Foregut Erosion Related to Biomedical Implants: A Scoping Review.

Introduction: Biomedical devices implanted transabdominally have gained popularity over the past 50 years in the treatment of gastroesophageal reflux disease, paraesophageal hiatal hernia, and morbid obesity. Device-related foregut erosions (FEs) represent a challenging event that demands special attention owing to the potential of severe postoperative complications and death. Purpose: The aim was to provide an overview of full-thickness foregut injury leading to erosion associated with four types of biomedical devices. Methods: The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed, EMBASE, and Web of Science databases were queried until December 31, 2023. Eligible studies included all articles reporting data, management, and outcomes on device-related FE. Results: Overall, 132 articless were included for a total of 1292 patients suffering from device-related FE. Four different devices were included: the Angelchik antireflux prosthesis (AAP) (n = 25), nonabsorbable mesh for crural repair (n = 60), adjustable gastric banding (n = 1156), and magnetic sphincter augmentation device (n = 51). The elapsed time from device implant to erosion ranged from 1 to 480 months. Most commonly reported symptoms were dysphagia and epigastric pain, while acute presentation was reported rarely and mainly for gastric banding. The technique for device removal evolved from more invasive open approaches toward minimally invasive and endoscopic techniques. Esophagectomy and gastrectomy were mostly reported for nonabsorbable mesh FE. Overall mortality was .17%. Conclusions: Device-related FE is rare but may occur many years after AAP, nonabsorbable mesh, adjustable gastric banding, and magnetic sphincter augmentation implant. FE-related mortality is infrequent, however, increased postoperative morbidity and the need for esophagogastric resection were observed for nonabsorbable mesh-reinforced cruroplasty.

Assessment of PrEP and PEP furnishing in San Francisco Bay Area pharmacies; an observational cross-sectional study.

BACKGROUND: Over 1 million people in the US are infected with human immunodeficiency virus (HIV). As of 2021, pharmacists in California can prescribe PrEP and PEP without establishing a collaborative practice agreement in an effort to reduce HIV transmission. However, in 2021 less than 3% of independent pharmacies in the San Francisco Bay Area did so. To our knowledge, there has been no follow-up research assessing potential changes in PrEP/PEP furnishing rates in the region. OBJECTIVE: Assess the extent of PrEP/PEP furnishing in San Francisco Bay Area pharmacies 3 years after policy implementation. METHODS: We conducted an observational, cross-sectional study to identify independent community and mail-order pharmacies furnishing PrEP/PEP in the 9-county San Francisco Bay Area in 2024. Furnishing pharmacies were identified via phone calls and the findings were validated with in-person visits. We also identified the number of retail chain pharmacies furnishing PrEP/PEP in San Francisco County. RESULTS: We contacted 202 independent community and mail order pharmacies in the 9-county San Francisco Bay Area by telephone; of these, 16 reported furnishing PEP/PrEP and all confirmed their ability to furnish when visited in person. We contacted 67 retail chain pharmacies in San Francisco County; of these, 11 pharmacies reported furnishing PrEP/PEP (10 Safeway; 1 Walgreens). CONCLUSIONS: More pharmacies furnished PrEP/PEP in the 9-county San Francisco Bay Area in 2024 (8%) than in 2021 (3%); in addition, one retail chain pharmacy had instituted a furnishing protocol. However, furnishing rates remained low. Past research suggests that advertising and the development of furnishing protocols may help increase furnishing and increase medication access.

Prevalence and factors associated with unhealthy metabolic status according to body mass index: analysis of a national nutritional survey.

INTRODUCTION: Although obesity substantially influences public health owing to related comorbidities, it has been discovered that the incidence of such issues is not directly related to obesity but to the patient's unhealthy metabolic status (MUS) independent of the body mass index (BMI). OBJECTIVES: To describe the prevalence of UMS overall and according to BMI and determine the factors associated with it. METHODS: A cross-sectional analytical study was used based on the analysis of secondary databases called the Life Stage Nutritional Surveillance Survey (VIANEV). Participants were selected in two stages, finally obtaining 885 participants. UMS was defined based on the criteria of the Adult Treatment Panel III used to define metabolic status in a set of 5 parameters, if the subject presented two or more alterations it was considered UMS. Six groups were formed according to BMI: metabolically healthy, average weight (MHNW) and unhealthy (MUNW), metabolically healthy, overweight (MHOW) and unhealthy (MUOW), metabolically healthy, obese (MHO) and unhealthy (MUO).). RESULTS: The total prevalence of UMS was 73.11%, with MUNW, MUOW, and MUO being 47.90%, 80.34%, and 96.44%, respectively. Only 5.31% did not present any metabolic alteration. The multivariable analysis found variations globally according to sex, age, marital status, geographical region, smoking habit, and altitude. CONCLUSIONS: A high prevalence of UMS was observed in Peru, indicating that BMI alone is not a sufficient indicator of metabolic status. These findings suggest that strategies should be prioritized to address the growing problem of UMS, considering the particularities of each subpopulation and using a multifaceted approach that addresses modifiable and non-modifiable risk factors.

Surgical reconstruction of a composite nasomaxillary and superior labial defect in a dog with a fascia lata graft, titanium mesh implant and angularis oris axial pattern flap.

Objective: To document the successful surgical reconstruction of a composite nasomaxillary and superior labial defect using a fascia lata graft, titanium mesh and angularis oris axial pattern flap in a dog. Case summary: An estimated 2-year-old female intact mixed-breed dog was presented with a composite (hard and soft tissue) nasomaxillary defect, suspected to be caused by a chemical burn. Physical examination revealed nasal discharge, exposed bilateral maxilla and nasal bone, nasomaxillary fistula with air movement, and intrinsic discoloration of the left maxillary canine tooth. The soft tissue lesion extended from the nasal planum rostrally to the medial canthus of the left eye distally and from the right maxillary bone to include a full thickness loss of the left maxillary labium laterally. Computed tomographic images of the head showed chronic osteomyelitis of the maxilla, zygomatic and nasal bones with nasomaxillary fistula and numerous exposed roots of the left maxillary premolars. Staged surgical procedures to address the dentition and nasomaxillary defect were planned. The first procedure consisted of the extraction of periodontally compromised left maxillary premolars, and standard root canal therapy of bilateral maxillary canine teeth. The second procedure consisted of debridement of the non-vital soft and hard tissues and surgical reconstruction of the nasomaxillary defect after virtual surgical planning. Head computed tomography performed 5 months post-operatively revealed a decrease in the size of the osseous defect as well as the resolution of rhinitis. Clinical relevance: This case demonstrates the feasibility of using a combination of soft tissue graft, titanium mesh, and axial pattern flap in managing nasomaxillary defects. Such defects can lead to chronic rhinitis, infection, discomfort, and long-term morbidity. This case report provides a novel but practical approach for managing defects in the nasomaxillary region in dogs.

Idiopathic cardiac ossification with Chiari mesh in the right atrium: a case report and literature review.

Background: Idiopathic cardiac osseous metaplasia in the right atrium of a 9-year-old boy, accompanied by right atrial Chiari network and right pulmonary artery embolism. This case is rare and can easily be misdiagnosed. Case Description: We encountered a case of a 9-year-old boy with a 3.5 cm diameter neoplasm in the right atrium. Preoperative imaging diagnosis could not determine the nature of the tumor, and the initial clinical suspicion of cardiac myxoma. After admission, a cardiotomy to remove foreign bodies and a pulmonary artery thrombectomy were performed. Conclusions: Idiopathic cardiac osseous metaplasia is relatively rare, and it is even rarer to be accompanied by a Chiari network in the right atrium. Due to the location and characteristics of the lesion in this case, it is easy to be misdiagnosed as atrial myxoma in clinical practice. Whether it is idiopathic osseous metaplasia or myxoma, it needs to be performed surgical treatment and pathological examination can easily rule out the diagnosis of myxoma. However, as idiopathic cardiac metaplasia is difficult to encounter in clinical work and there are few reports in the literature, clinicians and pathologists need to consult more relevant literature. Learn to understand and master the disease through multi-party consultation.

Experience of a centre of excellence in hip fractures of the elderly in Colombia: influence of time-to-surgery on inpatient mortality and complications.

PURPOSE: To analyse the time-to-surgery of a centre of excellence in hip fractures of the elderly and its influence on inpatient mortality and postoperative complications. METHODS: A cross-sectional cohort study was conducted. The sample universe consisted of 4,364 patients admitted to a university clinic in Chía, Colombia during the year 2018 to 2023 with ICD-10 diagnoses corresponding to femur fractures. After eliminating duplicates and application of inclusion and exclusion criteria, the final sample included was 269 patients. Qualitative and quantitative variables were analysed, such as: sex, age, age group, type of fracture, type of surgical procedure, time-to-surgery, time to discharge, inpatient mortality and postoperative complications. RESULTS: The mean time-to-surgery from admission was 70.16 h or 2.92 days (IQR 37-87). Patients were divided into three subgroups of time in which they were taken to surgery: <24 h (11.89%), 24-48 h (33.82%) and > 48 h (54.27%). The overall mortality rate was 1.85% for a total of five deceased patients, two of whom belonged to the 24-48-hour group and three to the > 48 h group. Higher rates of postoperative complications were observed in the > 48-hours group (n: 39, 14.49%), followed by the 24-48-hour group (n: 25, 9.29%) and the < 24-hour group (n: 7, 2.6%). CONCLUSIONS: Patients operated for a hip fracture in > 48 h since admission had a slightly higher rate of postoperative complications. No significant difference was observed regarding inpatient mortality when compared to the 24-48-hour group.

Usability and Tolerability of Virtual Reality-Based Cognitive Stimulation in Healthy Elderly Volunteers-A Feasibility Clinical Trial.

Background: The aim of the current pilot study was to evaluate the usability, acceptability, and tolerability of virtual reality (VR)-based cognitive stimulation exercises (CSEs) in healthy young versus old populations before health care integration. A secondary aim was to assess the accuracy of VR games as a proxy for cognitive stimulation, specifically for attention. VR-based CSEs promise to improve attention and brain function through varied learning systems. Methods: This is a Phase 1 feasibility clinical trial at a single center. It involves 30 healthy volunteers randomly selected using the American Society of Anesthesiologists (ASA) physical status classification system. Participants fall into ASA 1 (age >18-35 years, n = 15) or ASA 2 (age >60 years, n = 15) categories. All participants tested the ReCognitionVR-based CSEs. Feasibility criterion: Participants in each group were monitored for completion of 20 minutes of VR-based CSEs. Acceptability criterion: Proportion of participants with system usability scale (SUS) >35 or SUS score of 87.5. Safety (tolerability) monitoring: Sessions were monitored for neurological, cardiovascular, or pulmonary adverse events (AEs). Safety criterion: No more than 10% of sessions stopped due to neurological, cardiovascular, or pulmonary AEs. Results: The primary outcome (feasibility) of ReCognitionVR-based CSEs was 100%. For the secondary outcome (acceptability), there was no group difference in SUS scores (ASA 1 = 88.17 ± 12.83 vs. ASA 2 = 88.39 ± 10.22, P = 0.81). For the tertiary outcome (safety), mild transient uneasiness was reported by two (13.4%) ASA 1 participants (resolved in 2 minutes), and one (6.67%) ASA 1 participant experienced a temporary >20% increase in blood pressure from baseline. No ASA 2 participants had AEs. Conclusion: The feasibility, acceptability, and safety of ReCognitionVR-based CSEs in healthy elderly volunteers are acceptable, indicating that the evaluation of the ReCognitionVR-based CSEs in hospitalized patients is reasonable.

Cordotomy for pain control and opioid reduction in cancer patients: A cancer center 11-year experience.

BACKGROUND: Percutaneous lateral cervical cordotomy (PLCC) is a treatment option for predominantly nociceptive pain of oncological origin that is refractory to conservative methods, with unilateral distribution, particularly in the lower trunk or lower limbs of patients with a life expectancy of less than one year. OBJECTIVE: The aim of this study was to assess the analgesic efficacy and opioid utilization alteration in patients undergoing PLCC. METHODS: We retrospectively collected data from patients undergoing PLCC between 2011 and 2021 at the AC Camargo Cancer Center in São Paulo, Brazil. RESULTS: Sixty-three patients and their respective surgical outcomes were analyzed. The mean preoperative pain intensity, as assessed by the mean numerical rating scale (NRS), was 8.4 (range: 4-10), while postoperatively, it decreased to 0.78 (range: 0-8). Lower postoperative NRS scores were observed for pain in the lower limbs and abdomen compared to the lower thorax. The mean preoperative oral morphine equivalent (OME) consumption was 231.0 mg (range: 30.0-1015.2). At 30 days postoperative, the mean consumption of OME was 120.2 mg (range: 0.0-705.0). Twelve months after surgery, the average consumption of OME was 98.3 mg (range: 0.0-396.0). CONCLUSION: PLCC is a valuable therapeutic intervention for patients experiencing cancer pain that is unresponsive to conservative treatments. The anticipated analgesic outcomes are generally favorable, particularly in cases where the pain is localized unilaterally in the abdomen or lower body segments.

Surface treatment of artificial implants with hybrid nanolayers: results of antibacterial tests, leachates and scanning electron microscope analysis.

Purpose: The aim of this study was to evaluate the antibacterial efficacy of surface-treated hernia implants modified by a hybrid nanolayer with incorporated Ag, Cu, and Zn cations using the sol-gel method. Methods: The materials (polypropylene, polyester, and polyvinylidene difluoride) were activated by vacuum plasma treatment or UV C radiation, then modified and tested for bacterial strains of Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). The AATCC 100 (2019) method for quantitative and the ISO 20645 agar plate propagation method for qualitative evaluation of microbiological efficacy were used. The gradual release of incorporated ions was monitored over time in simulated body fluids (blood plasma, peritoneal fluid) and physiological saline using an inductively coupled plasma mass spectrometer. The thickness and the homogeneity of the layers were measured for individual random samples with scanning electron microscope analysis (SEMA) and evaluated with an elemental analysis. Results: Qualitative and quantitative microbiological tests clearly show the great suitability of vacuum plasma and UV C with sol AD30 (dilution 1:1) surface treatment of the implants. The absolute concentration of Ag, Cu, and Zn cations in leachates was very low. SEMA showed a high degree of homogeneity of the layer and only very rare nanocracks by all tested materials appear after mechanical stress. Conclusion: This study confirms that surface treatment of meshes using the sol-gel method significantly increases the antibacterial properties. The nanolayers are sufficiently mechanically resistant and stable and pose no threat to health.

Finerenone and diabetic renal disease: a narrative review.

Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor (MR) antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (also known as Kerendia) is more potent than spironolactone in reducing the progression of CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate (GFR) if taken alone or in combination with sodium-glucose transporter 2 inhibitors (SGLT2i). Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this narrative review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes.

Recruiting Persons With Dementia: A Systematic Review of Facilitators, Barriers, and Strategies.

Study recruitment of persons with dementia is challenging. We aimed to assess facilitators, barriers, and strategies to identify and approach persons with dementia for recruitment to dementia care studies. We systematically searched MEDLINE/PubMed, CINAHL, Web of Science, and other sources (ORRCA [Online Resource for Research in Clinical triAls]; pertinent evidence syntheses; citation searching) and narratively summarised the results (PROSPERO CRD42022342600). Facilitators and barriers consisted of "characteristics of participants, researchers, clinical contact persons", "study characteristics", and "communication with participants". The highest number of participants were recruited by study information in electronic and print formats, as well as by networking and collaboration. Advertisements proved to be the most expensive way of recruitment. There is limited evidence on the impact of recruitment strategies to identify persons with dementia for recruitment to dementia care studies. Our analysis of facilitators and barriers may inform research teams in designing strategies to identify persons with dementia for recruitment purposes.

Repair of parastomal hernias with the intraperitoneal funnel meshes IPST-R and IPST.

The treatment of parastomal hernias (PSH) represents a major challenge in hernia surgery. Various techniques have been reported with different outcomes in terms of complication and recurrence rates. The aim of this study is to share our initial experience with the implantation of the DynaMesh-IPST-R and -IPST, intraperitoneal funnel meshes made of polyvinylidene fluoride (PVDF). This is a retrospective observational cohort study of patients treated for PSH between March 2019 and April 2023 using the chimney technique with the intraperitoneal funnel meshes IPST-R or IPST. The primary outcome was recurrence and the secondary outcomes were intraoperative and postoperative complications, the latter assessed using the Clavien-Dindo classification. A total of 21 consecutive patients were treated with intraperitoneal PVDF funnel meshes, 17 with IPST-R and 4 with IPST. There were no intraoperative complications. Overall, no complications occurred in 61.9% (n = 12) of the patients. Major postoperative complications (defined as Clavien-Dindo ≥ 3b) were noted in four cases (19.0%). During the mean follow-up period of 21.6 (range 4.8-37.5) months, one patient (4.8%) had a recurrence. In conclusion, for the treatment of parastomal hernias, the implantation of IPST-R or IPST mesh has proven to be efficient, easy to handle, and very safe. In particular, the low recurrence rate of 4.8%, which is in line with the current literature, is convincing. However, a larger number of patients would improve the validity of the results.

Loose Intraperitoneal Spiral Tack Causing Small Bowel Obstruction Following Laparoscopic Intraperitoneal Onlay Mesh Repair of Ventral Incisional Hernia: A Case Report.

This case report discusses a rare complication of small bowel obstruction occurring in the early course following Intraperitoneal Onlay Mesh (IPOM) repair for an incisional hernia. The bowel obstruction, which failed to respond to conservative measures, was caused by band adhesions resulting from the presence of a loose intraperitoneal migrated surgical tack. This was successfully managed laparoscopically resulting in complete recovery. We present the clinical and radiological findings and review the relevant literature in this area.

A review on guided bone regeneration using titanium mesh.

The gold standard for bone regeneration in atrophic ridge patients is guided bone regeneration (GBR). This makes it possible to get enough bone volume for an appropriate implant-prosthetic rehabilitation. The barrier membranes must meet the primary GBR design requirements, which include adequate integration with the surrounding tissue, spaciousness and clinical manageability. Titanium mesh's superior mechanical qualities and biocompatibility have broadened the indications of GBR technology, enabling it to be used to restore alveolar ridges with more significant bone defects. GBR with titanium mesh is being used in many clinical settings and for a range of clinical procedures. Furthermore, several advancements in digitalization and material modification have resulted from the study of GBR using titanium mesh. Hence, we report a review on the various characteristics of titanium mesh and its current use in clinical settings for bone augmentation.

Military Family Physicians' Readiness to Provide Gender-Affirming Care: A Serial Cross-Sectional Study.

PURPOSE: Family physicians are increasingly more likely to encounter transgender and gender-diverse (TGD) patients requesting gender-affirming care. Given the significant health inequities faced by the TGD community, this study aimed to assess changes in military-affiliated clinicians' perspectives toward gender-affirming care over time. METHODS: Using a serial cross-sectional survey design of physicians at the 2016 and 2023 Uniformed Services Academy of Family Physicians conferences, we studied participants' perception of, comfort with, and education on gender-affirming care using Fisher's Exact tests and logistic regression. RESULTS: Response rates were 68% (n = 180) and 69% (n = 386) in 2016 and 2023, respectively. Compared to 2016, clinicians in 2023 were significantly more likely to report receiving relevant education during training, providing care to >1 patient with gender dysphoria, and being able to provide nonjudgmental care. In 2023, 26% reported an unwillingness to prescribe gender-affirming hormones (GAH) to adults due to ethical concerns. In univariable analysis, female-identifying participants were more likely to report willingness to prescribe GAH (OR = 2.6, 95%CI = 1.7-4.1) than male-identifying participants. Willingness to prescribe was also associated with ≥4 h of education (OR = 2.2, 95%CI = 1.1-4.2) compared to those with fewer than 4 h, and those who reported the ability to provide nonjudgmental care compared to those who were neutral (OR = 0.09, 95%CI = 0.04-0.2) or disagreed (OR = 0.11, 95%CI = 0.03-0.39). Female-identifying clinicians were more likely to agree additional training would benefit their practice (OR = 5.3, 95%CI = 3.3-8.5). CONCLUSIONS: Although military-affiliated family physicians endorsed more experience with and willingness to provide nonjudgmental gender-affirming care in 2023 than 2016, profound gaps in patient experience may remain based on the assigned clinician. Additional training opportunities should be available, and clinicians unable to provide gender-affirming care should ensure timely referrals. Future research should explore trends across clinical specialties.

Perioperative and extended outcomes of patients undergoing parastomal hernia repair following cystectomy and ileal conduit.

PURPOSE: To report perioperative and long-term postoperative outcomes of cystectomy patients with ileal conduit (IC) urinary diversion undergoing parastomal hernia (PSH) repair. METHOD: We reviewed patients who underwent cystectomy and IC diversion between 2003 and 2022 in our center. Baseline variables, including surgical approach of PSH repair and repair technique, were captured. Multivariable Cox regressionanalysis was performed to test for the associations between different variables and PSH recurrence. RESULTS: Thirty-six patients with a median (IQR) age of 79 (73-82) years were included. The median time between cystectomy and PSH repair was 30 (14-49) months. Most PSH repairs (32/36, 89%) were performed electively, while 4 were due to small bowel obstruction. Hernia repairs were performed through open (n=25), robotic (10), and laparoscopic approaches (1). Surgical techniques included direct repair with mesh (20), direct repair without mesh (4), stoma relocation with mesh (5), and stomarelocation without mesh (7). The 90-day complication rate was 28%. In a median follow-up of 24 (7-47) months, 17 patients (47%) had a recurrence. The median time to recurrence was 9 (7-24) months. On multivariable analysis, 90-day complication following PSH repair was associated with an increased risk of recurrence. CONCLUSIONS: In this report of one of the largest series of PSH repair in the Urology literature, 47% of patients had a recurrence following hernia repair with a median follow-up time of 2 years. There was no significant difference in recurrence rates when comparing repair technique or the use of open or minimally invasive approaches.

Infection prevention and control in 2030: a first qualitative survey by the Crystal Ball Initiative.

BACKGROUND: Healthcare delivery is undergoing radical changes that influence effective infection prevention and control (IPC). Futures research (short: Futures), the science of deliberating on multiple potential future states, is increasingly employed in many core societal fields. Futures might also be helpful in IPC to facilitate current education and organisational decisions. Hence, we conducted an initial survey as part of the IPC Crystal Ball Initiative. METHODS: In 2019, international IPC experts were invited to answer a 10-item online questionnaire, including demographics, housekeeping, and open-ended core questions (Q) on the "status of IPC in 2030" (Q1), "people in charge of IPC" (Q2), "necessary skills in IPC" (Q3), and "burning research questions" (Q4). The four core questions were submitted to a three-step inductive and deductive qualitative content analysis. A subsequent cross-case matrix produced overarching leitmotifs. Q1 statements were additionally coded for sentiment analysis (positive, neutral, or negative). RESULTS: Overall, 18 of 44 (41%) invited experts responded (from 11 countries; 12 physicians, four nurses, one manager, one microbiologist; all of them in senior positions). The emerging leitmotifs were "System integration", "Beyond the hospital", "Behaviour change and implementation", "Automation and digitalisation", and "Anticipated scientific progress and innovation". The statements reflected an optimistic outlook in 66% of all codes of Q1. CONCLUSIONS: The first exercise of the IPC Crystal Ball Initiative reflected an optimistic outlook on IPC in 2030, and participants envisioned leveraging technological and medical progress to increase IPC effectiveness, freeing IPC personnel from administrative tasks to be more present at the point of care and increasing IPC integration and expansion through the application of a broad range of skills. Enhancing participant immersion in future Crystal Ball Initiative exercises through simulation would likely further increase the authenticity and comprehensiveness of the envisioned futures.

TEAM: Triangular-mEsh Adaptive and Multiscale proton spot generation method.

BACKGROUND: Proton therapy is preferred for its dose conformality to spare normal tissues and organs-at-risk (OAR) via Bragg peaks with negligible exit dose. However, proton dose conformality can be further optimized: (1) the spot placement is based on the structured (e.g., Cartesian) grid, which may not offer conformal shaping to complex tumor targets; (2) the spot sampling pattern is uniform, which may be insufficient at the tumor boundary to provide the sharp dose falloff, and at the same time may be redundant at the tumor interior to provide the uniform dose coverage, for example, due to multiple Coulomb scattering (MCS); and (3) the lateral spot penumbra increases with respect to the depth due to MCS, which blurs the lateral dose falloff. On the other hand, while (1) the deliverable spots are subject to the minimum-monitor-unit (MMU) constraint, and (2) the dose rate is proportional to the MMU threshold, the current spot sampling method is sensitive to the MMU threshold and can fail to provide satisfactory plan quality for a large MMU threshold (i.e., high-dose-rate delivery). PURPOSE: This work will develop a novel Triangular-mEsh-based Adaptive and Multiscale (TEAM) proton spot generation method to address these issues for optimizing proton dose conformality and plan delivery efficiency. METHODS: Compared to the standard clinically-used spot placement method, three key elements of TEAM are as follows: (1) a triangular mesh instead of a structured grid: the triangular mesh is geometrically more conformal to complex target shapes and therefore more efficient and accurate for dose shaping inside and around the target; (2) adaptive sampling instead of uniform sampling: the adaptive sampling consists of relatively dense sampling at the tumor boundary to create the sharp dose falloff, which is more accurate, and coarse sampling at the tumor interior to uniformly cover the target, which is more efficient; and (3) depth-dependent sampling instead of depth-independent sampling: the depth-dependent sampling is used to compensate for MCS, that is, with increasingly dense sampling at the tumor boundary to improve dose shaping accuracy, and increasingly coarse sampling at the tumor interior to improve dose shaping efficiency, as the depth increases. In the TEAM method the spot locations are generated for each energy layer and layer-by-layer in the multiscale fashion; and then the spot weights are derived by solving the IMPT problem of dose-volume planning objectives, MMU constraints, and robustness optimization with respect to range and setup uncertainties. RESULTS: Compared to the standard clinically-used spot placement method UNIFORM, TEAM achieved (1) better plan quality using <60% number of spots of UNIFORM; (2) better robustness to the number of spots; (3) better robustness to a large MMU threshold. Furthermore, TEAM provided better plan quality with fewer spots than other adaptive methods (Cartesian-grid or triangular-mesh). CONCLUSIONS: A novel triangular-mesh-based proton spot placement method called TEAM is proposed, and it is demonstrated to improve plan quality, robustness to the number of spots, and robustness to the MMU threshold, compared to the clinically-used spot placement method and other adaptive methods.

Synthesis of geometrically realistic and watertight neuronal ultrastructure manifolds for in silico modeling.

Understanding the intracellular dynamics of brain cells entails performing three-dimensional molecular simulations incorporating ultrastructural models that can capture cellular membrane geometries at nanometer scales. While there is an abundance of neuronal morphologies available online, e.g. from NeuroMorpho.Org, converting those fairly abstract point-and-diameter representations into geometrically realistic and simulation-ready, i.e. watertight, manifolds is challenging. Many neuronal mesh reconstruction methods have been proposed; however, their resulting meshes are either biologically unplausible or non-watertight. We present an effective and unconditionally robust method capable of generating geometrically realistic and watertight surface manifolds of spiny cortical neurons from their morphological descriptions. The robustness of our method is assessed based on a mixed dataset of cortical neurons with a wide variety of morphological classes. The implementation is seamlessly extended and applied to synthetic astrocytic morphologies that are also plausibly biological in detail. Resulting meshes are ultimately used to create volumetric meshes with tetrahedral domains to perform scalable in silico reaction-diffusion simulations for revealing cellular structure-function relationships. Availability and implementation: Our method is implemented in NeuroMorphoVis, a neuroscience-specific open source Blender add-on, making it freely accessible for neuroscience researchers.