologically simplified data, e.g., via isosurfaces of simplified topology (fewer components and handles). We apply our approach to the extraction of prominent filament structures in three-dimensional data. Specifically, we show that our pre-simplification of the data leads to practical improvements over standard topological techniques for removing filament loops. We also show how our approach can be used to repair genus defects in surface processing. Finally, we provide a C++ implementation for reproducibility purposes.

The Recovery of Consciousness via Evidence-Based Medicine and Research (RECOVER) Program: A Paradigm for Advancing Neuroprognostication.

Background: Neuroprognostication for disorders of consciousness (DoC) after severe acute brain injury is a major challenge, and the conventional clinical approach struggles to keep pace with a rapidly evolving literature. Lacking specialization, and fragmented between providers, conventional neuroprognostication is variable, frequently incongruent with guidelines, and prone to error, contributing to avoidable mortality and morbidity. Recent Findings: We review the limitations of the conventional approach to neuroprognostication and DoC care, and propose a paradigm entitled the Recovery of Consciousness Via Evidence-Based Medicine and Research (RECOVER) program to address them. The aim of the RECOVER program is to provide specialized, comprehensive, and longitudinal care that synthesizes interdisciplinary perspectives, provides continuity to patients and families, and improves the future of DoC care through research and education. Implications for Practice: This model, if broadly adopted, may help establish neuroprognostication as a new subspecialty that improves the care of this vulnerable patient population.

Functional outcomes and complications of plate fixation for midshaft clavicle fractures by type and location: a systematic review and meta-analysis.

Background: Various plate types are used in the surgical treatment of displaced midshaft clavicle fractures. These plates can be positioned in different locations on the clavicle, although no studies to date have elucidated optimal plate type and location of fixation. This systematic review compares the functional outcomes and complications in the management of displaced midshaft clavicle fractures using plate fixation by stratifying by both plate type and location. Methods: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted to identify all papers reporting functional outcomes, union rates, and/or complications using plates for the management of midshaft clavicle fractures. Multiple databases and trial registries were searched from inception until March 2022. A meta-analysis was conducted for functional outcomes and type of complication, stratified by plate type (locking, compression, or reconstruction) and location (superior or anteroinferior). Pooled estimates of functional outcome scores and incidence of complications were calculated using a random effects model. Risk of bias and quality were assessed using the risk of bias version 2 and ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tools. The confidence in estimates were rated and described according to the recommendations of the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) working group. Results: Forty-five studies were included in the systematic review and 43 were included in the meta-analysis. Depending on plate type and location, pooled Constant-Murley Scores ranged from 89.23 to 93.48 at 12 months. Nonunion rates were 3% (95% confidence interval [CI] 1-6) for superior locking plates (GRADE Low). Rates of any complication (nonunion, hardware failure, hardware irritation, wound dehiscence, keloid, superficial infection, deep infection, delayed union, malunion, and/or persistent pain) by plate type and location ranged from 3% to 17% (GRADE Very Low to Moderate). Superior compression plates had the highest incidence of any complications (17% [95% CI 5-44], GRADE Very Low), while anterior inferior compression plates had the lowest incidence of any complication (3% [95% CI 0-15], GRADE Very Low). Hardware irritation was the most reported individual complication for superior locking plates and superior compression plates, 11% (95% CI 7-17, GRADE Low) and 11% (95% CI 3-33, GRADE Very Low), respectively. Conclusion: Although most studies were of low quality, studies reporting functional outcomes generally showed good functional results and similar incidence of any complication regardless of plate type and location. There is no evidence of a plate and location combination to optimize patient functional outcomes or complications. We were unable to reliably evaluate union rates or individual complications for most plate types stratified by location.

Model-based simulation of glycaemic effect and body weight loss when switching from semaglutide or dulaglutide to once weekly tirzepatide.

OBJECTIVE: To evaluate the efficacy endpoints of HbA1c and body weight loss after switching from the GLP-1 receptor agonists, semaglutide or dulaglutide, to treatment with the GIP/GLP-1 receptor agonist (RA) tirzepatide. METHODS: Models were developed and validated to describe the HbA1c and weight loss time course for semaglutide (SUSTAIN 1-10), dulaglutide (AWARD-11) and tirzepatide (SURPASS 1-5, phase 3 global T2D program). The impact of switching from once weekly GLP-1 RAs to tirzepatide was described by simulating the efficacy time course. Semaglutide and dulaglutide doses were escalated in accordance with their respective labels. RESULTS: Model-predicted mean decreases from baseline in HbA1c and body weight for semaglutide 0.5 mg, 1 mg, and 2 mg were 1.22 to 1.79% and 3.62 to 6.87 kg respectively, at Week 26. Model-predicted mean decreases from baseline in HbA1c and body weight for dulaglutide 1.5 mg, 3 mg and 4.5 mg were 1.53 to 1.84% and 2.55 to 3.71 kg respectively, at Week 26. After switching to tirzepatide 5, 10 and 15 mg HbA1c reductions were predicted to range between 1.95 to 2.46% and body weight reductions between 6.50 to 12.1 kg by Week 66. CONCLUSION: In this model-based simulation, switching from approved maintenance doses of semaglutide or dulaglutide to tirzepatide, even at the lowest approved maintenance dose of 5 mg, showed the potential to further improve HbA1c and body weight reductions.

Type 2 diabetes is a disease of elevated blood sugar levels. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type of medication used to treat type 2 diabetes that work on GLP-1 receptors in the body. Semaglutide and dulaglutide are examples of GLP-1 RAs, which lower blood sugar and body weight. Tirzepatide is a newer medication, which works on both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. It reduces blood sugar and body weight in people living with type 2 diabetes. Healthcare professionals and patients are interested in how switching medication from semaglutide or dulaglutide to tirzepatide might change blood glucose levels and body weight. However, because tirzepatide is a newer medication, there is not much information available on this aspect. Data from clinical trials of these medications were used to predict the effects of switching from semaglutide or dulaglutide to tirzepatide. These model-based simulations showed that switching to tirzepatide may further reduce HbA1c (a measure of blood sugar) and body weight. This may provide useful information to healthcare professionals and patients when making decisions about treatment with these medications.

Surgical Delay of Thoracodorsal Artery Perforator Flaps for Total Autologous Breast Reconstruction.

BACKGROUND: When abdomen-based free flap reconstruction is contraindicated, the muscle-sparing thoracodorsal artery perforator (TDAP) flap may be considered for total autologous breast reconstruction. The TDAP flap is often limited by volume and is prone to distal flap necrosis. We aim to demonstrate our experience combining the delay phenomenon with TDAP flaps for total autologous breast reconstruction. METHODS: Patients presenting for autologous breast reconstruction between April 2021 and August 2023 were recruited for surgically delayed TDAP flap reconstruction when abdominally based free flap reconstruction was contraindicated because of previous abdominal surgery or poor perforator anatomy. We dissected the TDAP flap except for a distal skin bridge and then reconstructed the breast 1 to 7 days later. Data included flap dimensions (in centimeters × centimeters), delay time (in days), predelay and postdelay perforator caliber (in millimeters) and flow (in centimeters per second), operative time (in minutes), hospital length of stay (in days), complications/revisions, and follow-up time (in days). RESULTS: Fourteen patients and 16 flaps were included in this study. Mean age and body mass index of patients were 55.9 ± 9.6 years and 30.1 ± 4.3 kg/m2, respectively. Average flap skin island length and width were 32.1 ± 3.3 cm (n = 8 flaps) and 8.8 ± 0.7 cm (n = 5 flaps), respectively. Beveled flap width reached 16.0 ± 2.2 cm (n = 3 flaps). Average time between surgical delay and reconstruction was 2.9 days, ranging from 1 to 7 days (n = 18 flaps). Mean predelay and postdelay TDAP vessel caliber and flow measured by Doppler ultrasound increased from 1.4 ± 0.3 to 1.8 ± 0.3 mm (P = 0.03) and 13.3 ± 5.2 to 43.4 ± 18.8 cm/s (P = 0.03), respectively (n = 4 flaps). Complications included 1 donor site seroma and 1 mastectomy skin flap necrosis. Follow-up ranged from 4 to 476 days (n = 17 operations). CONCLUSIONS: We demonstrate surgically delayed TDAP flaps as a viable option for total autologous breast reconstruction. Our series of flaps demonstrated increased perforator caliber and flow and enlarged volume capabilities and had no incidences of flap necrosis.

Angioinvasive Trichophyton rubrum associated necrotizing fasciitis in an immunocompromised patient.

Angioinvasive dermatophytosis with necrotizing fasciitis can be a rare complication in immunocompromised patients with early surgical debridement, 12 weeks of oral terbinafine, and reduction in immunosuppression being a viable management strategy.

Predictors of ≥15% Weight Reduction and Associated Changes in Cardiometabolic Risk Factors With Tirzepatide in Adults With Type 2 Diabetes in SURPASS 1-4.

OBJECTIVE: To identify predictors of body weight (BW) reduction of ≥15% with tirzepatide treatment and to describe associated clinical parameters of participants with type 2 diabetes (T2D) who achieved different categorical measures of BW reduction (<5%, ≥5 to <10%, ≥10 to <15%, and ≥15%) across four studies from the phase 3 SURPASS clinical trial program for T2D. RESEARCH DESIGN AND METHODS: The multivariate model for predictor of a BW reduction of ≥15% included age, sex, race, BW, HbA1c, tirzepatide dose and baseline metformin use, fasting serum glucose, and non-HDL cholesterol. Baseline characteristics and change from baseline to week 40/42 for efficacy parameters were described and analyzed in treatment-adherent participants (≥75% doses administered and on treatment at week 40/42) receiving once weekly tirzepatide (5 mg, 10 mg, or 15 mg) (N = 3,188). RESULTS: Factors significantly associated with achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, and lower HbA1c, fasting serum glucose, and non-HDL cholesterol at baseline. With higher categorical BW reduction, there were greater reductions in HbA1c, triglycerides, ALT, waist circumference, and blood pressure. CONCLUSIONS: Baseline factors associated with a higher likelihood of achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, better glycemic status, and lower non-HDL cholesterol. With greater BW reduction, participants with T2D achieved larger improvements in glycemia and cardiometabolic risk parameters. These findings help inform which people with T2D are most likely to achieve greater BW reduction with improved cardiometabolic risk factors with tirzepatide.

Histoplasmosis mimicking a tumor of the thumb in a patient with neurofibromatosis type I: A case report and review of the literature.

We describe an immunocompromised 73-year-old male with a history of neurofibromatosis type 1 (NF1) who presented with a lesion on the thumb concerning for malignancy that was found to be histoplasmosis. This unique case highlights the importance of a thorough history and a broad differential diagnosis in the management of new osteoarticular lesions.

Stroke and Disseminated Intravascular Coagulation in a Patient With Metastatic Prostate Cancer.

Cancer and stroke comprise two of the most common causes of death worldwide. Despite a significantly increased risk of stroke among patients with cancer, most stroke trials have excluded patients with malignancy. There is thus limited evidence to help guide management decisions in this complex population. We present the case of a 78-year-old man with recurrent strokes - both ischemic and hemorrhagic - in the setting of newly-identified metastatic prostate cancer. An atypical cause of cancer-associated stroke is reviewed and the management is discussed.

A Case Series of Young Patients with Low-Energy Femoral Neck Fractures.

Background: Fragility femoral neck fractures are traditionally seen in elderly patients after a low-energy fall. In contrast, displaced femoral neck fractures in young patients are usually associated with high-energy mechanisms such as a fall from height or high-speed motor vehicle collisions. However, patients under the age of 45 with fragility femoral neck fractures represent a unique population, and one that is not well-described. This study aims to describe this population and their current workup. Methods: A single institution retrospective chart review of patients who underwent open reduction internal fixation or percutaneous pinning of femoral neck fractures from 2010-2020 was conducted. Inclusion criteria were patients 16-45 years old and femoral neck fractures with a low-energy mechanism of injury (MOI). Exclusion criteria were high-energy fractures, pathologic fractures, and stress fractures. Patient demographics, MOI, past medical history, imaging studies, treatment plan, lab values, DEXA results, and surgical outcomes were recorded. Results: The average age in our cohort was 33 ± 8.5 y/o. 44% (12/27) were male. Vitamin D level was obtained in 78% (21/27) patients and 71% (15/21) those patients were found to be abnormally low. A DEXA scan was obtained in 48% (13/27) of patients and abnormal bone density was found in 90% (9/10) of available results. 41% (11/27) patients received a bone health consultation. Conclusion: A significant portion of femoral neck fractures in young patients were fragility fractures. Many of these patients did not receive bone health workup and their underlying health condition remained untreated. Our study highlighted a missed opportunity of treatment for this unique and poorly understood population. Level of Evidence: III.

Major ß cell-specific functions of NKX2.2 are mediated via the NK2-specific domain.

The consolidation of unambiguous cell fate commitment relies on the ability of transcription factors (TFs) to exert tissue-specific regulation of complex genetic networks. However, the mechanisms by which TFs establish such precise control over gene expression have remained elusive-especially in instances in which a single TF operates in two or more discrete cellular systems. In this study, we demonstrate that ß cell-specific functions of NKX2.2 are driven by the highly conserved NK2-specific domain (SD). Mutation of the endogenous NKX2.2 SD prevents the developmental progression of ß cell precursors into mature, insulin-expressing ß cells, resulting in overt neonatal diabetes. Within the adult ß cell, the SD stimulates ß cell performance through the activation and repression of a subset of NKX2.2-regulated transcripts critical for ß cell function. These irregularities in ß cell gene expression may be mediated via SD-contingent interactions with components of chromatin remodelers and the nuclear pore complex. However, in stark contrast to these pancreatic phenotypes, the SD is entirely dispensable for the development of NKX2.2-dependent cell types within the CNS. Together, these results reveal a previously undetermined mechanism through which NKX2.2 directs disparate transcriptional programs in the pancreas versus neuroepithelium.

The delay procedure in deep inferior epigastric artery perforator flap breast reconstruction.

BACKGROUND: The delay procedure in DIEP flap breast reconstruction, in which the reduced-caliber choke vessels play a major role, can provide more well-perfused tissue than a standard DIEP flap. The aim of this study was to review our experience with this technique, to evaluate the indications, and to analyze the surgical outcomes. METHODS: A retrospective study was conducted of all consecutive DIEP delay procedures performed between March 2019 and June 2021. Patient demographics, operative details, and complications were registered. Patients had preoperative imaging by MRA to select dominant perforators. The surgical technique involves a two-stage operation. During the first operation the flaps were pedicled on a dominant perforator and a lateral skin bridge extending towards the lateral flank and lumbar fat, and in a second stage the flap is harvested and transferred. RESULTS: A total of 82 extended DIEP delay procedures were performed to reconstruct 154 breasts. The majority were bilateral breast reconstructions (87.8%). The delay procedure was used for 38 primary reconstructions (46.3%) and 32 tertiary reconstructions (39.0%). The primary indication was the need for additional volume (79.3%), followed by extensive abdominal scarring and liposuction. After the first operation seroma was the most frequently observed complication (7.3%). After the second operation three total flap losses (1.9%) were observed. CONCLUSIONS: The delay procedure in DIEP flap breast reconstruction results in the harvest of a good amount of abdominal tissue by adding a preliminary procedure. This technique can convert patients previously considered unsuitable into suitable candidates for abdominal-based breast reconstruction.

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers.

This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.

A Case Series Evaluating Postoperative Complications of Foot and Ankle Surgeries in Adult Patients With Neuromuscular Disease.

Background: Patients with neuromuscular diseases such as cerebral palsy (CP) are living longer because of advances in medicine, yielding a larger number of adult patients that could benefit from corrective surgery. However, some surgeons are hesitant to offer surgery to these patients because of concern for postoperative complications. A paucity of literature exists that describes complications in patients undergoing foot and ankle surgery for neuromuscular diseases. The primary study outcome was to identify the postoperative complication rates associated with foot and ankle surgery in adult patients with neuromuscular disease. Methods: The charts of patients with neuromuscular diseases who had foot and ankle surgery by the senior author at a single institution from March 2010 to March 2020 were reviewed. Patient charts were reviewed for demographic data, medical history and diagnoses, and surgical treatment information. Only patients' index procedures with the senior author were evaluated for surgical data. Patient charts were assessed to determine the presence or absence of a postoperative complication following an index procedure. Results: In a cohort of 42 patients, females comprised 60% of the patient cohort. The average age was 35 (range, 20-69) years old. CP was the most common neuromuscular diagnosis at 52% (22 of 42) patients. Eighteen percent (11 of 60) of the index surgeries had 1 or more complication with a total of 13 complications. The overall wound complication rate was 10% (6 of 60), infection rate was 8% (5 of 60), and the nonunion rate following arthrodesis was 10% (2 of 21). Conclusion: We conclude that foot and ankle surgery in this complex population can be done safely, with postoperative complication rates similar to the average population. Although these patients may present with unique challenges, surgeons should not forgo surgery out of concern for postoperative complications. Level of Evidence: Level IV, retrospective cohort study at a single institution.

Computing a Stable Distance on Merge Trees.

Distances on merge trees facilitate visual comparison of collections of scalar fields. Two desirable properties for these distances to exhibit are 1) the ability to discern between scalar fields which other, less complex topological summaries cannot and 2) to still be robust to perturbations in the dataset. The combination of these two properties, known respectively as stability and discriminativity, has led to theoretical distances which are either thought to be or shown to be computationally complex and thus their implementations have been scarce. In order to design similarity measures on merge trees which are computationally feasible for more complex merge trees, many researchers have elected to loosen the restrictions on at least one of these two properties. The question still remains, however, if there are practical situations where trading these desirable properties is necessary. Here we construct a distance between merge trees which is designed to retain both discriminativity and stability. While our approach can be expensive for large merge trees, we illustrate its use in a setting where the number of nodes is small. This setting can be made more practical since we also provide a proof that persistence simplification increases the outputted distance by at most half of the simplified value. We demonstrate our distance measure on applications in shape comparison and on detection of periodicity in the von Kármán vortex street.

Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies.

AIM: To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, ≤ 6.5% or < 5.7%) with weight loss (≥ 5%, ≥ 10% or ≥ 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D). MATERIALS AND METHODS: Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2) or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52. RESULTS: The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide. CONCLUSIONS: Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups.

Demonstration of a two-bit controlled-NOT quantum-like gate using classical acoustic qubit-analogues.

The Controlled-NOT (CNOT) gate is the key to unlock the power of quantum computing as it is a fundamental component of a universal set of gates. We demonstrate the operation of a two-bit C-NOT quantum-like gate using classical qubit acoustic analogues, called herein logical phi-bits. The logical phi-bits are supported by an externally driven nonlinear acoustic metamaterial composed of a parallel array of three elastically coupled waveguides. A logical phi-bit has a two-state degree of freedom associated with the two independent relative phases of the acoustic wave in the three waveguides. A simple physical manipulation involving the detuning of the frequency of one of the external drivers is shown to operate on the complex vectors in the Hilbert space of pairs of logical phi-bits. This operation achieves a systematic and predictable C-NOT gate with unambiguously measurable input and output. The possibility of scaling the approach to more phi-bits is promising.