Urothelial carcinoma associated with a long-term indwelling cystostomy component of a subcutaneous ureteral bypass device in a domestic shorthair cat.

Urothelial carcinoma (UC) occurs uncommonly in cats and no association has previously been observed with long-term indwelling urinary implants. An 18-year-old male castrated domestic shorthair cat initially was presented for hematuria, leading to the diagnosis of a right-sided ureterolithiasis and severe pyelectasia on ultrasound examination, prompting right-sided subcutaneous ureteral bypass (SUB) device placement. The cat subsequently had intermittent hematuria and dysuria, without ultrasonographic abnormality of the bladder or positive urine culture. Thirteen months later the patient developed refractory lower urinary tract signs, azotemia, a proliferative mass in the region of the cystostomy tube component of the SUB device and evidence of left ureteral obstruction. Cystostomy tube revision and left-sided SUB device placement were performed, as well as a partial cystectomy for removal of the mass. Upon histopathology, the mass was diagnosed as a UC. To our knowledge, UC associated with a long-term indwelling cystostomy catheter component of a SUB device has not been reported in veterinary medicine.

Thoracoscopic removal of cranial mediastinal masses in dogs is associated with a low conversion rate, excellent survival to discharge, and good long-term outcome.

OBJECTIVE: To report the complications and outcomes associated with thoracoscopic cranial mediastinal mass resection in dogs. ANIMALS: 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal. METHODS: This was a retrospective cohort study (January 1, 2014, to July 31, 2023), and the medical records of 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal were reviewed. The signalment, history, clinicopathologic features, perioperative complications, and long-term outcome were recorded. RESULTS: Preoperative myasthenia gravis (MG) and megaesophagus (ME) were identified in 17 of 49 (35%) dogs and 11 of 49 (22%) dogs, respectively. The median maximal tumor diameter on CT images was 4.7 cm (range, 2.7 to 8.5 cm). Nonemergent conversion to an open procedure was necessary in 4 of 49 (8%) dogs, and dogs with conversion to an open procedure had a significantly larger median maximal CT tumor diameter than dogs without conversion (P = .03). The most common tumor type was thymoma (37/49 [76%]). The overall median survival time for dogs with thymoma was 1,102 days (95% CI, 482 to upper bound not reached). The median survival time for dogs with thymoma and concurrent presurgical MG was 182 days (95% CI, 14 to upper bound not reached). Presurgical diagnosis of MG (P = .44) or ME (P = .69) was not associated with survival time. CLINICAL RELEVANCE: Thoracoscopic removal of cranial mediastinal masses was associated with low conversion and complication rates. Long-term survival is possible, and thoracoscopic removal should be considered for select cases.

Spatial and Temporal Relationships Between Atrophy and Hypometabolism in Behavioral-Variant Frontotemporal Dementia.

PURPOSE: Individuals with behavioral-variant frontotemporal dementia (bvFTD) show changes in brain structure as assessed by MRI and brain function assessed by 18FDG-PET hypometabolism. However, current understanding of the spatial and temporal interplay between these measures remains limited. METHODS: Here, we examined longitudinal atrophy and hypometabolism relationships in 15 bvFTD subjects with 2 to 4 follow-up MRI and PET scans (56 visits total). Subject-specific slopes of atrophy and hypometabolism over time were extracted across brain regions and correlated with baseline measures both locally, via Pearson correlations, and nonlocally, via sparse canonical correlation analyses (SCCA). RESULTS: Notably, we identified a robust link between initial hypometabolism and subsequent cortical atrophy rate changes in bvFTD subjects. Network-level exploration unveiled alignment between baseline hypometabolism and ensuing atrophy rates in the dorsal attention, language, and default mode networks. SCCA identified 2 significant and highly localized components depicting the connection between baseline hypometabolism and atrophy slope over time. The first centered around bilateral orbitofrontal, frontopolar, and medial prefrontal lobes, whereas the second concentrated in the left temporal lobe and precuneus. CONCLUSIONS: This study highlights 18FDG-PET as a dependable predictor of forthcoming atrophy in spatially adjacent brain regions for individuals with bvFTD.

Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology.

INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aß) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aß, as assessed by 18F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aß were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aß. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aß-vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aß pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.

Evaluation of mediastinoscopy for cranial mediastinal and tracheobronchial lymphadenectomy in canine cadavers.

OBJECTIVE: To report technical feasibility and describe procedural details of a novel single incision minimally invasive approach to the mediastinum in cadaver dogs. STUDY DESIGN: Cadaveric study. ANIMALS: Large breed (25-40 kg) cadaver dogs (n = 10). METHODS: Three of 10 cadavers were used for preliminary technique development without data recording. Cadaver specimens underwent pre- and postoperative thoracic computed tomographic scans. Seven dogs were placed in dorsal recumbency and mediastinoscopy was performed via a SILS port placed cranial to the thoracic inlet with CO2 insufflation of the mediastinum at 2-4 mmHg. Retrieval of all CT and visually identified mediastinal lymph nodes (LN) was attempted; endoscopic compartmental and individual LN dissection times and subjective operative challenges were recorded. Procedural success scores for visualization and dissection as well as NASA-task force index scores were recorded per lymph node, per cadaver. RESULTS: Median time required for initial approach including SILS placement was 5 min (range 5-10 min). Individual LN retrieval times ranged from 2 to 32 min. Mediastinoscopic retrieval of LNs was most commonly successful for the left tracheobronchial LN (7/7), followed by the right tracheobronchial LN (4/7), the left and right sternal LNs (3/7 each), and the cranial mediastinal LNs (1/7). Post-procedure pleural gas was identified on CT in 4/7 cadavers. CONCLUSIONS: Mediastinoscopy as reported was feasible in large breed canine cadavers and retrieval or cup biopsy of a variety of lymph nodes is possible from the described approach. Application in living animals and its associated challenges should be further investigated. CLINICAL SIGNIFICANCE: Mediastinoscopy may provide a novel minimally invasive approach to the evaluation and oncologic staging of the cranial mediastinum in dogs.

Next Directions in the Neuroscience of Cancers Arising outside the CNS.

SUMMARY: The field of cancer neuroscience has begun to define the contributions of nerves to cancer initiation and progression; here, we highlight the future directions of basic and translational cancer neuroscience for malignancies arising outside of the central nervous system.

Canine Prostate Cancer: Current Treatments and the Role of Interventional Oncology.

Prostate carcinoma is one of the most common cancers worldwide in men, with over 3 million men currently living with prostate carcinoma. In men, routine screening and successful treatment schemes, including radiation, prostatectomy, or hormone therapy, have allowed for high survivability. Dogs are recognized as one of the only mammals to spontaneously develop prostate neoplasia and are an important translational model. Within veterinary medicine, treatment options have historically been limited in efficacy or paired with high morbidity. Recently, less invasive treatment modalities have been investigated in dogs and people and demonstrated promise. Below, current treatment options available in dogs and people are reviewed, as well as a discussion of current and future trends within interventional treatment for canine PC.

Precise timing of audiovisual stimulation conquers chemobrain.

In a recent study, Kim et al. utilized gamma entrainment using sensory stimuli (GENUS) to rescue cognitive impairment and glial dysregulation associated with cisplatin and methotrexate chemotherapy, specifically when applied both throughout and after chemotherapy administration. GENUS provides a time-dependent, non-invasive method for treating chemobrain, with broader implications for resolving neurodegenerative neuroinflammation.

Oligodendrocytes: Myelination, Plasticity, and Axonal Support.

The myelination of axons has evolved to enable fast and efficient transduction of electrical signals in the vertebrate nervous system. Acting as an electric insulator, the myelin sheath is a multilamellar membrane structure around axonal segments generated by the spiral wrapping and subsequent compaction of oligodendroglial plasma membranes. These oligodendrocytes are metabolically active and remain functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of metabolites and macromolecules to and from the internodal periaxonal space under the myelin sheath. Increasing evidence indicates that oligodendrocyte numbers, specifically in the forebrain, and myelin as a dynamic cellular compartment can both respond to physiological demands, collectively referred to as adaptive myelination. This review summarizes our current understanding of how myelin is generated, how its function is dynamically regulated, and how oligodendrocytes support the long-term integrity of myelinated axons.

Augmenting Veterinary Minimally Invasive Surgery: Evidence-based Review of Foundational and Novel Devices and Technology.

Veterinary minimally invasive surgery continues to grow as a specialty. With increasing experience in this field, comes improved accessibility as well as progressive complexity of procedures performed. Advancement in technology has been both a response to the growth and a necessary driver of continued refinement of this field. Innovative research leading to advancements in surgical equipment has led to the development of novel image acquisition platforms, cannulas, smoke evacuation systems, antifog devices, instrumentation, and ligating/hemostatic devices. These innovations will be reviewed and potential clinical applications are discussed.

Impact of the Communities That HEAL Intervention on Buprenorphine-Waivered Practitioners and Buprenorphine Prescribing: A Prespecified Secondary Analysis of the HCS Randomized Clinical Trial.

Importance: Buprenorphine significantly reduces opioid-related overdose mortality. From 2002 to 2022, the Drug Addiction Treatment Act of 2000 (DATA 2000) required qualified practitioners to receive a waiver from the Drug Enforcement Agency to prescribe buprenorphine for treatment of opioid use disorder. During this period, waiver uptake among practitioners was modest; subsequent changes need to be examined. Objective: To determine whether the Communities That HEAL (CTH) intervention increased the rate of practitioners with DATA 2000 waivers and buprenorphine prescribing. Design, Setting, and Participants: This prespecified secondary analysis of the HEALing Communities Study, a multisite, 2-arm, parallel, community-level, cluster randomized, open, wait-list-controlled comparison clinical trial was designed to assess the effectiveness of the CTH intervention and was conducted between January 1, 2020, to December 31, 2023, in 67 communities in Kentucky, Massachusetts, New York, and Ohio, accounting for approximately 8.2 million adults. The participants in this trial were communities consisting of counties (n = 48) and municipalities (n = 19). Trial arm randomization was conducted using a covariate constrained randomization procedure stratified by state. Each state was balanced by community characteristics including urban/rural classification, fatal opioid overdose rate, and community population. Thirty-four communities were randomized to the intervention and 33 to wait-list control arms. Data analysis was conducted between March 20 and September 29, 2023, with a focus on the comparison period from July 1, 2021, to June 30, 2022. Intervention: Waiver trainings and other educational trainings were offered or supported by the HEALing Communities Study research sites in each state to help build practitioner capacity. Main Outcomes and Measures: The rate of practitioners with a DATA 2000 waiver (overall, and stratified by 30-, 100-, and 275-patient limits) per 100 000 adult residents aged 18 years or older during July 1, 2021, to June 30, 2022, were compared between the intervention and wait-list control communities. The rate of buprenorphine prescribing among those waivered practitioners was also compared between the intervention and wait-list control communities. Intention-to-treat and per-protocol analyses were performed. Results: A total of 8 166 963 individuals aged 18 years or older were residents of the 67 communities studied. There was no evidence of an effect of the CTH intervention on the adjusted rate of practitioners with a DATA 2000 waiver (adjusted relative rate [ARR], 1.04; 95% CI, 0.94-1.14) or the adjusted rate of practitioners with a DATA 2000 waiver who actively prescribed buprenorphine (ARR, 0.97; 95% CI, 0.86-1.10). Conclusions and Relevance: In this randomized clinical trial, the CTH intervention was not associated with increases in the rate of practitioners with a DATA 2000 waiver or buprenorphine prescribing among those waivered practitioners. Supporting practitioners to prescribe buprenorphine remains a critical yet challenging step in the continuum of care to treat opioid use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04111939.

Minimally invasive splenectomy is associated with a low perioperative complication rate and short operative time in cats.

OBJECTIVE: To report the perioperative outcome and complications in cats undergoing minimally invasive splenectomy. ANIMALS: 17 client-owned cats. METHODS: Perioperative data were collected from cats undergoing minimally invasive splenectomy from September 2010 to June 2023. Data included history, signalment, preoperative examination and diagnostic testing results, operative technique and time, perioperative outcomes, complications, hospitalization duration, histopathological diagnosis, and outcome. RESULTS: 13 spayed females and 4 neutered males were included, with a median age of 144 months (48 to 196 months). Seven cats underwent total laparoscopic splenectomy (TLS), with 1 cat requiring conversion from TLS to laparoscopic-assisted splenectomy (LAS) due to splenomegaly and an additional cat requiring conversion from TLS to open splenectomy due to uncontrollable splenic capsular hemorrhage. Ten cats underwent LAS, with 1 cat requiring conversion to open splenectomy due to splenomegaly. Additional procedures were performed in 13 cats, with the most common being liver biopsy in 10 cats. Median operative times were 50 minutes (45 to 90 minutes) for TLS and 35 minutes (25 to 80 minutes) for LAS. An intraoperative complication occurred in 1 cat. All but 1 cat survived to discharge. Median follow-up time was 234 days (18 to 1,761 days), with 15 of 16 cats confirmed alive at 30 days and 9 of 16 cats alive at 180 days postoperatively. CLINICAL RELEVANCE: Minimally invasive splenectomy in this cohort of cats was associated with short operative times and a low perioperative complication rate. Veterinary surgeons may consider minimally invasive splenectomy as an efficient and feasible technique in the treatment of splenomegaly or modestly sized splenic masses for diagnostic and therapeutic purposes in cats.

Development and validation of a community-level social determinants of health index for drug overdose deaths in the HEALing Communities Study.

INTRODUCTION: Social determinants of health (SDoH), such as socioeconomic status, education level, and food insecurity, are believed to influence the opioid crisis. While global SDoH indices such as the CDC's Social Vulnerability Index (SVI) and Area Deprivation Index (ADI) combine the explanatory power of multiple social factors for understanding health outcomes, they may be less applicable to the specific challenges of opioid misuse and associated outcomes. This study develops a novel index tailored to opioid misuse outcomes, tests the efficacy of this index in predicting drug overdose deaths across contexts, and compares the explanatory power of this index to other SDoH indices. METHODS: Focusing on four HEALing Communities Study (HCS) states (Kentucky, Massachusetts, New York and Ohio; encompassing 4269 ZIP codes), we identified multilevel SDoH potentially associated with opioid misuse and aggregated publicly available data for each measure. We then leveraged a random forest model to develop a composite measure that predicts age-adjusted drug overdose mortality rates based on SDoH. We used this composite measure to understand HCS and non-HCS communities in terms of overdose risk across areas of varying racial composition. Finally, we compared variance in drug overdose deaths explained by this index to variance explained by the SVI and ADI. RESULTS: Our composite measure included 28 SDoH measures and explained approximately 89 % percent of variance in age-adjusted drug overdose mortality across HCS states. Health care measures, including emergency department visits and primary care provider availability, were top predictors within the index. Index accuracy was robust within and outside of HCS communities and states. This measure identified high levels of overdose mortality risk in segregated communities. CONCLUSIONS: Existing SDoH indices fail to explain much variation in area-level overdose mortality rates. Having tailored composite indices can help us to identify places in which residents are at highest risk based on their composite contexts. A comprehensive index can also help to develop effective community interventions for programs such as HCS by considering the context in which people live.

BMAL1 loss in oligodendroglia contributes to abnormal myelination and sleep.

Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time-of-day dependent. Knockout of Bmal1 in mouse OPCs during development disrupts the expression of genes associated with circadian rhythms, proliferation, density, morphology, and migration, leading to changes in OPC dynamics in a spatiotemporal manner. Furthermore, these deficits translate into thinner myelin, dysregulated cognitive and motor functions, and sleep fragmentation. OPC-specific Bmal1 loss in adulthood does not alter OPC density at baseline but impairs the remyelination of a demyelinated lesion driven by changes in OPC morphology and migration. Lastly, we show that sleep fragmentation is associated with increased prevalence of the demyelinating disorder multiple sclerosis (MS), suggesting a link between MS and sleep that requires further investigation. These findings have broad mechanistic and therapeutic implications for brain disorders that include both myelin and sleep phenotypes.

Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021).

OBJECTIVE: To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture. ANIMALS: 59 dogs and 3 cats. METHODS: Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival). RESULTS: Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival. CLINICAL RELEVANCE: Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.

Laparoscopic adrenalectomy for resection of unilateral noninvasive adrenal masses in dogs is associated with excellent outcomes in experienced centers.

OBJECTIVE: To report the short- and long-term outcomes of laparoscopic adrenalectomy (LA) for resection of unilateral adrenal masses and to document risk factors for conversion and peri- and postoperative morbidity. ANIMALS: 255 client-owned dogs. METHODS: Dogs were included if LA was attempted for resection of a unilateral adrenal mass. Medical records were evaluated and relevant data were reported, including complications, conversion, perioperative death, and long-term outcomes. Signalment, clinicopathological data, and surgical experience were factors statistically evaluated for possible associations with capsular penetration during surgery, conversion, surgical time, duration of hospital stay, death prior to discharge, mass recurrence, and survival time. RESULTS: 155 dogs had left-sided tumors, and 100 had right-sided tumors. Conversion to an open approach was performed in 9.4% of cases. Capsular penetration (19.2%) and major hemorrhage (5.4%) were the most prevalent intraoperative complications. Of the dogs operated on, 94.9% were discharged from the hospital. Lesion side, portion of the gland affected, and surgeon experience influenced surgical time. Conversion rate increased with increasing body condition score and lesion size. Risk of death prior to discharge increased with increasing lesion size. Risk of conversion and death prior to discharge were lower when performed by more experienced surgeons. Capsular penetration during LA increased the risk of tumor recurrence. CLINICAL RELEVANCE: LA for resection of unilateral adrenal masses is associated with excellent outcomes in experienced centers. Surgeons with greater experience with LA have lower surgical times, conversion rates, and risk of death prior to discharge.

Timing matters: A protective role of astrocyte reactivity in neurodegeneration.

Sheehan and Nadarajah et al.1 identified that Bmal1 loss from astrocytes induces the expression of BAG3, a macroautophagy chaperone enriched in Alzheimer's disease patients and in disease-associated astrocytes, enhancing the phagocytosis of misfolded proteins and preventing tau and alpha-synuclein pathologies.

A Qualitative Study of Health Equity's Role in Community Coalition Development.

Opioid overdose deaths are dramatically increasing in the United States and disproportionately affecting minority communities, with the increasing presence of fentanyl exacerbating this crisis. Developing community coalitions is a long-standing strategy used to address public health issues. However, there is a limited understanding of how coalitions operate amid a serious public health crisis. To address this gap, we leveraged data from the HEALing Communities Study (HCS)-a multisite implementation study aiming to reduce opioid overdose deaths in 67 communities. Researchers analyzed transcripts of 321 qualitative interviews conducted with members of 56 coalitions in the four states participating in the HCS. There were no a priori interests in themes, and emergent themes were identified through inductive thematic analysis and then mapped to the constructs of the Community Coalition Action Theory (CCAT). Themes emerged related to coalition development and highlighted the role of health equity in the inner workings of coalitions addressing the opioid epidemic. Coalition members reported seeing the lack of racial and ethnic diversity within their coalitions as a barrier to their work. However, when coalitions focused on health equity, they noted that their effectiveness and ability to tailor their initiatives to their communities' needs were strengthened. Based on our findings, we suggest two additions to enhance the CCAT: (a) incorporating health equity as an overarching construct that affects all stages of development, and (b) ensuring that data about individuals served are included within the pooled resource construct to enable monitoring of health equity.

Neuroimaging feature extraction using a neural network classifier for imaging genetics.

BACKGROUND: Dealing with the high dimension of both neuroimaging data and genetic data is a difficult problem in the association of genetic data to neuroimaging. In this article, we tackle the latter problem with an eye toward developing solutions that are relevant for disease prediction. Supported by a vast literature on the predictive power of neural networks, our proposed solution uses neural networks to extract from neuroimaging data features that are relevant for predicting Alzheimer's Disease (AD) for subsequent relation to genetics. The neuroimaging-genetic pipeline we propose is comprised of image processing, neuroimaging feature extraction and genetic association steps. We present a neural network classifier for extracting neuroimaging features that are related with the disease. The proposed method is data-driven and requires no expert advice or a priori selection of regions of interest. We further propose a multivariate regression with priors specified in the Bayesian framework that allows for group sparsity at multiple levels including SNPs and genes. RESULTS: We find the features extracted with our proposed method are better predictors of AD than features used previously in the literature suggesting that single nucleotide polymorphisms (SNPs) related to the features extracted by our proposed method are also more relevant for AD. Our neuroimaging-genetic pipeline lead to the identification of some overlapping and more importantly some different SNPs when compared to those identified with previously used features. CONCLUSIONS: The pipeline we propose combines machine learning and statistical methods to benefit from the strong predictive performance of blackbox models to extract relevant features while preserving the interpretation provided by Bayesian models for genetic association. Finally, we argue in favour of using automatic feature extraction, such as the method we propose, in addition to ROI or voxelwise analysis to find potentially novel disease-relevant SNPs that may not be detected when using ROIs or voxels alone.