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1.
Toxicol Appl Pharmacol ; 475: 116636, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37487938

ABSTRACT

In utero exposure to the toxic metal cadmium (Cd) alters fetoplacental growth in rodents and has been inversely associated with birth weight and infant size in some birth cohorts. Moreover, studies suggest that Cd may have differential effects on growth and development according to offspring sex. The purpose of the current study was to evaluate changes in male and female fetoplacental development following a single injection of saline (5 ml/kg ip) or cadmium chloride (CdCl2, 2.5, 5 mg/kg, ip) on gestational day (GD) 9. By GD18, no changes in fetal or placental weights were observed after treatment with 2.5 mg/kg CdCl2. By comparison, the weight and length of male fetuses and their placentas were reduced following treatment with 5 mg/kg CdCl2 whereas no change was observed in females. In addition, the area of maternal and fetal blood vessels as well as the expression of the glucose transporters, Glut1 and Glut3, and the endothelial marker, CD34, were reduced in the placentas of CdCl2-treated male offspring compared to females. Interestingly, the placentas of females accumulated 80% more Cd than males after CdCl2 (5 mg/kg) administration. Female placentas also had higher concentrations of zinc and the zinc transporter Znt1 compared to males which may explain the limited changes in fetal growth observed following CdCl2 treatment. Taken together, disruption of vasculature development and reduced expression of glucose transporters in the placenta provide potential mechanisms underlying reduced fetal growth in male offspring despite the greater accumulation of Cd in female placentas.


Subject(s)
Cadmium , Placenta , Pregnancy , Female , Male , Humans , Placenta/metabolism , Cadmium/toxicity , Cadmium/metabolism , Fetal Development , Fetus , Glucose/metabolism
2.
J Transl Med ; 20(1): 514, 2022 11 08.
Article in English | MEDLINE | ID: mdl-36348415

ABSTRACT

BACKGROUND: Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are the most commonly used vectors in the manufacturing process. However, the integration pattern of these viral vectors and subsequent effect on CAR T-cell products is still unclear. METHODS: We used a modified viral integration sites analysis (VISA) pipeline to evaluate viral integration events around the whole genome in pre-infusion CAR T-cell products. We compared the differences of integration pattern between lentiviral and γ-retroviral products. We also explored whether the integration sites correlated with clinical outcomes. RESULTS: We found that γ-retroviral vectors were more likely to insert than lentiviral vectors into promoter, untranslated, and exon regions, while lentiviral vector integration sites were more likely to occur in intron and intergenic regions. Some integration events affected gene expression at the transcriptional and post-transcriptional level. Moreover, γ-retroviral vectors showed a stronger impact on the host transcriptome. Analysis of individuals with different clinical outcomes revealed genes with differential enrichment of integration events. These genes may affect biological functions by interrupting amino acid sequences and generating abnormal proteins, instead of by affecting mRNA expression. These results suggest that vector integration is associated with CAR T-cell efficacy and clinical responses. CONCLUSION: We found differences in integration patterns, insertion hotspots and effects on gene expression vary between lentiviral and γ-retroviral vectors used in CAR T-cell products and established a foundation upon which we can conduct further analyses.


Subject(s)
Lentivirus , Retroviridae , Humans , Lentivirus/genetics , Retroviridae/genetics , Genetic Vectors , Virus Integration , T-Lymphocytes , DNA
3.
J Am Chem Soc ; 143(16): 6176-6184, 2021 04 28.
Article in English | MEDLINE | ID: mdl-33856804

ABSTRACT

In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo hydrothiolation to provide cyclopropyl sulfides or allylic sulfides. The choice of bisphosphine ligand dictates whether the pathway involves ring-retention or ring-opening. Mechanistic studies reveal the origin for this switchable selectivity. Our results suggest the two pathways share a common cyclopropyl-Rh(III) intermediate. Electron-rich Josiphos ligands promote direct reductive elimination from this intermediate to afford cyclopropyl sulfides in high enantio- and diastereoselectivities. Alternatively, atropisomeric ligands (such as DTBM-BINAP) enable ring-opening from the cyclopropyl-Rh(III) intermediate to generate allylic sulfides with high enantio- and regiocontrol.


Subject(s)
Cyclopropanes/chemistry , Ligands , Sulfhydryl Compounds/chemistry , Allyl Compounds/chemistry , Catalysis , Coordination Complexes/chemistry , Rhodium/chemistry , Stereoisomerism , Sulfides/chemistry
4.
J Am Chem Soc ; 140(32): 10126-10130, 2018 08 15.
Article in English | MEDLINE | ID: mdl-30084247

ABSTRACT

We report a Rh-catalyst for accessing olefins from primary alcohols by a C-C bond cleavage that results in dehomologation. This functional group interconversion proceeds by an oxidation-dehydroformylation enabled by N, N-dimethylacrylamide as a sacrificial acceptor of hydrogen gas. Alcohols with diverse functionality and structure undergo oxidative dehydroxymethylation to access the corresponding olefins. Our catalyst protocol enables a two-step semisynthesis of (+)-yohimbenone and dehomologation of feedstock olefins.


Subject(s)
Alcohols/chemistry , Alkenes/chemical synthesis , Catalysis , Methylation , Molecular Structure , Oxidation-Reduction
5.
J Am Chem Soc ; 139(40): 14049-14052, 2017 10 11.
Article in English | MEDLINE | ID: mdl-28953374

ABSTRACT

We report a Rh-catalyzed hydroamination of 1,3-dienes to generate homoallylic amines. Our work showcases the first case of anti-Markovnikov selectivity in the intermolecular coupling of amines and 1,3-dienes. By tuning the ligand properties and Brønsted acid additive, we find that a combination of rac-BINAP and mandelic acid is critical for achieving anti-Markovnikov selectivity.


Subject(s)
Allyl Compounds/chemical synthesis , Amines/chemical synthesis , Alkenes/chemical synthesis , Alkenes/chemistry , Allyl Compounds/chemistry , Amination , Amines/chemistry , Catalysis , Ligands , Mandelic Acids/chemical synthesis , Mandelic Acids/chemistry , Naphthalenes/chemical synthesis , Naphthalenes/chemistry , Rhodium/chemistry
6.
J Am Chem Soc ; 138(25): 7824-7, 2016 06 29.
Article in English | MEDLINE | ID: mdl-27276235

ABSTRACT

Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate.

7.
Med Image Anal ; 97: 103254, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38968908

ABSTRACT

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries. To improve clarity of vascular anatomy and intra-procedural utility, this work proposes a targeted motion estimation and compensation framework that removes the need for any prior information or external tracking and for user interaction. Motion estimation is performed in two stages: (i) a target identification stage that segments arteries and catheters in the projection domain using a multi-view convolutional neural network to construct a coarse 3D vascular mask; and (ii) a targeted motion estimation stage that iteratively solves for the time-varying motion field via optimization of a vessel-enhancing objective function computed over the target vascular mask. The vessel-enhancing objective is derived through eigenvalues of the local image Hessian to emphasize bright tubular structures. Motion compensation is achieved via spatial transformer operators that apply time-dependent deformations to partial angle reconstructions, allowing efficient minimization via gradient backpropagation. The framework was trained and evaluated in anatomically realistic simulated motion-corrupted CBCTs mimicking TACE of hepatic tumors, at intermediate (3.0 mm) and large (6.0 mm) motion magnitudes. Motion compensation substantially improved median vascular DICE score (from 0.30 to 0.59 for large motion), image SSIM (from 0.77 to 0.93 for large motion), and vessel sharpness (0.189 mm-1 to 0.233 mm-1 for large motion) in simulated cases. Motion compensation also demonstrated increased vessel sharpness (0.188 mm-1 before to 0.205 mm-1 after) and reconstructed vessel length (median increased from 37.37 to 41.00 mm) on a clinical interventional CBCT. The proposed anatomy-aware motion compensation framework presented a promising approach for improving the utility of CBCT for intra-procedural vascular imaging, facilitating selective embolization procedures.

8.
Med Phys ; 51(6): 4158-4180, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38733602

ABSTRACT

PURPOSE: Interventional Cone-Beam CT (CBCT) offers 3D visualization of soft-tissue and vascular anatomy, enabling 3D guidance of abdominal interventions. However, its long acquisition time makes CBCT susceptible to patient motion. Image-based autofocus offers a suitable platform for compensation of deformable motion in CBCT, but it relies on handcrafted motion metrics based on first-order image properties and that lack awareness of the underlying anatomy. This work proposes a data-driven approach to motion quantification via a learned, context-aware, deformable metric, VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ , that quantifies the amount of motion degradation as well as the realism of the structural anatomical content in the image. METHODS: The proposed VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ was modeled as a deep convolutional neural network (CNN) trained to recreate a reference-based structural similarity metric-visual information fidelity (VIF). The deep CNN acted on motion-corrupted images, providing an estimation of the spatial VIF map that would be obtained against a motion-free reference, capturing motion distortion, and anatomic plausibility. The deep CNN featured a multi-branch architecture with a high-resolution branch for estimation of voxel-wise VIF on a small volume of interest. A second contextual, low-resolution branch provided features associated to anatomical context for disentanglement of motion effects and anatomical appearance. The deep CNN was trained on paired motion-free and motion-corrupted data obtained with a high-fidelity forward projection model for a protocol involving 120 kV and 9.90 mGy. The performance of VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ was evaluated via metrics of correlation with ground truth VIF ${\bm{VIF}}$ and with the underlying deformable motion field in simulated data with deformable motion fields with amplitude ranging from 5 to 20 mm and frequency from 2.4 up to 4 cycles/scan. Robustness to variation in tissue contrast and noise levels was assessed in simulation studies with varying beam energy (90-120 kV) and dose (1.19-39.59 mGy). Further validation was obtained on experimental studies with a deformable phantom. Final validation was obtained via integration of VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ on an autofocus compensation framework, applied to motion compensation on experimental datasets and evaluated via metric of spatial resolution on soft-tissue boundaries and sharpness of contrast-enhanced vascularity. RESULTS: The magnitude and spatial map of VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ showed consistent and high correlation levels with the ground truth in both simulation and real data, yielding average normalized cross correlation (NCC) values of 0.95 and 0.88, respectively. Similarly, VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ achieved good correlation values with the underlying motion field, with average NCC of 0.90. In experimental phantom studies, VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ properly reflects the change in motion amplitudes and frequencies: voxel-wise averaging of the local VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ across the full reconstructed volume yielded an average value of 0.69 for the case with mild motion (2 mm, 12 cycles/scan) and 0.29 for the case with severe motion (12 mm, 6 cycles/scan). Autofocus motion compensation using VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ resulted in noticeable mitigation of motion artifacts and improved spatial resolution of soft tissue and high-contrast structures, resulting in reduction of edge spread function width of 8.78% and 9.20%, respectively. Motion compensation also increased the conspicuity of contrast-enhanced vascularity, reflected in an increase of 9.64% in vessel sharpness. CONCLUSION: The proposed VI F D L ${\bm{VI}}{{\bm{F}}}_{DL}$ , featuring a novel context-aware architecture, demonstrated its capacity as a reference-free surrogate of structural similarity to quantify motion-induced degradation of image quality and anatomical plausibility of image content. The validation studies showed robust performance across motion patterns, x-ray techniques, and anatomical instances. The proposed anatomy- and context-aware metric poses a powerful alternative to conventional motion estimation metrics, and a step forward for application of deep autofocus motion compensation for guidance in clinical interventional procedures.


Subject(s)
Cone-Beam Computed Tomography , Image Processing, Computer-Assisted , Movement , Cone-Beam Computed Tomography/methods , Image Processing, Computer-Assisted/methods , Humans
9.
Hepatol Commun ; 8(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38780301

ABSTRACT

BACKGROUND: Vertical sleeve gastrectomy (SGx) is a type of bariatric surgery to treat morbid obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The molecular mechanisms of SGx to improve MASLD are unclear, but increased bile acids (BAs) and FGF19 (mouse FGF15) were observed. FGF15/19 is expressed in the ileum in response to BAs and is critical in not only suppressing BA synthesis in the liver but also promoting energy expenditure. We hypothesized the reduction of obesity and resolution of MASLD by SGx may be mediated by FGF15/19. METHODS: First, we conducted hepatic gene expression analysis in obese patients undergoing SGx, with the results showing increased expression of FGF19 in obese patients' livers. Next, we used wild-type and intestine-specific Fgf15 knockout mice (Fgf15ile-/-) to determine the effects of FGF15 deficiency on improving the metabolic effects. RESULTS: SGx improved metabolic endpoints in both genotypes, evidenced by decreased obesity, improved glucose tolerance, and reduced MASLD progression. However, Fgf15ile-/- mice showed better improvement compared to wild-type mice after SGx, suggesting that other mediators than FGF15 are also responsible for the beneficial effects of FGF15 deficiency. Further gene expression analysis in brown adipose tissue suggests increased thermogenesis. CONCLUSIONS: FGF15 deficiency, the larger BA pool and higher levels of secondary BAs may increase energy expenditure in extrahepatic tissues, which may be responsible for improved metabolic functions following SGx.


Subject(s)
Fatty Liver , Fibroblast Growth Factors , Gastrectomy , Mice, Knockout , Obesity, Morbid , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Animals , Gastrectomy/methods , Mice , Obesity, Morbid/surgery , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , Humans , Male , Fatty Liver/genetics , Fatty Liver/metabolism , Female , Bile Acids and Salts/metabolism , Liver/metabolism , Adult , Middle Aged , Bariatric Surgery , Mice, Inbred C57BL
11.
J Vasc Surg Cases Innov Tech ; 9(1): 101099, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36852317

ABSTRACT

Spontaneous external iliac artery dissection in highly trained athletes is becoming more recognized, but the reason as to why they are occurring remains a mystery. We present a patient with acute limb ischemia secondary to arterial dissection after strenuous exercise. Imaging showed complete occlusion of the distal common iliac artery, and the patient underwent successful revascularization of the right lower extremity using a hybrid approach.

12.
Cureus ; 15(11): e48894, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38106784

ABSTRACT

Carcinosarcomas of the biliary tract are an extremely rare type of malignancy and may be low on a differential when presenting as multiple metastatic masses. In this case report, we report a case of a female who presented with an aggressive late-stage disease whose initial workup did not indicate a malignant process. Further complicating her care, biopsy samples taken from extra-hepatic masses were culture-positive for Lactobacillus rhamnosu. Given the late stage of the patient's disease, hospice care was initiated. The patient passed away four months after the initial presentation.

13.
Otolaryngol Head Neck Surg ; 169(4): 988-998, 2023 10.
Article in English | MEDLINE | ID: mdl-36883992

ABSTRACT

OBJECTIVE: Preoperative planning for otologic or neurotologic procedures often requires manual segmentation of relevant structures, which can be tedious and time-consuming. Automated methods for segmenting multiple geometrically complex structures can not only streamline preoperative planning but also augment minimally invasive and/or robot-assisted procedures in this space. This study evaluates a state-of-the-art deep learning pipeline for semantic segmentation of temporal bone anatomy. STUDY DESIGN: A descriptive study of a segmentation network. SETTING: Academic institution. METHODS: A total of 15 high-resolution cone-beam temporal bone computed tomography (CT) data sets were included in this study. All images were co-registered, with relevant anatomical structures (eg, ossicles, inner ear, facial nerve, chorda tympani, bony labyrinth) manually segmented. Predicted segmentations from no new U-Net (nnU-Net), an open-source 3-dimensional semantic segmentation neural network, were compared against ground-truth segmentations using modified Hausdorff distances (mHD) and Dice scores. RESULTS: Fivefold cross-validation with nnU-Net between predicted and ground-truth labels were as follows: malleus (mHD: 0.044 ± 0.024 mm, dice: 0.914 ± 0.035), incus (mHD: 0.051 ± 0.027 mm, dice: 0.916 ± 0.034), stapes (mHD: 0.147 ± 0.113 mm, dice: 0.560 ± 0.106), bony labyrinth (mHD: 0.038 ± 0.031 mm, dice: 0.952 ± 0.017), and facial nerve (mHD: 0.139 ± 0.072 mm, dice: 0.862 ± 0.039). Comparison against atlas-based segmentation propagation showed significantly higher Dice scores for all structures (p < .05). CONCLUSION: Using an open-source deep learning pipeline, we demonstrate consistently submillimeter accuracy for semantic CT segmentation of temporal bone anatomy compared to hand-segmented labels. This pipeline has the potential to greatly improve preoperative planning workflows for a variety of otologic and neurotologic procedures and augment existing image guidance and robot-assisted systems for the temporal bone.


Subject(s)
Deep Learning , Ear, Inner , Humans , Temporal Bone/diagnostic imaging , Cone-Beam Computed Tomography , Tomography, X-Ray Computed/methods , Image Processing, Computer-Assisted/methods
14.
Article in English | MEDLINE | ID: mdl-37937266

ABSTRACT

Purpose: Cone-beam CT (CBCT) is used in interventional radiology (IR) for identification of complex vascular anatomy, difficult to visualize in 2D fluoroscopy. However, long acquisition time makes CBCT susceptible to soft-tissue deformable motion that degrades visibility of fine vessels. We propose a targeted framework to compensate for deformable intra-scan motion via learned full-sequence models for identification of vascular anatomy coupled to an autofocus function specifically tailored to vascular imaging. Methods: The vessel-targeted autofocus acts in two stages: (i) identification of vascular and catheter targets in the projection domain; and, (ii) autofocus optimization for a 4D vector field through an objective function that quantifies vascular visibility. Target identification is based on a deep learning model that operates on the complete sequence of projections, via a transformer encoder-decoder architecture that uses spatial-temporal self-attention modules to infer long-range feature correlations, enabling identification of vascular anatomy with highly variable conspicuity. The vascular autofocus function is derived through eigenvalues of the local image Hessian, which quantify the local image structure for identification of bright tubular structures. Motion compensation was achieved via spatial transformer operators that impart time dependent deformations to NPAR = 90 partial angle reconstructions, allowing for efficient minimization via gradient backpropagation. The framework was trained and evaluated in synthetic abdominal CBCTs obtained from liver MDCT volumes and including realistic models of contrast-enhanced vascularity with 15 to 30 end branches, 1 - 3.5 mm vessel diameter, and 1400 HU contrast. Results: The targeted autofocus resulted in qualitative and quantitative improvement in vascular visibility in both simulated and clinical intra-procedural CBCT. The transformer-based target identification module resulted in superior detection of target vascularity and a lower number of false positives, compared to a baseline U-Net model acting on individual projection views, reflected as a 1.97x improvement in intersection-over-union values. Motion compensation in simulated data yielded improved conspicuity of vascular anatomy, and reduced streak artifacts and blurring around vessels, as well as recovery of shape distortion. These improvements amounted to an average 147% improvement in cross correlation computed against the motion-free ground truth, relative to the un-compensated reconstruction. Conclusion: Targeted autofocus yielded improved visibility of vascular anatomy in abdominal CBCT, providing better potential for intra-procedural tracking of fine vascular anatomy in 3D images. The proposed method poses an efficient solution to motion compensation in task-specific imaging, with future application to a wider range of imaging scenarios.

15.
Cancer Res Commun ; 3(12): 2497-2509, 2023 12 08.
Article in English | MEDLINE | ID: mdl-37956312

ABSTRACT

The BCL2 inhibitor venetoclax promotes apoptosis in blood cancer cells and is approved for treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, multiple myeloma cells are frequently more dependent on MCL-1 for survival, conferring resistance to venetoclax. Here we report that mevalonate pathway inhibition with statins can overcome resistance to venetoclax in multiple myeloma cell lines and primary cells. In addition, statins sensitize to apoptosis induced by MCL-1 inhibitor, S63845. In retrospective analysis of venetoclax clinical studies in multiple myeloma, background statin use was associated with a significantly enhanced rate of stringent complete response and absence of progressive disease. Statins sensitize multiple myeloma cells to venetoclax by upregulating two proapoptotic proteins: PUMA via a p53-independent mechanism and NOXA via the integrated stress response. These findings provide rationale for prospective testing of statins with venetoclax regimens in multiple myeloma. SIGNIFICANCE: BH3 mimetics including venetoclax hold promise for treatment of multiple myeloma but rational combinations are needed to broaden efficacy. This study presents mechanistic and clinical data to support addition of pitavastatin to venetoclax regimens in myeloma. The results open a new avenue for repurposing statins in blood cancer.


Subject(s)
Antineoplastic Agents , Hematologic Neoplasms , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Multiple Myeloma , Humans , Myeloid Cell Leukemia Sequence 1 Protein , Multiple Myeloma/drug therapy , Proto-Oncogene Proteins c-bcl-2/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Retrospective Studies , Prospective Studies , Antineoplastic Agents/pharmacology , Hematologic Neoplasms/drug therapy
16.
Case Rep Med ; 2022: 2612544, 2022.
Article in English | MEDLINE | ID: mdl-35222647

ABSTRACT

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease characterized by the formation of cutaneous and visceral telangiectasias and arteriovenous malformations (AVM). Multiple organs may be affected, including the nasal mucosa, skin, lungs, gastrointestinal tract, and brain. The following case highlights a unique manifestation of HHT in a patient with a gastrointestinal hemorrhage and epistaxis, resulting in hyperammonemia and diffuse cerebral edema and herniation. Clinicians should be aware of this potential complication in such patients and initiate ammonia-reducing agents early to avoid this devastating consequence.

17.
ACS Chem Biol ; 17(8): 2024-2030, 2022 08 19.
Article in English | MEDLINE | ID: mdl-35839076

ABSTRACT

cAMP is a ubiquitous second messenger with many functions in diverse organisms. Current cAMP sensors, including Föster resonance energy transfer (FRET)-based and single-wavelength-based sensors, allow for real time visualization of this small molecule in cultured cells and in some cases in vivo. Nonetheless the observation of cAMP in living animals is still difficult, typically requiring specialized microscopes and ex vivo tissue processing. Here we used ligand-dependent protein stabilization to create a new cAMP sensor. This sensor allows specific and sensitive detection of cAMP in living zebrafish embryos, which may enable new understanding of the functions of cAMP in living vertebrates.


Subject(s)
Biosensing Techniques , Cyclic AMP , Animals , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Fluorescence Resonance Energy Transfer , Ligands , Zebrafish/metabolism
18.
J Cardiothorac Surg ; 17(1): 173, 2022 Jul 08.
Article in English | MEDLINE | ID: mdl-35804449

ABSTRACT

BACKGROUND: Papillary muscle rupture due to infective endocarditis is a rare event and proper management of this condition has not been described in the literature. Our case aims to shed light on treatment strategies for these patients using the current guidelines. CASE PRESENTATION: This case presents a 58-year-old male with acute heart failure secondary to papillary muscle rupture. He underwent an en bloc resection of his mitral valve with a bioprosthetic valve replacement. Specimen pathology later showed necrotic papillary muscle due to infective endocarditis. The patient was further treated with antibiotic therapy. He recovered well post-operatively and continued to do well after discharge. CONCLUSION: In patients who present with papillary muscle rupture secondary to infective endocarditis, clinical symptoms should drive the treatment strategy. Despite the etiology, early mitral valve surgery remains treatment of choice for patients who have papillary muscle rupture leading to acute heart failure. Culture-guided prolonged antibiotic treatment is vital in this category of patients, especially those who have a prosthetic valve implanted.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Heart Failure , Heart Rupture , Mitral Valve Insufficiency , Acute Disease , Endocarditis/complications , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/pathology , Endocarditis, Bacterial/surgery , Heart Failure/complications , Heart Rupture/complications , Heart Rupture/surgery , Humans , Male , Middle Aged , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/surgery , Papillary Muscles/surgery
19.
Otol Neurotol ; 43(6): e679-e687, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35761465

ABSTRACT

HYPOTHESIS: Automated image registration techniques can successfully determine anatomical variation in human temporal bones with statistical shape modeling. BACKGROUND: There is a lack of knowledge about inter-patient anatomical variation in the temporal bone. Statistical shape models (SSMs) provide a powerful method for quantifying variation of anatomical structures in medical images but are time-intensive to manually develop. This study presents SSMs of temporal bone anatomy using automated image-registration techniques. METHODS: Fifty-three cone-beam temporal bone CTs were included for SSM generation. The malleus, incus, stapes, bony labyrinth, and facial nerve were automatically segmented using 3D Slicer and a template-based segmentation propagation technique. Segmentations were then used to construct SSMs using MATLAB. The first three principal components of each SSM were analyzed to describe shape variation. RESULTS: Principal component analysis of middle and inner ear structures revealed novel modes of anatomical variation. The first three principal components for the malleus represented variability in manubrium length (mean: 4.47 mm; ±2-SDs: 4.03-5.03 mm) and rotation about its long axis (±2-SDs: -1.6° to 1.8° posteriorly). The facial nerve exhibits variability in first and second genu angles. The bony labyrinth varies in the angle between the posterior and superior canals (mean: 88.9°; ±2-SDs: 83.7°-95.7°) and cochlear orientation (±2-SDs: -4.0° to 3.0° anterolaterally). CONCLUSIONS: SSMs of temporal bone anatomy can inform surgeons on clinically relevant inter-patient variability. Anatomical variation elucidated by these models can provide novel insight into function and pathophysiology. These models also allow further investigation of anatomical variation based on age, BMI, sex, and geographical location.


Subject(s)
Ear, Inner , Temporal Bone , Humans , Imaging, Three-Dimensional , Incus , Malleus , Models, Statistical , Temporal Bone/anatomy & histology , Temporal Bone/diagnostic imaging
20.
Otolaryngol Head Neck Surg ; 167(4): 731-738, 2022 10.
Article in English | MEDLINE | ID: mdl-35133916

ABSTRACT

OBJECTIVE: Proposed methods of minimally invasive and robot-assisted procedures within the temporal bone require measurements of surgically relevant distances and angles, which often require time-consuming manual segmentation of preoperative imaging. This study aims to describe an automatic segmentation and measurement extraction pipeline of temporal bone cone-beam computed tomography (CT) scans. STUDY DESIGN: Descriptive study of temporal bone measurements. SETTING: Academic institution. METHODS: A propagation template composed of 16 temporal bone CT scans was formed with relevant anatomical structures and landmarks manually segmented. Next, 52 temporal bone CT scans were autonomously segmented using deformable registration techniques from the Advanced Normalization Tools Python package. Anatomical measurements were extracted via in-house Python algorithms. Extracted measurements were compared to ground truth values from manual segmentations. RESULTS: Paired t test analyses showed no statistical difference between measurements using this pipeline and ground truth measurements from manually segmented images. Mean (SD) malleus manubrium length was 4.39 (0.34) mm. Mean (SD) incus short and long processes were 2.91 (0.18) mm and 3.53 (0.38) mm, respectively. The mean (SD) maximal diameter of the incus long process was 0.74 (0.17) mm. The first and second facial nerve genus had mean (SD) angles of 68.6 (6.7) degrees and 111.1 (5.3) degrees, respectively. The facial recess had a mean (SD) span of 3.21 (0.46) mm. Mean (SD) minimum distance between the external auditory canal and tegmen was 3.79 (1.05) mm. CONCLUSIONS: This is the first study to automatically extract relevant temporal bone anatomical measurements from CT scans using segmentation propagation. Measurements from these models can streamline preoperative planning, improve future segmentation techniques, and help develop future image-guided or robot-assisted systems for temporal bone procedures.


Subject(s)
Temporal Bone , Tomography, X-Ray Computed , Algorithms , Cone-Beam Computed Tomography , Facial Nerve , Humans , Image Processing, Computer-Assisted/methods , Temporal Bone/diagnostic imaging , Temporal Bone/surgery , Tomography, X-Ray Computed/methods
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