Enhanced Multiscale Human Brain Imaging by Semi-supervised Digital Staining and Serial Sectioning Optical Coherence Tomography.

A major challenge in neuroscience is to visualize the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features, but suffers from staining variability, tissue damage and distortion that impedes accurate 3D reconstructions. Here, we present a new 3D imaging framework that combines serial sectioning optical coherence tomography (S-OCT) with a deep-learning digital staining (DS) model. We develop a novel semi-supervised learning technique to facilitate DS model training on weakly paired images. The DS model performs translation from S-OCT to Gallyas silver staining. We demonstrate DS on various human cerebral cortex samples with consistent staining quality. Additionally, we show that DS enhances contrast across cortical layer boundaries. Furthermore, we showcase geometry-preserving 3D DS on cubic-centimeter tissue blocks and visualization of meso-scale vessel networks in the white matter. We believe that our technique offers the potential for high-throughput, multiscale imaging of brain tissues and may facilitate studies of brain structures.

Oral histories document community mobilisation to participate in decision-making regarding a hazardous waste thermal treatment facility.

Colfax, Louisiana hosts a commercial hazardous waste thermal treatment (TT) facility, which treats fireworks, explosives, and military ordnances by open-burn/open-detonation one mile from the edge of the nearest community. Seventy-one percent of Colfax's residents are Black, and forty-six percent live below poverty, indicating the community's structural vulnerability. This community-based study originated at the behest of Colfax community members. We hypothesized that the close relationships among members of this enclave may have enhanced the community's ability to mobilize in opposition to the TT facility. We conducted semi-structured oral history interviews with nineteen community members and examined the social and interorganizational networks used by the Colfax community to claim its role in decision-making regarding the TT facility after years of exclusion from this process. Interview transcripts were analyzed through the lens of community capacity theory to gain insight into how interactions among community members about the environmental hazards led to social mobilization and improved participation in the decision-making process using codes for communication, organization, and outcome. Additionally, we reviewed Louisiana Department of Environmental Quality records for complaints about the facility to gauge public participation. One notable theme across several interviews was exclusion from the initial decision-making process related to the facility. However, interviewees noted a sustained effort was made among community members to educate themselves about the facility, organize a response through neighbor-to-neighbor contact, and take action by submitting formal complaints and participating in public hearings. Through the lens of environmental justice, this study illustrates an evolving condition of procedural justice.

Indocyanine green (ICG) fluorescence-enhanced applications in pediatric surgery.

The breadth of pediatric surgical practice and variety of anatomic anomalies that characterize surgical disease in children and neonates require a unique level of operative mastery and versatility. Intraoperative navigation of small, complex, and often abnormal anatomy presents a particular challenge for pediatric surgeons. Clinical experience with fluorescent tissue dye, specifically indocyanine green (ICG), is quickly gaining widespread incorporation into adult surgical practice as a safe, non-toxic means of accurately visualizing tissue perfusion, lymphatic flow, and biliary anatomy to enhance operative speed, safety, and patient outcomes. Experience in pediatric surgery, however, remains limited. ICG-fluorescence guided surgery is poised to address the challenges of pediatric and neonatal operations for a growing breadth of surgical pathology. Fluorescent angiography has permitted intraoperative visualization of colorectal flap perfusion for complex pelvic reconstruction and anastomotic perfusion after esophageal atresia repair, while its hepatic absorption and biliary excretion has made it an excellent agent for delineating the dissection plane in the Kasai portoenterostomy and identifying both primary and metastatic hepatoblastoma lesions. Subcutaneous and intra-lymphatic ICG injection can identify iatrogenic chylous leaks and improved yields in sentinel lymph node biopsies. ICG-guided surgery holds promise for more widespread use in pediatric surgical conditions, and continued evaluation of efficacy will be necessary to better inform clinical practice and identify where to focus and develop this technical resource.

Framework for pediatric robotic surgery program development.

Pediatric robotic surgery has seen increasing implementation for its many benefits over the past two decades. As more pediatric surgeons gain exposure to robotic surgery, the interest in utilizing this technology is growing. However, there are no guidelines or existing framework for developing pediatric general surgery robotic programs. Programmatic development can be challenging, requiring institutional support, a minimum 12-month multistep process in partnership with the robot manufacturer, and organization of a local dedicated team. A cornerstone to all program building is collaboration and communication with key stakeholders who are committed to establishing a robotic surgery program. In this manuscript, we detail numerous best practices for implementation, followed by three variations of programmatic development, each drawing lessons from one of three practice settings: (i) A children's hospital in a large medical center associated with an adult hospital, (ii) a free-standing children's hospital, and (iii) a community-based practice. We aim for this article to provide a framework that can serve as a guide for those beginning this process, consolidating the key resources and strategies used to develop a robust pediatric robotic surgery program.

Suspected tick-borne flavivirus meningoencephalomyelitis in dogs from the UK: six cases (2021).

OBJECTIVES: Tick-borne encephalitis virus and louping ill virus are neurotropic flaviviruses transmitted by ticks. Epidemiologically, tick-borne encephalitis is endemic in Europe whereas louping ill's predominant geographical distribution is the UK. Rarely, these flaviviruses affect dogs causing neurological signs. This case series aimed to describe the clinical, clinicopathological, and imaging findings, as well as the outcomes in six dogs with meningoencephalitis and/or meningomyelitis caused by a flavivirus in the UK in 2021. MATERIALS AND METHODS: Observational retrospective case-series study. Clinical data were retrieved from medical records of dogs with positive serological or immunohistochemical results from three different institutions from spring to winter 2021. RESULTS: Six dogs were included in the study. All dogs presented an initial phase of pyrexia and/or lethargy followed by progressive signs of spinal cord and/or intracranial disease. Magnetic resonance imaging showed bilateral and symmetrical lesions affecting the grey matter of the thalamus, pons, medulla oblongata, and thoracic or lumbar intumescences with none or mild parenchymal and meningeal contrast enhancement. Serology for tick-borne encephalitis virus was positive in five dogs with the presence of seroconversion in two dogs. The viral distinction between flaviviruses was not achieved. One dog with negative serology presented positive immunohistochemistry at post-mortem examination. Three dogs survived but presented neurological sequelae. Three dogs were euthanased due to the rapid progression of the clinical signs or static neurological signs. CLINICAL SIGNIFICANCE: These cases raise awareness of the presence of tick-borne encephalitis as an emergent disease or the increased prevalence of louping ill virus affecting dogs in the UK.

Transcystic Laparoscopic Common Bile Duct Exploration for Pediatric Patients with Choledocholithiasis: A Multi-Center Study.

BACKGROUND: Patients with choledocholithiasis are often treated with endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Upfront LC, intraoperative cholangiogram (IOC), and possible transcystic laparoscopic common bile duct exploration (LCBDE) could potentially avoid the need for ERCP. We hypothesized that upfront LC + IOC ± LCBDE will decrease length of stay (LOS) and the total number of interventions for children with suspected choledocholithiasis. METHODS: A multicenter, retrospective cohort study was performed on pediatric patients (<18 years) between 2018 and 2022 with suspected choledocholithiasis. Demographic and clinical data were compared for upfront LC + IOC ± LCBDE and possible postoperative ERCP (OR1st) versus preoperative ERCP prior to LC (OR2nd). Complications were defined as postoperative pancreatitis, recurrent choledocholithiasis, bleeding, or abscess. RESULTS: Across four centers, 252 children with suspected choledocholithiasis were treated with OR1st (n = 156) or OR2nd (n = 96). There were no differences in age, gender, or body mass index. Of the LCBDE patients (72/156), 86% had definitive intraoperative management with the remaining 14% requiring postoperative ERCP. Complications were fewer and LOS was shorter with OR1st (3/156 vs. 15/96; 2.39 vs 3.84 days, p < 0.05). CONCLUSION: Upfront LC + IOC ± LCBDE for children with choledocholithiasis is associated with fewer ERCPs, lower LOS, and decreased complications. Postoperative ERCP remains an essential adjunct for patients who fail LCBDE. Further educational efforts are needed to increase the skill level for IOC and LCBDE in pediatric patients with suspected choledocholithiasis. LEVEL OF EVIDENCE: Level III.

Lessons Learned From the First-In-Human Compassionate Use of Connect-EA™ in Ten Patients With Esophageal Atresia.

INTRODUCTION: Delayed primary repair of esophageal atresia in patients with high-risk physiologic and anatomic comorbidities remains a daunting challenge with an increased risk for peri-operative morbidity and mortality via conventional repair. The Connect-EA device facilitates the endoscopic creation of a secure esophageal anastomosis. This follow-up study reports our long-term outcomes with the novel esophageal magnetic compression anastomosis (EMCA) Connect-EA device for EA repair, as well as lessons learned from the ten first-in-human cases. We propose an algorithm to maximize the advantages of the device for EA repair. METHODS: Under compassionate use approval, from June 2019 to December 2022, ten patients with prohibitive surgical or medical risk factors underwent attempted EMCA with this device. All patients underwent prior gastrostomy, tracheoesophageal fistula ligation (if necessary), and demonstrated pouch apposition prior to EMCA. RESULTS: Successful device deployment and EMCA formation were achieved in nine patients (90%). Mean time to anastomosis formation was 8 days (range 5-14) and the device was retrieved endoscopically in five (56%) cases. At median follow-up of 22 months (range 4-45), seven patients (78%) are tolerating oral nutrition. Balloon dilations (median 4, range 1-11) were performed either prophylactically for radiographic asymptomatic anastomotic narrowing (n = 7, 78%) or to treat clinically-significant anastomotic narrowing (n = 2, 22%) with no ongoing dilations at 3-month follow up post-repair. CONCLUSION: EMCA with the Connect-EA device is a safe and feasible minimally-invasive alterative for EA repair in high-risk surgical patients. Promising post-operative outcomes warrant further Phase I investigation. LEVEL OF EVIDENCE: IV, Case series of novel operative technique without comparison group.

Use of an elastic-scattering spectroscopy and artificial intelligence device in the assessment of lesions suggestive of skin cancer: A comparative effectiveness study.

Background: Skin cancer is the most common form of cancer worldwide. As artificial intelligence (AI) expands its scope within dermatology, leveraging technology may aid skin cancer detection. Objective: To assess the safety and effectiveness of an elastic-scattering spectroscopy (ESS) device in evaluating lesions suggestive of skin cancer. Methods: This prospective, multicenter clinical validation study was conducted at 4 US investigational sites. Patients with skin lesions suggestive of melanoma and nonmelanoma skin cancers were clinically assessed by expert dermatologists and evaluated by a device using AI algorithms comparing current ESS lesion readings with training data sets. Statistical analyses included sensitivity, specificity, AUROC, negative predictive value (NPV), and positive predictive value (PPV). Results: Overall device sensitivity was 97.04%, with subgroup sensitivity of 96.67% for melanoma, 97.22% for basal cell carcinoma, and 97.01% for squamous cell carcinoma. No statistically significant difference was found between the device and dermatologist performance (P = .8203). Overall specificity of the device was 26.22%. Overall NPV of the device was 89.58% and PPV was 57.54%. Conclusion: The ESS device demonstrated high sensitivity in detecting skin cancer. Use of this device may assist primary care clinicians in assessing suspicious lesions, potentially reducing skin cancer morbidity and mortality through expedited and enhanced detection and intervention.

Multiscale label-free imaging of myelin in human brain tissue with polarization-sensitive optical coherence tomography and birefringence microscopy.

The combination of polarization-sensitive optical coherence tomography (PS-OCT) and birefringence microscopy (BRM) enables multiscale assessment of myelinated axons in postmortem brain tissue, and these tools are promising for the study of brain connectivity and organization. We demonstrate label-free imaging of myelin structure across the mesoscopic and microscopic spatial scales by performing serial-sectioning PS-OCT of a block of human brain tissue and periodically sampling thin sections for high-resolution imaging with BRM. In co-registered birefringence parameter maps, we observe good correspondence and demonstrate that BRM enables detailed validation of myelin (hence, axonal) organization, thus complementing the volumetric information content of PS-OCT.

Progressive mechanical and structural changes in anterior cerebral arteries with Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease and the main cause for dementia. The irreversible neurodegeneration leads to a gradual loss of brain function characterized predominantly by memory loss. Cerebrovascular changes are common neuropathologic findings in aged subjects with dementia. Cerebrovascular integrity is critical for proper metabolism and perfusion of the brain, as cerebrovascular remodeling may render the brain more susceptible to pulse pressure and may be associated with poorer cognitive performance and greater risk of cerebrovascular events. The objective of this study is to provide understanding of cerebrovascular remodeling with AD progression. Anterior cerebral arteries (ACAs) from a total of 19 brain donor participants from controls and pathologically diagnosed AD groups (early-Braak stages I-II; intermediate-Braak stages III-IV; and advanced-Braak stages V-VI) were included in this study. Mechanical testing, histology, advanced optical imaging, and mass spectrometry were performed to study the progressive structural and functional changes of ACAs with AD progression. Biaxial extension-inflation tests showed that ACAs became progressively less compliant, and the longitudinal stress in the intermediate and advanced AD groups was significantly higher than that from the control group. With pathological AD development, the inner and outer diameters of the ACAs remained almost unchanged; however, histology study revealed progressive smooth muscle cell atrophy and loss of elastic fibers which led to compromised structural integrity of the arterial wall. Multiphoton imaging demonstrated elastin degradation at the media-adventitia interface, which led to the formation of an empty band of 21.0 ± 15.4 µm and 32.8 ± 9.24 µm in width for the intermediate and advanced AD groups, respectively. Furthermore, quantitative birefringence microscopy showed disorganized adventitial collagen with AD development. Mass spectrometry analysis provided further evidence of altered collagen content and other extracellular matrix (ECM) molecule and smooth muscle cell changes that were consistent with the mechanical and structural alterations. Collectively, our study provides understanding of the mechanical and structural cerebrovascular deterioration in cerebral arteries with AD, which may be related to neurodegenration and pathology in the brain.

Progressive Mechanical and Structural Changes in Anterior Cerebral Arteries with Alzheimer's Disease.

Alzheimer disease (AD) is a neurodegenerative disease and the main cause for dementia. The irreversible neurodegeneration leads to a gradual loss of brain function characterized predominantly by memory loss. Cerebrovascular changes are common neuropathologic findings in aged subjects with dementia. Cerebrovascular integrity is critical for proper metabolism and perfusion of the brain, as cerebrovascular remodeling may render the brain more susceptible to pulse pressure and may be associated with poorer cognitive performance and greater risk of cerebrovascular events. The objective of this study is to provide understanding of cerebrovascular remodeling with AD progression. A total of 28 brain donor participants with human anterior cerebral artery (ACA) from controls and pathologically diagnosed AD groups (early - Braak stages I-II; intermediate - Braak stages III-IV; and advanced - Braak stages V-VI) were included in this study. Mechanical testing, histology, advanced optical imaging, and mass spectrometry were performed to study the progressive structural and functional changes of ACAs with AD progression. Biaxial extension-inflation tests showed that ACAs became progressively less compliant, and the longitudinal stress in the intermediate& advanced AD groups was significantly higher than that from the control group. With pathological AD development, the inner and outer diameter of ACA remained almost unchanged; however, histology study revealed progressive smooth muscle cell atrophy and loss of elastic fibers which led to compromised structural integrity of the arterial wall. Multiphoton imaging demonstrated elastin degradation at the media-adventitia interface, which led to the formation of an empty band of 21.0 ± 15.4 µm and 32.8 ± 9.24 µm in width for the intermediate& advanced AD groups, respectively. Furthermore, quantitative birefringence microscopy showed disorganized adventitial collagen with AD development. Mass spectrometry analysis provided further evidence of altered collagen content and other extracellular matrix (ECM) molecule and smooth muscle cell changes that were consistent with the mechanical and structural alterations. Collectively, our study provides understanding of the mechanical and structural cerebrovascular deterioration in cerebral arteries with AD, which may be related to neurodegenration and pathology in the brain.

Identification and management of tomato brown rugose fruit virus in greenhouses in Mexico.

Tomato brown rugose fruit virus (ToBRFV) has become a cause of great concern in the global tomato agro-industry since its first report in Israel in 2014. Global tomato production is affected by ToBRFV, and management practices are being evaluated. We tested seed lots from international producers as well as greenhouse substrates and water wells as possible sources of virus contamination. We identified a second introduction of ToBRFV in Mexico by a strain closely resembling isolates from the Netherlands and the Middle East. ToBRFV was detected by RT-PCR in seed coats and epicotyls (from commercial seeds and seedlings obtained from infected tomato plants), indicating a transmission rate of 9%. Virus-like particles (VLPs) were found in wells used for irrigation in greenhouses, but these exhibited low infectivity. These findings suggest that water sources could serve as ToBRFV reservoirs. We evaluated four chemical and six thermal methods for sanitizing substrates, plasticware, and other greenhouse utensils, using detached leaf bioassays in Nicotiana rugosa. The most effective chemical sanitization method was treatment with glutaraldehyde plus quaternary ammonium salts and pentapotassium salts. The most effective heat treatment was at 92°C for 30 minutes, which inactivated the virus. Tomato producers could implement these sanitization methods to control ToBRFV.

Infectious Complications and Antibiotic Use in Gastroschisis.

Background: Gastroschisis is a challenging neonatal condition often with prolonged hospitalizations, need for parenteral nutrition, infectious complications, and can even result in death. Infection is reported to occur in up to two-thirds of patients with gastroschisis and is a strong risk factor for increased morbidity and mortality. Increased days with a central venous catheter, complex gastroschisis, and delayed abdominal wall closure have been consistently found to be associated with increased risk of infection, whereas sutureless gastroschisis closure has been associated with fewer infections. Although one of the most common complications of gastroschisis is infection, the use of antibiotic agents varies widely with variability in the literature to guide management. Antibiotic usage should be selective and short-term, especially in neonates with simple gastroschisis regardless of method for abdominal wall closure. Conclusions: Future initiatives should focus on development of evidence-based guidelines on the care of these patients with the goal of reducing variability and improve outcomes within and across institutions.

Esophageal Surveillance Practices in Esophageal Atresia Patients: A Survey by the Eastern Pediatric Surgery Network.

INTRODUCTION: Endoscopic surveillance guidelines for patients with repaired esophageal atresia (EA) rely primarily on expert opinion. Prior to embarking on a prospective EA surveillance registry, we sought to understand EA surveillance practices within the Eastern Pediatric Surgery Network (EPSN). METHODS: An anonymous, 23-question Qualtrics survey was emailed to 181 physicians (surgeons and gastroenterologists) at 19 member institutions. Likert scale questions gauged agreement with international EA surveillance guideline-derived statements. Multiple-choice questions assessed individual and institutional practices. RESULTS: The response rate was 77%. Most respondents (80%) strongly agree or agree that EA surveillance endoscopy should follow a set schedule, while only 36% claimed to perform routine upper GI endoscopy regardless of symptoms. Many institutions (77%) have an aerodigestive clinic, even if some lack a multi-disciplinary EA team. Most physicians (72%) expressed strong interest in helping develop evidence-based guidelines. CONCLUSIONS: Our survey reveals physician agreement with current guidelines but weak adherence. Surveillance methods vary greatly, underscoring the lack of evidence-based data to guide EA care. Aerodigestive clinics may help implement surveillance schedules. Respondents support evidence-based protocols, which bodes well for care standardization. Results will inform the first multi-institutional EA databases in the United States (US), which will be essential for evidence-based care. LEVEL OF EVIDENCE: This is a prognosis study with level 4 evidence.

Laparoscopic Resection of Pediatric Solid Pseudopapillary Tumors of the Pancreas.

BACKGROUND: Solid pseudopapillary tumors (SPTs) of the pancreas arise rarely in children, are often large, and can associate intimately with splenic vessels. Splenic preservation is a fundamental consideration when resecting distal SPT. Occasionally, the main splenic vessels must be divided to resect the SPT with negative margins, but the spleen can be preserved if the short gastric vessels remain intact (ie, Warshaw procedure). The purpose of this study was to evaluate outcomes of distal pancreatectomy (DP) for SPT in children and to highlight 2 cases of splenic preservation using the Warshaw procedure. METHODS: Patients 19 years and younger who were treated at a single children's hospital between July 2004 and January 2021 were examined. Patient characteristics were collected from the electronic medical record. A pediatric radiologist calculated SPT and pre- and post-operative (ie, non-infarcted) splenic volumes. RESULTS: Eleven patients received DP for SPT. Six DPs were performed open and 5 laparoscopically. The spleen was preserved in 3 open and 4 laparoscopic DPs. A laparoscopic Warshaw procedure was performed in 2 patients. Laparoscopic resection associated with less frequent epidural use (P = .015), shorter time to full diet (P = .030), and post-operative length of stay (P = .009), compared to open resection. Average residual splenic volume after the laparoscopic Warshaw procedure was 70% of preoperative volume. DISCUSSION: Laparoscopic DP for pediatric SPT achieved similar oncologic goals to open resection. Splenic preservation was feasible with laparoscopy in most cases and was successfully supplemented with the Warshaw procedure, which has not been previously reported for SPT resection in children.

Thoracoscopic Resection of a Rare Congenital Lung Lesion With a Tracheal Bronchus.

A tracheal bronchus is a rare anatomic variant characterized by a bronchus originating from the trachea rather than the carina. These are most commonly asymptomatic and found incidentally but can cause recurrent pneumonias in children. Here, we present a case of a thoracoscopic resection of an azygous lobe with a tracheal bronchus in a 9-year-old female.

Multicenter Assessment of Cryoanalgesia Use in Minimally Invasive Repair of Pectus Excavatum: A 20-center Retrospective Cohort Study.

OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.