Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

BACKGROUND: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product. METHODS: Starting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach. RESULTS: Calculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment. CONCLUSIONS: Overall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

High data-rate communication link supported through the exploitation of optical channels in a characterized turbulent underwater environment.

Underwater turbulence presents a myriad of challenges for underwater optical systems through wavefront distortion and beam deflection. In this work, an underwater turbulence emulator is developed and thoroughly characterized to experimentally test the proposed underwater turbulence mitigation technique. This technique applies a modified HOBBIT system introduced in atmospheric turbulence to the relatively unknown underwater turbulence domain. By varying a beam's spatial position and relative phase gradient, a volume of turbulence is rapidly probed to determine the beam state for optimal propagation. This probe and control method is applied in multiple facets, including improved optical power transmission as well as supporting a 25-Gbps communication link through a dynamic environment.

Scanning mirror based higher order Bessel-gaussian beams integrated in time (HOBBIT) with applications toward the photoacoustic effect.

We demonstrate a new method for the generation of beams with rapidly tunable orbital angular momentum (OAM). This method is based on using a single-axis scanning galvanometer mirror to add a phase tilt on an elliptical Gaussian beam that is then wrapped to a ring using optics that perform a log-polar transformation. This system can switch between modes in the kHz range and use relatively high power with high efficiency. This scanning mirror HOBBIT system was applied to a light/matter interaction application using the photoacoustic effect, with a 10 dB enhancement of the generated acoustics at a glass/water interface.

Computed tomographic lymphangiography following percutaneous intrahepatic injection of iopamidol in cats.

OBJECTIVE: To determine if computed tomographic lymphangiography (CTL) after ultrasound-guided percutaneous injection of intrahepatic iopamidol (Isovue 370) in healthy cats would safely and effectively lead to opacification of the hepatic lymphatics, cisterna chyli, and thoracic ducts (TDs). STUDY DESIGN: A prospective pilot study design with randomization of the sides of the liver injected. SAMPLE POPULATION: 6 purpose-bred cats. PROCEDURES: Cats were anesthetized and based on random assignment, and the left or right liver was injected with iodinated contrast material. CTL images were taken at 5, 10, and 15 minutes postinjection to determine the quality of opacification of the cisterna chyli and TDs. RESULTS: Eleven hepatic injections from 6 cats were available for review. One CT file was corrupted and unusable. Seven out of 11 hepatic contrast injections yielded a diagnostic study. Five out of 11 were graded as excellent, 0/11 were graded as good, and 2/11 were graded as fair. Opacification of the cisterna chyli and TDs was absent in 4/11 studies. Three out of 6 cats had mild to moderate increases in hepatocellular enzymes when assayed 3 months postprocedure. The hepatic lymphatics, cisterna chyli, and TDs were opacified in all studies deemed diagnostic. CLINICAL RELEVANCE: Intrahepatic contrast injection offers a novel portal for thoracic duct lymphangiography that documents the hepatic contribution to the mesenteric lymphatics, cisterna chyli, and thoracic duct. The procedure may be helpful in the preoperative diagnostic evaluation of cats with chylothorax.

MRI characteristics of canine prostatic neoplasia.

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics. The most consistent characteristics were heterogeneous hyperintensity of the tumor on T2-weighted images (10/10) and short tau inversion recovery images (10/10), prostatic capsular margin distortion by the tumor (10/10), cavitations (10/10), complete effacement of the prostatic architecture (9/10), neurovascular bundle (NVB) compression or invasion (9/10), heterogeneous isointensity of the tumor on T1-weighted images (9/10), and strong contrast enhancement of the tumor (8/10). Additional features included an overlying pattern of distorted radiating striations (7/10), regional lymphadenomegaly (5/10), mineralization within the mass (5/10), urinary bladder trigone involvement (6/10), and post-prostatic urethral involvement (7/10). These findings supported the use of MRI as an adjunct imaging modality for diagnosis and therapeutic planning of prostatic neoplasia and including prostatic neoplasia as a likely differential diagnosis for dogs with these MRI characteristics.

Continuing Chronic Buprenorphine Perioperatively is Associated With Reduced Postoperative Opioid Use.

INTRODUCTION: Buprenorphine is a frequently used medication for opioid use disorder and misunderstanding buprenorphine's unique pharmacology has historically complicated perioperative analgesia. The purpose of this study was to evaluate the association of perioperative buprenorphine continuation in patients with substance use disorder on perioperative opioid use. MATERIALS AND METHODS: This was a single-center retrospective study at a level 1 trauma academic medical center. Adult patients using outpatient buprenorphine for medication for opioid use disorder admitted with an operating room booking were included. Patients were grouped (continuation, withheld) retrospectively based upon the decision to continue or omit buprenorphine therapy while admitted. The primary outcome of the study was any use of full mu-opioid agonists during days 1-7 of admission. Secondary outcomes included length of stay and average pain scores during days 1-7 of admission. RESULTS: 43.4% of patients in the continuation cohort used no full mu-opioid agonists during days 1-7 compared to 3.1% of patients in the withheld cohort (P < 0.001). No significant difference in median length of stay was noted (4.7 d [2.8-6.6] versus 6.1 d [4.0-8.2], P = 0.36). There was no statistical difference in average pain scores on postoperative days 1 (5.2 versus 6.9, P = 0.82) and 7 (0 versus 0, P = 0.41). CONCLUSIONS: Perioperative continuation of buprenorphine is associated with reduced use of alternative full mu-opioid agents while admitted without impacting pain scores.

Sensing and coupling of optical channels in dynamic atmospheric turbulence using OAM beamlets for improved power and data transmission.

Propagation of laser light is distorted in the presence of atmospheric turbulence. This poses an issue for sensing, free-space optical communications, and transmission of power. The presented system offers a novel solution to mitigate the effects of turbulence. By rapidly probing a turbulent volume by varying a beam's spatial and phase characteristics, the best transmission mode can be determined and updated in real time. Unlike a traditional tip-tilt system, this scheme is fully electronic, and has a scalable architecture to leverage multiple optical transmission paths simultaneously. This optical control system greatly improves power efficiency and successful recovery of data through environments with strong turbulence.

Resolution, recurrence, and chyle redistribution after thoracic duct ligation with or without pericardiectomy in dogs with naturally occurring idiopathic chylothorax.

OBJECTIVE: To document outcomes of thoracoscopic treatment of idiopathic chylothorax (IC) in dogs with and without constrictive pericardial physiology (CPP) and evaluate patterns of chyle flow redistribution after thoracic duct ligation (TDL). ANIMALS: 26 client-owned dogs. PROCEDURES: In this prospective cohort study, echocardiography and cardiac catheterization were performed to document CPP in dogs with IC. Thoracoscopic TDL with pericardiectomy was performed if CPP was present (TDL/P group). Dogs without evidence of CPP underwent thoracoscopic TDL alone (TDL group). Dogs underwent preoperative, immediate postoperative, and 3-month postoperative CT lymphangiography studies when possible. Perioperative morbidity, resolution and late recurrence rates, and long-term outcome were recorded. RESULTS: 17 dogs underwent TDL, and 9 underwent TDL/P. Twenty-five of 26 (96%) survived the perioperative period. One dog died from ventricular fibrillation during pericardiectomy. Resolution rates for TDL and TDL/P were 94% and 88%, respectively (P = .55), with 1 late recurrence occurring in the TDL group in a median follow-up of 25 months (range, 4 to 60 months). On 3-month postoperative CT lymphangiography studies, ongoing chyle flow past the ligation site was demonstrated in 5 of 17 dogs, of which 1 dog developed recurrence at 13 months postoperatively. In 15 of 17 dogs, chylous redistribution after TDL was principally by retrograde flow to the lumbar lymphatic plexus. CLINICAL RELEVANCE: In dogs without evidence of CPP, TDL alone was associated with a very good prognosis for treatment of IC. In the absence of CPP, the additional benefit of pericardiectomy in the treatment of IC is questionable.

OAM-based optical wavelet using a single pixel detection system for probing dynamic environments with application to real-time measurements of strong atmospheric turbulence.

This paper presents a novel method for optical probing by generating optical fields with characteristics of wavelets. The optical wavelets form a basis of rotated asymmetric beams with scaled orbital angular momentum (OAM) and beam sizes. The probing method was used experimentally to measure the continuous wavelet transform of a turbulent propagation path, giving insight into the angular properties about a fixed radius. The wavelet transform of a three-dimensional turbulence distribution was measured; the measurements are much faster than the turbulence changes, allowing characterization of an instantaneous realization of turbulence over time. Results show highly localized regions of OAM in space through the turbulence and characteristics of the turbulence can be extracted from the wavelet transforms.

Remote sensing using a spatially and temporally controlled asymmetric perfect vortex basis generated with a 2D HOBBIT.

Orbital angular momentum (OAM) is a potential tool for remote sensing applications since amplitude/phase distributions can be decomposed into an OAM basis for analysis. We demonstrate the generation of a spatially asymmetric perfect vortex (APV) basis based on a pulsed 2D HOBBIT (Higher Order Bessel Beams Integrated in Time) system using two acousto-optic deflectors and optical coordinate transformation optics. Results are demonstrated for numerous radii and OAM charges as high as 20, with switching speeds greater than 400 kHz. The spatial APV basis is used to design different types of pulse trains for amplitude object pattern recognition and phase object wavefront sensing. Experimental results of sensing are provided for an amplitude object and a phase object to demonstrate the feasibility of the spatial APV on remote sensing tasks.

Low-dose adjuvant dexmedetomidine did not decrease propofol sedation requirements in children undergoing gastrointestinal endoscopy.

BACKGROUND: Propofol is the cornerstone of deep sedation during pediatric esophagogastroduodenoscopy (EGD), though adjuvant dexmedetomidine may provide propofol-sparing benefits. OBJECTIVE: The objective of the study was to evaluate whether adjuvant dexmedetomidine decreases the total propofol dose in pediatric patients undergoing EGD. METHODS: This single-center, retrospective, cohort study evaluated the total propofol dose in pediatric patients undergoing EGD with and without the use of adjuvant dexmedetomidine. Secondary outcomes included the change in hemodynamics across the perioperative continuum and post-procedure recovery time. A multivariable general linear regression was performed to identify associated variables for recovery time post-procedure. RESULTS: A total of 159 patients were included in the study; 88 patients received dexmedetomidine and propofol (DEX-PRO), and 71 patients received propofol only (PRO). The median [interquartile range (IQR)] propofol dose in the DEX-PRO group was 0.26 [IQR, 0.17-0.36] mg kg-1  min-1 which was not significantly different than the PRO group at 0.27 [IQR, 0.21-0.34] mg kg-1  min-1 , p = 0.730. Evaluation of secondary end points showed the DEX-PRO group had more cases of post-anesthesia care unit (PACU) hypotension (61% vs. 34%, p = 0.001) and a longer recovery time (32.9 ± 14.1 vs. 25.6 ± 10.8 min, p < 0.001) versus the PRO group, respectively. Multivariable linear regression demonstrated that age and the use of dexmedetomidine were associated with prolonged recovery. CONCLUSION: Adjuvant dexmedetomidine did not reduce propofol requirements compared with propofol alone in pediatric patients undergoing EGD. More hypotension and a longer postoperative recovery time were also seen in patients receiving adjuvant dexmedetomidine for their endoscopic procedure.

Diagnostic yield of uroendoscopy compared to ultrasonography for evaluating lower urinary tract disorders in dogs.

BACKGROUND: Cystourethroscopy and vaginoscopy (uroendoscopy) is often used in the diagnostic evaluation of dogs with lower urinary tract disorders (LUTD). OBJECTIVE/HYPOTHESIS: To evaluate if uroendoscopy is warranted in dogs with various LUTD, the agreement between uroendoscopic and ultrasonographic diagnoses were compared. Dogs with recurrent urinary tract infections (rUTI) will have the highest diagnostic agreement between uroendoscopy and ultrasonography (US) compared to dogs presenting for other LUTD. ANIMALS: Two hundred thirty-seven dogs presenting between 2014 and 2019 with lower urinary tract signs (LUTS) that had US within 60 days preceding uroendoscopy. METHODS: Retrospective study. Dogs were categorized by primary indication for ultrasound. Pertinent uroendoscopic findings were recorded and agreements (κ analysis) between the final uroendoscopic diagnosis were compared with the final ultrasonographic diagnosis. RESULTS: Pertinent uroendoscopic findings were recorded for 69/237 (29%) cases. For dogs presenting primarily for urinary incontinence (UI), agreement between uroendoscopy and US was 71% (46/65; κ = 0.47, 95% CI 0.28-0.66), for dogs with stranguria, 58% (29/50; κ = 0.47, 95% CI 0.31-0.62) and for dogs with rUTI the agreement was substantial at 87% (26/30; κ = 0.70, 95% CI 0.43-0.98). Urethral strictures were the majority (14/21; 67%) of pertinent uroendoscopic findings for dogs with stranguria, of which 12 were male dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Agreement between uroendoscopy and US was moderate for all dogs. Based on these data, recommendation for uroendoscopy should be tailored to individual clinical presentation and signalment; transabdominal US is not the preferred modality for urethral lesions.

Space-time wave packets localized in all dimensions.

Optical wave packets that are localized in space and time, but nevertheless overcome diffraction and travel rigidly in free space, are a long sought-after field structure with applications ranging from microscopy and remote sensing, to nonlinear and quantum optics. However, synthesizing such wave packets requires introducing non-differentiable angular dispersion with high spectral precision in two transverse dimensions, a capability that has eluded optics to date. Here, we describe an experimental strategy capable of sculpting the spatio-temporal spectrum of a generic pulsed beam by introducing arbitrary radial chirp via two-dimensional conformal coordinate transformations of the spectrally resolved field. This procedure yields propagation-invariant 'space-time' wave packets localized in all dimensions, with tunable group velocity in the range from 0.7c to 1.8c in free space, and endowed with prescribed orbital angular momentum. By providing unprecedented flexibility in sculpting the three-dimensional structure of pulsed optical fields, our experimental strategy promises to be a versatile platform for the emerging enterprise of space-time optics.

Evaluation of the use of a novel bioabsorbable polymer drug-eluting microsphere for transarterial embolization of hepatocellular neoplasia in dogs.

In dogs with non-resectable hepatic neoplasia, treatment options are limited. The objectives of this study were to describe the use of a novel drug-eluting embolic microsphere containing paclitaxel for use during transarterial chemoembolization (TACE), to compare results of liver-specific owner questionnaires and tumor volume pre- and post-TACE, and to measure systemic paclitaxel concentration post-TACE. Client-owned dogs with non-resectable hepatic neoplasia were prospectively enrolled. All owners completed questionnaires validated for the assessment of subjective outcomes in dogs with cancer before the TACE procedure and approximately 4 weeks after the TACE procedure. A CT scan was performed before TACE and 1 month after TACE; results were compared. Blood samples were obtained at specified time points post-TACE to determine systemic paclitaxel concentrations. Seven dogs (median weight: 8.9 kg; range, 4.3-31 kg) were enrolled. TACE was successfully performed in all dogs, and no intra-procedural complications were encountered. Questionnaire scores improved significantly post-TACE. Among the 6 dogs for which full data were available, median pre-TACE tumor volume was 390 cc (range 152-1,484; interquartile range 231-1,139) and median post-TACE tumor volume was 203 cc (range 98-889; interquartile range 151-369), which was significantly (P = .028) lower. All 6 dogs had a reduction in volume at the post-TACE measurement. Mean percent change in tumor volume was -45.6% (95%CI -58.6 to -32.6%). The mean plasma paclitaxel concentration in canine blood peaked at 4 days post-TACE procedure and was 25.7 ng/mL (range = 3.09-110 ng/mL) Median survival time was 629 days (95%CI 18 to upper limit not reached). The use of a novel paclitaxel-eluting microsphere in this cohort of dogs successfully decreased tumor volume significantly after TACE and improved clinical signs. Future investigation into the use of TACE and other similar therapies is warranted due to the promising outcomes noted in this cohort.

Inhaled recombinant human IL-15 in dogs with naturally occurring pulmonary metastases from osteosarcoma or melanoma: a phase 1 study of clinical activity and correlates of response.

PURPOSE: Although recombinant human interleukin-15 (rhIL-15) has generated much excitement as an immunotherapeutic agent for cancer, activity in human clinical trials has been modest to date, in part due to the risks of toxicity with significant dose escalation. Since pulmonary metastases are a major site of distant failure in human and dog cancers, we sought to investigate inhaled rhIL-15 in dogs with naturally occurring lung metastases from osteosarcoma (OSA) or melanoma. We hypothesized a favorable benefit/risk profile given the concentrated delivery to the lungs with decreased systemic exposure. EXPERIMENTAL DESIGN: We performed a phase I trial of inhaled rhIL-15 in dogs with gross pulmonary metastases using a traditional 3+3 cohort design. A starting dose of 10 µg twice daily × 14 days was used based on human, non-human primate, and murine studies. Safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) were the primary objectives, while response rates, progression-free and overall survival (OS), and pharmacokinetic and immune correlative analyses were secondary. RESULTS: From October 2018 to December 2020, we enrolled 21 dogs with 18 dogs reaching the 28-day response assessment to be evaluable. At dose level 5 (70 µg), we observed two DLTs, thereby establishing 50 µg twice daily × 14 days as the MTD and recommended phase 2 dose. Among 18 evaluable dogs, we observed one complete response >1 year, one partial response with resolution of multiple target lesions, and five stable disease for an overall clinical benefit rate of 39%. Plasma rhIL-15 quantitation revealed detectable and sustained rhIL-15 concentrations between 1-hour and 6 hour postnebulization. Decreased pretreatment lymphocyte counts were significantly associated with clinical benefit. Cytotoxicity assays of banked peripheral blood mononuclear cells revealed significant increases in peak cytotoxicity against canine melanoma and OSA targets that correlated with OS. CONCLUSIONS: In this first-in-dog clinical trial of inhaled rhIL-15 in dogs with advanced metastatic disease, we observed promising clinical activity when administered as a monotherapy for only 14 days. These data have significant clinical and biological implications for both dogs and humans with refractory lung metastases and support exploration of combinatorial therapies using inhaled rhIL-15.

Effects of a walking program in patients with chronic unilateral vestibular hypofunction.

[Purpose] Patients with chronic unilateral vestibular hypofunction show decreased postural stability and low levels of physical activity and also experience much anxiety. Physical activity is known to improve these symptoms; however, no study has reported any positive effects of physical activity, such as symptom reduction or improvement in function in these patients. In this study, we investigated the role of a walking program in improvement of dizziness, anxiety, and postural stability in this patient population. [Participants and Methods] This study included 21 patients with unilateral vestibular hypofunction and chronic dizziness. Patients were instructed to walk 30 min daily for 3 months. Physical activity levels and questionnaires for clinical symptoms, anxiety, and postural stability were evaluated before and after intervention. [Results] We observed significant differences in the amount of moderate-to-vigorous physical activity, clinical symptoms, and self-perceived handicap before and after the intervention. Additionally, anxiety levels were significantly reduced and postural stability was significantly improved in these patients. [Conclusion] A walking program improved physical activity levels, clinical symptoms, and postural stability and reduced self-perceived handicap and anxiety in patients with chronic unilateral vestibular hypofunction. These results highlight the effectiveness of a walking program for these patients and emphasize its role as a complementary vestibular rehabilitation strategy.

Pharmacotherapeutic prophylaxis and post-operative outcomes within an Enhanced Recovery After Surgery (ERAS®) program: A randomized retrospective cohort study.

BACKGROUND: Pharmacotherapy prophylaxis embedded in Enhanced Recovery After Surgery (ERAS®) protocols is largely unknown because data related to agent choice, dosing, timing, and duration of treatment currently are not collected in the ERAS Interactive Audit System (EIAS®). This exploratory retrospective randomized cohort study characterized pharmacologic regimens pertaining to prophylaxis of surgical site infections (SSI), venous thromboembolism (VTE), and post-operative nausea and vomiting (PONV). MATERIALS AND METHODS: The records of 250 randomly-selected adult patients that underwent elective colorectal (CR) and gynecologic/oncology procedures (GO) at an ERAS® site in North America were abstracted using REDCap. In addition to descriptive statistics, bivariate associations between categorical variables were compared. RESULTS: Rates of SSI, VTE, & PONV were 3.3%, 1.1%, and 53.6%, respectively. Mean length of stay (LOS) for CR was 6.9 days and for GO, 3.5 days (p < 0.001). The most common antibiotic prophylaxis was one-time combination cefazolin 2 g and metronidazole 500 mg between 16 and 30 min preoperatively after chlorhexidine skin preparation. The most frequent VTE prophylaxis was tinzaparin 4500 units SC daily continued for at least 7 days after hospital discharge in oncology patients. PONV was related to longer LOS in both groups. Total morphine milligram equivalents (MME) was positively related to PONV and LOS in both CR & GO groups. CONCLUSION: Guideline-consistent pharmacologic prophylaxis for SSI and VTE for both CR and GO patients was associated with low complication, LOS, and readmission rates. LOS in both groups was highly influenced by total MME, incidence of PONV and multi-modal anesthesia.

Correlation between anxiety and chronic motion sensitivity.

BACKGROUND: Chronic motion sensitivity (CMS) is a combination of autonomic symptoms provoked by exposure to motion. The correlation between anxiety and CMS is not yet well understood. OBJECTIVES: 1) To compare median anxiety levels between young adults with and without CMS. 2) To examine the effect of anxiety on postural stability with immersion virtual reality. 3) To compare anxiety levels between sexes. METHODS: Participants included 60 adults (20-40 years), with and without CMS. After determining their current and general anxiety levels, postural stability was measured. RESULTS: There were significant differences in median (minimum, maximum) state- and trait-anxiety scores between participants with and without CMS, but no significant differences in median state- and trait-anxiety scores between males and females with CMS. There was a significant inverse relationship between state- and trait-anxiety scores and postural stability (ρ= -0.28, p = 0.03, and ρ= -0.32, p = 0.01, respectively). The stepwise regression analysis showed the Motion Sickness Susceptibility Questionnaire-Short Form score to be the only variable contributing significantly to postural stability (R2 = 26.2%; t = -4.5, p < 0.001). CONCLUSIONS: Young adults with CMS are more anxious, although anxiety does not contribute to postural stability in this group. Anxiety levels do not appear to differ between young adult males and females with CMS.

Thoracoscopic detection of thoracic ducts after ultrasound-guided intrahepatic injection of indocyanine green detected by near-infrared fluorescence and methylene blue in dogs.

OBJECTIVE: To describe and compare onset and intensity of thoracic duct (TD) coloration in healthy dogs after intrahepatic injection of either indocyanine green (ICG) visualized by intraoperative near-infrared fluorescence lymphography (NIRFL) or direct thoracoscopic visualization of methylene blue dye (MB). STUDY DESIGN: Prospective study. ANIMALS: Healthy adult Beagle dogs (n = 5). METHODS: All dogs had biochemical panels and complete blood counts preoperatively. Computed tomography lymphography (CTL) was performed prior to a standard 3-port thoracoscopic approach. A mixture of MB and ICG was injected by ultrasound-guided percutaneous injection into right or left-sided hepatic lobes. Data collected included dose of contrast agent (MB vs. ICG), injection site, timing, and quality of operative TD identification. Potential hepatic injury was assessed by repeat laboratory evaluation and abdominal ultrasound 14 days postoperatively. RESULTS: Preoperative CTL provided a diagnostic study in 5/5 dogs. After intrahepatic injection of combined dyes, NIRFL allowed visualization of TDs in 5/5 dogs, but MB did not result in visible TD coloration in any dog. Intrahepatic injection of ICG achieved successful NIRFL in a median time of 6 minutes and persisted for the 20 minute observation period in all five dogs. All dogs recovered without complication and were subsequently adopted. CONCLUSION: NIRFL of the TD can be achieved with intraoperative hepatic injection of ICG. Intrahepatic injection of MB did not result in visible TD coloration. CLINICAL SIGNIFICANCE: Hepatic intra-parenchymal injection is a reliable alternative portal into the TD system for intraoperative visualization of TD anatomy using ICG in dogs.

Association of ultrasonographic features with histologic findings in 71 dogs with protein-losing nephropathy (2008-2018).

OBJECTIVE: To determine whether ultrasonographic features in dogs with protein-losing nephropathy (PLN) were associated with renal biopsy findings and compare corticomedullary ratios between dogs with PLN versus non-renal disease. ANIMALS: 71 dogs with PLN and 33 dogs without renal disease. PROCEDURES: Medical records and archived ultrasonographic images for dogs with PLN that underwent renal biopsy between 2008 and 2018 were reviewed. Corticomedullary ratios were measured. RESULTS: In dogs with PLN, median serum creatinine and BUN concentrations and urine-protein-to-creatinine-ratio prior to renal biopsy were 3.4 mg/dL (interquartile range [IQR], 1.2 to 5.3 mg/dL), 80 mg/dL (IQR, 28 to 105 mg/dL), and 11.4 (IQR, 6.4 to 18.3), respectively. Histologic abnormalities within the tubulointerstitial space were associated with cortical echogenicity. Gastric wall thickness > 5 mm was associated with a histologic diagnosis of acute glomerular disease. Dogs with immune complex-mediated glomerular disease were more likely to have abnormal gastric mural architecture. Other ultrasonographic features of the kidneys, liver, and stomach and the presence of ascites did not help to differentiate immune complex-mediated from non-immune complex-mediated glomerular disease, acute from chronic disease, or amyloid from non-amyloid disease or distinguish whether tubulointerstitial disease was present or absent. Median left corticomedullary ratio for 66 dogs with PLN (1.2) was significantly higher than that for the 33 dogs without renal disease (1.0). CLINICAL RELEVANCE: Ultrasonographic features were poorly associated with specific pathological disorders in dogs with PLN. In this study, the corticomedullary ratio was higher in dogs with PLN, indicating the presence of cortical thickening, but the clinical relevance is unknown.